Hepatotoxicity and Associated Risk Factors in Hiv-Infected Patients Receiving Antiretroviral Therapy at Felege Hiwot Referral Hospital, Bahirdar, Ethiopia

Background: In Human Immunodeficiency Virus (HIV) infected patients on antiretroviral treatment (ART), hepatotoxicity is life threatening. Its outcome may lead to liver failure and death. This study was conducted to determine the rate and determinants of elevated alanine amino transferase (ALT) (referred as >40IU/L for both males and females).Methods: A cross sectional study was conducted on HIV infected individuals who are on ART and suspected of drug resistance at Felege Hiwot Referral Hospital, Bahir Dar from July to December 2012. Venous bloods were collected from each patient and processed parallely to determine ALT, number of HIV RNAs, CD4 and CD8 T cells count, anti hepatitis C virus (HCV) and hepatitis B surface antigen.Results: Out of 269 HIV infected patients receiving ART, 32% were confirmed of grades 1-4 levels of elevated ALT. The rate of severe hepatotoxicity (grade 3 and 4) was 1.84%. Patients with increased CD8 T cell counts (P=0.011; AOR=1.82; CI: 1.12 - 2.54), alcohol over use (P=0.014; AOR = 1.23; CI: 1.36- 3.29) and detectable HIV-1 RNA copies (P=0.015; AOR=2.07; CI: 1.15-3.74) independently predicts the elevation of ALT.Conclusions: In HIV infected patients on ART, extreme elevations of ALT were infrequent but minor elevations were common so that patient-linked variables such as use of alcohol intake must be taken in to account for better clinical management of ART patients. The role of active HCV co-infection on the treatment outcome of ART should be further studied.Key words: ALT, HIV, ART, Bahir Dar, Ethiopi

Improving primary healthcare access for asylum seekers and refugees: a qualitative study from a swiss family physician perspective

Since 2015 the need for evidence-based guidance in primary health care management of refugees, asylum seekers, and immigrants has dramatically increased. The aims of this study were to identify the challenges met by primary care physicians in Switzerland, by performing semi-structured interviews and to identify possible approaches and interventions. Between January 2019 and January 2020, 20 GPs in 3 Swiss cantons were interviewed. The interviews were transcribed, coded with MAXQDA 18, and analyzed using the framework methodology. Following relevant findings were highlighted; (i) problems relating to health insurance companies among (health-insured) asylum seekers and refugees were negligible; (ii) there is a high acceptance for vaccination by refugees, asylum seekers, and immigrants; (iii) limitations in time for consultations and adequate reimbursement for practitioners pose a serious challenge; (iv) the majority of consultations are complaint-oriented, preventive consultations are rare; and (v) the language barrier is a major challenge for psychosocial consultations, whereas this appears less relevant for somatic complaints. The following issues were identified as high priority needs by the study participants; (i) increased networking between GPs, that is, establishing bridging services with asylum centers, (ii) improved training opportunities for GPs in Migration Medicine with regular updates of current guidelines, and (iii) a standardisation of health documentation facilitating exchange of medical data, that is, digital/paper-based "health booklet" or "health pass.

Mechanical Property of Plastic Lumber Produced from Recycled High Density Polyethylene (HDPE)

Recycling is a strategy to combat environmental pollution due to plastic wastes. Of the many plastic wastes, researchers confirmed the possibility to produce plastic lumber from used HDPE plastics. The aim of this study is to experimentally determine the mechanical property of the plastic lumber produced from pure HDPE and its composite with wood to proof usability and applicability for different purpose. The experiment considered different conditions. Pure plastic lumber and wood plastic composite lumber is initially produced and examined under room temperature and below room temperature. Under each condition, bending, tensile and impact strength were examined. For each test eight specimens were prepared based on international standards and the experiments were conducted using standard testing machines. The result shows that pure plastic lumber has demonstrated superior load carrying capability, tensile load resistance capability and impact load resistance at room temperature. Moreover, the pure plastic lumber has an elastic nature and the wood composite has a brittle nature. In both cases the mechanical property of the plastic lumber permits to use for different applications. This has been also tested and resulted in similar phenomena at 20C below room temperature

Mental health and resilience among Eritrean refugees at arrival and one-year post-registration in Switzerland: a cohort study

