Search results for: candidate gene of type-2 diabetes

Authors: Ibrahim Turfanda, Soniya Rai, Karan Vadher

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Objectives— The study aims to compare real-world adherence to and persistence with dulaglutide and liraglutide in patients with type 2 diabetes (T2D) initiating treatment in UAE. Methods— This was a retrospective, non-interventional study (observation period: 01 March 2017–31 August 2019) using the UAE Dubai e-Claims database. Included: adult patients initiating dulaglutide/liraglutide 01 September 2017–31 August 2018 (index period) with: ≥1 claim for T2D in the 6 months before index date (ID); ≥1 claim for dulaglutide/liraglutide during index period; and continuous medical enrolment for ≥6 months before and ≥12 months after ID. Key endpoints, assessed 3/6/12 months after ID: adherence to treatment (proportion of days covered [PDC; PDC ≥80% considered ‘adherent’], per-group mean±standard deviation [SD] PDC); and persistence (number of continuous therapy days from ID until discontinuation [i.e., >45 days gap] or end of observation period). Patients initiating dulaglutide/liraglutide were propensity score matched (1:1) based on baseline characteristics. Between-group comparison of adherence was analysed using the McNemar test (α=0.025). Persistence was analysed using Kaplan–Meier estimates with log-rank tests (α=0.025) for between-group comparisons. This study presents 12-month outcomes. Results— Following propensity score matching, 263 patients were included in each group. Mean±SD PDC for all patients at 12 months was significantly higher in the dulaglutide versus the liraglutide group (dulaglutide=0.48±0.30, liraglutide=0.39±0.28, p=0.0002). The proportion of adherent patients favored dulaglutide (dulaglutide=20.2%, liraglutide=12.9%, p=0.0302), as did the probability of being adherent to treatment (odds ratio [97.5% CI]: 1.70 [0.99, 2.91]; p=0.03). Proportion of persistent patients also favoured dulaglutide (dulaglutide=15.2%, liraglutide=9.1%, p=0.0528), as did the probability of discontinuing treatment 12 months after ID (p=0.027). Conclusions— Based on the UAE Dubai e-Claims database data, dulaglutide initiators exhibited significantly greater adherence in terms of mean PDC versus liraglutide initiators. The proportion of adherent patients and the probability of being adherent favored the dulaglutide group, as did treatment persistence.

Keywords: adherence, dulaglutide, effectiveness, liraglutide, persistence

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Authors: Ajay Kumar, Satwinderjeet Kaur

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Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.

Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species

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Authors: Ayo Osisanya, Promise Ebuka Okonkwo

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Reduced hearing sensitivity among the elderly has been attributed to some risk factors and influence of age-related degenerative conditions such as diabetes, cardiovascular disease, Alzheimer’s disease, bipolar disorder, and hypertension. Hearing loss; especially the age-related type (presbycusis), has been reported as one of the global burden affecting the general well-being and quality of life of the elderly with hypertension. Thus, hearing loss has been observed to be associated with hypertension and functional decline in elderly, as this condition makes them experience poor communication, fatigue, reduced social functions, mood-swing, and withdrawal syndrome. Emerging research outcomes indicate a strong relationship between hypertension and reduced auditory performance among the elderly. Therefore, this study determined the prevalence, types, and patterns of hearing loss associated with hypertension, with a bid to suggesting comprehensive management strategies and a model of creating awareness towards promoting good healthy living among the elderly in Nigeria. One hundred and seventy-two elderly, aged 65–85 with hypertension were purposively selected from patients undergoing treatment for hypertension in some tertiary hospitals in southwest Nigeria for the study. Participants were suggested to Pure-Tone Audiometry (PTA) through the use of Maico 53 Diagnostic Audiometer to determine the degree, types ad patterns of hearing loss among the elderly with hypertension. Results showed that 148 (86.05%) elderly with hypertension presented with different degrees, types, and patterns of hearing loss. Out of this number, 123 (83.11%) presented with bilateral hearing loss, while 25 (16.89%) had unilateral hearing loss. Degree of hearing loss, 74 moderate hearing loss, 118 moderately severe and 50 severe hearing loss. 36% of the hearing loss appeared as flat audiometric configuration, 24% were slopping, 19% were rising, while 21% were tough-shaped audiometric configurations. The findings showed high prevalence of hearing loss among the elderly with hypertension in Southwest, Nigeria. Based on the findings, management of elderly with hypertension should include regular audiological rehabilitation and total adherence to hearing conservation principles, otological management, regulation of blood pressure and adequate counselling / follow-up services.

Keywords: auditory performance, elderly, hearing loss, hypertension

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Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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Authors: Salma E. Ahmed

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Since the mid 50’s, enormous attention has been paid towards nanocarriers and their applications in drug and gene delivery. Among these vesicles, liposomes and micelles have been heavily investigated due to their many advantages over other types. Liposomes, for instance, are mostly distinguished by their ability to encapsulate hydrophobic, hydrophilic and amphiphilic drugs. Micelles, on the other hand, are self-assembled shells of lipids, amphiphilic or oppositely charged block copolymers that, once exposed to aqueous media, can entrap hydrophobic agents, and possess prolonged circulation in the bloodstream. Both carriers are considered compatible and biodegradable. Nevertheless, they have limited stabilities, chemical versatilities, and drug encapsulation efficiencies. In order to overcome these downsides, strategies for optimizing a novel drug delivery system that has the architecture of liposomes and polymeric characteristics of micelles have been evolved. Polymersomes are vehicles with fluidic cores and hydrophobic shells that are protected and isolated from the aqueous media by the hydrated hydrophilic brushes which give the carrier its distinctive polymeric bilayer shape. Similar to liposomes, this merit enables the carrier to encapsulate a wide range of agents, despite their affinities and solubilities in water. Adding to this, the high molecular weight of the amphiphiles that build the body of the polymersomes increases their colloidal and chemical stabilities and reduces the permeability of the polymeric membranes, which makes the vesicles more protective to the encapsulated drug. These carriers can also be modified in ways that make them responsive when targeted or triggered, by manipulating their composition and attaching moieties and conjugates to the body of the carriers. These appealing characteristics, in addition to the ease of synthesis, gave the polymersomes greater potentials in the area of drug delivery. Thus, their design and characterization, in comparison with liposomes and micelles, are briefly reviewed in this work.

