Search results for: acute toxicity

Authors: Atitallah Sofien, Bouyahia Olfa, Romdhani Meriam, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Spondylothoracic dysostosis, also known as Jarcho-Levin syndrome, is defined by a shortened neck and thorax, a protruding abdomen, inguinal and umbilical hernias, atypical spinal structure and rib fusion, leading to restricted chest movement or difficulty in breathing, along with urinary tract abnormalities and, potentially severe scoliosis. Aim: This is the case of a patient diagnosed with Jarcho-Levin syndrome, aiming to detail the range of abnormalities observed in this syndrome, the observed complications, and the therapeutic approaches employed. Results: A three-month-old male infant, born of a consanguineous marriage, delivered at full term by cesarean section, was admitted to the pediatric department for severe acute bronchiolitis. In his prenatal history, morphological ultrasound revealed macrosomia, a shortened spine, irregular vertebrae with thickened skin, normal fetal cardiac ultrasound, and the absence of the right kidney. His perinatal history included respiratory distress, requiring ventilatory support for five days. Upon physical examination, he had stunted growth, scoliosis, a short neck and trunk, longer upper limbs compared to lower limbs, varus equinus in the right foot, a neural tube defect, a low hairline, and low-set ears. Spondylothoracic dysostosis was suspected, leading to further investigations, including a normal transfontaneous ultrasound, a spinal cord ultrasound revealing a lipomyelocele-type closed dysraphism with a low-attached cord, an abdominal ultrasound indicating a single left kidney, and a cardiac ultrasound identifying Kommerell syndrome. Due to a lack of resources, genetic testing could not be performed, and the diagnosis was based on clinical criteria. Conclusion: Jarcho-Levin syndrome can result in a mortality rate of about 50%, primarily due to respiratory complications associated with thoracic insufficiency syndrome. Other complications, like heart and neural tube defects, can also lead to premature mortality. Therefore, early diagnosis and comprehensive treatment involving various specialists are essential.

Keywords: Jarcho-Levin syndrome, congenital disorder, scoliosis, spondylothoracic dysostosis, neural tube defect

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Authors: R. Prinsloo

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis, and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: best interest of the child, children's rights, parent and child relationship, parental responsibilities and rights

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Authors: Ana Carolina Kogawa, Selma Gutierrez Antonio, Hérida Regina Nunes Salgado

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Rifaximin is an oral antimicrobial, gut - selective and not systemic with adverse effects compared to placebo. It is used for the treatment of hepatic encephalopathy, travelers diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis and acute diarrhea. The crystalline form present in the rifaximin with minimal systemic absorption is α, being the amorphous form significantly different. Regulators are increasingly attention to polymorphisms. Polymorphs can change the form by altering the drug characteristics compromising the effectiveness and safety of the finished product. International Conference on Harmonization issued the ICH Guidance Q6A, which aim to improve the control of polymorphism in new and existing pharmaceuticals. The objective of this study was to obtain polymorphic forms of rifaximin employing recrystallization processes and characterize them by thermal analysis (thermogravimetry - TG and differential scanning calorimetry - DSC), X-ray diffraction, scanning electron microscopy and solubility test. Six polymorphic forms of rifaximin, designated I to VI were obtained by the crystallization process by evaporation of the solvent. The profiles of the TG curves obtained from polymorphic forms of rifaximin are similar to rifaximin and each other, however, the DTG are different, indicating different thermal behaviors. Melting temperature values of all the polymorphic forms were greater to that shown by the rifaximin, indicating the higher thermal stability of the obtained forms. The comparison of the diffractograms of the polymorphic forms of rifaximin with rifaximin α, β and γ constant in patent indicate that forms III, V and VI are formed by mixing polymorph β and α and form III is formed by polymorph β. The polymorphic form I is formed by polymorph β, but with a significant amount of amorphous material. Already, the polymorphic form II consists of polymorph γ, amorphous. In scanning electron microscope is possible to observe the heterogeneity of morphological characteristics of crystals of polymorphic forms among themselves and with rifaximin. The solubility of forms I and II was greater than the solubility of rifaximin, already, forms III, IV and V presented lower solubility than of rifaximin. Similarly, the bioavailability of the amorphous form of rifaximin is considered significantly higher than the form α, the polymorphic forms obtained in this work can not guarantee the excellent tolerability of the reference medicine. Therefore, studies like these are extremely important and they point to the need for greater requirements by the regulatory agencies competent about polymorphs analysis of the raw materials used in the manufacture of medicines marketed globally. These analyzes are not required in the majority of official compendia. Partnerships between industries, research centers and universities would be a viable way to consolidate researches in this area and contribute to improving the quality of solid drugs.

Keywords: electronic microscopy, polymorphism, rifaximin, solubility, X-ray diffraction

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Authors: Heather Fulford, Melanie Liddell

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The recruitment and retention of high quality employees can prove to be challenging for social enterprises, particularly in some of the core business support functions such as marketing, communications, IT and finance. This holds true for social enterprises in urban contexts, where roles with more attractive remuneration in these business functions can often be found quite readily in the private sector. For social enterprises situated in rural locations, the challenges of staff recruitment and retention are even more acute. Such challenges can lead to a skills deficit in rural social enterprises, which can, at best, hinder their growth potential, and worse, jeopardise their chances of survival. This in turn, can have a negative impact on the sustainability and resilience of the surrounding rural community in which the social enterprise is located. The purpose of this paper is to report on aspects of a collaborative initiative established to stimulate innovation and business growth in remote rural businesses in Scotland. Launched in 2010, this initiative was designed to attract young students and graduates from the region to stay in the region upon completion of their studies, and to attract others from outside the region to re-locate there post-university. To facilitate this, SMEs in the region were offered wage subsidies to encourage them to recruit a student or graduate on a work placement for up to one year to participate in an innovation or business growth-oriented project. A number of the employers offering work placements were social enterprises. Through analysis of the placement project and role specifications devised by the participating social enterprises, an overview is provided of their business development needs and the skills they require to stimulate innovation and growth. Scrutiny of the reflective accounts compiled by the students and graduates at the close of their work placements highlights the benefits they derived from being able to put their academic knowledge and skills into action within a social enterprise. Examination of interviews conducted with a sample of placement employers reveals the contribution the students and graduates made during the business development projects with the social enterprises. The challenges of hosting such placements are also discussed. The paper concludes with indications of the lessons learned and an outline of the wider implications for other remote rural locations in which social enterprises play an important role in the local economy and life of the community.

Keywords: resilience, rural development, regeneration, regional development, recruitment, resource management, retention, remuneration

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Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: Sridhar A. Malkaram, Tamer E. Fandy

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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.

Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics

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Authors: Amir Asadi, Karim Habib, Robert J. Moon, Kyriaki Kalaitzidou

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There has been considerable interest in cellulose nanomaterials (CN) as polymer and polymer composites reinforcement due to their high specific modulus and strength, low density and toxicity, and accessible hydroxyl side groups that can be readily chemically modified. The focus of this study is making lightweight composites for better fuel efficiency and lower CO2 emission in auto industries with no compromise on mechanical performance using a scalable technique that can be easily integrated in sheet molding compound (SMC) manufacturing lines. Light weighting will be achieved by replacing part of the heavier components, i.e. glass fibers (GF), with a small amount of cellulose nanocrystals (CNC) in short GF/epoxy composites made using SMC. CNC will be introduced as coating of the GF rovings prior to their use in the SMC line. The employed coating method is similar to the fiber sizing technique commonly used and thus it can be easily scaled and integrated to industrial SMC lines. This will be an alternative route to the most techniques that involve dispersing CN in polymer matrix, in which the nanomaterials agglomeration limits the capability for scaling up in an industrial production. We have demonstrated that incorporating CNC as a coating on GF surface by immersing the GF in CNC aqueous suspensions, a simple and scalable technique, increases the interfacial shear strength (IFSS) by ~69% compared to the composites produced by uncoated GF, suggesting an enhancement of stress transfer across the GF/matrix interface. As a result of IFSS enhancement, incorporation of 0.17 wt% CNC in the composite results in increases of ~10% in both elastic modulus and tensile strength, and 40 % and 43 % in flexural modulus and strength respectively. We have also determined that dispersing 1.4 and 2 wt% CNC in the epoxy matrix of short GF/epoxy SMC composites by sonication allows removing 10 wt% GF with no penalty on tensile and flexural properties leading to 7.5% lighter composites. Although sonication is a scalable technique, it is not quite as simple and inexpensive as coating the GF by passing through an aqueous suspension of CNC. In this study, the above findings are integrated to 1) investigate the effect of CNC content on mechanical properties by passing the GF rovings through CNC aqueous suspension with various concentrations (0-5%) and 2) determine the optimum ratio of the added CNC to the removed GF to achieve the maximum possible weight reduction with no cost on mechanical performance of the SMC composites. The results of this study are of industrial relevance, providing a path toward producing high volume lightweight and mechanically enhanced SMC composites using cellulose nanomaterials.

Keywords: cellulose nanocrystals, light weight polymer-matrix composites, mechanical properties, sheet molding compound (SMC)

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Authors: Alexandra Shipley

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Background: Undergraduate paediatric teaching must overcome two major challenges: 1) balancing patient safety with active student engagement and 2) exposing students to a comprehensive range of pathologies within a relatively short clinical placement. Whilst lectures and shadowing on paediatric wards constitute the mainstay of learning, Simulation and Virtual Reality (VR) are emerging as effective teaching tools, which - immune to the unpredictability and seasonal variation of hospital presentations - could expose students to the entire syllabus more reliably, efficiently, and independently. We aim to evaluate the potential utility of Simulation and VR in addressing gaps within the traditional paediatric curriculum from the perspective of medical students. Summary of Work: Exposure to and perceived utility of various learning opportunities within the Paediatric and Emergency Medicine courses were assessed through a questionnaire completed by 5th year medical students (n=23). Summary of Results: Students reported limited exposure to several common acute paediatric presentations, such as bronchiolitis (41%), croup (32%) or pneumonia (14%), and to clinical emergencies, including cardiac/respiratory arrests or trauma calls (27%). Across all conditions, average self-reported confidence in assessment and management to the level expected of an FY1 is greater amongst those who observed at least one case (e.g. 7.6/10 compared with 3.6/10 for croup). Students rated exposure through Simulation or VR to be of similar utility to witnessing a clinical scenario on the ward. In free text responses, students unanimously favoured being ‘challenged’ through ‘hands-on’ patient interaction over passive shadowing, where it is ‘easy to zone out.’ In recognition of the fact that such independence is only appropriate in certain clinical situations, many students reported wanting more Simulation and VR teaching. Importantly, students raised the necessity of ‘proper debriefs’ after these sessions to maximise educational value. Discussion and Conclusion: Our questionnaire elicited several student-perceived challenges in paediatric education, including incomplete exposure to common pathologies and limited opportunities for active involvement in patient care. Indeed, these experiences seem to be important predictors of confidence. Quantitative and qualitative feedback suggests that VR and Simulation satisfy students’ self-reported appetite for independent engagement with authentic clinical scenarios. Take-aways: Our findings endorse further development of VR and Simulation as high-yield adjuncts to paediatric education.

Keywords: paediatric emergency education, simulation, virtual reality, medical education

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Authors: Alireza Barari, Saeed Shirali, Ahmad Abdi

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Introduction: Exercise has contradictory effects on the immune system. Glutamine supplementation may increase the resistance of the immune system in athletes. The Glutamine is one of the most recognized immune nutrients that as a fuel source, substrate in the synthesis of nucleotides and amino acids and is also known to be part of the antioxidant defense. Several studies have shown that improving glutamine levels in plasma and tissues can have beneficial effects on the function of immune cells such as lymphocytes and neutrophils. This study aimed to investigate the effects of resistance training and training combined with glutamine supplementation to improve the levels of cortisol and immunoglobulin in untrained young men. The research shows that physical training can increase the cytokines in the athlete’s body of course; glutamine can counteract the negative effects of resistance training on immune function and stability of the mast cell membrane. Materials and methods: This semi-experimental study was conducted on 30 male non-athletes. They were randomly divided into three groups: control (no exercise), resistance training, resistance training and glutamine supplementation, respectively. Resistance training for 4 weeks and glutamine supplementation in 0.3 gr/kg/day after practice was applied. The resistance-training program consisted of eight exercises (leg press, lat pull, chest press, squat, seatedrow, abdominal crunch, shoulder press, biceps curl and triceps press down) four times per week. Participants performed 3 sets of 10 repetitions at 60–75% 1-RM. Anthropometry indexes (weight, body mass index, and body fat percentage), oxygen uptake (VO2max) Maximal, cortisol levels of immunoglobulins (IgA, IgG, IgM) were evaluated Pre- and post-test. Results: Results showed four week resistance training with and without glutamine cause significant increase in body weight, BMI and significantly decreased (P < 0/001) in BF. Vo2max also increased in both groups of exercise (P < 0/05) and exercise with glutamine (P < 0/001), such as in both groups significant reduction in IgG (P < 0/05) was observed. But no significant difference observed in levels of cortisol, IgA, IgM in any of the groups. No significant change observed in either parameter in the control group. No significant difference observed between the groups. Discussion: The alterations in the hormonal and immunological parameters can be used in order to assess the effect overload on the body, whether acute or chronically. The plasmatic concentration of glutamine has been associated to the functionality of the immunological system in individuals sub-mitted to intense physical training. resistance training has destructive effects on the immune system and glutamine supplementation cannot neutralize the damaging effects of power exercise on the immune system.

