Association of Skeletal Muscle Oxidative Capacity and Cardiometabolic Health in an Overweight Population

Background: Cardiometabolic health factors are becoming increasingly front and center in prevalence and cost of treatment in the U.S.. Incidence rates and complications from diseases related to these factors including obesity, heart disease, type 2 diabetes and certain types of cancers have not only cost over $1 trillion annually but are increasing mortality rates across the country. Skeletal muscle mitochondrial function has been connected to these factors, and research has shown that it can be used as an in vivo assessment of cardiometabolic health. Near Infrared Spectroscopy has recently seen an increase in interest for being used as a non-invasive method of assessing in vivo-mitochondrial function providing a simpler, cheaper and accurate way to determine cardiometabolic health both for practitioners and researchers. Studies have shown that NIRS assessments are similar in accuracy to other more expensive standards of assessment, such as 31P-MRS. Thus, we aim to examine the relationship between factors of cardiometabolic health and assessment of mitochondrial function using NIRS. Purpose: To examine how indices of cardiometabolic health, and VO2max associate with NIRS assessment of mitochondrial function. Methods: Overweight subjects (n=17) with a body mass index (BMI) of 25.0-29.9 kg/m2 were screened for varying factors of cardiometabolic health. Body composition was measured by a DEXA scan, 3-D body scan, and participants also underwent a maximal exercise test on a cycle ergometer and measures of resting metabolic rate. For a measure of mitochondrial function, subjects performed a NIRS assessment before and after three days of a high-fat diet. Results: Measures of cardiometabolic health were not statistically significant with mitochondrial function assessment with NIRS pre- or post- three day high-fat diet. Conclusion: The results from the current study show that mitochondrial function as assessed by NIRS has no statistically significant relationships with factors of cardiometabolic health or following an acute high-fat diet

Pancreatic Cancer: The Role of Pancreatic Stellate Cells in Tumor Progression.

Pancreatic ductal adenocarcinoma is an aggressive and highly lethal disease frequently characterized by a dense stromal or desmoplastic response. Accumulating evidence exists that tumor desmoplasia plays a central role in disease progression and that e.g. activated pancreatic stellate cells (PSCs) are responsible for the excess matrix production. The mechanisms underlying the tumor versus stroma interplay are complex. Pancreatic cancer cells release mitogenic and fibrogenic stimulants, such as transforming growth factor β(1), platelet-derived growth factor (PDGF), sonic hedgehog, galectin 3, endothelin 1 and serine protease inhibitor nexin 2, all of which may promote the activated PSC phenotype. Stellate cells in turn secrete various factors, including PDGF, stromal-derived factor 1, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, secreted protein acidic and rich in cysteine, matrix metalloproteinases, small leucine-rich proteoglycans, periostin and collagen type I that mediate effects on tumor growth, invasion, metastasis and resistance to chemotherapy. This review intends to shed light on the mechanisms by which PSCs in the stroma influence pancreatic cancer development. The increased understanding of this interaction will be of potential value in designing new modalities of targeted therapy. and IAP

Declining prevalence rates of syphilis among police officers in Guinea-bissau, west Africa, 1990-2010.

We analyzed prevalence rates of syphilis (positive Treponema pallidum hemagglutinin antigen/T. pallidum particle antigen and venereal disease research laboratory test) among police officers in Guinea-Bissau from 1990 to 2010 and found a significant decline from 4.5% to 0.4% (P = 0.0065). Our results are in line with other recent reports from West Africa. More research is needed to identify the reasons for this decline

Performance of Bio-Rad HIV-1/2 Confirmatory Assay in HIV-1, HIV-2 and HIV-1/2 dually reactive patients - comparison with INNO-LIA and immunocomb discriminatory assays

Background: Being able to discriminate between HIV-1, HIV-2 and HIV-1/2 dual infection is imperative for the appropriate selection of antiretroviral therapy (ART) in regions with high HIV-2 endemicity. Objectives: To evaluate Bio-Rad Geenius HIV-1/2 Confirmatory Assay against INNO-LIA HIV 1/2 Score and ImmunoComb HIV 1/2 BiSpot with an emphasis towards ability to discriminate between HIV-1, HIV-2 and HIV-1/2 dual infection. Material and Methods: 131 samples from ART naïve HIV infected patients in Guinea-Bissau were selected retrospectively and tested with Geenius, INNO-LIA and Immunocomb. HIV-1/2 RNA were measured in all samples and HIV-1/2 DNA in 59 samples. Results: The Geenius reader typed 62 samples as HIV-1 reactive, 37 samples as HIV-2 reactive and 32 samples as HIV-1/2 dually reactive. Geenius manual reading classified 10% more samples as HIV-1/2 dually reactive (n = 35). INNO-LIA typed 63 samples as HIV-1 reactive, 36 samples as HIV-2 reactive and 32 samples as HIV-1/2 dually reactive while Immunocomb classified a large proportion of samples as HIV-1/2 dually reactive (n = 45). The measurement of agreement of the Geenius reader compared with INNO-LIA and Immunocomb was 92.4% and 84.0% respectively while the measurement of agreement of Geenius manual reading compared with INNO-LIA and Immuncomb was 93.1% and 89.3% respectively. Conclusions: Geenius has similar performance characteristics as INNO-LIA, and performs considerably better than Immunocomb, for differentiating between HIV types. This is especially true when using the Geenius reader while manual reading of the Geenius assay seemed to overestimate the numbers of HIV-1/2 dually reactive samples

Prevalence of HIV-1 pretreatment drug resistance among treatment naïve pregnant women in Bissau, Guinea Bissau