Keywords: controlled release, liposomes, micelles, polymersomes, targeting

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Authors: Shweh Fern Loo, Jun Yin Ong, Than Zaw Oo

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Acute respiratory distress syndrome (ARDS) is a common serious condition of bilateral lung infiltrates that develops secondary to various underlying conditions such as diseases or injuries. ARDS with severe hypercapnia is associated with higher ICU mortality and morbidity. Venovenous Extracorporeal membrane oxygenation (VV-ECMO) support has been established to avert life-threatening hypoxemia and hypercapnic respiratory failure despite optimal conventional mechanical ventilation. However, VV-ECMO is relatively not advisable in particular groups of patients, especially in multi-organ failure, advanced age, hemorrhagic complications and irreversible central nervous system pathology. We presented a case of a 79-year-old Chinese lady without any pre-existing lung disease admitted to our hospital intensive care unit (ICU) after acute presentation of breathlessness and chest pain. After extensive workup, she was diagnosed with rapidly progressing acute interstitial pneumonia with ARDS and hypercapnia respiratory failure. The patient received lung protective strategies of mechanical ventilation and neuromuscular blockage therapy as per clinical guidelines. However, hypercapnia respiratory failure was refractory, and she was deemed not a good candidate for VV-ECMO support given her advanced age and high vasopressor requirements from shock. Alternative therapy with extracorporeal CO2 removal (ECCO2R) was considered and implemented. The patient received 12 days of ECCO2R paired with muscle paralysis, optimization of lung-protective mechanical ventilation and dialysis. Unfortunately, the patient still had refractory hypercapnic respiratory failure with dual vasopressor support despite prolonged therapy. Given failed and futile medical treatment, the family opted for withdrawal of care, a conservative approach, and comfort care, which led to her demise. The effectivity of extracorporeal CO2 removal may depend on disease burden, involvement and severity of the disease. There is insufficient data to make strong recommendations about its benefit-risk ratio for ECCO2R devices, and further studies and data would be required. Nonetheless, ECCO2R can be considered an alternative treatment for refractory hypercapnic respiratory failure patients who are unsuitable for initiating venovenous ECMO.

Keywords: extracorporeal CO2 removal (ECCO2R), acute respiratory distress syndrome (ARDS), acute interstitial pneumonia (AIP), hypercapnic respiratory failure

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Authors: AliAkbar Hafezi, Jalal Taherian, Jamshid Abedi, Mahsa Elahi, Behnam Kadkhodaei

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Background: Soft tissue sarcomas (STS) are generally treated with a combination of limb preservation surgery and radiation therapy. Today, preoperative radiation therapy is considered for accurate treatment volume and smaller field size. Therefore, this study was performed to compare preoperative with postoperative radiation therapy in patients with extremity STS. Methods: In this non-randomized clinical trial, patients with localized extremity STS referred to the orthopedic clinics in Iran from 2021 to 2023 were studied. Patients were randomly divided into two groups: preoperative and postoperative radiation therapy. The two groups of patients were compared in terms of acute (wound dehiscence and infection) and late (limb edema, subcutaneous fibrosis, and joint stiffness) complications and their severity, as well as local recurrence and other one-year outcomes. Results: A total of 80 patients with localized extremity STS were evaluated in two treatment groups. The groups were matched in terms of age, sex, history of diabetes mellitus, hypertension, smoking, involved side, involved extremity, lesion location, and tumor histopathology. The acute complications of treatment in the two groups of patients did not differ significantly (P > 0.05). Of the late complications, only joint stiffness between the two groups had significant statistical differences (P < 0.001). The severity of all three late complications in the postoperative radiation therapy group was significantly higher (P < 0.05). There was no significant difference between the two groups in terms of the rate of local recurrence of other one-year outcomes (P > 0.05). Conclusion: This study showed that in patients with localized extremity STS, the two therapeutic approaches of adjuvant and neoadjuvant radiation therapy did not differ significantly in terms of local recurrence and distant metastasis during the one-year follow-up period and due to fewer late complications in preoperative radiotherapy group, this treatment approach can be a better choice than postoperative radiation therapy.

Keywords: soft tissue sarcoma, extremity, preoperative radiation therapy, postoperative radiation therapy

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Authors: Murat Emre, Zeynep Tufekcioglu

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Objective: We describe a patient with late onset phenylketonuria which presented with rapidly progressive dementia and parkinsonism that were reversible after management. Background: Phenylketonuria is an autosomal recessive disorder due to mutations in the phenylalanine hydroxlase gene. It normally presents in childhood, in rare cases, however, it may have its onset in adulthood and may mimic other neurological disorders. Case description: A previously normal functioning, 59 year old man was admitted for blurred vision, cognitive impairment and gait difficulty which emerged over the past eight months. In neurological examination he had brisk reflexes, slow gait and left-dominant parkinsonism. Mini-mental state examination score was 25/30, neuropsychological testing revealed a dysexecutive syndrome with constructional apraxia and simultanagnosia. In cranial MRI there were bilateral diffuse hyper-intense lesions in parietal and occipital white matter with no significant atrophy. Electroencephalography showed diffuse slowing with predominance of teta waves. In cerebrospinal fluid examination protein level was slightly elevated (61mg/dL), oligoclonal bands were negative. Electromyography was normal. Routine laboratory examinations for rapidly progressive dementia and parkinsonism were also normal. Serum amino acid levels were determined to explore metabolic leukodystrophies and phenylalanine level was found to be highly elevated (1075 µmol/L) with normal tyrosine (61,20 µmol/L). His cognitive impairment and parkinsonian symptoms improved following three months of phenylalanine restricted diet. Conclusions: Late onset phenylketonuria is a rare, potentially reversible cause of rapidly progressive parkinsonism with dementia. It should be considered in the differential diagnosis of patients with suspicious features.