Keywords: glutamine, resistance traning, immuglobulins, cortisol

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Authors: Rajish Shil, Mohammad Ali Houri, Mohammad Milad Ismail, Fatimah Al Kaabi

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The clinical presentation of Primary hyperparathyroidism can vary from simple asymptomatic hypercalcemia to severe life-threatening hypercalcemic crisis with multi-organ dysfunction, which can be due to parathyroid adenoma or sometimes with malignant cancer. This cascade of clinical presentation can lead to a diagnostic and therapeutic challenge for treating the disease. We are presenting a case of severe hypercalcemic crisis due to parathyroid adenoma with an emphasis on early management, diagnosis, and interventions to prevent any lifelong complications and any permanent organ dysfunction. A 30 years old female with a history of primary Infertility, admitted to Al Ain Hospital critical care unit with Acute Severe Necrotizing Pancreatitis. She initially had a 1-month history of abdominal pain on and off, for which she was treated conservatively with no much improvement, and later on, she developed life-threatening severe pancreatitis, which required her to be admitted to the critical care unit. She was transferred from a private healthcare facility, where she was found to have a very high level of calcium up to 15mmol/L. She received systemic Zoledronic Acid, which lowered her calcium level transiently and later was increased again. She went on to develop multiple end-organ damages along with multiple electrolytes disturbances. She was found to have high levels of Parathyroid hormone, which was correlated with a parathyroid mass on the neck via radiological imaging. After a long course of medical treatment to lower the calcium to a near-normal level, parathyroidectomy was done, which showed parathyroid adenoma on histology. She developed hungry bone syndrome after the surgery and pancreatic pseudocyst after resolving of pancreatitis. She required aggressive treatment with Intravenous calcium for her hypocalcemia as she received zoledronic acid at the beginning of the disease. Later on, she was discharged on long term calcium and other electrolytes supplements. In patients presenting with hypercalcemia, it is prudent to investigate and start treatment early to prevent complications and end-organ damage from hypercalcemia and also to treat the primary cause of the hypercalcemia, with conscious follow up to prevent hypocalcemic complications after treatment. It is important to follow up patients with parathyroid adenomas for a long period in order to detect any recurrence of the tumor or to make sure if the primary tumor is either benign or malignant.

Keywords: hypercalcemia, pancreatitis, hypocalcemia, hyperparathyroidism

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Authors: Raju K. Thadikkaran

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Introduction: The IPR have come to the centre stage of development discourse today for a variety of reasons: It ranges from the arbitrariness in the enforcement, overlapping and mismatch with various international agreements and conventions, divergence in the definition, nature and content and the duration as well as severe adverse consequences to technologically weak developing countries. In turn, the IPR have acquired prominence in the foreign policy making as well as in the relations among nations. Quite naturally, there is ample scope for an examination of the correlation between Technology, IPR and International Relations in the contemporary world. Nature and Scope: A cursory examination of the realm of IPR and its protection shall reveals the acute divergence that exists in the perspectives, on all matters related to the very definition, nature, content, scope and duration. The proponents of stronger protection, mostly technologically advanced countries, insist on a stringent IP Regime whereas technologically weak developing countries seem to advocate for flexibilities. From the perspective of developing countries like India, one of the most crucial concerns is related to the patenting of life forms and the protection of TK and BD. There have been several instances of Bio-piracy and Bio-prospecting of the resources related to BD and TK from the Bio-rich Global South. It is widely argued that many provisions in the TRIPS are capable of offsetting the welcome provisions in the CBD such as the Access and Benefit Sharing and Prior Informed Consent. The point that is being argued out is as to how the mismatch between the provisions in the TRIPS Agreement and the CBD could be addressed in a healthy manner so that the essential minimum legitimate interests of all stakeholders could be secured thereby introducing a new direction to the international relations. The findings of this study reveal that the challenges roused by the TRIPS Regime over-weigh the opportunities. The mismatch in the provisions in this regard has generated various crucial issues such as Bio-piracy and Bio-prospecting. However, there is ample scope for managing and protecting IP through institutional innovation, legislative, executive and administrative initiative at the global, national and regional levels. The Indian experience is quite reflective of the same and efforts are being made through the new national IPR policy. This paper, employing Historical Analytical Method, has Three Sections. The First Section shall trace the correlation between the Technology, IPR and international relations. The Second Section shall review the issues and potential concerns in the protection and management of IP related to the BD and TK in the developing countries in the wake of the TRIPS and the CBD. The Final Section shall analyze the Indian Experience in this regard and the experience of the bio-rich Kerala in particular.

Keywords: IPR, technology and international relations, bio-diversity, traditional knowledge

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.

Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles

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Authors: Lilian Mbinya Muasa

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Climate change is inevitable and a global challenge with long term implications to the sustainable development of many countries today. The negative impacts of climate change are creating far reaching social, economic and environmental problems threatening lives and livelihoods of millions of people in the world. Developing countries especially sub-Saharan countries are more vulnerable to climate change due to their weak ecosystem, low adaptive capacity and high dependency on rain fed agriculture. Countries in Sub-Saharan Africa are more vulnerable to climate change impacts due to their weak adaptive capacity and over-reliance on rain fed agriculture. In Kenya, 78% of the rural communities are poor farmers who heavily rely on rain fed agriculture thus are directly affected by climate change impacts.Currently, many parts of Kenya are experiencing successive droughts which are contributing to persistently unstable and declining agricultural productivity especially in semi arid eastern Kenya. As a result, thousands of rural communities repeatedly experience food insecurity which plunge them to an ever over-reliance on relief food from the government and Non-Governmental Organization In addition, they have adopted poverty coping strategies to diversify their income, for instance, deforestation to burn charcoal, sand harvesting and overgrazing which instead contribute to environmental degradation.This research was conducted in Makueni County which is classified as one of the most food insecure counties in Kenya and experiencing acute environmental degradation. The study aimed at analyzing the adaptive capacity to climate change across farming households of Makueni County in Kenya by, 1) analyzing adaptive capacity to climate change and agricultural productivity across farming households, 2) identifying factors that contribute to differences in adaptive capacity across farming households, and 3) understanding the relationship between climate change, agricultural productivity and adaptive capacity. Analytical Hierarchy Process (AHP) was applied to determine adaptive capacity and Total Factor Productivity (TFP) to determine Agricultural productivity per household. Increase in frequency of prolonged droughts and scanty rainfall. Preliminary findings indicate a magnanimous decline in agricultural production in the last 10 years in Makueni County. In addition, there is an over reliance of households on indigenous knowledge which is no longer reliable because of the unpredictability nature of climate change impacts. These findings on adaptive capacity across farming households provide the first step of developing and implementing action-oriented climate change policies in Makueni County and Kenya.

