Low Level of Transmitted HIV Drug Resistance at Two HIV Care Centres in Ghana: A Threshold Survey

Background: As access to antiretroviral therapy (ART) increases, the emergence and transmission of HIV drug resistant strains becomes a major problem. The World Health Organization (WHO) therefore recommends an initial minimum-resource method to signal when transmitted HIV drug resistance (HIVDR) requires action.Objective: This survey sought to generate information on the presence of HIV drug-resistant strains in the locality where Ghana’s ART for HIV was first introduced.Methods: The Ghana HIVDR threshold survey (TS) was conducted and analyzed according to WHO strategy for surveillance of HIVDR in the Eastern Region of Ghana. Sixty (60) plasma specimens were collected from 2007 to 2009 by an unlinked anonymous method from HIV seropositive pregnant women, aged between 15 to24 years, who were with their first pregnancy and ART naive. Genotyping was done as follows; Ribonucleic acid (RNA) was extracted from the samples and the protease (PR) and reverse transcriptase (RT) genes amplified and sequenced. The sequences were then analyzed for HIV drug resistance mutations using Stanford University HIV Drug Resistance Database.Results: Only two individuals were found with major HIVDR mutations: one each in the PR and RT genes. Thus the level of HIVDR in the study population in 2009 was classified as low (< 5%).Conclusion: As at February 2009, transmitted drug resistance was not a serious problem in the Eastern Region of Ghana. However, it is important to continue monitoring tHIVDR in order to understand the dynamics of the evolution of HIV drug resistance in the country

Sustainable Decommission of Mining Lands: Landform Design for Eaton Tuner Shaft (ETS) Area, Obuasi, Ghana

Ghana is the first country in the Sub-Sahara African region to reform its mining sector and has become the poster child for such change in the developing world. Obuasi is the hub of gold mining in Ghana. The Obuasi mine is currently operated by AngloGold Ashanti (AGA), and contributes immensely to the Gross Domestic Product (GDP) of Ghana. Mining is however, an activity that causes disturbance to the natural habitat and threatens biodiversity. Mining of mineral resources results in extensive soil damage, altering microbial communities and affecting vegetation leading to destruction of vast amounts of land which needs to be reclaimed and restored. Reclamation is the process to restore the ecological integrity of these disturbed mine land areas. Mining at the Eaton Tuner Shaft (ETS) area has been decommissioned and this paper seeks to explain processes leading to the sustainable design of a safe and suitable landform for the ETS as part of closure plan by reclaiming the vast land currently in the heart of Obuasi town. This is an exploratory study employing survey methods, geotechnical profiling and topographical survey to obtain data for the landform design and ultimate land reclamation. The study revealed that the soils at the ETS area have an upper stratum of sandy Gravels underlain by strata of silts or sands with average plasticity index of 14.46% and can be used as fill material with mean allowable bearing capacity between 781KPa and 1,413KPa. For a sustainable landform design, the study recommends a gentle slope transitions of about 2.5% and 1:2 for embankments. Keywords: Reclamation, Mining lands, Sustainable decommissioning, Landform design, Obuasi DOI: 10.7176/JEES/9-12-07 Publication date: December 31st 201

Health Services Utilization, Work Absenteeism and Costs of Pandemic Influenza A (H1N1) 2009 in Spain: A Multicenter-Longitudinal Study

Background: The aim of this study was to estimate healthcare resource utilization, work absenteeism and cost per patient with pandemic influenza (H1N1)2009, from its beginning to March 2010, in Spain. We also estimated the economic impact on healthcare services. Methods and Findings: Longitudinal, descriptive,multicenter study of in- and outpatients with confirmed diagnosis of influenza A (H1N1) in Spain. Temporal distribution of cases was comparable to that in Spain. Information of healthcare and social resources used from one week before admission (inpatient) or index-medical visit (outpatient) until recovery was gathered. Unit cost was imputed to utilization frequency for the monetary valuation of use. Mean cost per patient was calculated. A sensitivity analysis was conducted, and variables correlated with cost per patient were identified. Economic impact on the healthcare system was estimated using healthcare costs per patient and both, the reported number of confirmed and clinical cases in Spain. 172 inpatients and 224 outpatients were included. Less than 10% were over 65 years old and more than 50% had previous comorbidities. 12.8% of inpatients were admitted to the Intensive Care Unit. Mean length of hospital stay of patients not requiring critical care was 5 days (SD =4.4). All working-inpatients and 91.7% working-outpatients went on sick leave. On average, work absenteeism was 30.5 days (SD=20.7) for the first ones and 9 days (SD= 6.3) for the latest. Caregivers of 21.7% of inpatients and 8.5% of outpatients also had work absenteeism during 10.7 and 4.1 days on average respectively. Mean cost was J6,236/inpatient (CI95%=1,384-14,623) and J940/outpatient (CI95% =66-3,064). The healthcare economic burden of patients with confirmed influenza was J144,773,577 (IC95% 13,753,043-383,467,535). More than 86% of expenditures were a result of outpatients" utilization. Conclusion: Cost per H1N1-patient did not defer much from seasonal influenza estimates. Hospitalizations and work absenteeism represented the highest cost per patient