Keywords: dementia, neurology, Phenylketonuria, rapidly progressive parkinsonism

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Authors: Katie Kilgour, Brendan Turner, Carly Catella, Michael Daniele, Stefano Menegatti

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In vivo, the extracellular matrix (ECM) provides biochemical and mechanical properties that are instructional to resident cells to form complex tissues with characteristics to develop and support vascular networks. In vitro, the development of vascular networks can be guided by biochemical patterning of substrates via spatial distribution and display of peptides and growth factors to prompt cell adhesion, differentiation, and proliferation. We have developed a technique utilizing peptide ligands that specifically bind vascular endothelial growth factor (VEGF), erythropoietin (EPO), or angiopoietin-1 (ANG1) to spatiotemporally distribute growth factors to cells. This allows for the controlled release of each growth factor, ultimately enhancing the formation of a vascular network. Our engineered tissue constructs (ETCs) are fabricated out of gelatin methacryloyl (GelMA), which is an ideal substrate for tailored stiffness and bio-functionality, and covalently patterned with growth factor specific peptides. These peptides mimic growth factor receptors, facilitating the non-covalent binding of the growth factors to the ETC, allowing for facile uptake by the cells. We have demonstrated in the absence of cells the binding affinity of VEGF, EPO, and ANG1 to their respective peptides and the ability for each to be patterned onto a GelMA substrate. The ability to organize growth factors on an ETC provides different functionality to develop organized vascular networks. Our results demonstrated a method to incorporate biochemical cues into ETCs that enable spatial and temporal control of growth factors. Future efforts will investigate the cellular response by evaluating gene expression, quantifying angiogenic activity, and measuring the speed of growth factor consumption.

Keywords: growth factor, hydrogel, peptide, angiogenesis, vascular, patterning

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Authors: Atefeh Abedini, Pegah Soltani, Arda Kiani

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Background: Sarcoidosis and Tuberculosis are both considered granulomatous chronic diseases with some similar pulmonary and extra-pulmonary manifestations. It is hypothesized that given these morphological similarities, the genome of mycobacterium could have an impact on the development of Sarcoidosis. Identifying the potential correlation of these diseases may assist in the management of sarcoidosis. Herein, we aimed to inspect the lymph node biopsy of sarcoidosis patients for the existence of the HSP-65 mycobacterium DNA sequence. Methods: This cross-sectional survey was conducted on 1188 Sarcoidosis patients without active/latent tuberculosis infection who were diagnosed in Masih Daneshvari Hospital in Tehran, Iran, from January 2020 to January 2022. Trans-bronchial needle aspiration (TBNA) was performed due to bilateral hilar lymphadenopathy to take a specimen. Results: The under-evaluated patients were mainly women (N=815 (68.6%)), none-smoker (N=1016 (85.5%)), and middle-aged (50.1 (SD=4.22)) with average angiotensin-converting enzyme (ACE) index of 75.6 (SD=6.42). Dyslipidemias (n=314 (26.4%), Hypertension (n=295 (24.8%)), Diabetes mellitus (n=131 (11.0%)), and chronic heart diseases (n=97 (8.2%)) had the highest prevalence between comorbidities. Skin lesions (n= 655 (55.1%)), ophthalmic (n=341 (28.7%)), and cardiac involvement (n=229 (19.3%)) were obtained as the most common extra-pulmonary characteristics of the patients. Amongst 1188 enrolled patients who were not afflicted with Mycobacterium tuberculosis based on smear/culture essay, clinical symptoms, and Chest x-ray screening, 121 (10.2%) cases had detectable amplified DNA for Mycobacterium Tuberculosis extracted from mediastinal lung lymph nodes. Conclusion: In this survey, the mycobacterium genome was detected in almost 1 per 10 case biopsies of sarcoidosis. The remarkable number of cases (n=1188) evaluated in this study was the strength of this study which supported the hypothesis regarding sarcoidosis and mycobacterium genome correlation. Further investigation, such as case-control surveys, is required to better clarify this association.

Keywords: mycobacterium tuberculosis, sarcoidosis, genome, DNA, trans-bronchial needle aspiration

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Authors: Misuk Kim, Seokho Kang, Jehyuk Lee, Hyunchang Cho, Sungzoon Cho

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In semiconductor manufacturing, virtual metrology (VM) refers to methods to predict properties of a wafer based on machine parameters and sensor data of the production equipment, without performing the (costly) physical measurement of the wafer properties (Wikipedia). Additional benefits include avoidance of human bias and identification of important factors affecting the quality of the process which allow improving the process quality in the future. It is however rare to find VM applied to other areas of manufacturing. In this work, we propose to use VM to copper clad laminate (CCL) manufacturing. CCL is a core element of a printed circuit board (PCB) which is used in smartphones, tablets, digital cameras, and laptop computers. The manufacturing of CCL consists of three processes: Treating, lay-up, and pressing. Treating, the most important process among the three, puts resin on glass cloth, heat up in a drying oven, then produces prepreg for lay-up process. In this process, three important quality factors are inspected: Treated weight (T/W), Minimum Viscosity (M/V), and Gel Time (G/T). They are manually inspected, incurring heavy cost in terms of time and money, which makes it a good candidate for VM application. We developed prediction models of the three quality factors T/W, M/V, and G/T, respectively, with process variables, raw material, and environment variables. The actual process data was obtained from a CCL manufacturer. A variety of variable selection methods and learning algorithms were employed to find the best prediction model. We obtained prediction models of M/V and G/T with a high enough accuracy. They also provided us with information on “important” predictor variables, some of which the process engineers had been already aware and the rest of which they had not. They were quite excited to find new insights that the model revealed and set out to do further analysis on them to gain process control implications. T/W did not turn out to be possible to predict with a reasonable accuracy with given factors. The very fact indicates that the factors currently monitored may not affect T/W, thus an effort has to be made to find other factors which are not currently monitored in order to understand the process better and improve the quality of it. In conclusion, VM application to CCL’s treating process was quite successful. The newly built quality prediction model allowed one to reduce the cost associated with actual metrology as well as reveal some insights on the factors affecting the important quality factors and on the level of our less than perfect understanding of the treating process.