Keywords: adaptive capacity, agricultural productivity, climate change, vulnerability

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Authors: Majid Farsadrouh Rashti, Alireza Mohammadinejad, Amir Shafiee Kisomi

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Lead (Pb²⁺), a cation, is a prime constituent of the majority of the industrial effluents such as mining, smelting and coal combustion, Pb-based painting and Pb containing pipes in water supply systems, paper and pulp refineries, printing, paints and pigments, explosive manufacturing, storage batteries, alloy and steel industries. The maximum permissible limit of lead in the water used for drinking and domesticating purpose is 0.01 mg/L as advised by Bureau of Indian Standards, BIS. This becomes the acceptable 'safe' level of lead(II) ions in water beyond which, the water becomes unfit for human use and consumption, and is potential enough to lead health problems and epidemics leading to kidney failure, neuronal disorders, and reproductive infertility. Superabsorbent hydrogels are loosely crosslinked hydrophilic polymers that in contact with aqueous solution can easily water and swell to several times to their initial volume without dissolving in aqueous medium. Superabsorbents are kind of hydrogels capable to swell and absorb a large amount of water in their three-dimensional networks. While the shapes of hydrogels do not change extensively during swelling, because of tremendously swelling capacity of superabsorbent, their shape will broadly change.Because of their superb response to changing environmental conditions including temperature pH, and solvent composition, superabsorbents have been attracting in numerous industrial applications. For instance, water retention property and subsequently. Natural-based superabsorbent hydrogels have attracted much attention in medical pharmaceutical, baby diapers, agriculture, and horticulture because of their non-toxicity, biocompatibility, and biodegradability. Novel superabsorbent hydrogel nanocomposites were prepared by graft copolymerization of acrylamide and itaconic acid in the presence of nanoclay (laponite), using methylene bisacrylamide (MBA) and potassium persulfate, former as a crosslinking agent and the second as an initiator. The superabsorbent hydrogel nanocomposites structure was characterized by FTIR spectroscopy, SEM and TGA Spectroscopy adsorption of metal ions on poly (AAm-co-IA). The equilibrium swelling values of copolymer was determined by gravimetric method. During the adsorption of metal ions on polymer, residual metal ion concentration in the solution and the solution pH were measured. The effects of the clay content of the hydrogel on its metal ions uptake behavior were studied. The NC hydrogels may be considered as a good candidate for environmental applications to retain more water and to remove heavy metals.

Keywords: adsorption, hydrogel, nanocomposite, super adsorbent

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Authors: Aarti Sharma, Sarita Kumar, Pushplata Tripathi

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Aedes aegypti L. is one of the most important insect vectors in the world transmitting several diseases of concern; dengue fever, dengue haemorrhagic fever and yellow fever. Though since ages the control of dengue vector is primarily relied upon the use of synthetic chemical insecticides, the continued and indiscriminate use of insecticides for their control has received wide public apprehension because of multifarious problems including insecticide resistance, resurgence of pest species, environmental pollution, toxic hazards to humans and non-target organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly and bio-degradable plant products. Bio-insecticides, despite being the focus of research nowadays, have not been investigated much regarding their physiological effects on the mosquitoes. Thus, the present studies were carried out to investigate the anti-mosquito potential of the leaf and stem hexane extracts of Achyranthes aspera against early fourth instars of Aedes aegypti L and their effects on the histological architecture of their midgut. The larvicidal bioassays conducted with the A. aspera leaf hexane extracts revealed the respective LC30, LC50 and LC90 values of 66.545 ppm, 82.555 ppm, 139.817 ppm while the assays with stem hexane extracts resulted in respective values of 54.982 ppm, 68.133 ppm, 115.075 ppm. The studies clearly indicate the efficacy of extracts as larvicidal agents against Ae. aegypti, the stem extracts being found more effective than the leaf extracts. When the larvae assayed with extracts were investigated for the modifications in the histo-architecture of the midgut, the studies showed significant damage, shrinkage, distortion and vacuolization of gut tissues and peritrophic membrane causing disintegration of epithelial cells and cytoplasmic organelles; extent of toxicity and damage varied depending upon the concentration and exposure time period. These changes revealed appreciable stomach poison potential of A. aspera extracts against Ae. aegypti larvae, which may have also caused adverse impact on the growth and development of larvae. These effects were also found to be more pronounced with the stem extract than the leaf extract. Our findings may prove significant suggesting the use of A. aspera extract as a bio-insecticide against early fourth instar larvae of Ae. aegypti. Further studies are needed to identify the bioactive component in the extracts and to ascertain the use of component in the fields as anti-mosquito control agent.

Keywords: Achyranthes aspera, Aedes aegypti, histological architecture, larvicidal, midgut, stomach poison

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Authors: Valeria T. Dilcheva, Svetlozara L. Petkova, Ivelin Vladov

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Trichinellosis is a food-borne parasitic disease caused by nematodes of the genus Trichinella which are zoonotic parasites with cosmopolitan distribution and major socio-economic importance. Human infection is acquired through consumption of undercooked meat from domestic or wild animal. Penetration of Trichinella larvae into striated skeletal muscle cells results in ultrastructural and metabolic changes. Migration of larvae causes the typical symptoms and signs of the disease. The severity of the symptoms depends on the number of ingested Trichinella larvae and the immune response of the host. Eosinophilia is present, with few exceptions, in most cases of human trichinellosis, inasmuch as it is the earliest and most important host response. Even in human asymptomatic cases, increases in eosinophilia of up to 15% have been observed. Eosinophilia appears at an early stage of infection between the second and fifth weeks of infection. By 2005 it was considered that only two species of Trichinella genus were found in the country. After routine trichinelloscopy procedure disseminated single muscle larvae in samples of wild boars and badger were PCR-identified as T. pseudospiralis. The study aimed to observed hematological changes occurring during experimentally induced infection with Trichinella spiralis, T. britovi and T. pseudospiralis in mice. We performed hematological blood profile, tracking 15 blood indicators. In statistical analysis made by Two-way ANOVA, there were significant differences of HGB, MCHC, PLT, Lymph%, Gran% in all three types of trichinellosis compared to control animals. Capsule-forming T. spiralis showed statistically significant differences in HGB, MCHC, Lymph% and PLT compared to the other two species. Non capsule-forming T. pseudospiralis showed statistically significant differences in Lymph%, Gran% relative to the control and in Gran% relative to T. spiralis. It appears rather substantial the process of capsule formation for prolonged immune response and retention of high content of percentage of lymphocytes(Lymph%) and low of granulocyte(Gran%) in T. pseudospiralis, which is contrary to studies for T. spiralis and eosinophilia. Studies and analyzes of some specific blood profile parameters can provide additional data in favor of early diagnosis and adequate treatment as well as provide a better understanding of acute and chronic trichinosis.