Real-time flow simulation of indoor environments using lattice Boltzmann method

A novel lattice Boltzmann method (LBM) based 3D computational fluid dynamics (CFD) technique has been implemented on the graphics processing unit (GPU) for the purpose of simulating the indoor environment in real-time. We study the time evolution of the turbulent airflow and temperature inside a test chamber and in a simple model of a four-bed hospital room. The predicted results from LBM are compared with traditional CFD based large eddy simulations (LES). Reasonable agreement between LBM results and LES method is observed with significantly faster computational times

Therapeutic targeting of CK2 in acute and chronic leukemias

Phosphorylation can regulate almost every property of a protein and is involved in all fundamental cellular processes. Thus, proper regulation of phosphorylation events is critical to the homeostatic functions of cell signaling. Indeed, deregulation of signaling pathways underlies many human diseases, including cancer.[1] The importance of phosphorylation makes protein kinases and phosphatases promising therapeutic targets for a wide variety of disorders.[2] CK2, formerly known as casein kinase II, was discovered in 1954, [3] although only recently, and especially over the last two decades, it has become one of the most studied protein kinases, due to its ubiquity, pleiotropy and constitutive activity. In particular, appreciation of its pleiotropy has completely changed our vision of CK2 biology, from an ordinary cell homeostasis-maintaining enzyme to a master kinase potentially implicated in many human physiological and pathological events. CK2 is responsible for about 25% of the phosphoproteome,[4] as it catalyzes the phosphorylation of >300 substrates.[5] This partly explains the CK2 interconnected roles that underlie its involvement in many signaling pathways. However, CK2 prevalent roles are promotion of cell growth and suppression of apoptosis. Accordingly, several lines of evidence support the notion that CK2 is a key player in the pathogenesis of cancer. High levels of CK2 transcript and protein expression, as well as increased kinase activity are associated with the pathological functions of CK2 in a number of neoplasias.[6] It was only over the last decade, after extensive analyses in solid tumors, that basic and translational studies have provided evidence for a pivotal role of CK2 in driving the growth of different blood cancers as well, although the first report demonstrating increased CK2 expression in acute myelogenous leukemia (AML) dates back to 1985.[7] Since then, CK2 overexpression/activity has been demonstrated in other hematological malignancies, including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML). [8] With the notable exceptions of CML and pediatric ALL, many patients with leukemias still have a poor outcome, despite the development of protocols with optimized chemotherapy combinations. Insufficient response to first-line therapy and unsalvageable relapses present major therapeutic challenges. Moreover, chemotherapy, even if successful, could have deleterious long-term biological and psychological effects, especially in children.[9] Furthermore, CML patients can develop resistance to tyrosine kinase inhibitors (TKIs), while both primary chemoresistant and relapsed pediatric ALL cases still remain an unresolved issue.[9

Microtubular Stability Affects pVHL-Mediated Regulation of HIF-1alpha via the p38/MAPK Pathway in Hypoxic Cardiomyocytes

BACKGROUND: Our previous research found that structural changes of the microtubule network influence glycolysis in cardiomyocytes by regulating the hypoxia-inducible factor (HIF)-1α during the early stages of hypoxia. However, little is known about the underlying regulatory mechanism of the changes of HIF-1α caused by microtubule network alternation. The von Hippel-Lindau tumor suppressor protein (pVHL), as a ubiquitin ligase, is best understood as a negative regulator of HIF-1α. METHODOLOGY/PRINCIPAL FINDINGS: In primary rat cardiomyocytes and H9c2 cardiac cells, microtubule-stabilization was achieved by pretreating with paclitaxel or transfection of microtubule-associated protein 4 (MAP4) overexpression plasmids and microtubule-depolymerization was achieved by pretreating with colchicine or transfection of MAP4 siRNA before hypoxia treatment. Recombinant adenovirus vectors for overexpressing pVHL or silencing of pVHL expression were constructed and transfected in primary rat cardiomyocytes and H9c2 cells. With different microtubule-stabilizing and -depolymerizing treaments, we demonstrated that the protein levels of HIF-1α were down-regulated through overexpression of pVHL and were up-regulated through knockdown of pVHL in hypoxic cardiomyocytes. Importantly, microtubular structure breakdown activated p38/MAPK pathway, accompanied with the upregulation of pVHL. In coincidence, we found that SB203580, a p38/MAPK inhibitor decreased pVHL while MKK6 (Glu) overexpression increased pVHL in the microtubule network altered-hypoxic cardiomyocytes and H9c2 cells. CONCLUSIONS/SIGNIFICANCE: This study suggests that pVHL plays an important role in the regulation of HIF-1α caused by the changes of microtubular structure and the p38/MAPK pathway participates in the process of pVHL change following microtubule network alteration in hypoxic cardiomyocytes