OBJECTIVE: Eritrea is the most frequent country of origin among asylum seekers in Switzerland. On their journey through the desert and across the Mediterranean Sea, Eritrea refugees are often exposed to traumatizing experiences. The aim of this study is to assess the mental health status and resilience of Eritrean migrants in Switzerland upon arrival and one-year post-arrival, using standardized mental health screening and resilience assessment tools. RESULTS: At baseline, 107 refugees (11.2% female, median age 25) were interviewed: 52 (48.6%) screened positive for Post-Traumatic Stress Disorder (score ≥ 30), 10.3% for anxiety (≥ 10) and 15.0% for depression (≥ 10); 17.8% scored as risk/hazardous drinkers (≥ 8). The majority (94.4%) had a high resilience score (≥ 65). For one-year follow-up, 48 asylum seekers could be reached. In interviews 18 (38%) of these reported imprisonment in a transit country and 28 (58%) that they had witnessed the death of a close person along the migration route. At the one year assessment, rates of risky/hazardous alcohol use remained unchanged, rates of positive PTSD screening tended to be lower (50.0% (24/48) at baseline vs 25.0% (12/48) at follow-up), as were rates of positive screening for anxiety (8.3% vs 4.2%) and depression (14.6 vs 6.3%)

Sensitive diagnosis and post-treatment follow-up of Schistosoma mansoni infections in asymptomatic Eritrean refugees by Circulating Anodic Antigen (CAA) detection and PCR

The increasing number of refugees coming from or passing through Schistosoma-endemic areas and arriving in Europe highlights the importance of screening for schistosomiasis on arrival, and focuses attention on the choice of diagnostic test. We evaluate the diagnostic performance of circulating anodic antigen (CAA) detection in 92 asymptomatic refugees from Eritrea. Results were compared with already-available stool microscopy, serology, and urine point-of-care circulating cathodic antigen (POC-CCA) data. For a full diagnostic comparison, real-time polymerase chain reaction (PCR) and the POC-CCA were included. All outcomes were compared against a composite reference standard. Urine and serum samples were subjected to the ultra-sensitive and highly specific up-converting particle lateral flow CAA test, Schistosoma spp. real-time PCR was performed on urine and stool, and the POC-CCA was used on urine using the G-score method. CAA was detected in 43% of urine and in 40% of serum samples. Urine PCR was negative in all 92 individuals, whereas 25% showed Schistosoma DNA in stool. POC-CCA was positive in 30% of individuals. The CAA test confirmed all microscopy positives, except for two cases that were also negative by all other diagnostic procedures. Post-treatment, a significant reduction in the number of positives and infection intensity was observed, in particular regarding CAA levels. Our findings confirm that microscopy, serology, and POC-CCA lack the sensitivity to detect all active Schistosoma infections. Accuracy of stool PCR was similar to microscopy, indicating that this method also lacks sensitivity. The CAA test appeared to be the most accurate method for screening active Schistosoma infections and for monitoring treatment efficacy

Genomics of Ocular Chlamydia trachomatis After 5 Years of SAFE Interventions for Trachoma in Amhara, Ethiopia.

BACKGROUND: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident. METHODS: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct. RESULTS: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence. CONCLUSIONS: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity

Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs

Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer’s disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-coupled receptor (GPCR) have failed, largely due to cholinergic adverse responses. Employing novel chemogenetic and phosphorylation-deficient, G protein-biased, mouse models, paired with a toolbox of probe molecules, we establish previously unappreciated pharmacologically targetable M1 mAChR neurological processes, including anxiety-like behaviors and hyper-locomotion. By mapping the upstream signaling pathways regulating these responses, we determine the importance of receptor phosphorylation-dependent signaling in driving clinically relevant outcomes and in controlling adverse effects including ‘epileptic-like’ seizures. We conclude that M1 mAChR ligands that promote receptor phosphorylation-dependent signaling would protect against cholinergic adverse effects in addition to driving beneficial responses such as learning and memory and anxiolytic behavior relevant for the treatment of AD

Bioelectrical signals and ion channels in the modeling of multicellular patterns and cancer biophysics

Bioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects in small multicellular ensembles, ignoring slow diffusional processes. The spatio-temporal patterns obtained for the local map of cell electric potentials illustrate the normalization of regions with abnormal cell electrical states. The effects of intercellular coupling and blocking of specific channels on the electrical patterns are described. These patterns can regulate the electrically-induced redistribution of charged nanoparticles over small regions of a model tissue. The inclusion of bioelectrical signals provides new insights for the modeling of cancer biophysics because collective multicellular states show electrical coupling mechanisms that are not readily deduced from biochemical descriptions at the individual cell level