Keywords: hematological test, T. britovi, T. spiralis, T. pseudospiralis

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Authors: Shyam lamsal

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Introduction: Karnali Academy of Health Sciences (KAHS) has been established in 2011, by an Act of parliament of Nepal, in Jumla, to provide health services in easy way in backward areas, to produce skilled health professionals & conduct research. The backward areas mentioned in act of KAHS are Humla, Jumla, Kalikot, Dolpa, Mugu districts of Karnali zone, Jajarkot district of Bheri zone & Bajura, Baghang & Achham districts of Seti zone in Nepal occupying around 25 % of the total national geography. Backward area of Nepal is specific to having worst health indicators with life expectancy (47 years), HDI (0.35), Literacy rate (58%), global acute malnutrition (13%), crude birth rate (33.6), crude death rate (9.6), Total fertility rate (4.2), infant mortality rate (61.5 per 1000 live births), under five mortality rate (59 per 1000 live births) and maternal mortality ratio (400 per 1000 live births). History of health facilities in backward region: All the nine districts of this region have a district hospital with very few grass root level health manpower. Government of Nepal regularly deploys one or two medical officers to each district who generally are not regular to their care. Jumla district itself was having one medical officer before the establishment of KAHS. Development activities: Establishment of 100 bedded specialty teaching hospital with 10 medical officers and five specialists, accredited its own nursing school for running diploma nursing programme, started “Karnali health survey” which covers 55 thousand households of backward region, started community care and school health camps, planning phase completed for 300 bedded teaching hospital construction. Future Plan: Expansion of the teaching hospital to 300 beds within 3 years, start health assistant and bachelor midwifery course in 2015 AD, start bachelor in laboratory and bachelor in public health course in 2016 AD and start MBBS course in 2018 AD. Deploy the medical officers and family physicians to all the district hospitals within 3 years. KAHS provides reservation up to 45% students from backward region with the commitment to stay for at least five years of their service period. Conclusion: This institution may be the example for the rest of the world in providing nursing care, education in remote areas as well as the best model for nursing manpower retention in remote areas of developing countries.

Keywords: backward area, nursing school

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Authors: Mirjana Petronijević, Sanja Panić, Aleksandra Cvetanović, Branko Kordić, Nenad Grba

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Enzyme peroxidases are biological catalysts and play a major role in phenolic wastewater treatments and other environmental applications. The most studied species from the peroxidases family is horseradish peroxidase (HRP). In environmental processes, HRP could be used in its free or immobilized form. Enzyme immobilization onto solid support is performed to improve the enzyme properties, prolong its lifespan and operational stability and allow its reuse in industrial applications. One of the enzyme supports of a newer generation is magnetic particles (MPs). Fe₃O₄ MPs are the most widely pursued immobilization of enzymes owing to their remarkable advantages of biocompatibility and non-toxicity. Also, MPs can be easily separated and recovered from the water by applying an external magnetic field. On the other hand, metals and metal oxides are not suitable for the covalent binding of enzymes, so it is necessary to perform their surface modification. Fe₃O₄ MPs functionalization could be performed during the process of their synthesis if it takes place in the presence of plant extracts. Extracts of plant material, such as wild plants, herbs, even waste materials of the food and agricultural industry (bark, shell, leaves, peel), are rich in various bioactive components such as polyphenols, flavonoids, sugars, etc. When the synthesis of magnetite is performed in the presence of plant extracts, bioactive components are incorporated into the surface of the magnetite, thereby affecting its functionalization. In this paper, the suitability of bio-magnetite as solid support for covalent immobilization of HRP across glutaraldehyde was examined. The activity of immobilized HRP at different pH values (4-9) and temperatures (20-80°C) and reusability were examined. Bio-MP was synthesized by co-precipitation method from Fe(II) and Fe(III) sulfate salts in the presence of water extract of the Allium cepa peel. The water extract showed 81% of antiradical potential (according to DPPH assay), which is connected with the high content of polyphenols. According to the FTIR analysis, the bio-magnetite contains oxygen functional groups (-OH, -COOH, C=O) suitable for binding to glutaraldehyde, after which the enzyme is covalently immobilized. The immobilized enzyme showed high activity at ambient temperature and pH 7 (30 U/g) and retained ≥ 80% of its activity at a wide range of pH (5-8) and temperature (20-50°C). The HRP immobilized onto bio-MPs showed remarkable stability towards temperature and pH variations compared to the free enzyme form. On the other hand, immobilized HRP showed low reusability after the first washing cycle enzyme retains 50% of its activity, while after the third washing cycle retains only 22%.

Keywords: bio-magnetite, enzyme immobilization, water extracts, environmental protection

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

Procedia PDF Downloads 61

Authors: Spencer Liu, William Chan, Marlena Komatz, Tommy Ramos, Mark Trentalange, Faye Rim, Dae Kim, Mary Kelly, Samuel Schuessler, Roberta Stack, Justas Lauzadis, Kathryn DelPizzo, Seth Waldman, Alexandra Sideris

