Social and cultural aspects of HIV and AIDS in West Africa: A narrative review of qualitative research

With the increasing focus on the role of social aspects of the HIV epidemic in sub-Saharan Africa, the need for an overview of existing research dealing with such issues has become more urgent. The objective of this article is to provide a thematic overview of existing qualitative research on HIV and AIDS in the West African region and to analyze the main researchfindings in order to identify possible gaps and recommend new research themes to inform future research-based interventions. The analysis is based on a total of 58 articles published from 2001 to 2009 in English or French identified through a literature search in seven scientific, bibliographical databases. Searches included terms related to qualitative studies combined with various terms related to HIV/AIDS. The results of this narrative review show that there was a geographical concentration on Nigeria, Ghana, Burkina Faso and Coˆte d’Ivoire and a strong urban bias, with most studies taking place in the capital cities of these countries. The majority of the studies focused on women or women and men; only four articles dealt exclusively with men, of which only two were on men who have sex with men. The main study groups were people living with HIV, young people or female sex workers. Sexual risk-taking and  stigmatization were the themes that were most prominently explored in the articles we reviewed. We conclude that research needs to be strengthened in relation to the analysis of experiences with antiretroviraltherapy and the non-optimal access to treatment in West Africa. Also, more research is needed on men and their exposure to HIV/AIDS, as well as on the role of concurrent partnership in the spread of HIV

A novel mutation of KIF11 in a child with 22q11.2 deletion syndrome associated with MCLMR

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR; OMIM 152950) is a rare autosomal dominantly inherited syndrome. Mutations in the kinesin family member 11 (KIF11) gene have been associated with this condition. Here, we report a de novo novel heterozygous missense mutation in exon 12 of the KIF11 gene [c.1402T>G; p.(Leu468Val)] in a boy with 22q11.2 microdeletion syndrome. His major features were microcephaly, ventricular septal defect, congenital lymphedema of the feet, and distinct facial appearance including upslanting palpebral fissures, a broad nose with rounded tip, anteverted nares, long philtrum with a thin upper lip, pointed chin, and prominent ears. His right eye was enucleated due to subretinal hemorrhage and retinal detachment at age 3 months. Lacunae of chorioretinal atrophy and the pale optic disc were present in the left eye. He also had a de novo 1.6-Mb microdeletion in the Di George/VCFS region of chromosome 22q11.2 in SNP array, which was confirmed by FISH analysis. In this study, for the first time, we describe the co-occurrence of a KIF11 mutation and 22q11.2 deletion syndrome in a patient with MCLMR

Hardness Distribution and Defect Formation in Aluminium Alloys Fabricated via Additive Friction Stir Deposition (AFSD)

Additive friction stir deposition (AFSD) is an emerging solid-state additive manufacturing technique where material is deposited layer-by-layer. Unlike fusion-based additive manufacturing processes, AFSD relies on a rotating tool to extrude and bond feedstock material through frictional heat and pressure, keeping the material below its melting point to eliminate fusion-related defects. It is suitable for large structure fabrication due to its high deposition rate. However, AFSD is still in development, with questions concerning hardness variation along the build height, defect formation, and residual stress distribution. In this research, an AFSD-manufactured structure is examined using optical microscopy, Vickers hardness testing, and neutron diffraction. Optical microscopy reveals defects at first layer and substrate interface as well as deposit edges, while hardness testing indicates deposit hardness decreases from final layer to first layer. Neutron diffraction shows tensile residual stress near the fusion zone in the substrate with compressive residual stress in majority of deposit

Low immediate scientific yield of the PhD among medical doctors

BACKGROUND: We studied the scientific yield of the medical PhD program at all Danish Universities. METHODS: We undertook a retrospective observational study. Three PhD schools in Denmark were included in order to evaluate the postdoctoral research production over more than 18 years through individual publications accessed by PubMed. RESULTS: A total of 2686 PhD-graduates (1995–2013) with a medical background were included according to registries from all PhD schools in Denmark. They had a median age of 35 years (interquartile range (IQR), 32–38) and 53 % were women at the time of graduation. Scientific activity over time was assessed independently of author-rank and inactivity was measured relative to the date of graduation. Factors associated with inactivity were identified using multivariable logistic regression. 88.6 % of the PhD theses were conducted in internal medicine vs. 11.4 % in surgery. During follow-up (median 6.9 years, IQR 3.0–11.7), PubMed data searches identified that 87 (3.4 %) of the PhD graduates had no publication after they graduated from the PhD program, 40 % had 5 or less, and 90 % had 30 or less. The median number of publications per year after PhD graduation was 1.12 (IQR 0.61–1.99) papers per year. About 2/3 of the graduates became inactive after 1 year and approximately 21 % of the graduates remained active during the whole follow-up. Female gender was associated with inactivity: adjusted odds ratio 1.59 (95 % confidence interval 1.24–2.05). CONCLUSIONS: The scientific production of Danish medic PhD-graduates was mainly produced around the time of PhD-graduation. After obtaining the PhD-degree the scientific production declines suggesting that scientific advance fails and resources are not harnessed

