Search results for: blood profile

Authors: Asim Abbasi, Muhammad Sufyan, Iqra, Hafiza Javaria Ashraf

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The share of vector-borne diseases (VBDs) in the global burden of infectious diseases is almost 17%. The advent of new drugs and latest research in medical science helped mankind to compete with these lethal diseases but still diseases transmitted by different mosquito species, including filariasis, malaria, viral encephalitis and dengue are serious threats for people living in disease endemic areas. Injudicious and repeated use of pesticides posed selection pressure on mosquitoes leading to development of resistance. Hence biological control agents are under serious consideration of scientific community to be used in vector control programmes. Fish have a history of predating immature stages of different aquatic insects including mosquitoes. The noteworthy examples in Africa and Asia includes, Aphanius discolour and a fish in the Panchax group. Moreover, common mosquito fish, Gambusia affinis predates mostly on temporary water mosquitoes like anopheline as compared to permanent water breeders like culicines. Mosquitoes belonging to genus Toxorhynchites have a worldwide distribution and are mostly associated with the predation of other mosquito larvae habituating with them in natural and artificial water containers. These species are harmless to humans as their adults do not suck human blood but feeds on floral nectar. However, their activity is mostly temperature dependent as Toxorhynchites brevipalpis consume 359 Aedes aegypti larvae at 30-32 ºC in contrast to 154 larvae at 20-26 ºC. Although many bacterial species were isolated from mosquito cadavers but those belonging to genus Bacillus are found highly pathogenic against them. The successful species of this genus include Bacillus thuringiensis and Bacillus sphaericus. The prime targets of B. thuringiensis are mostly the immatures of genus Aedes, Culex, Anopheles and Psorophora while B. sphaericus is specifically toxic against species of Culex, Psorophora and Culiseta. The entomopathogenic nematodes belonging to family, mermithidae are also pathogenic to different mosquito species. Eighty different species of mosquitoes including Anopheles, Aedes and Culex proved to be highly vulnerable to the attack of two mermithid species, Romanomermis culicivorax and R. iyengari. Cytoplasmic polyhedrosis virus was the first described pathogenic virus, isolated from the cadavers of mosquito specie, Culex tarsalis. Other viruses which are pathogenic to culicine includes, iridoviruses, cytopolyhedrosis viruses, entomopoxviruses and parvoviruses. Protozoa species belonging to division microsporidia are the common pathogenic protozoans in mosquito populations which kill their host by the chronic effects of parasitism. Moreover, due to their wide prevalence in anopheline mosquitoes and transversal and horizontal transmission from infected to healthy host, microsporidia of the genera Nosema and Amblyospora have received much attention in various mosquito control programmes. Fungal based mycopesticides are used in biological control of insect pests with 47 species reported virulent against different stages of mosquitoes. These include both aquatic fungi i.e. species of Coelomomyces, Lagenidium giganteum and Culicinomyces clavosporus, and the terrestrial fungi Metarhizium anisopliae and Beauveria bassiana. Hence, it was concluded that the integrated use of all these biological control agents can be a healthy contribution in mosquito control programmes and become a dire need of the time to avoid repeated use of pesticides.

Keywords: entomopathogenic nematodes, protozoa, Toxorhynchites, vector-borne

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Boris Nemzer, Nebiyu Abshiru, Z. B. Pietrzkowski

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Coffee cherry is one of the most ubiquitous agricultural commodities which possess nutritional and human health beneficial properties. Between the two most widely used coffee cherries Coffea arabica (Arabica) and Coffea canephora (Robusta), Coffea arabica remains superior due to its sensory properties and, therefore, remains in great demand in the global coffee market. In this study, the phytochemical contents and pharmacokinetics of Coffeeberry® Energy (CBE), a commercially available Arabica whole coffee fruit caffeine extract, are investigated. For phytochemical screening, 20 mg of CBE was dissolved in an aqueous methanol solution for analysis by mass spectrometry (MS). Quantification of caffeine and chlorogenic acids (CGAs) contents of CBE was performed using HPLC. For the bioavailability study, serum samples were collected from human subjects before and after 1, 2 and 3 h post-ingestion of 150mg CBE extract. Protein precipitation and extraction were carried out using methanol. Identification of compounds was performed using an untargeted metabolomic approach on Q-Exactive Orbitrap MS coupled to reversed-phase chromatography. Data processing was performed using Thermo Scientific Compound Discover 3.3 software. Phytochemical screening identified a total of 170 compounds, including organic acids, phenolic acids, CGAs, diterpenoids and hydroxytryptamine. Caffeine & CGAs make up more than, respectively, 70% & 9% of the total CBE composition. For serum samples, a total of 82 metabolites representing 32 caffeine- and 50 phenolic-derived metabolites were identified. Volcano plot analysis revealed 32 differential metabolites (24 caffeine- and 8 phenolic-derived) that showed an increase in serum level post-CBE dosing. Caffeine, uric acid, and trimethyluric acid isomers exhibited 4- to 10-fold increase in serum abundance post-dosing. 7-Methyluric acid, 1,7-dimethyluric acid, paraxanthine and theophylline exhibited a minimum of 1.5-fold increase in serum level. Among the phenolic-derived metabolites, iso-feruloyl quinic acid isomers (3-, 4- and 5-iFQA) showed the highest increase in serum level. These compounds were essentially absent in serum collected before dosage. More interestingly, the iFQA isomers were not originally present in the CBE extract, as our phytochemical screen did not identify these compounds. This suggests the potential formation of the isomers during the digestion and absorption processes. Pharmacokinetics parameters (Cmax, Tmax and AUC0-3h) of caffeine- and phenolic-derived metabolites were also investigated. Caffeine was rapidly absorbed, reaching a maximum concentration (Cmax) of 10.95 µg/ml in just 1 hour. Thereafter, caffeine level steadily dropped from the peak level, although it did not return to baseline within the 3-hour dosing period. The disappearance of caffeine from circulation was mirrored by the rise in the concentration of its methylxanthine metabolites. Similarly, serum concentration of iFQA isomers steadily increased, reaching maximum (Cmax: 3-iFQA, 1.54 ng/ml; 4-iFQA, 2.47 ng/ml; 5-iFQA, 2.91 ng/ml) at tmax of 1.5 hours. The isomers remained well above the baseline during the 3-hour dosing period, allowing them to remain in circulation long enough for absorption into the body. Overall, the current study provides evidence of the potential health benefits of a uniquely formulated whole coffee fruit product. Consumption of this product resulted in a distinct serum profile of bioactive compounds, as demonstrated by the more than 32 metabolites that exhibited a significant change in systemic exposure.

Keywords: phytochemicals, mass spectrometry, pharmacokinetics, differential metabolites, chlorogenic acids

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Authors: Aleksandra Chałupnik, Zuzanna Chilimoniuk, Joanna Borowik, Aleksandra Borkowska, Anna Torres

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Background: Precocious puberty is the occurrence of secondary sexual characteristics in girls before the age of 8. The diverse etiology of premature puberty is crucial to determine whether it is true precocious puberty, depending on the activation of the hypothalamic-pituitary-gonadal axis, or pseudo-precocious, which is independent of the activation of this axis. Whatever the cause, premature action of the sex hormones leads to the common symptoms of various forms of puberty. These include the development of sexual characteristics, acne, acceleration of growth rate and acceleration of skeletal maturation. Due to the possible genetic basis of the disorders, an interdisciplinary search for the cause is needed. Case report: The case report concerns a patient of a pediatric gynecology clinic who, at the age of two years, developed advanced thelarhe (M3) and started recurrent vaginal bleeding. In August 2019, gonadotropin suppression initially and after LHRH stimulation and high estradiol levels were reported at the Endocrinology Department. Imaging examinations showed a cyst in the right ovary projection. The bone age was six years. The entire clinical picture indicated pseudo- (peripheral) precocious in the course of ovarian autonomic cyst. In the follow-up ultrasound performed in September, the image of the cyst was stationary and normalization of estradiol levels and clinical symptoms was noted. In December 2019, cyst regression and normal gonadotropin and estradiol concentrations were found. In June 2020, white mucus tinged with blood on the underwear, without any other disturbing symptoms, was observed for several days. Two consecutive USG examinations carried out in the same month confirmed the change in the right ovary, the diameter of which was 25 mm with a very high level of estradiol. Germinal tumor markers were normal. On the Tanner scale, the patient scored M2P1. The labia and hymen had puberty features. The correct vaginal entrance was visible. Another active vaginal bleeding occurred in the first week of July 2020. The considered laparoscopic treatment was abandoned due to the lack of oncological indications. Treatment with Tamoxifen was recommended in July 2020. In the initiating period of treatment, no maturation progression, and even reduction of symptoms, no acceleration of growth and a marked reduction in the size of the cysts were noted. There was no bleeding. After the size of the cyst and hormonal activity increased again, the treatment was changed to Anastrozole, the effect of which led to a reduction in the size of the cyst. Conclusions: The entire clinical picture indicates alleged (peripheral) puberty. Premature puberty in girls, which is manifested as enlarged mammary glands with high levels of estrogens secreted by autonomic ovarian cysts and prepubertal levels of gonadotropins, may indicate McCune-Albright syndrome. Vaginal bleeding may also occur in this syndrome. Cancellation of surgical treatment of the cyst made it impossible to perform a molecular test that would allow to confirm the diagnosis. Taking into account the fact that cysts are often one of the first symptoms of McCune-Albrigt syndrome, it is important to remember about multidisciplinary care for the patient and careful search for skin and bone changes or other hormonal disorders.

