Knowledge and perception of risk for HIV and condom use among male injecting drug users in Cebu City,Philippines

Injecting drug users (IDU) represent a small fraction of the HIV and AIDS cases in the Philippines. To determine if these people are engaging in behaviors that put them at risk for HIV, interviews were conducted with 360 male IDUs in Cebu City, Philippines, from 1997 to 1999, as part of a national surveillance system. The interviews assessed knowledge about HIV transmission, sources of information about HIV/AIDS, perceived risks of contracting HIV, needle-sharing practices, condom use, self-reported signs and symptoms of STDs and number of sex partners. Although most of the men were able to recognize behaviors accurately that put them at risk for HIV, more than two-thirds claimed that they shared needles and almost two-thirds of those who were sexually active claimed that they never used condoms. Intervention strategies must be developed for this population if the nation is to avoid the dramatic increase in HIV infection among IDUs that has been witnessed in neighboring Southeast Asian nations such as Malaysia and Vietnam.     

Changes in the striatal extracellular levels of dopamine and dihydroxyphenylacetic acid evoked by ammonia and N-methyl-D-aspartate: modulation by taurine

Acute hyperammonemia is associated with motor disturbances that are thought to involve striatal dopaminergic dysfunction. Discharge of striatal dopaminergic neurons is controlled by N-methyl-D-aspartate (NMDA) receptors, the excessive activation of which contributes to ammonia neurotoxicity. Here we show that ammonium chloride ("ammonia", extracellular concentration 5 mM) or NMDA (1 mM), when directly administered to the rat striatum via a microdialysis probe, evoke a prompt accumulation of dopamine (DA) in the microdialysates. However, while ammonia increases, NMDA decreases, the extracellular dihydroxyphenylacetate (DOPAC) level. The results point to the NMDA receptor-mediated enhancement of DA release and increased DA metabolism as two independent ways by which ammonia affects the striatal dopaminergic system. Taurine (extracellular concentration 10 mM) attenuated the NMDA- and ammonia-evoked DA release and ammonia-induced accumulation of DOPAC, reflecting two different neuroprotective mechanisms of this amino acid.     

The desirability and feasibility of scaling up community health insurance in low-income settings--lessons from Armenia

There is growing evidence that community financing mechanisms can raise additional revenue, increase equitable access to primary health care (PHC), and improve social protection. More recently there has been interest in scaling up community financing as a step towards universal coverage either via tax-based systems or social health insurance. Using key informant interviews and focus group discussions, this study sought to assess the desirability and feasibility of scaling-up community health insurance in Armenia. The results suggest that there is broad-based political support for scaling up the schemes and that community financing is synergistic with major health sector reforms. High levels of social capital within the rural communities should facilitate scaling up. Existing schemes have increased access and quality of care, but expansion of coverage is constrained by affordability, poor infrastructure, and weak linkages with the broader health system. Long-term subsidies and system-building will be essential if the expanded schemes are to be financially viable and pro-poor. Overall, successfully scaling up community financing in Armenia would depend on addressing a range of obstacles related to legislation, institutional capacity, human resources and resistance to change among certain stakeholders.     

Joint line elevation and tibial slope are associated with increased polyethylene wear in cruciate-retaining total knee replacement

The purpose of this retrieval study was to determine the effect of implant positioning on wear, taking patient-related factors into account. Therefore, the volumetric material loss of 59 retrieved tibial liners was quantitatively determined using a coordinate measuring-machine. All retrievals were made of the same polyethylene and design by a single manufacturer. Using time in-situ and linear regression, a wear rate for each liner was determined and corrected for bedding-in. Backside damage was qualitatively scored. The following implant positioning parameters were obtained from radiographs: anatomical lateral-distal femoral angle, anatomical medial-proximal tibial angle, femoral tilt angle, and posterior tibial slope. The patella position was assessed by the Blackburne-Peel index and the Insall-Salvati ratio. Unlike the Insall-Salvati ratio, the Blackburne-Peel index is known to detect surgical joint line elevation. Using general linear modeling the most impactful factors on wear rate and backside damage was determined, thereby taking patient demographic factors into account. The mean volumetric wear rate was 11.6 mm³/y. Wear decreased with older age (P = .021) and female sex (P = .001). The wear rate increased with joint line elevation as indicated from a decreased Blackburne-Peel index (P = .019), and increased with increased posterior tibial slope (P = .026). The backside damage score also increased with joint line elevation (P = .036). A Blackburne-Peel index decrease of 0.1, signifying joint line elevation, was found to increase the wear rate by 1.8 mm³/y and increase back-sided wear. A high tibial slope (>7°) led to a 9.3 mm³/y increase in wear rate compared with a low tibial slope (<3°). The results of this study demonstrate that tibial liner positioning has a significant impact on polyethylene wear with potential implications on osteolysis over time.     

Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis

The complement pathway has potential contributions to both white (WM) and grey matter (GM) pathology in Multiple Sclerosis (MS). A quantitative assessment of complement involvement is lacking. Here we describe the use of Tissue MicroArray (TMA) methodology in conjunction with immunohistochemistry to investigate the localization of complement pathway proteins in progressive MS cortical GM and subcortical WM. Antibodies targeting complement proteins C1q, C3b, regulatory proteins C1 inhibitor (C1INH, complement receptor 1 (CR1), clusterin, factor H (FH) and the C5a anaphylatoxin receptor (C5aR) were utilised alongside standard markers of tissue pathology. All stained slides were digitised for quantitative analysis. We found that numbers of cells immunolabelled for HLA‐DR, GFAP, C5aR, C1q and C3b were increased in WM lesions (WML) and GM lesions (GML) compared to normal appearing WM (NAWM) and GM (NAGM), respectively. The complement regulators C1INH, CR1, FH and clusterin were more abundant in WM lesions, while the number of C1q+ neurons were increased and the number of C1INH+, clusterin+, FH+ and CR1+ neurons decreased in GM lesions. The number of complement component positive cells (C1q, C3b) correlated with complement regulator expression in WM, but there was no statistical association between complement activation and regulator expression in the GM. We conclude that TMA methodology and quantitative analysis provides evidence of complement dysregulation in MS GML, including an association of the numerical density of C1q+ cells with tissue lesions. Our work confirms that complement activation and dysregulation occur in all cases of progressive MS and suggest that complement may provide potential biomarkers of the disease.     

Molecular Analysis of SARS-CoV-2 Lineages in Armenia

The sequencing of SARS-CoV-2 provides essential information on viral evolution, transmission, and epidemiology. In this paper, we performed the whole-genome sequencing of SARS-CoV-2 using nanopore and Illumina sequencing to describe the circulation of the virus lineages in Armenia. The analysis of 145 full genomes identified six clades (19A, 20A, 20B, 20I, 21J, and 21K) and considerable intra-clade PANGO lineage diversity. Phylodynamic and transmission analysis allowed to attribute specific clades as well as infer their importation routes. Thus, the first two waves of positive case increase were caused by the 20B clade, the third peak caused by the 20I (Alpha), while the last two peaks were caused by the 21J (Delta) and 21K (Omicron) variants. The functional analyses of mutations in sequences largely affected epitopes associated with protective HLA loci and did not cause the loss of the signal in PCR tests targeting ORF1ab and N genes as confirmed by RT-PCR. We also compared the performance of nanopore and Illumina short-read sequencing and showed the utility of nanopore sequencing as an efficient and affordable alternative for large-scale molecular epidemiology research. Thus, our paper describes new data on the genomic diversity of SARS-CoV-2 variants in Armenia in the global context of the virus molecular genomic surveillance.     

C-15-functionalized eudesmanolides from Mikania campanulata

The aerial parts of Mikania campanulata Gardner afforded the nine new eudesmanolides (1S,4S,5S,6S,7S,10R)-1-hydroxy-15-acetoxyeudesm-11(13)-en-6,12-olide (1), (1S,4S,5S,6S,7S,10R)-1,4-dihydroxy-15-acetoxyeudesm-11(13)-en-6,12-olide (2), (1R,4S,5S,6S,7S,10R)-1,4-dihydroxy-15-acetoxyeudesm-11(13)-en-6,12-olide (3), (1R,4S,5S,6S,7S,10R)-1-hydroxy-4,15-diacetoxyeudesm-11(13)-en-6,12-olide (4), (1S,4R,5S,6S,7S,10R)-1,15-diacetoxy-4-hydroxyeudesm-11(13)-en-6,12-olide (5), (1S,5S,6S,7S,10R)-1-hydroxy-15-acetoxyeudesma-4(15),11(13)-dien-6,12-olide (6), (1S,5S,6S,7S,10R)-1,15-dihydroxyeudesma-3,11(13)-dien-6,12-olide (7a), (1S,2R,5S,6S,7S,10R)-1,2,15-trihydroxyeudesma-3,11(13)-dien-6,12-olide (8a), and (1R,6S,7S,10R)-1,15-dihydroxyeudesma-4,11(13)-dien-6,12-olide (9a), among which the last three were characterized as their corresponding peracetates (7b-9b). The structures of 1-6 and 7b-9b were elucidated using 1D and 2D NMR measurements, while that of major constituent 1 was confirmed by single-crystal X-ray diffraction analysis, and its absolute configuration evidenced from vibrational circular dichroism measurements, which were compared to results obtained from density functional theory calculations. The chemistry of the large genus Mikania is briefly analyzed.     

Mobile assistive technologies for the visually impaired

There are around 285 million visually impaired people worldwide, and around 370,000 people are registered as blind or partially sighted in the UK. Ongoing advances in information technology (IT) are increasing the scope for IT-based mobile assistive technologies to facilitate the independence, safety, and improved quality of life of the visually impaired. Research is being directed at making mobile phones and other handheld devices accessible via our haptic (touch) and audio sensory channels. We review research and innovation within the field of mobile assistive technology for the visually impaired and, in so doing, highlight the need for successful collaboration between clinical expertise, computer science, and domain users to realize fully the potential benefits of such technologies. We initially reflect on research that has been conducted to make mobile phones more accessible to people with vision loss. We then discuss innovative assistive applications designed for the visually impaired that are either delivered via mainstream devices and can be used while in motion (e.g., mobile phones) or are embedded within an environment that may be in motion (e.g., public transport) or within which the user may be in motion (e.g., smart homes).