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Background & Significance: The increasing prevalence of cannabis use in the United States has important safety considerations in the perioperative setting, as chronic or heavy preoperative cannabis use may increase the risk of intraoperative complications, postoperative nausea and vomiting (PONV), increased postoperative pain levels, and acute side effects associated with cannabis use cessation. In this retrospective chart review study, we sought to determine the prevalence of self-reported cannabis use in the past 5-years at a single institution in New York City. We hypothesized that there is an increasing prevalence of preoperative self-reported cannabis use among adult and adolescent patients undergoing orthopedic surgery. Methods: After IRB approval for this retrospective study, surgical cases performed on patients 12 years of age and older at the hospital’s main campus and two ambulatory surgery centers between January 1st, 2018, and December 31st, 2023, with preoperatively self-disclosed cannabis use entered in the social history intake form were identified using the tool SlicerDicer in Epic. Case and patient characteristics were extracted, and trends in utilization over time were assessed by the Cochran-Armitage trend test. Results: Overall, the prevalence of self-reported cannabis use increased from 6.6% in 2018 to 10.6% in 2023. By age group, the prevalence of self-reported cannabis use among adolescents remained consistently low (2018: 2.6%, 2023: 2.6%) but increased with significant evidence for a linear trend (p < 0.05) within every adult age group. Among adults, patients who were 18-24 years old (2018: 18%, 2023: 20.5%) and 25-34 years old (2018: 15.9%, 2023: 24.2%) had the highest prevalences of disclosure, whereas patients who were 75 years of age or older had the lowest prevalence of disclosure (2018: 1.9%, 2023: 4.6%). Patients who were 25-34 years old had the highest percent difference in disclosure rates of 8.3%, which corresponded to a 52.2% increase from 2018 to 2023. The adult age group with the highest percent change was patients who were 75 years of age or older, with a difference of 2.7%, which corresponded to a 142.1% increase from 2018 to 2023. Conclusions: These trends in preoperative self-reported cannabis use among patients undergoing orthopedic surgery have important implications for perioperative care and clinical outcomes. Efforts are underway to refine and standardize cannabis use data capture at our institution.

Keywords: orthopedic surgery, cannabis, postoperative pain, postoperative nausea

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Rohit Kothari

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Background: Leprosyis a chronic granulomatous diseasecaused by Mycobacterium leprae (M. Lepra). Reactions may interrupt its usual chronic course.Type-1 (T1R)and type-2 lepra reaction(T2R) are acute events and signifytype-IV and type-III hypersensitivity responses, respectively. Various chemokines like CCL3, 5, 11, and CCL24 may be increased during the course of leprosy or during reactions and may serve as markers of early diagnosis, response to therapy, and prognosis. Objective: To find correlation of CCL3, 5, 11, and CCL24 in leprosy patients on multidrug therapy and their family contacts after ruling out active disease during leprosy treatment and during periods of lepra reactions. Methodology: This randomized control trial was conducted in 50 clinico-histopathologically diagnosed cases of leprosy in a tertiary care hospital in Bengaluru, India. 50 of their family contacts were adequately examined and investigated should the need be to rule out active disease. The two study-groups comprised of leprosy cases, and the age, sex, and area of residence matched healthy contactswho were given single-dose rifampicin prophylaxis, respectively. Blood samples were taken at baseline, six months, and after one yearin both the groups (on completion of MDT in leprosy cases)and also during periods of reaction if occurred in leprosy cases. Results: Our study found that at baseline, CCL5, 11, and 24 were higher in leprosy cases as compared to the healthy contacts, and the difference was statistically significant.CCL3 was also found to be higherat baseline in leprosy cases, however, the difference was not statistically significant. At six months and one year, the levels of CCL 5, 11, and 24 reduced, and the difference was statistically significant in leprosy cases, whereas it remained almost static in all the healthy contacts. Twenty patients of leprosy developed lepra reaction during the course of one year, and during reaction, the increase in CCL11 and 24 was statistically significant from baseline, whereas CCL3 and 5 did not rise significantly. One of the healthy contacts developed signs of leprosy in the form of hypopigmented numb patch and was clinico-histopathologically, and CCL11 and 24 were found to be higher with a statistically significant difference from the baseline values. Conclusion: CCL5, 11, and 24 are sensitive markers of diagnosing leprosy, response to MDT, and prognosis and are not increased in healthy contacts. CCL11 and 24 are sensitive markers of lepra reactions and may serve as one of the early diagnostic modalities for identifying lepra reaction and also leprosy in healthy contacts. To the best of our knowledge, this is the first study to evaluate these biomarkers in leprosy cases and their healthy contacts with a follow-up of upto one year with one of them developing the disease, and the same was confirmed based on these biomarkers as well.

Keywords: chemokine profile, healthy contacts, leprosy, lepra reactions

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Authors: Lina Wu

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The excessive discharge of nitrogen in sewage greatly intensifies the eutrophication of water bodies and poses a threat to water quality. Nitrogen pollution control has become a global concern. Currently, the problem of water pollution in China is still not optimistic. As a typical high ammonia nitrogen organic wastewater, landfill leachate is more difficult to treat than domestic sewage because of its complex water quality, high toxicity, and high concentration.Many studies have shown that the autotrophic anammox bacteria in nature can combine nitrous and ammonia nitrogen without carbon source through functional genes to achieve total nitrogen removal, which is very suitable for the removal of nitrogen from leachate. In addition, the process also saves a lot of aeration energy consumption than the traditional nitrogen removal process. Therefore, anammox plays an important role in nitrogen conversion and energy saving. The process composed of short-range nitrification and denitrification coupled an ammo ensures the removal of total nitrogen and improves the removal efficiency, meeting the needs of the society for an ecologically friendly and cost-effective nutrient removal treatment technology. Continuous flow process for treating late leachate [an up-flow anaerobic sludge blanket reactor (UASB), anoxic/oxic (A/O)–anaerobic ammonia oxidation reactor (ANAOR or anammox reactor)] has been developed to achieve autotrophic deep nitrogen removal. In this process, the optimal process parameters such as hydraulic retention time and nitrification flow rate have been obtained, and have been applied to the rapid start-up and stable operation of the process system and high removal efficiency. Besides, finding the characteristics of microbial community during the start-up of anammox process system and analyzing its microbial ecological mechanism provide a basis for the enrichment of anammox microbial community under high environmental stress. One research developed partial nitrification-Anammox (PN/A) using an internal circulation (IC) system and a biological aerated filter (BAF) biofilm reactor (IBBR), where the amount of water treated is closer to that of landfill leachate. However, new high-throughput sequencing technology is still required to be utilized to analyze the changes of microbial diversity of this system, related functional genera and functional genes under optimal conditions, providing theoretical and further practical basis for the engineering application of novel anammox system in biogas slurry treatment and resource utilization.

Keywords: nutrient removal and recovery, leachate, anammox, partial nitrification

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Authors: T. Poppendieker

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A new innovative tool for self-myofascial release is widely and increasingly used among athletes of various sports. The application of the foam roll is suggested to improve muscle performance and flexibility. Attempts to examine acute and somewhat long term effects of either have been conducted over the past ten years. However, the results of muscle performance have been inconsistent. It is suggested that regular use over a long period of time results in a different, muscle performance improving outcome. This study examines long-term effects of regular foam rolling combined with a short plyometric routine vs. solely the same plyometric routine on muscle performance and flexibility over a period of six weeks. Results of counter movement jump (CMJ), squat jump (SJ), and isometric maximal force (IMF) of a 90° horizontal squat in a leg-press will serve as parameters for muscle performance. Data on the range of motion (ROM) of the sit and reach test will be used as a parameter for the flexibility assessment. Muscle activation will be measured throughout all tests. Twenty male and twenty female members of a Frankfurt area fitness center chain (7.11) with an average age of 25 years will be recruited. Women and men will be randomly assigned to a foam roll (FR) and a control group. All participants will practice their assigned routine three times a week over the period of six weeks. Tests on CMJ, SJ, IMF, and ROM will be taken before and after the intervention period. The statistic software program SPSS 22 will be used to analyze the data of CMJ, SJ, IMF, and ROM under consideration of muscle activation by a 2 x 2 x 2 (time of measurement x gender x group) analysis of variance with repeated measures and dependent t-test analysis of pre- and post-test. The alpha level for statistic significance will be set at p ≤ 0.05. It is hypothesized that a significant difference in outcome based on gender differences in all four tests will be observed. It is further hypothesized that both groups may show significant improvements in their performance in the CMJ and SJ after the six-week period. However, the FR group is hypothesized to achieve a higher improvement in the two jump tests. Moreover, the FR group may increase IMF as well as flexibility, whereas the control group may not show likewise progress. The results of this study are crucial for the understanding of long-term effects of regular foam roll application. The collected information on the matter may help to motivate the incorporation of foam rolling into training routines, in order to improve athletic performances.

Keywords: counter movement jump, foam rolling, isometric maximal force, long term effects, self-myofascial release, squat jump

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Authors: R. Tariq, R. Lee

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Background: Additional demands placed on senior clinical teams with ongoing COVID-19 management has accelerated the need to harness the wider healthcare professional resources and upskill them to take on greater clinical responsibility safely. The UK NHS Long Term Plan (2019)¹ emphasises the importance of expanding Advanced Practitioners’ (APs) roles to take on more clinical diagnostic responsibilities to cope with increased demand. In acute settings, APs are often the first point of care for patients and require training to take on initial triage responsibilities efficiently and safely. Critically, their roles include determining which onward services the patients may require, and assessing whether they can be treated at home, avoiding unnecessary admissions to the hospital. Dem Dx is a Clinical Reasoning Platform (CRP) that claims to help frontline healthcare professionals independently assess and triage patients. It guides the clinician from presenting complaints through associated symptoms to a running list of differential diagnoses, media, national and institutional guidelines. The objective of this study was to compare the clinical referral rates and guidelines adherence registered by the HMR Urgent Community Care Team (UCCT)² and Dem Dx recommendations using retrospective cases. Methodology: 192 cases seen by the UCCT were anonymised and reassessed using Dem Dx clinical pathways. We compared the UCCT’s performance with Dem Dx regarding the appropriateness of onward referrals. We also compared the clinical assessment regarding adherence to NICE guidelines recorded on the clinical notes and the presence of suitable guidance in each case. The cases were audited by two medical doctors. Results: Dem Dx demonstrated appropriate referrals in 85% of cases, compared to 47% in the UCCT team (p<0.001). Of particular note, Dem Dx demonstrated an almost 65% (p<0.001) improvement in the efficacy and appropriateness of referrals in a highly experienced clinical team. The effectiveness of Dem Dx is in part attributable to the relevant NICE and local guidelines found within the platform's pathways and was found to be suitable in 86% of cases. Conclusion: This study highlights the potential of clinical decision support, as Dem Dx, to improve the quality of onward clinical referrals delivered by a multidisciplinary team in primary care. It demonstrated that it could support healthcare professionals in making appropriate referrals, especially those that may be overlooked by providing suitable clinical guidelines directly embedded into cases and clear referral pathways. Further evaluation in the clinical setting has been planned to confirm those assumptions in a prospective study.

Keywords: advanced practitioner, clinical reasoning, clinical decision-making, management, multidisciplinary team, referrals, triage

Procedia PDF Downloads 126

Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

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Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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Authors: Olga Gomez De Miranda, Jose R. Ochoa-Gomez, Stefaan De Wildeman, Luciano Monsegue, Soraya Prieto, Leire Lorenzo, Cristina Dineiro

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The chemical industry is facing a new revolution. As long as processes based on the exploitation of fossil resources emerged with force in the XIX century, Society currently demands a new radical change that will lead to the complete and irreversible implementation of a circular sustainable economic model. The implementation of biorefineries will be essential for this. There, renewable raw materials as sugars and other biomass resources are exploited for the development of new materials that will partially replace their petroleum-derived homologs in a safer, and environmentally more benign approach. Isosorbide, (1,4:3,6-dianhydro-d-glucidol) is a primary bio-based derivative obtained from the plant (poly) saccharides and a very interesting example of a useful chemical produced in biorefineries. It can, in turn, be converted to other secondary monomers as isosorbide bis-methyl carbonate (IBMC), whose main field of application can be as a key biodegradable intermediary substitute of bisphenol-A in the manufacture of polycarbonates, or as an alternative to the toxic isocyanates in the synthesis of new polyurethanes (non-isocyanate polyurethanes) both with a huge application market. New products will present advantageous mechanical or optical properties, as well as improved behavior in non-toxicity and biodegradability aspects in comparison to their petro-derived alternatives. A robust production process of IBMC, a biomass-derived chemical, is here presented. It can be used with different raw material qualities using dimethyl carbonate (DMC) as both co-reactant and solvent. It consists of the transesterification of isosorbide with DMC under soft operational conditions, using different basic catalysts, always active with the isosorbide characteristics and purity. Appropriate isolation processes have been also developed to obtain crude IBMC yields higher than 90%, with oligomers production lower than 10%, independently of the quality of the isosorbide considered. All of them are suitable to be used in polycondensation reactions for polymers obtaining. If higher qualities of IBMC are needed, a purification treatment based on nanofiltration membranes has been also developed. The IBMC reaction-isolation conditions established in the laboratory have been successfully modeled using appropriate software programs and moved to a pilot-scale (production of 100 kg of IBMC). It has been demonstrated that a highly efficient IBMC production process able to be up-scaled under suitable market conditions has been obtained. Operational conditions involved the production of IBMC involve soft temperature and energy needs, no additional solvents, and high operational efficiency. All of them are according to green manufacturing rules.