Keywords: McCune Albrigth's syndrome, ovarian cyst, pediatric gynaecology, precocious puberty

Procedia PDF Downloads 190

Authors: Sarah H. Davies

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In the year 146 BCE, the Roman general Scipio Aemilianus – soon to be ‘anointed,’ via mass-spilling of blood-on-land, as “(‘triumphal’) Africanus” – stood atop a hill, overlooking the city of Carthage, as its urban-scape was burned and people killed, violated, captured… ‘poetically’ consumed. From an ineffable-seeming distance – constructed, in imperial fascination – the scene was (and is, apparently) painted in a disturbingly ‘romantic’ light. Such a snap-shot vista, projected before a mind’s-eye in panorama, and in (ongoing) construction, has seeped across ancient and modern lines, with multiple, interwoven iterations. This study conducts a reading, both ‘postcolonial’ and anti-imperial, in interruption of an ongoing (re)iteration of imperial violence, mirrored in distortion between “ancient” and “modern” forms that are physical, ideological, and ontological. Using an analysis of ancient literary works, from the historiographical (Polybius’ Histories) to the epic-poetic (Vergil’s Aeneid), placed in juxtaposition with a range of modern material, both literary-historical (e.g., Gibbon’s Decline & Fall of the Roman Empire) and visual (Cole’s The Course of Empire), this study destabilizes ongoing formations. Such formations attempt to inflict ‘an assumed’ repetition, engaged in normalizing a city violently destroyed as somehow ‘natural’ and/or ‘inevitable,’ and by extension, ‘tragically necessary.’ The reiterations – across media and contexts – create a distorted aesthetic (itself an act of profound violence) that fetishizes and even produces sensory, illusory pleasures (of co-complicit harm, within and across communities) regarding ‘period-shifting events’ of mass-murder and cultural erasure. ‘The vista over Carthage burning’ was/is (but does not ever have to be) thereby a manufactured stage-set, a commodity for imperial reproduction. Such a projection frames an overly-simplistic, ‘safe’-seeming (and yet incredibly dangerous) binary regarding (caricatured) “victims” and “victors.” At the same time, the projection renders an epistemological frame whereby ‘The One’ and ‘The Other’ are asserted as inherently antagonistic categories of being, in which One ‘must’ replace Other – the latter portrayed in gendered, exoticized, and time-distorted ways, as a scripted-object. All the while, a very particular subset of narrative is woven, whereby Carthage (elided in ‘victim’ status) specifically is/was Troy (again, elided), is/was every ‘destroyed city’ (also elided), and is/was yet another essential marking-point of “History,” twisted into ‘becoming’ a ‘reset’ point in a ‘cyclical pattern,’ inscribed as a tragic plot or lifetime repeated. The script itself entails pervasive violence. And yet, there always remains a trip-wire written into the constructed-cyclical. In part, this realization comes from a deconstruction of the tiered violences of an over-worn trope. The realization then also comes from a revelation of erased realities of human-experiences, in which ‘victim’ and ‘victor’ suffer, in fractured differences of ongoing, system(at)ic (re)trauma. The contours and silences of the historical records contain all the ongoing scars. This study therefore unravels the intersectional tableaux of ‘Carthage-burning’ and ‘Rome-reiterative,’ providing a collective investigation into conceptual formations, fractured across millennia. Ultimately, perhaps, such a re-reading – occurring via a commodified past will echo words from the Aeneid: “perhaps, once upon a time, to have remembered even these things, it will have been healing.

Keywords: antiquity, carthage, empire, historiography, rome, ruination

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

Procedia PDF Downloads 131

Authors: Siti Rahayu, Khairulniza Mohd Puat, Kesavan R., Mohammad Harris A., Jalila, Kunalan G., Fazir Mohamad

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The greatest challenge has been in establishing and maintaining the dedicated nursing team. Continuity is served when nurses are assigned exclusively for managing wound, where they can continue to build expertise and skills. In addition, there is a growing incidence of chronic wounds and recognition of the complexity involved in caring for these patients. We would like to share 4 cases with different techniques of wound management. 1st case, 39 years old gentleman with underlying rheumatoid arthritis with chronic periprosthetic joint infection of right total knee replacement presented with persistent drainage over right knee. Patient was consulted for two stage revision total knee replacement. However, patient only agreed for debridement and retention of implant. After debridement, large medial and lateral wound was treated with Instillation Negative Pressure Wound Therapy Dressings. After several cycle, the wound size reduced, and conventional dressing was applied. 2nd case, 58 years old gentleman with underlying diabetes presented with right foot necrotizing fasciitis with gangrene of 5th toe. He underwent extensive debridement of foot with rays’ amputation of 5th toe. Post debridement patient was started on Instillation Negative Pressure Wound Therapy Dressings. After several cycle of VAC, the wound bed was prepared, and he underwent split skin graft over right foot. 3 rd case, 60 years old gentleman with underlying diabetes mellitus presented with right foot necrotizing soft tissue infection. He underwent rays’ amputation and extensive wound debridement. Upon stabilization of general condition, patient was discharge with regular wound dressing by same nurse and doctor during each visit to clinic follow up. After 6 months of follow up, the wound healed well. 4th case, 38-year-old gentleman had alleged motor vehicle accident and sustained closed fracture right tibial plateau. Open reduction and proximal tibial locking plate were done. At 2 weeks post-surgery, the patient presented with warm, erythematous leg and pus discharge from the surgical site. Empirical antibiotic was started, and wound debridement was done. Intraoperatively, 50cc pus was evacuated, unhealthy muscle and tissue debrided. No loosening of the implant. Patient underwent multiple wound debridement. At 2 weeks post debridement wound healed well, but the proximal aspect was unable to close immediately. This left the proximal part of the implant to be exposed. Patient was then put on VAC dressing for 3 weeks until healthy granulation tissue closes the implant. Meanwhile, antibiotic was change according to culture and sensitivity. At 6 weeks post the first debridement, the wound was completely close, and patient was discharge home well. At 3 months post operatively, patient wound and fracture healed uneventfully and able to ambulate independently. Complex wounds are too serious to be dealt with. Team managing complex wound need continuous support through the provision of educational tools to support their professional development, engagement with local and international expert, as well as highquality products that increase efficiencies in services

Keywords: VAC (Vacuum Assisted Closure), empirical- initial antibiotics, NPWT- negative pressure wound therapy, NF- necrotizing fasciitis, gangrene- blackish discoloration due to poor blood supply

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Authors: Irmak Karaduman, Tugba Corlu, Sezin Galioglu, Burcu Akata, M. Ali Yildirim, Aytunç Ateş, Selim Acar

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Breath analysis represents a promising non-invasive, fast and cost-effective alternative to well-established diagnostic and monitoring techniques such as blood analysis, endoscopy, ultrasonic and tomographic monitoring. Portable, non-invasive, and low-cost breath analysis devices are becoming increasingly desirable for monitoring different diseases, especially asthma. Beacuse of this, NO gas sensing at low concentrations has attracted progressive attention for clinical analysis in asthma. Recently, nanomaterials based sensors are considered to be a promising clinical and laboratory diagnostic tool, because its large surface–to–volume ratio, controllable structure, easily tailored chemical and physical properties, which bring high sensitivity, fast dynamic processand even the increasing specificity. Among various nanomaterials, semiconducting metal oxides are extensively studied gas-sensing materials and are potential sensing elements for breathanalyzer due to their high sensitivity, simple design, low cost and good stability.The sensitivities of metal oxide semiconductor gas sensors can be enhanced by adding noble metals. Doping contents, distribution, and size of metallic or metal oxide catalysts are key parameters for enhancing gas selectivity as well as sensitivity. By manufacturing doping MOS structures, it is possible to develop more efficient sensor sensing layers. Zeolites are perhaps the most widely employed group of silicon-based nanoporous solids. Their well-defined pores of sub nanometric size have earned them the name of molecular sieves, meaning that operation in the size exclusion regime is possible by selecting, among over 170 structures available, the zeolite whose pores allow the pass of the desired molecule, while keeping larger molecules outside.In fact it is selective adsorption, rather than molecular sieving, the mechanism that explains most of the successful gas separations achieved with zeolite membranes. In view of their molecular sieving and selective adsorption properties, it is not surprising that zeolites have found use in a number of works dealing with gas sensing devices. In this study, the Cu doped ZnO nanostructure film was produced by SILAR method and investigated the NO gas sensing properties. To obtain the selectivity of the sample, the gases including CO,NH3,H2 and CH4 were detected to compare with NO. The maximum response is obtained at 85 C for 20 ppb NO gas. The sensor shows high response to NO gas. However, acceptable responses are calculated for CO and NH3 gases. Therefore, there are no responses obtain for H2 and CH4 gases. Enhanced to selectivity, Cu doped ZnO nanostructure film was coated with zeolite A thin film. It is found that the sample possess an acceptable response towards NO hardly respond to CO, NH3, H2 and CH4 at room temperature. This difference in the response can be expressed in terms of differences in the molecular structure, the dipole moment, strength of the electrostatic interaction and the dielectric constant. The as-synthesized thin film is considered to be one of the extremely promising candidate materials in electronic nose applications. This work is supported by The Scientific and Technological Research Council of Turkey (TUBİTAK) under Project No, 115M658 and Gazi University Scientific Research Fund under project no 05/2016-21.