The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint

This paper presents the wrist joint MR images of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas. Reference images for scoring synovitis, bone oedema, and bone erosions according to the OMERACT RA MRI scoring (RAMRIS) system are provided. All grades (0–3) of synovitis are illustrated in each of the three wrist joint areas defined in the scoring system—that is, the distal radioulnar joint, the radiocarpal joint, and the intercarpal-carpometacarpal joints. For reasons of feasibility, examples of bone abnormalities are limited to five selected bones: the radius, scaphoid, lunate, capitate, and a metacarpal base. In these bones, grades 0–3 of bone oedema are illustrated, and for bone erosion, grades 0–3 and examples of higher grades are presented. The presented reference images can be used to guide scoring of wrist joints according to the OMERACT RA MRI scoring system

The pattern-recognition molecule H-ficolin in relation to diabetic kidney disease, mortality, and cardiovascular events in type 1 diabetes

H-ficolin recognizes patterns on microorganisms and stressed cells and can activate the lectin pathway of the complement system. We aimed to assess H-ficolin in relation to the progression of diabetic kidney disease (DKD), all-cause mortality, diabetes-related mortality, and cardiovascular events. Event rates per 10-unit H-ficolin-increase were compared in an observational follow-up of 2,410 individuals with type 1 diabetes from the FinnDiane Study. DKD progression occurred in 400 individuals. The unadjusted hazard ratio (HR) for progression was 1.29 (1.18-1.40) and 1.16 (1.05-1.29) after adjustment for diabetes duration, sex, HbA(1c), systolic blood pressure, and smoking status. After adding triglycerides to the model, the HR decreased to 1.07 (0.97-1.18). In all, 486 individuals died, including 268 deaths of cardiovascular causes and 192 deaths of complications to diabetes. HRs for all-cause mortality and cardiovascular mortality were 1.13 (1.04-1.22) and 1.05 (0.93-1.17), respectively, in unadjusted analyses. These estimates lost statistical significance in adjusted models. However, the unadjusted HR for diabetes-related mortality was 1.19 (1.05-1.35) and 1.18 (1.02-1.37) with the most stringent adjustment level. Our results, therefore, indicate that H-ficolin predicts diabetes-related mortality, but neither all-cause mortality nor fatal/non-fatal cardiovascular events. Furthermore, H-ficolin is associated with DKD progression, however, not independently of the fully adjusted model.Peer reviewe

Synthetic RNA modules for fine-tuning gene expression levels in yeast by modulating RNase III activity

The design of synthetic gene networks requires an extensive genetic toolbox to control the activities and levels of protein components to achieve desired cellular functions. Recently, a novel class of RNA-based control modules, which act through post-transcriptional processing of transcripts by directed RNase III (Rnt1p) cleavage, were shown to provide predictable control over gene expression and unique properties for manipulating biological networks. Here, we increase the regulatory range of the Rnt1p control elements, by modifying a critical region for enzyme binding to its hairpin substrates, the binding stability box (BSB). We used a high throughput, cell-based selection strategy to screen a BSB library for sequences that exhibit low fluorescence and thus high Rnt1p processing efficiencies. Sixteen unique BSBs were identified that cover a range of protein expression levels, due to the ability of the sequences to affect the hairpin cleavage rate and to form active cleavable complexes with Rnt1p. We further demonstrated that the activity of synthetic Rnt1p hairpins can be rationally programmed by combining the synthetic BSBs with a set of sequences located within a different region of the hairpin that directly modulate cleavage rates, providing a modular assembly strategy for this class of RNA-based control elements

MRI identifies plantar plate pathology in the forefoot of patients with rheumatoid arthritis

Previous cadaveric studies have suggested that forefoot deformities at the metatarsophalangeal (MTP) joints in patients with rheumatoid arthritis (RA) might result from the failure of the ligamentous system and displacement of the plantar plates. This study aimed to examine the relationship between plantar plate pathology and the rheumatoid arthritis magnetic resonance imaging score (RAMRIS) of the lesser (second to fifth) MTP joints in patients with RA using high-resolution 3 T magnetic resonance imaging (MRI). In 24 patients with RA, the forefoot was imaged using 3 T MRI. Proton density fat-suppressed, T2-weighted fat-suppressed and T1-weighted post gadolinium sequences were acquired through 96 lesser MTP joints. Images were scored for synovitis, bone marrow oedema and bone erosion using the RAMRIS system and the plantar plates were assessed for pathology. Seventeen females and 7 males with a mean age of 55.5 years (range 37–71) and disease duration of 10.6 years (range 0.6–36) took part in the study. Plantar plate pathology was most frequently demonstrated on MRI at the fifth MTP joint. An association was demonstrated between plantar plate pathology and RAMRIS-reported synovitis, bone marrow oedema and bone erosion at the fourth and fifth MTP joints. In patients with RA, 3 T MRI demonstrates that plantar plate pathology at the lesser MTP joints is associated with features of disease severity. Plantar plate pathology is more common at the fourth and fifth MTP joints in subjects with RA in contrast to the predilection for the second MTP reported previously in subjects without RA

Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections