Fighting HIV/AIDS: Reconfiguring the State?

The author wishes to thank the anonymous reviewers of the article and the ESRC for funding part of this research

Statins inhibit C-reactive protein-induced chemokine secretion, ICAM-1 upregulation and chemotaxis in adherent human monocytes

Objectives. We have recently shown that CRP induces chemokine secretion and adhesion molecule up-regulation in human primary monocytes cultured in adherence. Given the increasing evidence on direct immunomodulatory properties of statins, we investigated their possible anti-inflammatory role on CRP-treated human monocytes. Methods. Monocytes were isolated by Ficoll-Percoll gradients and cultured in adherence to polystyrene. Chemokine secretion and adhesion molecule expression were detected by ELISA and flow cytometry. Migration assays were performed in modified Boyden chambers. Intracellular kinase activation was assessed by western blot. Results. Treatment with simvastatin or atorvastatin decreased CRP-induced release of CCL2, CCL3 and CCL4. In addition, both statins reduced CRP-induced intercellular adhesion molecule (ICAM-1) up-regulation, but had no effects on CD11b and CD18. Treatments with 1 μM simvastatin or atorvastatin significantly inhibited monocyte migration in response to CRP. CD32 and CD64 (CRP receptors) expression on monocytes was not affected by statins. Statin-induced inhibition of CRP-mediated chemokine secretion, ICAM-1 up-regulation and migration occurred through the inhibition of extracellular signal-regulated kinase (ERK) 1/2. Treatment with l-mevalonate or farnesylpyrophosphate, but not geranylgeranyl-pyrophosphate reversed the statin-induced effect on CRP-mediated functions and ERK 1/2 phosphorylation, confirming that statins blocked CRP-induced ERK 1/2 phosphorylation through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Conclusions. Statins inhibited CRP-induced chemokine secretion, ICAM-1 up-regulation and migration in human adherent monocytes, through the inhibition of HMG-CoA reductase-ERK 1/2 pathway. This pathway could represent a very promising target to reduce CRP-induced activities in monocyte-mediated diseases, such as atherosclerosis or R

Clinical Risk Factors for Osteoporosis in Ireland and the UK: A Comparison of FRAX and QFractureScores

Recently two algorithms have become available to estimate the 10-year probability of fracture in patients suspected to have osteoporosis on the basis of clinical risk factors: the FRAX algorithm and QFractureScores algorithm (QFracture). The aim of this study was to compare the performance of these algorithms in a study of fracture patients and controls recruited from six centers in the United Kingdom and Ireland. A total of 246 postmenopausal women aged 50-85 years who had recently suffered a low-trauma fracture were enrolled and their characteristics were compared with 338 female controls who had never suffered a fracture. Femoral bone mineral density was measured by dual-energy X-ray absorptiometry, and fracture risk was calculated using the FRAX and QFracture algorithms. The FRAX algorithm yielded higher scores for fracture risk than the QFracture algorithm. Accordingly, the risk of major fracture in the overall study group was 9.5% for QFracture compared with 15.2% for FRAX. For hip fracture risk the values were 2.9% and 4.7%, respectively. The correlation between FRAX and QFracture was R = 0.803 for major fracture and R = 0.857 for hip fracture (P ≤ 0.0001). Both algorithms yielded high specificity but poor sensitivity for prediction of osteoporosis. We conclude that the FRAX and QFracture algorithms yield similar results in the estimation of fracture risk. Both of these tools could be of value in primary care to identify patients in the community at risk of osteoporosis and fragility fractures for further investigation and therapeutic intervention. © 2011 Springer Science+Business Media, LLC

Molecular diagnosis for the novel coronavirus SARS-CoV-2: lessons learnt from the Ghana experience

Background: A novel coronavirus, SARS-CoV-2 is currently causing a worldwide pandemic. The first cases of SARS-CoV-2 infection were recorded in Ghana on March 12, 2020. Since then, the country has been combatting countrywide community spread. This report describes how the Virology Department, Noguchi Memorial Institute for Medical Research (NMIMR) is supporting the Ghana Health Service (GHS) to diagnose infections with this virus in Ghana.Methods: The National Influenza Centre (NIC) in the Virology Department of the NMIMR, adopted real-time Polymerase Chain Reaction (rRT-PCR) assays for the diagnosis of the SARS-CoV-2 in January 2020. Samples from suspected cases and contact tracing across Ghana were received and processed for SARS-CoV-2. Samples were ‘pooled’ to enable simultaneous batch testing of samples without reduced sensitivity.Outcomes: From February 3 to August 21, the NMIMR processed 283 946 (10%) samples. Highest number of cases were reported in June when the GHS embarked on targeted contact tracing which led to an increase in number of samples processed daily, peaking at over 7,000 samples daily. There were several issues to overcome including rapid consumption of reagents and consumables. Testing however continued successfully due to revised procedures, additional equipment and improved pipeline of laboratory supplies. Test results are now provided within 24 to 48 hours of sample submission enabling more effective response and containment.Conclusion: Following the identification of the first cases of SARS-CoV-2infection by the NMIMR, the Institute has trained other centres and supported the ramping up of molecular testing capacity in Ghana. This provides a blueprint to enable Ghana to mitigate further epidemics and pandemics

Genomic epidemiological analysis identifies high relapse among individuals with recurring tuberculosis and provides evidence of household recent TB transmission in Ghana

OBJECTIVE: We investigated the cause of recurring tuberculosis (rcTB) among pulmonary TB participants recruited from a prospective population-based study conducted between July 2012 and December 2015. METHODS: Mycobacterium tuberculosis complex isolates obtained from rcTB cases were characterized by standard mycobacterial genotyping tools in addition to whole genome sequencing, followed by phylogenetic analysis to assess strain relatedness. RESULTS: A greater proportion (58.3%, 21/36) of individuals with rcTB episodes had TB recurrence within 12 months post treatment. Only 19.4% (7/36) of participants with rcTB harbored a strain with isoniazid (INH) resistance at baseline of which 29% (2/7) were additionally resistant to rifampicin. However, 27.8% (10/36) harbored an INH resistant strain upon recurring of which 40% (4/10) were MDR-TB strains. Recurrent TB was attributed to relapse (same strain) in 75.0% (27/36) of participants with 25.0% (9/36) attributed to re-infection. CONCLUSION: Our findings indicate that unresolved previous infection due to inadequate treatment may be the major cause of rcTB

Benign chondroid syringoma of the orbit: a rare cause of exophtalmos

Chondroid syringoma (CS) of the orbit is an extremely rare benign neoplasm. To the best of our knowledege, this is the second case reported in the english litérature

Culex pipiens development is greatly influenced by native bacteria and exogenous yeast

Culex pipiens is the most cosmopolitan mosquito of the Pipiens Assemblage. By studying the nature of interactions between this species and microorganisms common to its breeding environment we can unravel important pitfalls encountered during development. We tested the survival rate of larval stages, pupae and adults of a Cx. pipiens colony exposed to a variety of microorganisms in laboratory conditions and assessed the transmission to offspring (F1) by those organisms that secured development up to adulthood. Three complementary experiments were designed to: 1) explore the nutritional value of yeasts and other microorganisms during Cx. pipiens development; 2) elucidate the transstadial transmission of yeast to the host offspring; and 3) to examine the relevance of all these microorganisms in female choice for oviposition-substratum. The yeast Saccharomyces cerevisiae proved to be the most nutritional diet, but despite showing the highest survival rates, vertical transmission to F1 was never confirmed. In addition, during the oviposition trials, none of the gravid females was attracted to the yeast substratum. Notably, the two native bacterial strains, Klebsiella sp. and Aeromonas sp., were the preferred oviposition media, the same two bacteria that managed to feed neonates until molting into 2nd instar larvae. Our results not only suggest that Klebsiella sp. or Aeromonas sp. serve as attractants for oviposition habitat selection, but also nurture the most fragile instar, L1, to assure molting into a more resilient stage, L2, while yeast proves to be the most supportive diet for completing development. These experiments unearthed survival traits that might be considered in the future development of strategies of Cx. pipiens control. These studies can be extended to other members of the Pipiens Assemblag

The Global Health System: Actors, Norms, and Expectations in Transition

In the first in a series of four articles highlighting the changing nature of global health institutions, Nicole Szlezák and colleagues outline the origin and aim of the series