Keywords: Cu doped ZnO, electrical characterization, gas sensing, zeolite

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Authors: Faranak Felfeliyan, Parvaneh Shokrani, Maryam Atarod

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Introduction Using electron beam is widespread in radiotherapy. The main criteria in radiation therapy is to irradiate the tumor volume with maximum prescribed dose and minimum dose to vital organs around it. Using abutting fields is common in radiotherapy. The main problem in using abutting fields is dose inhomogeneity in the junction region. Electron beam divergence and lateral scattering may lead to hot and cold spots in the junction region. One solution for this problem is using of a spoiler to broaden the penumbra and uniform dose in the junction region. The goal of this research was to compare titanium and aluminum effects as a spoiler for dose uniformity achievement in the junction region of oblique electron fields with Monte Carlo simulation. Dose uniformity in the junction region depends on density, scattering power, thickness of the spoiler and the angle between two fields. Materials and Methods In this study, Monte Carlo model of Siemens Primus linear accelerator was simulated for a 5 MeV nominal energy electron beam using manufacture provided specifications. BEAMnrc and EGSnrc user code were used to simulate the treatment head in electron mode (simulation of beam model). The resulting phase space file was used as a source for dose calculations for 10×10 cm2 field size at SSD=100 cm in a 30×30×45 cm3 water phantom using DOSXYZnrc user code (dose calculations). An automatic MP3-M water phantom tank, MEPHYSTO mc2 software platform and a Semi-Flex Chamber-31010 with sensitive vol­ume of 0.125 cm3 (PTW, Freiburg, Germany) were used for dose distribution measurements. Moreover, the electron field size was 10×10 cm2 and SSD=100 cm. Validation of devel­oped beam model was done by comparing the measured and calculated depth and lateral dose distributions (verification of electron beam model). Simulation of spoilers (using SLAB compo­nent module) placed at the end of the electron applicator, was done using previously vali­dated phase space file for a 5 MeV nominal energy and 10×10 cm2 field size (simulation of spoiler). An in-house routine was developed in order to calculate the combined isodose curves re­sulting from the two simulated abutting fields (calculation of dose distribution in abutting electron fields). Results Verification of the developed 5.9 MeV elec­tron beam model was done by comparing the calculated and measured dose distributions. The maximum percentage difference between calculated and measured PDD was 1%, except for the build-up region in which the difference was 2%. The difference between calculated and measured profile was 2% at the edges of the field and less than 1% in other regions. The effect of PMMA, aluminum, titanium and chromium in dose uniformity achievement in abutting normal electron fields with equivalent thicknesses to 5mm PMMA was evaluated. Comparing R90 and uniformity index of different materials, aluminum was chosen as the optimum spoiler. Titanium has the maximum surface dose. Thus, aluminum and titanium had been chosen to use for dose uniformity achievement in oblique electron fields. Using the optimum beam spoiler, junction dose decreased from 160% to 110% for 15 degrees, from 180% to 120% for 30 degrees, from 160% to 120% for 45 degrees and from 180% to 100% for 60 degrees oblique abutting fields. Using Titanium spoiler, junction dose decreased from 160% to 120% for 15 degrees, 180% to 120% for 30 degrees, 160% to 120% for 45 degrees and 180% to 110% for 60 degrees. In addition, penumbra width for 15 degrees, without spoiler in the surface was 10 mm and was increased to 15.5 mm with titanium spoiler. For 30 degrees, from 9 mm to 15 mm, for 45 degrees from 4 mm to 6 mm and for 60 degrees, from 5 mm to 8 mm. Conclusion Using spoilers, penumbra width at the surface increased, size and depth of hot spots was decreased and dose homogeneity improved at the junc­tion of abutting electron fields. Dose at the junction region of abutting oblique fields was improved significantly by using spoiler. Maximum dose at the junction region for 15⁰, 30⁰, 45⁰ and 60⁰ was decreased about 40%, 60%, 40% and 70% respectively for Titanium and about 50%, 60%, 40% and 80% for Aluminum. Considering significantly decrease in maximum dose using titanium spoiler, unfortunately, dose distribution in the junction region was not decreased less than 110%.

Keywords: abutting fields, electron beam, radiation therapy, spoilers

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Authors: Michelle C. S. Azevedo, Priscila M. Colavite, Carolina F. Francisconi, Ana P. Trombone, Gustavo P. Garlet

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VIP (vasoactive intestinal peptide) know as a potential protective factor in the view of its marked immunosuppressive properties. In this work, we investigated a possible association of VIP with the clinical status of experimental periapical granulomas and the association with expression markers in the lesions potentially associated with periapical lesions pathogenesis. C57BL/6WT mice were treated or not with recombinant VIP. Animals with active/progressive (N=40), inactive/stable (N=70) periapical granulomas and controls (N=50) were anesthetized and the right mandibular first molar was surgically opened, allowing exposure of dental pulp. Endodontic pathogenic bacterial strains were inoculated: Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces viscosus, and Fusobacterium nucleatum subsp. polymorphum. The cavity was not sealed after bacterial inoculation. During lesion development, animals were treated or not with recombinant VIP 3 days post infection. Animals were killed after 3, 7, 14, and 21 days of infection and the jaws were dissected. The extraction of total RNA from periodontal tissues was performed and the integrity of samples was checked. qPCR reaction using TaqMan chemistry with inventoried primers were performed in ViiA7 equipment. The results, depicted as the relative levels of gene expression, were calculated in reference to GAPDH and β-actin expression. Periodontal tissues from upper molars were vested and incubated supplemented RPMI, followed by processing with 0.05% DNase. Cell viability and couting were determined by Neubauer chamber analysis. For flow cytometry analysis, after cell counting the cells were stained with the optimal dilution of each antibody; (PE)-conjugated and (FITC)-conjugated antibodies against CD4, CD25, FOXP3, IL-4, IL-17 and IFN-γ antibodies, as well their respective isotype controls. Cells were analyzed by FACScan and CellQuest software. Results are presented as the number of cells in the periodontal tissues or the number of positive cells for each marker in the CD4+FOXp3+, CD4+IL-4+, CD4+IFNg+ and CD4+IL-17+ subpopulations. The levels mRNA were measured by qPCR. The VIP expression was predominated in inactive lesions, as well part of the clusters of cytokine/Th markers identified as protective factors and a negative correlation between VIP expression and lesion evolution was observed. A quantitative analysis of IL1β, IL17, TNF, IFN, MMP2, RANKL, OPG, IL10, TGFβ, CTLA4, COL5A1, CTGF, CXCL11, FGF7, ITGA4, ITGA5, SERP1 and VTN expression was measured in experimental periapical lesions treated with VIP 7 and 14 days after lesion induction and healthy animals. After 7 days, all targets presented a significate increase in comparison to untreated animals. About migration kinetics, profile of chemokine receptors expression of TCD4+ subsets and phenotypic analysis of Tregs, Th1, Th2 and Th17 cells during the course of experimental periodontal disease evaluated by flow cytometry and depicted as the number of positive cells for each marker. CD4+IFNg+ and CD4+FOXp3+ cells migration were significate increased 7 days post VIP treatment. CD4+IL17+ cells migration were significate increased 7 and 14 days post VIP treatment, CD4+IL4+ cells migration were significate increased 14 and 21 days post VIP treatment compared to the control group. In conclusion, our experimental data support VIP involvement in determining the inactivity of periapical lesions. Financial support: FAPESP #2015/25618-2.

