SHBG, Bone Mineral Density, and Physical Function Among Injection Drug Users With and Without HIV and HCV.

CONTEXT: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates the bioavailability of sex hormones and is higher in people with HIV (PWH) and hepatitis C virus (HCV). SHBG is associated with aging-related diseases, including osteoporosis and frailty in the general population. However, the relationship between SHBG concentration and bone mineral density (BMD) and physical function among PWH and HCV is unclear. OBJECTIVE: This study aimed to evaluate the association between chronic infection with HIV and HCV and SHBG, and to assess the relationship of circulating SHBG concentrations with low BMD, physical function impairment, and frailty. METHODS: A cross-sectional study was conducted of 278 HCV-exposed (HCV antibody positive) adults enrolled with and without HIV and HCV from the AIDS Linked to the IntraVenous Experience cohort study into 4 groups: HCV-/HIV-, HCV-/HIV+, HCV+/HIV-, and HCV+/HIV+. We evaluated the association between SHBG concentrations and grip strength, gait speed, Short Physical Performance Battery score, frailty (Fried Frailty Phenotype), and BMD (lumbar spine, total hip, and femoral neck T-score) by using adjusted multivariable regression stratified by sex. RESULTS: SHBG concentrations were higher in women, in those with HIV RNA greater than 400 copies/mL (P = .02) and HCV RNA greater than 15 IU/mL (P < .001). In adjusted models, higher SHBG concentrations among women were statistically significantly associated with lower grip strength (-0.43 [95% CI, -0.77 to -0.081] kg/10 nmol/L, P < .05), higher odds of frailty (odds ratio, 1.49 [95% CI, 1.07 to 2.08], P < .05), and lower T-scores at the lumbar spine (-0.070 [95% CI, -0.15 to -0.001] SD/10 nmol/L T-score BMD, P < .05). Similar associations were not observed among men. CONCLUSION: Higher SHBG concentrations are associated with the presence of HIV and HCV viremia. Among women, but not men, higher SHBG concentrations were associated with lower grip strength, higher odds of frailty, and lower lumbar spine BMD. The underlying mechanisms of these associations require further investigation.

The combined effects of age and HIV on the anatomic distribution of cortical and cancellous bone in the femoral neck among men and women.

OBJECTIVE: To investigate HIV-related and age-related differences in hip bone structure in men and women. DESIGN: Cross sectional study of bone structure and HIV serostatus. METHODS: We used Quantitative Computed Tomography (QCT) data from the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) to examine cortical thickness (CT) and cortical (CBMD), trabecular (TBMD), and integral (IBMD) bone mineral density across anatomic quadrants of the femoral neck in older adult MSM and women with (PWH) and without (PWOH) HIV infection. The percentage difference (%diff) in the means for CT and BMD overall and by quadrant between PWH and PWOH were estimated. RESULTS: Among 322 MSM (median age 60 years) with bone measures, distributions were similar between HIV serostatus groups with %diff in the quadrant means ranging from -7 to -1% for CT and from -1 to 4% for BMD, and overall lower hip cortical thickness than expected. In contrast, in 113 women (median age 51 years), PWH had lower CT, IBMD and TBMD consistently across all quadrants, with differences ranging from -10 to -20% for CT, -6 to -11% for IBMD and -3 to -6% for TBMD. Estimates reached statistical significance in superoanterior quadrant for CT and IBMD and inferoposterior for CT. CONCLUSION: Among women, PWH appear to have a thinner cortex and less dense integral bone compared with PWOH, particularly in the superior quadrants whereas MSM overall had a thinner than expected hip cortex.

Peripheral Nerve Stimulation in Pain Management: A Systematic Review.

BACKGROUND: Peripheral nerve stimulation (PNS) has been increasingly used to manage acute and chronic pain. However, the level of clinical evidence to support its use is not clear. OBJECTIVES: To assess the clinical evidence of PNS in the treatment of acute or chronic pain. STUDY DESIGN: A systematic review of the efficacy and safety of PNS in managing acute or chronic pain. METHODS: Data sources were PubMed, Cochrane Library, Scopus, CINAHL Plus, Google Scholar, and reference lists. The literature search was performed up to December 2019. Study selection included randomized trials, observational studies, and case reports of PNS in acute or chronic pain. Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR). The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. Data syntheses: 227 studies met inclusion criteria and were included in qualitative synthesis. RESULTS: Evidence synthesis based on randomized controlled trials (RCTs) and observational studies showed Level I and II evidence of PNS in chronic migraine headache; Level II evidence in cluster headache, postamputation pain, chronic pelvic pain, chronic low back and lower extremity pain; and Level IV evidence in peripheral neuropathic pain, and postsurgical pain. Peripheral field stimulation has Level II evidence in chronic low back pain, and Level IV evidence in cranial pain. LIMITATIONS: Lack of high-quality RCTs. Meta-analysis was not possible due to wide variations in experimental design, research protocol, and heterogeneity of study population. CONCLUSIONS: The findings of this systematic review suggest that PNS may be effective in managing chronic headaches, postamputation pain, chronic pelvic pain, and chronic low back and lower extremity pain, with variable levels of evidence in favor of this technique.