Keywords: copper clad laminate, predictive modeling, quality control, virtual metrology

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Authors: Omer Burak Iskender, Keck Voon Ling, Vincent Dubanchet, Luca Simonini

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This paper presents Guidance and Control (G&C) strategy to approach and synchronize with potentially rotating targets. The proposed strategy generates and tracks a safe trajectory for space servicing missions, including tasks like approaching, inspecting, and capturing. The main objective of this paper is to validate the G&C laws using a Hardware-In-the-Loop (HIL) setup with realistic rendezvous and docking equipment. Throughout this work, the assumption of full relative state feedback is relaxed by onboard sensors that bring realistic errors and delays and, while the proposed closed loop approach demonstrates the robustness to the above mentioned challenge. Moreover, G&C blocks are unified via the Model Predictive Control (MPC) paradigm, and the coupling between translational motion and rotational motion is addressed via dual quaternion based kinematic description. In this work, G&C is formulated as a convex optimization problem where constraints such as thruster limits and the output constraints are explicitly handled. Furthermore, the Monte-Carlo method is used to evaluate the robustness of the proposed method to the initial condition errors, the uncertainty of the target's motion and attitude, and actuator errors. A capture scenario is tested with the robotic test bench that has onboard sensors which estimate the position and orientation of a drifting satellite through camera imagery. Finally, the approach is compared with currently used robust H-infinity controllers and guidance profile provided by the industrial partner. The HIL experiments demonstrate that the proposed strategy is a potential candidate for future space servicing missions because 1) the algorithm is real-time implementable as convex programming offers deterministic convergence properties and guarantee finite time solution, 2) critical physical and output constraints are respected, 3) robustness to sensor errors and uncertainties in the system is proven, 4) couples translational motion with rotational motion.

Keywords: dual quaternion, model predictive control, real-time experimental test, rendezvous and docking, spacecraft autonomy, space servicing

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Authors: Yasir Arafat, Asma Shah, Hua Shao

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Background and Aims: Legume/cereal intercropping is used worldwide for enhancement in biomass and yield of cereal crops. However, because of intercropping, the belowground biological and chemical interactions and their effect on physiological parameters and yield of crops are limited. Methods: Wheat faba bean (WF) intercropping was designed to understand the underlying changes in the soil's chemical environment, soil microbial communities, and effect on growth and yield parameters. Experimental plots were established as having no root partition (NRP), semi-root partition (SRP), complete root partition (CRP), and their sole cropping (CK). Low molecular weight organic acids (LMWOAs) were determined by GC-MS, and high throughput sequencing of the 16S rRNA gene was carried out to screen microbial structure and composition in different root partitions of the WF intercropping system. Results: We show that intercropping induced a shift in the relative abundance of some genera of plant growth promoting rhizobacteria (PGPR) such as Allorhizobium, Neorhizobium, Pararhizobium, and Rhizobium species and resulted in better growth and yield performance of wheat. Moreover, as the plant's distance of wheat from faba beans decreased, the diversity of microbes increased, and a positive effect was observed on physiological traits and crop yield. Furthermore, an abundance and positive correlations of palmitic acid, arachidic acid, stearic acid, and 9-Octadecenoic with PGPR were recorded in the root zone of WF intercropping, which can play an important role in this facilitative mechanism of enhancing growth and yield of cereals. Conclusion: The two treatments clearly affected soil microbial and chemical composition, which can be reflected in growth and yield enhancement.

Keywords: intercropping, microbial community, LMWOAs, PGPR, soil chemical environment

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Authors: Mohammad K. Parvez, Mohammed S. Al-Dosari

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Hepatitis E virus (HEV) is an emerging RNA virus that causes acute and chronic liver disease with a global mortality rate of about 2%. Despite milestone developments in understanding of HEV biology, there is still lack of a robust culture system or animal model. Therefore, in a novel approach, two recombinant-baculoviruses (vBac-ORF2 and vBac-ORF3) that could overexpress HEV ORF2 (structural/capsid) and ORF3 (nonstructural/regulatory) proteins, respectively were constructed. The established HEV-SAR55 (genotype 1) replicon that contained GFP gene, in place of ORF2/ORF3 sequences was in vitro transcribed, and GFP production in RNA transfected S10-3 cells was scored by FACS. Enhanced infectivity, if any, of nascent virions produced by exogenously-supplied ORF2 and viral RNA by co-expression of ORF3 was tested on naïve HepG2 cells. Co-transduction with vBac-ORF2/vBac-ORF3 (108 pfu/microL) produced high amounts of native ORF2/ORF3 in approximately 60% of S10-3 cells, determined by immunofluorescence microscopy and Western analysis. FACS analysis showed about 9% GFP positivity of S10-3 cells on day6 post-transfection (i.e, day5 post-transduction). Further, FACS scoring indicated that lysates from S10-3 cultures receiving the RNA plus vBac-ORF2 were capable of producing HEV particles with about 4% infectivity in HepG2 cells. However, lysates of cultures co-transduced with vBac-ORF3, were found to further enhance virion infectivity by approximately 17%. This supported a previously proposed role of ORF3 as a minor-structural protein in HEV virion assembly and infectivity. In conclusion, the present model for efficient genomic RNA packaging and production of infectious virions could be a valuable tool to study various aspects of HEV molecular biology, in vitro.

Keywords: chronic liver disease, hepatitis E virus, ORF2, ORF3, replicon

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Authors: Vaiyapuri Subbarayn Periasamy, Jegan Athinarayanan, Ali A. Alshatwi

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The widespread use of Titanium oxide nanoparticles (TiO2-NPs), now are found with different physic-chemical properties (size, shape, chemical properties, agglomeration, etc.) in many processed foods, agricultural chemicals, biomedical products, food packaging and food contact materials, personal care products, and other consumer products used in daily life. Growing evidences have been highlighted that there are risks of physico-chemical properties dependent toxicity with special attention to “TiO2-NPs and human immune system”. Unfortunately, agglomeration and aggregation have frequently been ignored in immuno-toxicological studies, even though agglomeration and aggregation would be expected to affect nanotoxicity since it changes the size, shape, surface area, and other properties of the TiO2-NPs. In this present investigation, we assessed the immune toxic effect of TiO2-NPs on human immune cells Total WBC including Lymphocytes (T cells (CD3+), T helper cells (CD3+, CD4+), Suppressor/cytotoxic T cells (CD3+/CD8+) and NK cells (CD3-/CD16+ and CD56+), Monocytes (CD14+, CD3-) and B lymphocytes (CD19+, CD3-) in order to find the immunological response (IL1A, IL1B, IL2 IL-4, IL5 IL-6, IL-10, IL-12, IL-13, IFN-γ, TGF-β, and TNF-a) and redox gene regulation (TNF, p53, BCl-2, CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1)-linking physicochemical properties with special reference to agglomeration of TiO2-NPs. Our findings suggest that TiO2-NPs altered cytokine production, enhanced phagocytic indexing, metabolic stress through specific immune regulatory- genes expression in different WBC subsets and may contribute to pro-inflammatory response. Although TiO2-NPs have great advantages in the personal care products, biomedical, food and agricultural products, its chronic and acute immune-toxicity still need to be assessed carefully with special reference to food and environmental safety.

Keywords: TiO2 nanoparticles, oxidative stress, cytokine, human immune cells

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Authors: Wafa Toumi, Alessandro Ripalti, Luigi Ricciardiello, Dalila Gargouri, Jamel Kharrat, Abderraouf Cherif, Ahmed Bouhafa, Slim Jarboui, Mohamed Zili, Ridha Khelifa

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Background & aims: Colorectal cancer (CRC) is one of the most common malignancies throughout the world. Several risk factors, both genetic and environmental, including viral infections, have been linked to colorectal carcinogenesis. A few studies report the detection of human polyomavirus JC (JCV) DNA and transformation antigen (T-Ag) in a fraction of the colorectal tumors studied and suggest an association of this virus with CRC. In order to investigate whether such an association of JCV with CRC will hold in a different epidemiological setting, we looked for the presence of JCV DNA and T-Ag expression in a group of Tunisian CRC patients. Methods: Fresh colorectal mucosa biopsies were obtained from 17 healthy volunteers and from both colorectal tumors and adjacent normal tissues of 47 CRC patients. DNA was extracted from fresh biopsies or from formalin-fixed, paraffin-embedded tissue sections using the Invitrogen Purelink Genomic DNA mini Kit. A simple PCR and a nested PCR were used to amplify a region of the T-Ag gene. The obtained PCR products revealed a 154 bp and a 98 bp bands, respectively. Specificity was confirmed by sequencing of the PCR products. T-Ag expression was determined by immunohistochemical staining using a mouse monoclonal antibody (clone PAb416) directed against SV40 T-Ag that cross reacts with JCV T-Ag. Results: JCV DNA was found in 12 (25%) and 22 (46%) of the CRC tumors by simple PCR and by nested PCR, respectively. All paired adjacent normal mucosa biopsies were negative for viral DNA. Sequencing of the DNA amplicons obtained confirmed the authenticity of T-Ag sequences. Immunohistochemical staining showed nuclear T-Ag expression in all 22 JCV DNA- positive samples and in 3 additional tumor samples which appeared DNA-negative by PCR. Conclusions: These results suggest an association of JCV with a subpopulation of Tunisian colorectal tumors.

Keywords: colorectal cancer, immunohistochemistry, Polyomavirus JC, PCR

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Authors: Meimei Shi

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Objectives: The identification of endangered species, especially simultaneous detection of multiple species in complex samples, plays a critical role in alleged wildlife crime incidents and prevents illegal trade. This study was to develop a multi-locus DNA metabarcoding method for endangered animal species identification. Methods: Several pairs of universal primers were designed according to the mitochondria conserved gene regions. Experimental mixtures were artificially prepared by mixing well-defined species, including endangered species, e.g., forest musk, bear, tiger, pangolin, and sika deer. The artificial samples were prepared with 1-16 well-characterized species at 1% to 100% DNA concentrations. After multiplex-PCR amplification and parameter modification, the amplified products were analyzed by capillary electrophoresis and used for NGS library preparation. The DNA metabarcoding was carried out based on Illumina MiSeq amplicon sequencing. The data was processed with quality trimming, reads filtering, and OTU clustering; representative sequences were blasted using BLASTn. Results: According to the parameter modification and multiplex-PCR amplification results, five primer sets targeting COI, Cytb, 12S, and 16S, respectively, were selected as the NGS library amplification primer panel. High-throughput sequencing data analysis showed that the established multi-locus DNA metabarcoding method was sensitive and could accurately identify all species in artificial mixtures, including endangered animal species Moschus berezovskii, Ursus thibetanus, Panthera tigris, Manis pentadactyla, Cervus nippon at 1% (DNA concentration). In conclusion, the established species identification method provides technical support for customs and forensic scientists to prevent the illegal trade of endangered animals and their products.

Keywords: DNA metabarcoding, endangered animal species, mitochondria nucleic acid, multi-locus

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Authors: Susmita Roy, Madhavan Nallani

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In recent years' polymersomes, self-assembled polymeric vesicles emerge from block copolymers, have been widely investigated due to their enhance stability and unique advantageous properties compared to their phospholipid counterpart, liposomes, dendrimers, and micelles. It provides a distinctive platform for advanced therapeutics and the creation of complex (bio) catalytically active systems for research in Nanomedicine and synthetic biology. Inspired by nature, where compartmentalization of biological components is all ubiquitous, we are interested in developing a platform technology of self-assembled multifunctional compartments with applications in areas from targeted drug/gene delivery, biosensing, pharmaceutical to cosmetics. Polymersome surfaces can be a proper choice of derivatization with a controlled amount of functional groups. To achieve site-specific targeting of polymersomes, biological recognition motives can be attached to the polymersomes surface by standard bioconjugation techniques, (like esterification, amidation, thiol-maleimide coupling, click-chemistry routes or other coupling methods). Herein, we are developing easy going, one-step bioconjugation strategies for site-specific surface functionalized biodegradable polymeric and/or polymer-lipid hybrid vesicles for targeted drug delivery. Biodegradable polymer, polycaprolactone-b-polyethylene glycol (PCL-PEG), polylactic acid-b-polyethylene glycol (PLA-PEG) and phospholipid, 1-palmitoyl-2- oleoyl-sn-glycero-3-phosphocholine (POPC) has been widely used for numerous vesicle formulations. Some of these drug-loaded formulations are being tested on mice for controlled release. These surface functionalized polymersomes are also appropriate for membrane protein reconstitution/insertion, antibodies conjugation and various bioconjugation with diverse targeted molecules for controlled drug delivery.