BACKGROUND: With increased access to antiretroviral treatment (ART) in sub-Saharan Africa emergence of HIV-1 pretreatment drug resistance constitutes a serious risk. This may lead to rapid virological failure in subjects initiating ART, and mother-to-child transmission despite prophylaxis.METHODS: Treatment-naïve pregnant women from four antenatal care clinics in Bissau, Guinea-Bissau, were enrolled from October 2016 to November 2017. Genotypic resistance testing and phylogenetic subtype analysis was performed on 48 specimens.RESULTS: Forty eight women met the survey inclusion criteria. All specimens were successfully amplified and genotyped. Specimens from five women were associated with HIV-1 drug resistance mutations. Four carried mutations exclusively linked to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (K103N, K103N/S) and one carried mutations to both NNRTIs (G190S, K101E) and nucleoside reverse transcriptase inhibitors (NRTIs) (M184V). These results corresponded to 10.4% (95% CI: 4.5-22.2%), 2.1% (95% CI: 0.4-10.9%) and 0% (95% CI: 0.0-7.4%) drug resistance mutations to NNRTIs, NRTIs and protease inhibitors, respectively. HIV-1 circulating recombinant form 02AG was most commonly found, followed by HIV-1 sub-subtype A3. Subtype/CRF was not associated with drug resistance mutations.CONCLUSION: Our study reports a 10.4% prevalence of pretreatment drug resistance to NNRTIs in HIV-1-infected pregnant women in the capital Bissau, Guinea Bissau. Since NNRTIs are part of first-line ART in the country, baseline resistance screenings or adjustment of national treatment guidelines should be considered as antiretroviral treatment programs are scaled up

The HIV care continuum and HIV-1 drug resistance among female sex workers : a key population in Guinea-Bissau

INTRODUCTION: Female sex workers (FSW) are considered a key group for HIV transmissions in sub-Saharan Africa. The HIV Care Continuum and HIV drug resistance (HIVDR) among FSW has not been well studied in most countries in West Africa. In the current study we describe the HIV Care continuum and prevalence of HIVDR among FSW in Guinea-Bissau. METHODS: A venue-based recruitment and peer-referral of FSW was used in seven cities in Guinea-Bissau from October 2014 to September 2017. We administered a questionnaire, performed discriminatory HIV-testing and collected blood specimens for CD4 count, viral load and HIVDR genotyping. RESULTS: The survey included 440 FSW. The overall HIV-prevalence among FSW was 26.8%. Of the HIV-1 (HIV-1 single- or dually HIV-1/HIV-2) infected FSW (N = 104), 58.7% were previously diagnosed with HIV-1 at enrolment and 41.4% reported taking antiretroviral therapy (ART) compared to 28.6% of the HIV-2 single-infected FSW (N = 14). Among HIV-1 infected FSW on ART (N = 43), 55.8% were virally suppressed (< 1000 copies/ml) and of all HIV-1 infected FSW, 29.8% were virally suppressed. Among ART experienced FSW (N = 22), 50.0% had HIVDR. HIVDR was also found in 9.4% of treatment naïve FSW (N = 53). CONCLUSION: The majority of FSW who knew their HIV status received ART, however a large proportion of FSW were not aware of their HIV positive status. This translated into a great majority of the HIV-infected FSW not being virally suppressed. Amongst treatment naïve FSW nearly a tenth had HIVDR, suggesting that sexual transmission of HIVDR is occurring in this at-risk-population

Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2

Disease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV disease severity, we have compared blood gene expression profiles between HIV seronegative and HIV-1, HIV-2 or dually HIV-1/HIV-2 infected individuals. In this study the gene encoding Interferon alpha-inducible protein 27 (IFI27) was found to be the most differentially expressed. Detailed expression analysis revealed significantly higher IFI27 expression in HIV infected individuals compared with seronegative individuals, irrespectively of HIV type. Moreover, IFI27 expression was higher in HIV-1 than in HIV-2 infected individuals. Multiple linear regression analysis, adjusting for age and sex, showed also that plasma viral load was the strongest predictor of IFI27 expression, followed by CD4% and HIV type. In line with this, IFI27 expression was found to be higher in HIV-2 viremic, compared with HIV-2 aviremic individuals. Still, HIV-2 aviremic individuals displayed elevated IFI27 expression compared with seronegative individuals. Furthermore, in HIV-2 infected individuals, IFI27 expression was also correlated with plasma markers previously linked to inflammation and disease progression in HIV infection. Taken together, our findings suggest that sustained elevation of type I interferon signaling, here reflected by elevated IFI27 expression in the chronic infection phase, is a key pathogenic feature of both HIV-1 and HIV-

HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling

Summary: Despite low or undetectable plasma viral load, people living with HIV-2 (PLWH2) typically progress toward AIDS. The driving forces behind HIV-2 disease progression and the role of viremia are still not known, but low-level replication in tissues is believed to play a role. To investigate the impact of viremic and aviremic HIV-2 infection on target and bystander cell pathology, we used data-independent acquisition mass spectrometry to determine plasma signatures of tissue and cell type engagement. Proteins derived from target and bystander cells in multiple tissues, such as the gastrointestinal tract and brain, were detected at elevated levels in plasma of PLWH2, compared with HIV negative controls. Moreover, viremic HIV-2 infection appeared to induce enhanced release of proteins from a broader range of tissues compared to aviremic HIV-2 infection. This study expands the knowledge on the link between plasma proteome remodeling and the pathological cell engagement in tissues during HIV-2 infection