Short Communication: Impact of Fat Changes on the Effect of Protease Inhibitors on Lumbar Spine Bone Mineral Density Changes with Antiretroviral Therapy Initiation.

People living with HIV (PLWH) who are on protease inhibitor (PI)-containing regimens have been shown to have increases in visceral adipose tissue (VAT) and a greater decrease in spine bone mineral density (BMD) than those receiving non-PI regimens when initiating treatment. This increase in VAT has been hypothesized to falsely lower spine BMD measured via dual-energy X-ray absorptiometry, suggesting that the PI-associated BMD loss is an artefact rather than real. To test this, data collected from two completed 96-week clinical trials, AIDS Clinical Trial Group studies A5224s and A5260s, of antiretroviral therapy-naive PLWH initiating treatment with PI and non-PI-containing regimens were analyzed comparing VAT accumulation and spine BMD loss. Results showed no significant decrease in spine BMD in persons in the highest quartile (Q4) of VAT gain versus the rest of the study population (Q1-3) in either the PI and non-PI arms, suggesting that PI-associated BMD loss is not likely to be an artefact of overlying VAT.

Comparison of the effects of CORM-2, CORM-3 and CORM-A1 on coagulation in human plasma.

Carbon monoxide derived from the catalytic action of heme oxygenase-1 or carbon monoxide-releasing molecules (CORMs) has been found to potentially be an anticoagulant or procoagulant agent. Of interest, two water-soluble CORMs, CORM-3 and CORM-A1, recently became commercially available. Thus, the purpose of the present study was to assess and compare the effects of the previously well studied CORM-2 to the effects of CORM-3 and CORM-A1 on coagulation in citrated human plasma with thrombelastography. Plasma exposed to CORMs was incubated at 37°C for at least one carbon monoxide release half-time, and then tissue factor-activated coagulation was commenced with calcium addition. CORM-2 and CORM-3 enhanced the velocity of clot formation and thrombus strength in a similar manner, whereas CORM-A1 did not affect coagulation. However, CORM-A1 did diminish tissue-type plasminogen activator initiated fibrinolysis. The similarity in effect on coagulation by CORM-2 and CORM-3 was likely secondary to the relatively inert effect of their ruthenium-containing carrier molecule, whereas the boron-containing CORM-A1 may have had no effect secondary to boron binding to fibrinogen, preventing carbon monoxide-mediated changes in fibrinogen protein structure via attached heme group(s). Future investigations with CORMs should have special attention to confounding effects of the carrier molecule.

Identification of the P3 promoter and distinct roles of the two promoters of the SaeRS two-component system in Staphylococcus aureus.

In Staphylococcus aureus, the SaeRS two-component system (TCS) encoded by the saePQRS operon controls expression of major virulence factors, such as coagulase and alpha-hemolysin. The saePQRS operon has two promoters: P1 and P3. The P1 promoter, a strong promoter, is autoinduced and can transcribe all four genes. Compared with P1, P3 shows fairly low but constitutive promoter activity, and it transcribes only saeR and saeS, the two genes encoding response regulator SaeR and sensor kinase SaeS. However, the role of each promoter in sae signaling has not been rigorously defined. In this study, we found that the genuine transcription start site (TSS) of P3 is located 78 nucleotides downstream of the previously reported TSS. Subsequently, the P3 promoter sequence was identified and validated by mutagenesis analyses. Deletion of the saePQ region including the P1 promoter did not significantly alter the expression patterns of coagulase and alpha-hemolysin, two well-known sae target genes. Due to its L18P substitution in a transmembrane domain, SaeS in strain Newman has a constitutive kinase activity. Interestingly, the mutation also rendered the protein unstable, but the protein stability was restored by SaeQ, suggesting a possible SaeQ-SaeS interaction. Ironically, the same mutation seems to increase mRNA stability. SaeR appears to be stabilized by SaeS, possibly by a protein-protein interaction. Chromosomal mutation of P1 did not affect the expression pattern of coagulase and alpha-hemolysin. Based on these results, we conclude that transcription of saeRS from P3 is sufficient for target gene activation and that P1 is not involved in the activation.