"I am nothing": experiences of loss among women suffering from severe birth injuries in Tanzania

\ud Despite the increased attention on maternal mortality during recent decades, which has resulted in maternal health being defined as a Millennium Development Goal (MDG), the disability and suffering from obstetric fistula remains a neglected issue in global health. Continuous leaking of urine and the physical, emotional and social suffering associated with it, has a profound impact on women's quality of life. This study seeks to explore the physical, cultural and psychological dimensions of living with obstetric fistula, and demonstrate how these experiences shape the identities of women affected by the condition. A cross-sectional study with qualitative and quantitative components was used to explore the experiences of Tanzanian women living with obstetric fistula and those of their husbands. The study was conducted at the Comprehensive Community Based Rehabilitation Tanzania hospital in Dar es Salaam, Bugando Medical Centre in Mwanza, and Mpwapwa district, in Dodoma region. Conveniently selected samples of 16 women were interviewed, and 151 additional women responded to a questionnaire. In addition, 12 women affected by obstetric fistula and six husbands of these affected women participated in a focus group discussions. Data were analysed using content data analysis framework and statistical package for the social sciences (SPSS) version 15 for Microsoft windows. The study revealed a deep sense of loss. Loss of body control, loss of the social roles as women and wives, loss of integration in social life, and loss of dignity and self-worth were located at the core of these experiences. The women living with obstetric fistula experience a deep sense of loss that had negative impact on their identity and quality of life. Acknowledging affected women's real-life experiences is important in order to understand the occurrence and management of obstetric fistula, as well as prospects after treatment. This knowledge will help to improve women's sense of self-worth and maintain their identity as women, wives, friends and community members. Educational programmes to empower women socially and economically and counselling of families of women living with obstetric fistula may help these women receive medical and social support that is necessary.\u

Repurposing an integrated national influenza platform for genomic surveillance of SARS-CoV-2 in Ghana: a molecular epidemiological analysis

Background Genomic surveillance of SARS-CoV-2 is crucial for monitoring the spread of COVID-19 and guiding public health decisions, but the capacity for SARS-CoV-2 testing and sequencing in Africa is low. We integrated SARS-CoV-2 surveillance into an existing influenza surveillance network with the aim of providing insights into SARS-CoV-2 transmission and genomics in Ghana. Methods In this molecular epidemiological analysis, which is part of a wider multifaceted prospective observational study, we collected national SARS-CoV-2 test data from 35 sites across 16 regions in Ghana from Sept 1, 2020, to Nov 30, 2021, via the Ghanaian integrated influenza and SARS-CoV-2 surveillance network. SARS-CoV-2-positive samples collected through this integrated national influenza surveillance network and from international travellers arriving in Accra were sequenced with Oxford Nanopore Technology sequencing and the ARTIC tiled amplicon method. The sequence lineages were typed with pangolin and the phylogenetic analysis was conducted with IQ-Tree2 and TreeTime. Findings During the study period, 5495 samples were submitted for diagnostic testing through the national influenza surveillance network (2121 [46·1%] of 4021 samples with complete demographic data were from female individuals and 2479 [53·9%] of 4021 samples were from male individuals). We also obtained 2289 samples from travellers who arrived in Accra and had a positive lateral flow test, of whom 1626 (71·0%, 95% CI 69·1–72·9) were confirmed to be SARS-CoV-2 positive. Co-circulation of influenza and SARS-CoV-2 in Ghana was detected, with increased cases of influenza in November, 2020, November, 2021, and January and June, 2021. In 4124 samples from individuals with influenza-like illness, SARS-CoV-2 was identified in 583 (14·1%, 95% CI 13·1–15·2) samples and influenza in 356 (8·6%, 7·8–9·5). Conversely, in 476 samples from individuals with of severe acute respiratory illness, SARS-CoV-2 was detected in 58 (12·2%, 9·5–15·5) samples and influenza in 95 (19·9%, 16·5–23·9). We detected four waves of SARS-CoV-2 infections in Ghana; each wave was driven by a different variant: B.1 and B.1.1 were the most prevalent lineages in wave 1, alpha (B.1.1.7) was responsible for wave 2, delta (B.1.617.2) and its sublineages (closely related to delta genomes from India) were responsible for wave 3, and omicron variants were responsible for wave 4. We detected omicron variants among 47 (32%) of 145 samples from travellers during the start of the omicron spread in Ghana (wave 4). Interpretation This study shows the value of repurposing existing influenza surveillance platforms to monitor SARS-CoV-2. Influenza continued to circulate in Ghana in 2020 and 2021, and remained a major cause of severe acute respiratory illness. We detected importations of SARS-CoV-2 variants into Ghana, including those that did or did not lead to onward community transmission. Investment in strengthening national influenza surveillance platforms in low-income and middle-income countries has potential for ongoing monitoring of SARS-CoV-2 and future pandemics. Funding The EDCTP2 programme supported by the EU