Keywords: biomass, catalyst, isosorbide bis-methyl carbonate, polycarbonate, polyurethane, transesterification

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Authors: Jacklyn Yek, Clara Tong, Shin Yuet Chong, Yee Yian Ong

Abstract:

Background: While emergency manuals and cognitive aids (CA) have been used in high-hazard industries for decades, this has been a nascent field in healthcare. CAs can potentially offset the large cognitive load involved in crisis resource management and possibly facilitate the efficient performance of key steps in treatment. A crisis manual was developed based on local guidelines and the latest evidence-based information and introduced to a tertiary hospital setting in Singapore. Hence, the objective of this study is to evaluate the effectiveness of the crisis manual in guiding response and management of critical events. Methods: 7 surgical teams were recruited to participate in a series of simulated emergencies in high-fidelity operating room simulator over the period of April to June 2018. All teams consisted of a surgical consultant and medical officer/registrar, anesthesia consultant and medical officer/registrar; as well as a circulating, scrub and anesthetic nurse. Each team performed a simulated operation in which 1 or more of the crisis events occurred. The teams were randomly assigned to a scenario of the crisis manual and all teams were deemed to be equal in experience and knowledge. Before the simulation, teams were instructed on proper checklist use but the use of the checklist was optional. Results: 7 simulation sessions were performed, consisting of the following scenarios: Airway fire, Massive Transfusion Protocol, Malignant Hyperthermia, Eclampsia, and Difficult Airway. Out of the 7 surgical teams, 2 teams made use of the crisis manual – of which both teams had encountered a ‘Malignant Hyperthermia’ scenario. These team members reflected that the crisis manual assisted allowed them to work in a team, especially being able to involve the surgical doctors who were unfamiliar with the condition and management. A run chart plotted showed a possible upward trend, suggesting that with increasing awareness and training, staff would become more likely to initiate the use of the crisis manual. Conclusion: Despite the high volume load in this tertiary hospital, certain crises remain rare and clinicians are often caught unprepared. A crisis manual is an effective tool and easy-to-use repository that can improve patient outcome and encourage teamwork. With training, familiarity would allow clinicians to be increasingly comfortable with reaching out for the crisis manual. More simulation training would need to be conducted to determine its effectiveness.

Keywords: crisis resource management, high fidelity simulation training, medical errors, visual aids

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Authors: Raphael Palucci Rosa, Giuseppe Rosace

Abstract:

Stereolithography (SLA) is one of the 3D-printing technologies that has been steadily growing in popularity for both industrial and personal applications due to its versatility, high accuracy, and low cost. Its printing process consists of using a light emitter to solidify photosensitive liquid resins layer-by-layer to produce solid objects. However, the majority of the resins used in SLA are derived from petroleum and characterized by toxicity, stability, and recalcitrance to degradation in natural environments. Aiming to develop an eco-friendly resin, in this work, different combinations of a standard commercial SLA resin (Peopoly UV professional) with a vegetable-based resin were investigated. To reach this goal, different mass concentrations (varying from 10 to 50 wt%) of acrylated epoxidized soybean oil (AESO), a vegetable resin produced from soyabean oil, were mixed with a commercial acrylate-based resin. 1.0 wt% of Diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (TPO) was used as photo-initiator, and the samples were printed using a Peopoly moai 130. The machine was set to operate at standard configurations when printing commercial resins. After the print was finished, the excess resin was drained off, and the samples were washed in isopropanol and water to remove any non-reacted resin. Finally, the samples were post-cured for 30 min in a UV chamber. FT-IR analysis was used to confirm the UV polymerization of the formulated resin with different AESO/Peopoly ratios. The signals from 1643.7 to 1616, which corresponds to the C=C stretching of the AESO acrylic acids and Peopoly acrylic groups, significantly decreases after the reaction. The signal decrease indicates the consumption of the double bonds during the radical polymerization. Furthermore, the slight change of the C-O-C signal from 1186.1 to 1159.9 decrease of the signals at 809.5 and 983.1, which corresponds to unsaturated double bonds, are both proofs of the successful polymerization. Mechanical analyses showed a decrease of 50.44% on tensile strength when adding 10 wt% of AESO, but it was still in the same range as other commercial resins. The elongation of break increased by 24% with 10 wt% of AESO and swelling analysis showed that samples with a higher concentration of AESO mixed absorbed less water than their counterparts. Furthermore, high-resolution prototypes were printed using both resins, and visual analysis did not show any significant difference between both products. In conclusion, the AESO resin was successful incorporated into a commercial resin without affecting its printability. The bio-based resin showed lower tensile strength than the Peopoly resin due to network loosening, but it was still in the range of other commercial resins. The hybrid resin also showed better flexibility and water resistance than Peopoly resin without affecting its resolution. Finally, the development of new types of SLA resins is essential to provide new sustainable alternatives to the commercial petroleum-based ones.

Keywords: 3D-printing, bio-based, resin, soybean, stereolithography

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Authors: Justyna Humięcka-Jakubowska

Abstract:

1. Background in music analysis. Traditionally, when we think about a composer’s sketches, the chances are that we are thinking in terms of the working out of detail, rather than the evolution of an overall concept. Since music is a “time art’, it follows that questions of a form cannot be entirely detached from considerations of time. One could say that composers tend to regard time either as a place gradually and partially intuitively filled, or they can look for a specific strategy to occupy it. In my opinion, one thing that sheds light on Stockhausen's compositional thinking is his frequent use of 'form schemas', that is often a single-page representation of the entire structure of a piece. 2. Background in music technology. Sonic Visualiser is a program used to study a musical recording. It is an open source application for viewing, analysing, and annotating music audio files. It contains a number of visualisation tools, which are designed with useful default parameters for musical analysis. Additionally, the Vamp plugin format of SV supports to provide analysis such as for example structural segmentation. 3. Aims. The aim of my paper is to show how SV may be used to obtain a better understanding of the specific musical work, and how the compositional strategy does impact on musical structures and musical surfaces. I want to show that ‘traditional” music analytic methods don’t allow to indicate interrelationships between musical surface (which is perceived) and underlying musical/acoustical structure. 4. Main Contribution. Stockhausen had dealt with the most diverse musical problems by the most varied methods. A characteristic which he had never ceased to be placed at the center of his thought and works, it was the quest for a new balance founded upon an acute connection between speculation and intuition. In the case with Mikrophonie I (1964) for tam-tam and 6 players Stockhausen makes a distinction between the "connection scheme", which indicates the ground rules underlying all versions, and the form scheme, which is associated with a particular version. The preface to the published score includes both the connection scheme, and a single instance of a "form scheme", which is what one can hear on the CD recording. In the current study, the insight into the compositional strategy chosen by Stockhausen was been compared with auditory image, that is, with the perceived musical surface. Stockhausen's musical work is analyzed both in terms of melodic/voice and timbre evolution. 5. Implications The current study shows how musical structures have determined of musical surface. My general assumption is this, that while listening to music we can extract basic kinds of musical information from musical surfaces. It is shown that an interactive strategies of musical structure analysis can offer a very fruitful way of looking directly into certain structural features of music.

Keywords: automated analysis, composer's strategy, mikrophonie I, musical surface, stockhausen

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