Keywords: drug delivery, membrane protein, polymersome, surface modification

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Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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Authors: Orlando Ketebu

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Ogbono seed is the seed obtained from African bush mango (Irvingia gabonenesis) and bitter bush mango (Irvingia wombolu). Irvingia gabonenesis is known for its sweet edible pulp while Irvingia wombolu has a bitter pulp. Their seed powder is used in cooking soup known as ogbono soup in Nigeria and in West Africa. The powder thickens when cooked and researches have shown that it has medicinal uses such as lowering cholesterol; aiding weight loss and helps in improving diabetes control. The nutritional composition of the seeds indicated that Irvingia gabonenesis contains 8.60% protein, 13.8% carbohydrate, 2.0% moisture, 1.5% crude fiber, 16.4% ash, and Irvingia wombolu contains 7.38% protein, 25.75% carbohydrate, 11.7% moisture, 0.84% crude fiber, 2.50% ash. Solvent extraction of these seeds has shown that the seed of the two species are oil seeds with approximately 70 % and 52 % for Irvingia gabonenesis and Irvingia wombolu respectively. One major setback using ogbono seed powder in cooking soup is identifying the specie of ogbono seed powder that thickens most within the same cooking condition and how temperature affects the thickness of ogbono seed powder which determines its viscosity and in turn affects the quality of the soup and its nutrients. This research work monitored how the viscosity of ogbono species after being sun dried for one week changes with temperature. The result showed that heating 20 grams of powdered Irvingia gabonenesis and Irvingia wombolu at 30 OC, 45 OC, 55 OC, 65 OC, 75 OC, 85 OC and 95OC respectively in 200 ml beaker mixed with 100 ml of water, the viscosity of both species decreases with increase temperature with Irvingia wombolu having higher average viscosity in Pascal seconds (Pa.s) of 1.059, 1.042, 0.961, 0.778, 0.684, 0.675, and 0.495 at 30 OC, 45 OC, 55 OC, 65 OC, 75 OC, 85 OC and 95 OC respectively compared to Irvingia gabonenesis with result 0.982, 0.920, 0.720, 0.646, 0.597 and 0.446 at 30 OC, 45 OC, 55 OC, 65 OC, 75 OC, 85 OC and 95 OC respectively. Also from the experiment carried out it was found out that the viscosity of both species decreases with ageing of the seeds and the quantity of ogbono seed powder used and amount of water added also affected the viscosity of both species. In conclusion, it was observed that under the same cooking conditions (temperature range, quantity of water added, time and quantity of ogbono seed powder used), Irvingia wombolu had higher viscosity which is a measure of its thickness and quality of nutrients compared to Irvingia gabonenesis and the viscosity of both species decreases with increasing temperature.

Keywords: ogbono seed powder, temperature, viscosity , soup

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Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

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Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

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Authors: Suvalux Chaichuchote, Ratchadaporn Thonghem

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Pleurotus mushroom is one of popular edible mushrooms in Thailand. It is much favored by consumers due to its delicious taste and high nutrition. It is commonly used as an ingredient in several dishes. The commercially cultivated strain grown in most farms is the Pleurotus sp., Hed Bhutan, that is widely distributed to mushroom farms throughout the country and can be cultivated almost all year round. However, it demands different cultivated strains from mushroom growers, therefore, the improving mushroom strains should be done to their benefits. In this study, we used a di-mon mating method to hybrid production from Hed Bhutan (P-3) as dikaryon material and monokaryotic mycelium were isolated from basidiospores of other three Pleurotus sp. by single spore isolation. The 3 hybrids: P-3XSA-6, P-3XSB-24 and P-3XSE-5 were recognized from the 12 hybridized successfully. They were appropriate hybridized in terms of fruiting body performance in the three time cycles of cultivation such as the number of days until growing, time for pinning, color and shape of fruiting bodies and yield. For genetic study, genomic DNAs of both Hed Bhutan (P-3) and three hybrids were extracted. A couple of primer ITS1 and ITS4 were used to amplify the gene coding for ITS1, ITS2 and 5.8S rRNA. The similarities between these amplified genes and databases of DNA revealed that Hed Bhutan (P-3) was the Pleurotus pulmonarius as well as P-3XSA-6, P-3XSB-24 and P-3XSE-5 hybrids. Furthermore, Hed Bhutan (P3) and three hybrids were distributed to 3 small-scale farms, with mushroom farming experience, in the countryside. To address this, one hundred and twenty mushroom bags of each strain were supplied to them. The findings, by interview, indicated two mushroom farmers were satisfied with P-3XSA-6 hybrid and P-3XSB-24 hybrid, thanks to their simultaneous fruiting time and good yield. While the other was satisfied with P-3XSB-24 hybrid due to its good yield and P-3XSE-5 hybrids thanks to its gradually fruiting body, benefiting in frequent harvest. Overall, farmers adopted all hybrids to grow as commercially cultivated strains as well as Hed Bhutan (P-3) strain.

Keywords: dikaryon, monokaryon, pleurotus, strain improvement

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Authors: Muhammad Suhail Ibrahim, Ahmad Mujtaba

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Background: The accuracy of the most frequently used tests for diagnosing Helicobacter pylori is always under consideration in clinical settings. A reliable diagnosis is crucial to confirm the success of therapy. Objective: The aim of this research was to study the isolation frequency of H. pylori from patients compatible with gastritis or gastric ulcer and to compare some feasible non-invasive and invasive methods for the diagnosis of infection. Materials and Methods: Ninety-six gastric biopsy and blood samples were obtained with various gastroduodenal symptoms after obtaining informed consent. The biopsies were analyzed and compared using the culture, microscopic examination, histopathology, Rapid urease RUT), serology, biochemical, antibiotic susceptibility test and molecular method. Results: A number of 40 (41.67%) were considered H. pylori positive in both histopathology and RUT. On the other hand, 46 patients were positive against anti IgA and IgG by ELISA. Eighteen biopsies were positive according to the culture test. This was further confirmed by endoscopic examination, urease, catalase and oxidase tests. A high percentage of resistance to polymyxin B, amoxicillin, and kanamycin was observed (100, 88.89, and 77.78%, respectively). A gene (Cag A) was also detected by using molecular technique which appeared positive in 16 patients. The sensitivity/specificity (%) of diagnostic method was 95/77 for histology, 100/83.5 for rapid urease, 85.7/90 for gram staining, 100/66.6 for IgG serology, 100/79.5 for IgA serology, 100/75.0 for PCR, 100/79.04 for combination of RUT and IgG serology and 100/92.4 for combination of RUT, gram staining and IgG serology. Conclusion: In view of the result obtained, PCR appeared to be the most reliable test. However, higher sensitivity and specificity were also recorded for other tests. So, for more accurate results, it is advisable not to rely solely on a single method for detection.