Keywords: chronic inflammation, cytokines, osteolytic lesions, VIP (Vasoactive Intestinal Peptide)

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Authors: Magdy I. A. Alshourbagi

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Background: The National Institute for Deafness and Communication Disorders defines idiopathic sudden sensorineural hearing loss as the idiopathic loss of hearing of at least 30 dB across 3 contiguous frequencies occurring within 3 days.The most common clinical presentation involves an individual experiencing a sudden unilateral hearing loss, tinnitus, a sensation of aural fullness and vertigo. The etiologies and pathologies of ISSNHL remain unclear. Several pathophysiological mechanisms have been described including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease, abnormal cochlear stress response, trauma, abnormal tissue growth, toxins, ototoxic drugs and cochlear membrane damage. The rationale for the use of hyperbaric oxygen to treat ISSHL is supported by an understanding of the high metabolism and paucity of vascularity to the cochlea. The cochlea and the structures within it require a high oxygen supply. The direct vascular supply, particularly to the organ of Corti, is minimal. Tissue oxygenation to the structures within the cochlea occurs via oxygen diffusion from cochlear capillary networks into the perilymph and the cortilymph. . The perilymph is the primary oxygen source for these intracochlear structures. Unfortunately, perilymph oxygen tension is decreased significantly in patients with ISSHL. To achieve a consistent rise of perilymph oxygen content, the arterial-perilymphatic oxygen concentration difference must be extremely high. This can be restored with hyperbaric oxygen therapy. Subject and Methods: A 37 year old man was presented at the clinic with a five days history of muffled hearing and tinnitus of the right ear. Symptoms were sudden onset, with no associated pain, dizziness or otorrhea and no past history of hearing problems or medical illness. Family history was negative. Physical examination was normal. Otologic examination revealed normal tympanic membranes bilaterally, with no evidence of cerumen or middle ear effusion. Tuning fork examination showed positive Rinne test bilaterally but with lateralization of Weber test to the left side, indicating right ear sensorineural hearing loss. Audiometric analysis confirmed sensorineural hearing loss across all frequencies of about 70- dB in the right ear. Routine lab work were all within normal limits. Clinical diagnosis of idiopathic sudden sensorineural hearing loss of the right ear was made and the patient began a medical treatment (corticosteroid, vasodilator and HBO therapy). The recommended treatment profile consists of 100% O2 at 2.5 atmospheres absolute for 60 minutes daily (six days per week) for 40 treatments .The optimal number of HBOT treatments will vary, depending on the severity and duration of symptomatology and the response to treatment. Results: As HBOT is not yet a standard for idiopathic sudden sensorineural hearing loss, it was introduced to this patient as an adjuvant therapy. The HBOT program was scheduled for 40 sessions, we used a 12-seat multi place chamber for the HBOT, which was started at day seven after the hearing loss onset. After the tenth session of HBOT, improvement of both hearing (by audiogram) and tinnitus was obtained in the affected ear (right). Conclusions: In conclusion, HBOT may be used for idiopathic sudden sensorineural hearing loss as an adjuvant therapy. It may promote oxygenation to the inner ear apparatus and revive hearing ability. Patients who fail to respond to oral and intratympanic steroids may benefit from this treatment. Further investigation is warranted, including animal studies to understand the molecular and histopathological aspects of HBOT and randomized control clinical studies.

Keywords: idiopathic sudden sensorineural hearing loss (issnhl), hyperbaric oxygen therapy (hbot), the decibel (db), oxygen (o2)

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Authors: Shikha Rani, Neeta Sehgal, Vipin Kumar Verma, Om Prakash

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Introduction: Fish is an important protein source for humans and has great economic value. Fish cultures are affected due to various anthropogenic activities that lead to bacterial and viral infections. Aeromonas hydrophila is a fish pathogenic bacterium that causes several aquaculture outbreaks throughout the world and leads to huge mortalities. In this study, plants of no commercial value were used to investigate their immunostimulatory, antioxidant, anti-inflammatory, anti-bacterial, and disease resistance potential in fish against Aeromonas hydrophila, through fish feed fortification. Methods: The plant was dried at room temperature in the shade, dissolved in methanol, and analysed for biological compounds through GC-MS/MS. DPPH, FRAP, Phenolic, and flavonoids were estimated following standardized protocols. In silico molecular docking was also performed to validate its broad-spectrum activities based on binding affinity with specific proteins. Fish were divided into four groups (n=6; total 30 in a group): Group 1, non-challenged fish (fed on a non-supplemented diet); Group 2, fish challenged with bacteria (fed on a non-supplemented diet); Group 3 and 4, fish challenged with bacteria (A. hydrophila) and fed on plant supplemented feed at 2.5% and 5%. Blood was collected from the fish on 0, 7th, 14th, 21st, and 28th days. Serum was separated for glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase assay (ALP), lysozyme activity assay, superoxide dismutase assay (SOD), lipid peroxidation assay (LPO) and molecular parameters (including cytokine levels) were estimated through ELISA. The phagocytic activity of macrophages from the spleen and head kidney, along with quantitative analysis of immune-related genes, were analysed in different tissue samples. The digestive enzymes (Pepsin, Trypsin, and Chymotrypsin) were also measured to evaluate the effect of plant-supplemented feed on freshwater fish. Results and Discussion: GC-MS/MS analysis of a methanolic extract of plant validated the presence of key compounds having antioxidant, anti-inflammatory, anti-bacterial, anti-inflammatory, and immunomodulatory activities along with disease resistance properties. From biochemical investigations like ABTS, DPPH, and FRAP, the amount of total flavonoids, phenols, and promising binding affinities towards different proteins in molecular docking analysis helped us to realize the potential of this plant that can be used for investigation in the supplemented feed of fish. Measurement liver function tests, ALPs, oxidation-antioxidant enzyme concentrations, and immunoglobulin concentrations in the experimental groups (3 and 4) showed significant improvement as compared to the positive control group. The histopathological evaluation of the liver, spleen, and head kidney supports the biochemical findings. The isolated macrophages from the group fed on supplemented feed showed a higher percentage of phagocytosis and a phagocytic index, indicating an enhanced cell-mediated immune response. Significant improvements in digestive enzymes were also observed in fish fed on supplemented feed, even after weekly challenges with bacteria. Hence, the plant-fortified feed can be recommended as a regular feed to enhance fish immunity and disease resistance against the Aeromonas hydrophila infection after confirmation from the field trial.

Keywords: immunostimulation, antipathogen, plant fortified feed, macrophages, GC-MS/MS, in silico molecular docking

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Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

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A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

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Authors: Jerome Dalphinis, Vishal Patel

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The Bailiwick of Jersey is an island British crown dependency situated off the coast of France. Jersey General Hospital’s emergency department sees approximately 40,000 patients a year. It’s outside the NHS, with secondary care being free at the point of care. Sedation is a continuum which extends from a normal conscious level to being fully unresponsive. Procedural sedation produces a minimally depressed level of consciousness in which the patient retains the ability to maintain an airway, and they respond appropriately to physical stimulation. The goals of it are to improve patient comfort and tolerance of the procedure and alleviate associated anxiety. Indications can be stratified by acuity, emergency (cardioversion for life-threatening dysrhythmia), and urgency (joint reduction). In the emergency department, this is most often achieved using a combination of opioids and benzodiazepines. Some departments also use ketamine to produce dissociative sedation, a cataleptic state of profound analgesia and amnesia. The response to pharmacological agents is highly individual, and the drugs used occasionally have unpredictable pharmacokinetics and pharmacodynamics, which can always result in progression between levels of sedation irrespective of the intention. Therefore, practitioners must be able to ‘rescue’ patients from deeper sedation. These practitioners need to be senior clinicians with advanced airway skills (AAS) training. It can lead to adverse effects such as dangerous hypoxia and unintended loss of consciousness if incorrectly undertaken; studies by the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) have reported avoidable deaths. The Royal College of Emergency Medicine, UK (RCEM) released an updated ‘Safe Sedation of Adults in the Emergency Department’ guidance in 2017 detailing a series of standards for staff competencies, and the required environment and equipment, which are required for each target sedation depth. The emergency department in Jersey undertook audit research in 2018 to assess their current practice. It showed gaps in clinical competency, the need for uniform care, and improved documentation. This spurred the development of a checklist incorporating the above RCEM standards, including contraindication for procedural sedation and difficult airway assessment. This was approved following discussion with the relevant heads of departments and the patient safety directorates. Following this, a second audit research was carried out in 2019 with 17 completed checklists (11 relocation of joints, 6 cardioversions). Data was obtained from looking at the controlled resuscitation drugs book containing documented use of ketamine, alfentanil, and fentanyl. TrakCare, which is the patient electronic record system, was then referenced to obtain further information. The results showed dramatic improvement compared to 2018, and they have been subdivided into six categories; pre-procedure assessment recording of significant medical history and ASA grade (2 fold increase), informed consent (100% documentation), pre-oxygenation (88%), staff (90% were AAS practitioners) and monitoring (92% use of non-invasive blood pressure, pulse oximetry, capnography, and cardiac rhythm monitoring) during procedure, and discharge instructions including the documented return of normal vitals and consciousness (82%). This procedural sedation checklist is a safe intervention that identifies pertinent information about the patient and provides a standardised checklist for the delivery of gold standard of care.

Keywords: advanced airway skills, checklist, procedural sedation, resuscitation

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Authors: V. Howard, R. Maguire, S. Corrigan

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Background: Type 1 Diabetes (T1D) is a chronic autoimmune disease, typically diagnosed in childhood. T1D puts an enormous strain on families; controlling blood-glucose in children is difficult and the consequences of poor control for patient health are significant. Successful illness management and better health outcomes can be dependent on quality of caregiving. On diagnosis, parent-caregivers face a steep learning curve as T1D care requires a significant level of knowledge to inform complex decision making throughout the day. The majority of illness management is carried out in the home setting, independent of clinical health providers. Parent-caregivers vary in their level of knowledge and their level of engagement in applying this knowledge in the practice of illness management. Enabling researchers to quantify these aspects of the caregiver experience is key to identifying targets for psychosocial support interventions, which are desirable for reducing stress and anxiety in this highly burdened cohort, and supporting better health outcomes in children. Currently, there are limited tools available that are designed to capture this information. Where tools do exist, they are not comprehensive and do not adequately capture the lived experience. Objectives: Development of quantitative tools, informed by lived experience, to enable researchers gather data on parent-caregiver knowledge and engagement, which accurately represents the experience/cohort and enables exploration of questions that are of real-world value to the cohort themselves. Methods: This research employed an engaged approach to address the problem of quantifying two key aspects of caregiver diabetes management: Knowledge and engagement. The research process was multi-staged and iterative. Stage 1: Working from a constructivist standpoint, literature was reviewed to identify relevant questionnaires, scales and single-item measures of T1D caregiver knowledge and engagement, and harvest candidate questionnaire items. Stage 2: Aggregated findings from the review were circulated among a PPI (patient and public involvement) expert panel of caregivers (n=6), for discussion and feedback. Stage 3: In collaboration with the expert panel, data were interpreted through the lens of lived experience to create a long-list of candidate items for novel questionnaires. Items were categorized as either ‘knowledge’ or ‘engagement’. Stage 4: A Delphi-method process (iterative surveys) was used to prioritize question items and generate novel questions that further captured the lived experience. Stage 5: Both questionnaires were piloted to refine wording of text to increase accessibility and limit socially desirable responding. Stage 6: Tools were piloted using an online survey that was deployed using an online peer-support group for caregivers for Juveniles with T1D. Ongoing Research: 123 parent-caregivers completed the survey. Data analysis is ongoing to establish face and content validity qualitatively and through exploratory factor analysis. Reliability will be established using an alternative-form method and Cronbach’s alpha will assess internal consistency. Work will be completed by early 2024. Conclusion: These tools will enable researchers to gain deeper insights into caregiving practices among parents of juveniles with T1D. Development was driven by lived experience, illustrating the value of engaged research at all levels of the research process.

Keywords: caregiving, engaged research, juvenile type 1 diabetes, quantified engagement and knowledge

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Authors: Enwin Anthony Dornubari, Visigah Kpobari Peter

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This research has developed a framework for the provision of sustainable and affordable housing to accommodate the low-income population of Greater Port Harcourt City. The objectives of this study among others, were to: examine UN-Habitat guidelines for acceptable and sustainable social housing provision, describe past efforts of the Rivers State Government and the Federal Government of Nigeria to provide housing for the poor in the Greater Port Harcourt City area; obtain a profile of prospective beneficiaries of the social housing proposed by this research as well as perceptions of their present living conditions, and living in the proposed self-sustaining social housing development, based on the initial simulation of the proposal; describe the nature of the framework, guideline and management of the proposed social housing development and explain the modalities for its implementation. The study utilized the mixed methods research approach, aimed at triangulating findings from the quantitative and qualitative paradigms. Opinions of professional of the built environment; Director, Development Control, Greater Port Harcourt City Development Authority; Directors of Ministry of Urban Development and Physical Planning; Housing and Property Development Authority and managers of selected Primary Mortgage Institutions were sought and analyzed. There were four target populations for the study, namely: members of occupational sub-groups for FGDs (Focused Group Discussions); development professionals for KIIs (Key Informant Interviews), household heads in selected communities of GPHC; and relevant public officials for IDI (Individual Depth Interview). Focus Group Discussions (FGDs) were held with members of occupational sub-groups in each of the eight selected communities (Fisherfolk). The table shows that there were forty (40) members across all occupational sub-groups in each selected community, yielding a total of 320 in the eight (8) communities of Mgbundukwu (Mile 2 Diobu), Rumuodomaya, Abara (Etche), Igwuruta-Ali(Ikwerre), Wakama(Ogu-Bolo), Okujagu (Okrika), Akpajo (Eleme), and Okoloma (Oyigbo). For key informant interviews, two (2) members were judgmentally selected from each of the following development professions: urban and regional planners; architects; estate surveyors; land surveyors; quantity surveyors; and engineers. Concerning Population 3-Household Heads in Selected Communities of GPHC, a stratified multi-stage sampling procedure was adopted: Stage 1-Obtaining a 10% (a priori decision) sample of the component communities of GPHC in each stratum. The number in each stratum was rounded to one whole number to ensure representation of each stratum. Stage 2-Obtaining the number of households to be studied after applying the Taro Yamane formula, which aided in determining the appropriate number of cases to be studied at the precision level of 5%. Findings revealed, amongst others, that poor implementation of the UN-Habitat global shelter strategy, lack of stakeholder engagement, inappropriate locations, undue bureaucracy, lack of housing fairness and equity and high cost of land and building materials were the reasons for the failure of past efforts towards social housing provision in the Greater Port Harcourt City area. The study recommended a public-private partnership approach for the implementation and management of the framework. It also recommended a robust and sustained relationship between the management of the framework and the UN-Habitat office and other relevant government agencies responsible for housing development and all investment partners to create trust and efficiency.

Keywords: development, framework, low-income, sustainable, social housing

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Authors: M. C. O. Ezeibe, F. I. O. Ezeibe

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Reasons viral diseases (including AI, HIV/AIDS, and COVID-19), tumors (including Cancers and Prostrate enlargement), and antimicrobial-resistant infections (AMR) are difficult to cure are features of the pathogens which normal cells do not have or need (biomedical markers) have not been identified; medicines that can counter the markers have not been invented; strategies and mechanisms for their treatments have not been developed. When cells become abnormal, they acquire negative electrical charges, and viruses are either positively charged or negatively charged, while normal cells remain neutral (without electrical charges). So, opposite charges' electrostatic attraction is a treatment mechanism for viral diseases and tumors. Medicines that have positive electrical charges would mop abnormal (infected and tumor) cells and DNA viruses (negatively charged), while negatively charged medicines would mop RNA viruses (positively charged). Molecules of Aluminum-magnesium silicate [AMS: Al₂Mg₃ (SiO₄)₃], an approved medicine and pharmaceutical stabilizing agent, consist of nanoparticles which have both positive electrically charged ends and negative electrically charged ends. The very small size (0.96 nm) of the nanoparticles allows them to reach all cells in every organ. By stabilizing antimicrobials, AMS reduces the rate at which the body metabolizes them so that they remain at high concentrations for extended periods. When drugs remain at high concentrations for longer periods, their efficacies improve. Again, nanoparticles enhance the delivery of medicines to effect targets. Both remaining at high concentrations for longer periods and better delivery to effect targets improve efficacy and make lower doses achieve desired effects so that side effects of medicines are reduced to allow the immunity of patients to be enhanced. Silicates also enhance the immune responses of treated patients. Improving antimicrobial efficacies and enhancing patients` immunity terminate infections so that none remains that could develop resistance. Some countries do not have natural deposits of AMS, but they may have Aluminum silicate (AS: Al₄ (SiO₄)₃) and Magnesium silicate (MS: Mg₂SiO₄), which are also approved medicines. So, AS and MS were used to formulate an AMS-brand, named Medicinal synthetic AMS {Al₄ (SiO₄)₃ + 3Mg₂SiO₄ → 2Al₂Mg₃ (SiO₄)₃}. To overcome the challenge of AMS, AS, and MS being un-absorbable, Dextrose monohydrate is incorporated in MSAMS-formulations for the simple sugar to convey the electrically charged nanoparticles into blood circulation by the principle of active transport so that MSAMS-antimicrobial formulations function systemically. In vitro, MSAMS reduced (P≤0.05) titers of viruses, including Avian influenza virus and HIV. When used to treat virus-infected animals, it cured Newcastle disease and Infectious bursa disease of chickens, Parvovirus disease of dogs, and Peste des petits ruminants disease of sheep and goats. A number of HIV/AIDS patients treated with it have been reported to become HIV-negative (antibody and antigen). COVID-19 patients are also reported to recover and test virus negative when treated with MSAMS. PSA titers of prostate cancer/enlargement patients normalize (≤4) following treatment with MSAMS. MSAMS has also potentiated ampicillin trihydrate, sulfadimidin, cotrimoxazole, piparazine citrate and chloroquine phosphate to achieve ≥ 95 % infection-load reductions (AMR-prevention). At 75 % of doses of ampicillin, cotrimoxazole, and streptomycin, supporting MSAMS-formulations' treatments with antioxidants led to the termination of even already resistant infections.

Keywords: electrical charges, viruses, abnormal cells, aluminum-magnesium silicate

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Authors: Denis Jordan, Daniel Golkowski, Mathias Lukas, Katharina Merz, Caroline Mlynarcik, Max Maurer, Valentin Riedl, Stefan Foerster, Eberhard F. Kochs, Andreas Bender, Ruediger Ilg

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Introduction: So far, clinical assessments that rely on behavioral responses to differentiate coma states or even predict outcome in coma patients are unreliable, e.g. because of some patients’ motor disabilities. The present study was aimed to provide prognosis in coma patients using markers from electroencephalogram (EEG), blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Unsuperwised principal component analysis (PCA) was used for multimodal integration of markers. Methods: Approved by the local ethics committee of the Technical University of Munich (Germany) 20 patients (aged 18-89) with severe brain damage were acquired through intensive care units at the Klinikum rechts der Isar in Munich and at the Therapiezentrum Burgau (Germany). At the day of EEG/fMRI/PET measurement (date I) patients (<3.5 month in coma) were grouped in the minimal conscious state (MCS) or vegetative state (VS) on the basis of their clinical presentation (coma recovery scale-revised, CRS-R). Follow-up assessment (date II) was also based on CRS-R in a period of 8 to 24 month after date I. At date I, 63 channel EEG (Brain Products, Gilching, Germany) was recorded outside the scanner, and subsequently simultaneous FDG-PET/fMRI was acquired on an integrated Siemens Biograph mMR 3T scanner (Siemens Healthineers, Erlangen Germany). Power spectral densities, permutation entropy (PE) and symbolic transfer entropy (STE) were calculated in/between frontal, temporal, parietal and occipital EEG channels. PE and STE are based on symbolic time series analysis and were already introduced as robust markers separating wakefulness from unconsciousness in EEG during general anesthesia. While PE quantifies the regularity structure of the neighboring order of signal values (a surrogate of cortical information processing), STE reflects information transfer between two signals (a surrogate of directed connectivity in cortical networks). fMRI was carried out using SPM12 (Wellcome Trust Center for Neuroimaging, University of London, UK). Functional images were realigned, segmented, normalized and smoothed. PET was acquired for 45 minutes in list-mode. For absolute quantification of brain’s glucose consumption rate in FDG-PET, kinetic modelling was performed with Patlak’s plot method. BOLD signal intensity in fMRI and glucose uptake in PET was calculated in 8 distinct cortical areas. PCA was performed over all markers from EEG/fMRI/PET. Prognosis (persistent VS and deceased patients vs. recovery to MCS/awake from date I to date II) was evaluated using the area under the curve (AUC) including bootstrap confidence intervals (CI, *: p<0.05). Results: Prognosis was reliably indicated by the first component of PCA (AUC=0.99*, CI=0.92-1.00) showing a higher AUC when compared to the best single markers (EEG: AUC<0.96*, fMRI: AUC<0.86*, PET: AUC<0.60). CRS-R did not show prediction (AUC=0.51, CI=0.29-0.78). Conclusion: In a multimodal analysis of EEG/fMRI/PET in coma patients, PCA lead to a reliable prognosis. The impact of this result is evident, as clinical estimates of prognosis are inapt at time and could be supported by quantitative biomarkers from EEG, fMRI and PET. Due to the small sample size, further investigations are required, in particular allowing superwised learning instead of the basic approach of unsuperwised PCA.

Keywords: coma states and prognosis, electroencephalogram, entropy, functional magnetic resonance imaging, machine learning, positron emission tomography, principal component analysis

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Authors: Reham K. Sebaih, Afaf I. Shehata , Awatif A. Hindi, Tarek Gheith, Amal A. Hazzani Anas Al-Orjan

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Staphylococci spp are ubiquitous gram-positive bacteria is often associated with infections, especially nosocomial infections, and antibiotic resistanceStudy pathogenic bacteria and its use as a tool in the technology of Nano biology and molecular genetics research of the latest research trends of modern characterization and definition of different multiresistant of bacteria including Staphylococci. The Staphylococci are widespread all over the world and particularly in Saudi Arabia The present work study was conducted to evaluate the effect of five different types of nanoparticles (biosynthesized zinc oxide, Spherical and rod of each silver and gold nanoparticles) and their antibacterial impact on the Staphylococcus species. Ninety-six isolates of Staphylococcus species. Staphylococcus aureus, Staphylococcus epidermidis, MRSA were collected from different sources during the period between March 2011G to June 2011G. All isolates were isolated from inpatients and outpatients departments at Royal Commission Hospital in Yanbu Industrial, Saudi Arabia. High percentage isolation from males(55%) than females (45%). Staphylococcus epidermidis from males was (47%), (28%), and(25%). For Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA. Isolates from females were Staphylococcus aureus with higher percent of (47%), (30%), and (23%) for MRSA, Staphylococcus epidermidis. Staphylococcus aureus from wound swab were the highest percent (51.42%) followed by vaginal swab (25.71%). Staphylococcus epidermidis were founded with higher percentage in blood (37.14%) and wound swab (34.21%) respectively related to other. The highest percentage of methicillin-resistant Staphylococcus aureus (MRSA)(80.77%) were isolated from wound swab, while those from nostrils were (19.23%). Staphylococcus species were isolates in highest percentage from hospital Emergency department with Staphylococcus aureus (59.37%), Methicillin-resistant Staphylococcus aureus (MRSA) (28.13%)and Staphylococcus epidermidis (12.5%) respectively. Evaluate the antibacterial property of Zinc oxide, Silver, and Gold nanoparticles as an alternative to conventional antibacterial agents Staphylococci isolates from hospital sources we screened them. Gold and Silver rods Nanoparticles to be sensitive to all isolates of Staphylococcus species. Zinc oxide Nanoparticles gave sensitivity impact range(52%) and (48%). The Gold and Silver spherical nanoparticles did not showed any effect on Staphylococci species. Zinc Oxide Nanoparticles gave bactericidal impact (25%) and bacteriostatic impact (75%) for of Staphylococci species. Detecting the association of nanoparticles with Staphylococci isolates imaging by scanning electron microscope (SEM) of some bacteriostatic isolates for Zinc Oxide nanoparticles on Staphylococcus aureus, Staphylococcus epidermidis and Methicillin resistant Staphylococcus aureus(MRSA), showed some Overlapping Bacterial cells with lower their number and appearing some appendages with deformities in external shape. Molecular analysis was applied by Multiplex polymerase chain reaction (PCR) used for the identification of genes within Staphylococcal pathogens. A multiplex polymerase chain reaction (PCR) method has been developed using six primer pairs to detect different genes using 50bp and 100bp DNA ladder marker. The range of Molecular gene typing ranging between 93 bp to 326 bp for Staphylococcus aureus and Methicillin resistant Staphylococcus aureus by TSST-1,mecA,femA and eta, while the bands border were from 546 bp to 682 bp for Staphylococcus epidermidis using icaAB and atlE. Sixteen isolation of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the femA gene at 132bp,this allowed the using of this gene as an internal positive control, fifteen isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for mecA gene at163bp.This gene was responsible for antibiotic resistant Methicillin, Two isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the TSST-1 gene at326bp which is responsible for toxic shock syndrome in some Staphylococcus species, None were positive for eta gene at 102bpto that was responsible for Exfoliative toxins. Six isolates of Staphylococcus epidermidis were positive for atlE gene at 682 bp which is responsible for the initial adherence, three isolates of Staphylococcus epidermidis were positive for icaAB gene at 546bp that are responsible for mediates the formation of the biofilm. In conclusion, this study demonstrates the ability of the detection of the genes to discriminate between infecting Staphylococcus strains and considered biological tests, they may potentiate the clinical criteria used for the diagnosis of septicemia or catheter-related infections.

Keywords: multiplex polymerase chain reaction, toxic shock syndrome, Staphylococcus aureus, nosocomial infections

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Authors: B.L. España-Sánchez, E. Luna-Hernández, R.A. Mauricio-Sánchez, M.E. Cruz-Soto, F. Padilla-Vaca, R. Muñoz, L. Granados-López, L.R. Ovalle-Flores, J.L. Menchaca-Arredondo, G. Luna-Bárcenas

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Treatment of burn injured has been considered an important clinical problem due to the fluid control and the presence of microorganisms during the healing process. Conventional treatment includes antiseptic techniques, topical medication and surgical removal of damaged skin, to avoid bacterial growth. In order to accelerate this process, different alternatives for tissue regeneration have been explored, including artificial skin, polymers, hydrogels and hybrid materials. Some requirements consider a nonreactive organic polymer with high biocompatibility and skin adherence, avoiding bacterial infections. Chitin-derivative biopolymer such as chitosan (CS) has been used in skin regeneration following third-degree burns. The biological interest of CS is associated with the improvement of tissue cell stimulation, biocompatibility and antibacterial properties. In particular, antimicrobial properties of CS can be significantly increased when is blended with nanostructured materials. Silver-based nanocomposites have gained attention in medicine due to their high antibacterial properties against pathogens, related to their high surface area/volume ratio at nanomolar concentrations. Silver nanocomposites can be blended or synthesized with chitin-derivative biopolymers in order to obtain a biodegradable/antimicrobial hybrid with improved physic-mechanical properties. In this study, nanocomposites based on chitosan/silver nanoparticles (CS/nAg) were synthesized by the in situ chemical reduction method, improving their antibacterial properties against pathogenic bacteria and enhancing the healing process in thermal burn injuries produced in an animal model. CS/nAg was prepared in solution by the chemical reduction method, using AgNO₃ as precursor. CS was dissolved in acetic acid and mixed with different molar concentrations of AgNO₃: 0.01, 0.025, 0.05 and 0.1 M. Solutions were stirred at 95°C during 20 hours, in order to promote the nAg formation. CS/nAg solutions were placed in Petri dishes and dried, to obtain films. Structural analyses confirm the synthesis of silver nanoparticles (nAg) by means of UV-Vis and TEM, with an average size of 7.5 nm and spherical morphology. FTIR analyses showed the complex formation by the interaction of hydroxyl and amine groups with metallic nanoparticles, and surface chemical analysis (XPS) shows low concentration of Ag⁰/Ag⁺ species. Topography surface analyses by means of AFM shown that hydrated CS form a mesh with an average diameter of 10 µm. Antibacterial activity against S. aureus and P. aeruginosa was improved in all evaluated conditions, such as nAg loading and interaction time. CS/nAg nanocomposites films did not show Ag⁰/Ag⁺ release in saline buffer and rat serum after exposition during 7 days. Healing process was significantly enhanced by the presence of CS/nAg nanocomposites, inducing the production of myofibloblasts, collagen remodelation, blood vessels neoformation and epidermis regeneration after 7 days of injury treatment, by means of histological and immunohistochemistry assays. The present work suggests that hydrated CS/nAg nanocomposites can be formed a mesh, improving the bacterial penetration and the contact with embedded nAg, producing complete growth inhibition after 1.5 hours. Furthermore, CS/nAg nanocomposites improve the cell tissue regeneration in thermal burn injuries induced in rats. Synthesis of antibacterial, non-toxic, and biocompatible nanocomposites can be an important issue in tissue engineering and health care applications.

