Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis.

Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis

Prevalence of HIV among blood donors at Juba Teaching Hospital Blood Bank, South Sudan

Objectives: The aim of this study is to determine the prevalence of HIV among blood donors in Juba Teaching Hospital Blood Bank, South Sudan in 2013.Method and Materials: This is a retrospective study that involved the abstraction of data from registers at the blood bank. Data were collected onto data sheets and entered into a computer database. Statistical analysis was performed using SPSS Version 20 Software. A p value of <0.05 was considered statistically significant.Results: Out of 1095 blood donors, 1074 (98.1%) were males and 21 (1.9%) were females. The mean age and the range for the whole group was 29+7.16 (15-69) yrs. The prevalence of HIV was higher among males than females 85 (7.9%) vs 1 (4.8%) respectively but this was not statistical significant (p=0.6). The 20 to 29 year age group had the highest prevalence of 49 (57%) with no statistical significance (p=0.3). The prevalence of HIV was 7. % (86) and there were co-infections between HIV and HBV, HCV and syphilis of14 (50%), 5 (18%), 9 (32%) with p=0.7, p=0.1, p=0.8 respectively. Blood group O positive had the highest percentage 58.1 % (n=50) and was the commonest group.Conclusion: In this study, HIV prevalence is very high among blood donors at the Juba Teaching Hospital blood bank

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Eye diseases in Akon Payam, South Sudan

Objectives: To determine the prevalence and causes of blindness and visual impairment among patients in Akon payam, Warrap State, South Sudan. Methods and materials: This was a cross-sectional study of 862 patients conducted at Akon in the period 18 – 31 September 2015. The Snellen E chart was used to measure visual acuity, and all patients had a basic eye examination. Their vision status was categorized according to the World Health Organization classification. Data were entered and analyzed using SPSS version 22(IBM). Results: The age range of the study population was 3 - 86 years; 81.9% were aged 41-80 years. 50.8% were males and 49.2% were females. There were 1483 bilaterally blind eyes giving a prevalence of blindness of 86% (95% CI: 3.2497-3.3531) with prevalence of visual impairment of 3.9 %( 95% CI: 2.5001-3.0944. Cataract (59.7%) was the commonest eye disease, followed by glaucoma (15.1%), corneal dystrophy (9.3%), allergic conjunctivitis (5.5%), corneal scar (1.9%), refractive errors(1.8%) and others(6.7%). Among those who are blind cataract (66%) was the major agent with females affected more than males .It was followed by glaucoma (16.7%), corneal dystrophy (10%), corneal scar(1.8%) and the rest of agents(5.4%). The main age group affected by blindness was the 41- 80 years age group (87%) and the least was below 20 years (1.1%). There was a strong association between age and sex with the causes of blindness. Conclusion: There was equal sex preponderance with more blindness in those aged 41 years or above. Cataract and glaucoma still remained major cause of blindness in this payam. More effort is needed by the government to reduce the burden of these diseases

The prevalence of HIV among blood donors at Juba Teaching Hospital Blood Bank, South Sudan

Objectives The aim of this study is to determine the prevalence of HIV among blood donors in Juba Teaching Hospital Blood Bank, South Sudan in 2013. Method and Materials This is a retrospective study that involved the abstraction of data from registers at the blood bank. Data were collected onto data sheets and entered into a computer database. Statistical analysis was performed using SPSS Version 20 Software. A p value of <0.05 was considered statistically significant. Results Out of 1095 blood donors, 1074 (98.1%) were males and 21 (1.9%) were females. The mean age and the range for the whole group was 29+7.16 (15-69) yrs. The prevalence of HIV was higher among males than females 85 (7.9%) vs 1 (4.8%) respectively but this was not statistical significant (p=0.6). The 20 to 29 year age group had the highest prevalence of 49 (57%) with no statistical significance (p=0.3).The prevalence of HIV was 7.0 % (86) and there were co-infections between HIV and HBV, HCV and syphilis of 14 (50%), 5 (18%), 9 (32%) with p=0.7, p=0.1, p=0.8 respectively. Blood group O positive had the highest percentage 58.1 % (n=50) and was the commonest group. Conclusion In this study, HIV prevalence is very high among blood donors at the Juba Teaching Hospital blood bank

HIV and TB co-infection in South Sudan: a three year retrospective study

Objective To determine the prevalence of HIV/TB co-infection among patients attending the HIV clinic at Juba Teaching Hospital (JTH) from 2011 to 2013. Method and Materials This was a retrospective study using data abstracted from the registration book in the HIV clinic. A data sheet was used to collect relevant variables. Data were entered, organized and analyzed using SPSS Version 20 Software. A p-value of 0.05 or less was considered significant. Results Out of 2,577 patients attending the HIV clinic in JTH from 2011 to 2013, 2,547 (99%) were included in this study. Of these, 27.4% were seen in 2011, 34.1% in 2012 and 38.5% in 2013. There were 1,010 (39.7%) males and 1,537(60.3%) females with a male to female ratio of 2:3. The mean age (x, SD, range) was 30.8 +/-10.8 (0.2-68) years which for males was 33.3+/- 12.2 (1-68) years and 29.1+/-9.5 (0.2-65) years for females. There were 2,318 (91%) HIV mono-infected patients and 229 (9%) HIV/TB co-infected patients. There were 122 HIV/TB co-infected males and 107 females. 39.3% of patients with HIV/TB were aged 25-34 years, and 9.3% were aged 0-14 years. The p-value between the groups and within the groups was statistically significant at p= 0.005. Munuki payam had the highest percentage (31.7%) of HIV/TB co-infection. Conclusion HIV/TB remains a major challenging health problem with a prevalence of 9%