Keywords: helicobacter pylori, isolation, detection, culture, urease, polymerase chain reaction, antibiotic susceptibility test, dyspeptic patients

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Authors: Silpita Paul, Susanta Sadhukhan, Biswanath Maity, Madhusudan Das

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Neural tube defects (NTDs) are one of the most common forms of birth defect and affect ~300,000 new born worldwide each year. The prevalence is higher in Northern India (11 per 1000 birth) compare to southern India (5 per 1000 birth). NTDs are one of the common birth defects related with low blood folate and Hcy concentration. Though the mechanism is still unknown, but it is now established that, NTDs in human are polygenic in nature and follow the heterogeneous trait. In spite of its heterogeneity, polymorphism in few genes affects significantly the trait of NTDs. Polymorphisms in the genes FOLH1 and MTHFR plays important role in NTDs. In this study, the polymorphisms of these genes were screened by bi-directional sequencing from 30 mothers with NTD babies as case. The result revealed that 26.67% patients had bi-allelic FOLH1 polymorphism. The polymorphism has been identified as p.Y60H and frequent to cause NTDs. The study of MTHFR gene showed 2 different SNPs rs1801131 (at exon 4) and rs1801131 (at exon 7). The study showed 6.67% patients of both mono- and bi-allelic MTHFR-rs1801131 polymorphism and 6.67% patients of bi-allelic MTHFR-rs1801131 polymorphism. These polymorphisms has been responsible for p.A222V and p.E429A change respectively and frequently involved in NTD formation. Those polymorphisms affect mainly the absorption of dietary folate from intestine and the formation of 5-methylenetetrahydrofolate (5 MTHF) from 5,10-methylenetetrahydrofolate (5,10- MTHF), which is the functional folate form in our system. Though the study is not complete yet, but these polymorphisms play crucial roles in the formation of NTDs in other world population. Based on the result till date, it can be concluded that they also play significant role in our population too as in control samples we have not found any changes.

Keywords: neural tube defects, polymorphism, FOLH1, MTHFR

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Authors: Allioua Meryem

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Similar to much of the developing world, Algeria is currently undergoing an epidemiological transition. While mal- and under-nutrition and infectious diseases used to be the main causes of poor health, today there is a higher proportion of chronic, non-communicable diseases (NCDs), including cardiovascular disease, diabetes mellitus, cancer, etc. According to estimates for Algeria from the World Health Organization (WHO), NCDs accounted for 63% of all deaths in 2010. The objective of this study was the assessment of eating habits and anthropometric characteristics in a group of youth aged 15 to 19 years in Tlemcen. This study was conducted on a total effective of 806 youth enrolled in a descriptive cross-sectional study; the classification of nutritional status has been established by international standards IOTF, youth were defined as obese if they had a BMI ≥ 95th percentile, and youth with 85th ≤ BMI ≤ 95th percentile were defined as overweight. Wc is classified by the criteria HD, Wc with moderate risk ≥ 90th percentile and Wc with high risk ≥ 95th percentile. The dietary assessment was based on a 24-hour dietary recall assisted by food records. USDA’S nutrient database for Nutrinux® program was used to analyze dietary intake. Nutrients adequacy ratio was calculated by dividing daily individual intake to dietary recommended intake DRI for each nutrient. 9% of the population was overweight, 3% was obese, 7.5% had abdominal obesity, foods eaten in moderation are chips, cookies, chocolate 1-3 times/day and increased consumption of fried foods in the week, almost half of youth consume sugary drinks more than 3 times per week, we observe a decreased intake of energy, protein (P < 0.001, P = 0.003), SFA (P = 0.018), the NAR of phosphorus, iron, magnesium, vitamin B6, vitamin E, folate, niacin, and thiamin reflecting less consumption of fruit, vegetables, milk, and milk products. Youth surveyed have eating habits at risk of developing obesity and chronic disease.

Keywords: food intake, health, anthropometric characteristics, Algeria

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Authors: Zeynep Aykul Yavuz

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Misconception about design is about making a product pretty. However, the holistic approaches such as design thinking or human-centered design could take the design from making things nice to things inspired by real people and work with real-world limitations. Design thinking helps companies to understand not only problem area but also opportunities. It can be used by any people from any background which provide a space for companies where employees from different departments work together to solve the same problem. While demanding skills changing year to year into the market, previous technical skills are commons anymore. The frontier companies in the sectors look for interactive methods to solve problems. Moreover, the recruiter aims to understand the candidate’s design thinking skills (. The study includes a case study where a 21st century creative services company “ATÖLYE” offers innovation transformation with design thinking to a banking company. Both companies are located in İstanbul in Turkey. The banking company contacted with the ATÖLYE in January 2018 because they heard design thinking in different markets and how it transformed the way of working. The transformation process had 3 phases which were basic training of teams while getting coaching from ATÖLYE’s employees, coaching training with graduates of basic training, facilitator training. Employees built new skills while solving the banking company’s strategic problems. ATÖLYE offered experiential learning which helped employees’ making sense of new skills and knowledge. One day workshops were organized to create awareness about the practice of design thinking. In addition to these, a community of practice was built to create an environment to make reflections and discuss good practice. Not only graduates from the training program but also other employees from the company participated in the community gatherings. ATÖLYE did not train some employees in the company. Rather than that, its aim was to build a contemporary organization for the company. This provided a sustainable system in terms of human resources and motivation. At the beginning of 2020, employees from the first cohort in the basic training who took coaching training and facilitator training have started to design training for different groups in the company. They have considered what could be better in their training experience and designed new ones according to that, so they have been using design thinking to design the design training. This is one of the outcomes which shows the impact of all process clearly.