Keywords: antibacterial, chitosan, healing process, nanocomposites, silver

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Authors: Adriana De Serio, Donato Forenza

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Aims. In this experimental research the Authors present the methodological plan “Musictherapy and Gardentherapy” that they created interconnected with the garden landscape ecosystems and aimed at PsychoPhysical Disability (MusGarPPhyD). In the context of the environmental education aimed at spreading the landscape culture and its values, it’s necessary to develop a solid perception of the environment sustainability to implement a multidimensional approach that pays attention to the conservation and enhancement of gardens and natural environments. The result is an improvement in the life quality also in compliance with the objectives of the European Agenda 2030. The MusGarPPhyD can help professionals such as musictherapists and environmental and landscape researchers strengthen subjects' motivation to learn to deal with the psychophysical discomfort associated with disability and to cope with the distress and the psychological fragility and the loneliness and the social seclusion and to promote productive social relationships. Materials and Methods. The MusGarPPhyD was implemented in multiple spaces. The musictherapy treatments took place first inside residential therapeutic centres and then in the garden landscape ecosystem. Patients: twenty, set in two groups. Weekly-sessions (50’) for three months. Methodological phases: - Phase P1. MusicTherapy treatments for each group in the indoor spaces. - Phase P2. MusicTherapy sessions inside the gardens. After each Phase, P1 and P2: - a Questionnaire for each patient (ten items / liking-indices) was administrated at t0 time, during the treatment and at tn time at the end of the treatment. - Monitoring of patients' behavioral responses through assessment scales, matrix, table and graph system. MusicTherapy methodology: pazient Sonorous-Musical Anamnesis, Musictherapy Assessment Document, Observation Protocols, Bodily-Environmental-Rhythmical-Sonorous-Vocal-Energy production first indoors and then outside, sonorous-musical instruments and edible instruments made by the Author/musictherapist with some foods; Administration of Patient-Environment-Music Index at time to and tn, to estimate the patient’s behavior evolution, Musictherapeutic Advancement Index. Results. The MusGarPPhyD can strengthen the individual sense of identity and improve the psychophysical skills and the resilience to face and to overcome the difficulties caused by the congenital /acquired disability. The multi-sensory perceptions deriving from contact with the plants in the gardens improve the psychological well-being and regulate the physiological parameters such as blood pressure, cardiac and respiratory rhythm, reducing the cholesterol levels. The secretions of the peptide hormones endorphins and the endogenous opioids enkephalins increase and bring a state of patient’s tranquillity and a better mood. The subjects showed a preference for musictherapy treatments within a setting made up of gardens and peculiar landscape systems. This resulted in greater health benefits. Conclusions. The MusGarPPhyD contributes to reduce psychophysical tensions, anxiety, depression and stress, facilitating the connections between the cerebral hemispheres, thus also improving intellectual performances, self-confidence, motor skills and social interactions. Therefore it is necessary to design hospitals, rehabilitation centers, nursing homes, surrounded by gardens. Ecosystems of natural and urban parks and gardens create fascinating skyline and mosaics of landscapes rich in beauty and biodiversity. The MusGarPPhyD is useful for the health management promoting patient’s psychophysical activation, better mood/affective-tone and relastionships and contributing significantly to improving the life quality.

Keywords: musictherapy, gardentherapy, disability, life quality

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Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

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Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

Procedia PDF Downloads 162

Authors: Divya SY. Ang, Mark B. Tan, Nicholas EM. Yeo, Siti RB. Sudirman, Khong Yik Chew

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Introduction: The importance of the amalgamation of technological and engineering advances with surgical principles of reconstruction cannot be overemphasized. With earlier detection of cancer, consequences of high-speed living and neglect, like traumatic injuries and infection, resulting in increasingly younger patients with bone defects. This may result in malformations and suboptimal function that is more noticeable and palpable in the younger, active demographic. Our team proposes a technique that encapsulates a mesh of multidisciplinary effort, tissue engineering and reconstructive principles. Methods/Materials: Our patient was a young competitive footballer in his early 30s who was diagnosed with submandibular adenoid cystic carcinoma with bony involvement. He was thus counselled for a right hemi mandibulectomy, the floor of mouth resection, right selective neck dissection, tracheostomy, and free fibular flap reconstruction of his mandible and required post-operative radiotherapy. Being young and in his prime sportsman years, he was unable to accept the morbidities associated with using his fibula to reconstruct his mandible despite it being the gold standard reconstructive option. The fibula is an ideal vascularized bone flap because it’s reliable and easily shaped with relatively minimal impact on functional outcomes. The fibula contributes to 30% of weightbearing and is the attachment for the lateral compartment muscles; it is stronger in footballers concerning lateral bending. When harvesting the fibula, the distal 6-8cm and up to 10% of the total length is preserved to maintain the ankle’s stability, thus, minimizing the impact on daily activities. There are studies that have noted gait variability post-operatively. Therefore, returning to a premorbid competitive level may be doubtful. To improve his functional outcomes, the decision was made to try and restore the fibula's form and function. Using the concept of Fused Deposition Modelling (FDM), our team comprising of Plastics, Otolaryngology, Orthopedics and Radiology, worked with Osteopore to design a 3D bioresorbable implant to regenerate the fibula defect (14.5cm). Bone marrow was harvested via reaming the contralateral hip prior to the wide resection. 30mls of his blood was obtained for extracting platelet rich plasma. These were packed into the Osteopore 3D-printed bone scaffold. This was then secured into the fibula defect with titanium plates and screws. The flexor hallucis longus and soleus were anchored along the construct and intraosseous membrane, done in a single setting. Results: He was reviewed closely as an outpatient over 10 months post operatively. He reported no discernable loss or difference in ankle function. He is satisfied and back in training and our team has video and photographs that substantiate his progress. Conclusion: FDM allows regeneration of long bone defects. However, we aimed to also restore his eversion and inversion that is imperative for footballers and hence reattached his previously dissected muscles along the length of the Osteopore implant. We believe that the reattachment of the muscle stabilizes not only the construct but allows optimum muscle tensioning when moving his ankle. This is a simple but effective technique in restoring complete function and form in a young patient whose minute muscle control is imperative to life.

Keywords: fused deposition modelling, functional reconstruction, lower limb bony defects, regenerative surgery, 3D printing, tissue engineering

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Authors: Anisa Suraya Ab Razak, Izza Hayat

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Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.

Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia

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Authors: P. C. Kutschera, Elena C. Tesoro, Mary Grace Talamera-Sandico, Jose Maria G. Pelayo III

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Second generation military Filipino Amerasians comprise a formidable contemporary segment of the estimated 250,000-plus biracial Amerasians in the Philippines today. Overall, they are a stigmatized and socioeconomically marginalized diaspora, historically; they were abandoned or estranged by U.S. military personnel fathers assigned during the century-long Colonial, Post-World War II and Cold War Era of permanent military basing (1898-1992). Indeed, U.S. military personnel remain stationed in smaller numbers in the Philippines today. This inquiry is an outgrowth of two recent small sample studies. The first surfaced the impact of the U.S. military prostitution system on formation of the ‘Derivative Amerasian Family Construct’ on first generation Amerasians; a second, qualitative case study suggested the continued effect of the prostitution systems' destructive impetuous on second generation Amerasians. The intent of this current qualitative, multiple-case study was to actively seek out second generation sex industry toilers. The purpose was to focus further on this human phenomenon in the post-basing and post-military prostitution system eras. As background, the former military prostitution apparatus has transformed into a modern dynamic of rampant sex tourism and prostitution nationwide. This is characterized by hotel and resorts offering unrestricted carnal access, urban and provincial brothels (casas), discos, bars and pickup clubs, massage parlors, local barrio karaoke bars and street prostitution. A small case study sample (N = 4) of female and male second generation Amerasians were selected. Sample formation employed a non-probability ‘snowball’ technique drawing respondents from the notorious Angeles, Metro Manila, Olongapo City ‘AMO Amerasian Triangle’ where most former U.S. military installations were sited and modern sex tourism thrives. A six-month study and analysis of in-depth interviews of female and male sex laborers, their families and peers revealed a litany of disturbing, and troublesome experiences. Results showed profiles of debilitating human poverty, history of family disorganization, stigmatization, social marginalization and the ghost of the military prostitution system and its harmful legacy on Amerasian family units. Emerging were testimonials of wayward young people ensnared in a maelstrom of deep economic deprivation, familial dysfunction, psychological desperation and societal indifference. The paper recommends that more study is needed and implications of unstudied psychosocial and socioeconomic experiences of distressed younger generations of military Amerasians require specific research. Heretofore apathetic or disengaged U.S. institutions need to confront the issue and formulate activist and solution-oriented social welfare, human services and immigration easement policies and alternatives. These institutions specifically include academic and social science research agencies, corporate foundations, the U.S. Congress, and Departments of State, Defense and Health and Human Services, and Homeland Security (i.e. Citizen and Immigration Services) It is them who continue to endorse a laissez-faire policy of non-involvement over the entire Filipino Amerasian question. Such apathy, the paper concludes, relegates this consequential but neglected blood progeny to the status of humiliating destitution and exploitation. Amerasians; thus, remain entrapped in their former colonial, and neo-colonial habitat. Ironically, they are unwitting victims of a U.S. American homeland that fancies itself geo-politically as a strong and strategic military treaty ally of the Philippines in the Western Pacific.

Keywords: Asian Americans, diaspora, Filipino Amerasians, military prostitution, stigmatization

Procedia PDF Downloads 487

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay, Ananya Mukhopadhyay, Harendra Nath Bhattacharya

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This study investigates the global issue of electronic waste (e-waste), focusing on its prevalence in India and other regions. E-waste has emerged as a significant worldwide problem, with India contributing a substantial share of annual e-waste generation. The primary sources of e-waste in India are computer equipment and mobile phones. Many developed nations utilize India as a dumping ground for their e-waste, with major contributions from the United States, China, Europe, Taiwan, South Korea, and Japan. The study identifies Maharashtra, Tamil Nadu, Mumbai, and Delhi as prominent contributors to India's e-waste crisis. This issue is contextualized within the broader framework of the United Nations' 2030 Agenda for Sustainable Development, which encompasses 17 Sustainable Development Goals (SDGs) and 169 associated targets to address poverty, environmental preservation, and universal prosperity. The study underscores the interconnectedness of e-waste management with several SDGs, including health, clean water, economic growth, sustainable cities, responsible consumption, and ocean conservation. Central Pollution Control Board (CPCB) data reveals that e-waste generation surpasses that of plastic waste, increasing annually at a rate of 31%. However, only 20% of electronic waste is recycled through organized and regulated methods in underdeveloped nations. In Europe, efficient e-waste management stands at just 35%. E-waste pollution poses serious threats to soil, groundwater, and public health due to toxic components such as mercury, lead, bromine, and arsenic. Long-term exposure to these toxins, notably arsenic in microchips, has been linked to severe health issues, including cancer, neurological damage, and skin disorders. Lead exposure, particularly concerning for children, can result in brain damage, kidney problems, and blood disorders. The study highlights the problematic transboundary movement of e-waste, with approximately 352,474 metric tonnes of electronic waste illegally shipped from Europe to developing nations annually, mainly to Africa, including Nigeria, Ghana, and Tanzania. Effective e-waste management, underpinned by appropriate infrastructure, regulations, and policies, offers opportunities for job creation and aligns with the objectives of the 2030 Agenda for SDGs, especially in the realms of decent work, economic growth, and responsible production and consumption. E-waste represents hazardous pollutants and valuable secondary resources, making it a focal point for anthropogenic resource exploitation. The United Nations estimates that e-waste holds potential secondary raw materials worth around 55 billion Euros. The study also identifies numerous challenges in e-waste management, encompassing the sheer volume of e-waste, child labor, inadequate legislation, insufficient infrastructure, health concerns, lack of incentive schemes, limited awareness, e-waste imports, high costs associated with recycling plant establishment, and more. To mitigate these issues, the study offers several solutions, such as providing tax incentives for scrap dealers, implementing reward and reprimand systems for e-waste management compliance, offering training on e-waste handling, promoting responsible e-waste disposal, advancing recycling technologies, regulating e-waste imports, and ensuring the safe disposal of domestic e-waste. A mechanism, Buy-Back programs, will compensate customers in cash when they deposit unwanted digital products. This E-waste could contain any portable electronic device, such as cell phones, computers, tablets, etc. Addressing the e-waste predicament necessitates a multi-faceted approach involving government regulations, industry initiatives, public awareness campaigns, and international cooperation to minimize environmental and health repercussions while harnessing the economic potential of recycling and responsible management.

Keywords: e-waste management, sustainable development goal, e-waste disposal, recycling technology, buy-back policy

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Authors: Maria João Ferreira, Natalia Sierra-Garcia, Javier Cremades, Carla António, Ana M. Rodrigues, Helena Silva, Ângela Cunha

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Salicornia ramosissima, a halophyte that grows naturally in coastal areas of the northern hemisphere, is often considered the most promising halophyte candidate for extensive crop cultivation and saline agriculture practices. The expanding interest in this plant surpasses its use as gourmet food and includes their potential application as a source of bioactive compounds for the pharmaceutical industry. Despite growing well in saline soils, sustainable and ecologically friendly techniques to enhance crop production and the nutritional value of this plant are still needed. The root microbiome of S. ramosissima proved to be a source of taxonomically diverse plant growth-promoting bacteria (PGPB). Halotolerant strains of Bacillus, Salinicola, Pseudomonas, and Brevibacterium, among other genera, exhibit a broad spectrum of plant-growth promotion traits [e.g., 3-indole acetic acid (IAA), 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, siderophores, phosphate solubilization, Nitrogen fixation] and express a wide range of extracellular enzyme activities. In this work, three plant growth-promoting bacteria strains (Brevibacterium casei EB3, Pseudomonas oryzihabitans RL18, and Bacillus aryabhattai SP20) isolated from the rhizosphere and the endosphere of S. ramosissima roots from different saltmarshes along the Portuguese coast were inoculated in S. ramosissima seeds. Plants germinated from inoculated seeds were grown for three months in pots filled with a mixture of perlite and estuarine sediment (1:1) in greenhouse conditions and later transferred to a growth chamber, where they were maintained two months with controlled photoperiod, temperature, and humidity. Pots were placed on trays containing the irrigation solution (Hoagland’s solution 20% added with 10‰ marine salt). Before reaching the flowering stage, plants were collected, and the fresh and dry weight of aerial parts was determined. Non-inoculated seeds were used as a negative control. Selected dried stems from the most promising treatments were later analyzed by GC-TOF-MS for primary metabolite composition. The efficiency of inoculation and persistence of the inoculum was assessed by Next Generation Sequencing. Inoculations with single strain EB3 and co-inoculations with EB3+RL18 and EB3+RL18+SP20 (All treatment) resulted in significantly higher biomass production (fresh and dry weight) compared to non-inoculated plants. Considering fresh weight alone, inoculation with isolates SP20 and RL18 also caused a significant positive effect. Combined inoculation with the consortia SP20+EB3 or SP20+RL18 did not significantly improve biomass production. The analysis of the profile of primary metabolites will provide clues on the mechanisms by which the growth-enhancement effect of the inoculants operates in the plants. These results sustain promising prospects for the use of rhizospheric and endophytic PGPB as biofertilizers, reducing environmental impacts and operational costs of agrochemicals and contributing to the sustainability and cost-effectiveness of saline agriculture. Acknowledgments: This work was supported by project Rhizomis PTDC/BIA-MIC/29736/2017 financed by Fundação para a Ciência e Tecnologia (FCT) through the Regional Operational Program of the Center (02/SAICT/2017) with FEDER funds (European Regional Development Fund, FNR, and OE) and by FCT through CESAM (UIDP/50017/2020 + UIDB/50017/2020), LAQV-REQUIMTE (UIDB/50006/2020). We also acknowledge FCT/FSE for the financial support to Maria João Ferreira through a PhD grant (PD/BD/150363/2019). We are grateful to Horta dos Peixinhos for their help and support during sampling and seed collection. We also thank Glória Pinto for her collaboration providing us the use of the growth chambers during the final months of the experiment and Enrique Mateos-Naranjo and Jennifer Mesa-Marín of the Departamento de Biología Vegetal y Ecología, the University of Sevilla for their advice regarding the growth of salicornia plants in greenhouse conditions.

Keywords: halophytes, PGPB, rhizosphere engineering, biofertilizers, primary metabolite profiling, plant inoculation, Salicornia ramosissima

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Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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