Keywords: design thinking, learning community, professional development, training, organizational transformation

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Authors: Nicholas Bayfield, Liam Bibo, Charley Budgeon, Robert Larbalestier, Tom Briffa

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Introduction: Stress hyperglycaemia is common following cardiac surgery. Its optimal management is uncertain and may differ by diabetic status. This study assesses the in-hospital glycaemic management of cardiac surgery patients and associated postoperative outcomes. Methods: A retrospective cohort analysis of all patients undergoing cardiac surgery at Fiona Stanley Hospital from February 2015 to May 2019 was undertaken. Management and outcomes of hyperglycaemia following cardiac surgery were assessed. Follow-up was assessed to 1 year postoperatively. Multivariate regression modelling was utilised. Results: 1050 non-diabetic patients and 689 diabetic patients were included. In the non-diabetic cohort, patients with mild (peak blood sugar level [BSL] < 14.3), transient stress hyperglycaemia managed without insulin were not at an increased risk of wound-related morbidity (P=0.899) or mortality at 1 year (P=0.483). Insulin management was associated with wound-related readmission to hospital (P=0.004) and superficial sternal wound infection (P=0.047). Prolonged or severe stress hyperglycaemia was predictive of hospital re-admission (P=0.050) but not morbidity or mortality (P=0.546). Diabetes mellitus was an independent risk factor 1-year mortality (OR; 1.972 [1.041–3.736], P=0.037), graft harvest site wound infection (OR; 1.810 [1.134–2.889], P=0.013) and wound-related readmission (OR; 1.866 [1.076–3.236], P=0.026). In diabetics, postoperative peak BSL > 13.9mmol/L was predictive of graft harvest site infections (OR; 3.528 [1.724-7.217], P=0.001) and wound-related readmission OR; 3.462 [1.540-7.783], P=0.003) regardless of modality of management. A peak BSL of 10.0-13.9 did not increase the risk of morbidity/mortality compared to a peak BSL of < 10.0 (P=0.557). Diabetics with a peak BSL of 13.9 or less did not have significantly increased morbidity/mortality outcomes compared to non-diabetics (P=0.418). Conclusion: In non-diabetic patients, transient mild stress hyperglycaemia following cardiac surgery does not uniformly require treatment. In diabetic patients, postoperative hyperglycaemia with peak BSL exceeding 13.9mmol/L was associated with wound-related morbidity and hospital readmission following cardiac surgery.

Keywords: cardiac surgery, pulmonary embolism, pulmonary embolectomy, cardiopulmonary bypass

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Authors: Reza Safdari, Goli Arji, Robab Abdolkhani Maryam zahmatkeshan

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Background and purpose: Cardiovascular diseases are among the most common diseases in all societies. The most important step in minimizing myocardial infarction and its complications is to minimize its risk factors. The amount of medical data is increasingly growing. Medical data mining has a great potential for transforming these data into information. Using data mining techniques to generate predictive models for identifying those at risk for reducing the effects of the disease is very helpful. The present study aimed to collect data related to risk factors of heart infarction from patients’ medical record and developed predicting models using data mining algorithm. Methods: The present work was an analytical study conducted on a database containing 350 records. Data were related to patients admitted to Shahid Rajaei specialized cardiovascular hospital, Iran, in 2011. Data were collected using a four-sectioned data collection form. Data analysis was performed using SPSS and Clementine version 12. Seven predictive algorithms and one algorithm-based model for predicting association rules were applied to the data. Accuracy, precision, sensitivity, specificity, as well as positive and negative predictive values were determined and the final model was obtained. Results: five parameters, including hypertension, DLP, tobacco smoking, diabetes, and A+ blood group, were the most critical risk factors of myocardial infarction. Among the models, the neural network model was found to have the highest sensitivity, indicating its ability to successfully diagnose the disease. Conclusion: Risk prediction models have great potentials in facilitating the management of a patient with a specific disease. Therefore, health interventions or change in their life style can be conducted based on these models for improving the health conditions of the individuals at risk.

Keywords: decision trees, neural network, myocardial infarction, Data Mining

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

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Authors: Alina Murtishcheva

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The development of an effective system of administrative supervision is a prerequisite for the functioning of local self-government on the basis of the rule of law. Administrative supervision of local self-government is of particular importance in the EU countries due to the influence of integration processes. The central authorities act on the international level; however, subnational authorities also have to implement European legislation in order to strengthen integration. Therefore, the central authority, being the connecting link between supranational and subnational authorities, should bear responsibility, including financial responsibility, for possible mistakes of subnational authorities. Consequently, the state should have sufficient mechanisms of control over local and regional authorities in order to correct their mistakes. At the same time, the control mechanisms do not deny the autonomy of local self-government. The paper analyses models of administrative supervision of local self-government in Ukraine, Poland, Lithuania, Belgium, Great Britain, Italy, and France. The research methods used in this paper are theoretical methods of analysis of scientific literature, constitutions, legal acts, Congress of Local and Regional Authorities of the Council of Europe reports, and constitutional court decisions, as well as comparative and logical analysis. The legislative basis of administrative supervision was scrutinized, and the models of administrative supervision were classified, including a priori control and ex-post control or their combination. The advantages and disadvantages of these models of administrative supervision are analysed. Compliance with Article 8 of the European Charter of Local Self-Government is of great importance for countries achieving common goals and sharing common values. However, countries under study have problems and, in some cases, demonstrate non-compliance with provisions of Article 8. Such non-conformity as the endorsement of a mayor by the Flemish Government in Belgium, supervision with a view to expediency in Great Britain, and the tendency to overuse supervisory power in Poland are analysed. On the basis of research, the tendencies of administrative supervision of local authorities’ activities in selected European countries are described. Several recommendations for Ukraine as a country that had been granted EU candidate status are formulated. Having emphasised its willingness to become a member of the European community, Ukraine should not only follow the best European practices but also avoid the mistakes of countries that have long-term experience in developing the local self-government institution. This project has received funding from the Research Council of Lithuania (LMTLT), agreement № S-PD-22-65.

Keywords: administrative supervision, decentralisation, legality, local authorities, local self-government

Procedia PDF Downloads 63