The Global Task Force for Chronic Pain in People with HIV (PWH): Developing a research agenda in an emerging field.

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.

Exercise-induced B cell mobilisation: Preliminary evidence for an influx of immature cells into the bloodstream.

The number of peripheral blood B lymphocytes doubles during acute exercise, but the phenotypic composition of this response remains unknown. In two independent exercise studies, using complimentary phenotyping strategies, we investigated the mobilisation patterns of distinct B cell subsets. In study one, nine healthy males (mean±SD age: 22.1±3.4years) completed a continuous cycling bout at 80% V̇O2MAX for 20min. In study two, seven healthy experienced cyclists (mean±SD age: 29.9±4.7years) completed a 30min cycling trial at a workload corresponding to +5% of the individual blood lactate threshold. In study one, CD3-CD19+ B cell subsets were classified into immature (CD27-CD10+), naïve (CD27-CD10-), memory (CD27+CD38-), plasma cells/plasmablasts (CD27+CD38+) and finally, recently purported 'B1' cells (CD27+ CD43+ CD69-). In study two, CD20+ B cells were classified into immature (CD27-IgD-), naïve (CD27-IgD+), and IgM+/IgG+/IgA+ memory cells (CD27+IgD-). Total B cells exhibited a mean increase of 88% (study one) and 60% (study two) during exercise. In both studies, immature cells displayed the greatest increase, followed by memory cells, then naïve cells (study one: immature 130%>mature 105%>naïve 84%; study two: immature 110%>mature 56%>naïve 38%). Our findings show that, unlike T cells and NK cells, B cell mobilisation is not driven by effector status, and, for the first time, that B cell mobilisation during exercise is comprised of immature CD27- IgD-/CD10+ cells.

Monitoring changes in thioredoxin and over-oxidised peroxiredoxin in response to exercise in humans.

INTRODUCTION: Peroxiredoxin (PRDX) and thioredoxin (TRX) are antioxidant proteins that control cellular signalling and redox balance, although their response to exercise is unknown. This study aimed to assess key aspects of the PRDX-TRX redox cycle in response to three different modes of exercise. METHODS: Healthy males (n = 10, mean ± SD: 22 ± 3 yrs) undertook three exercise trials on separate days: two steady-state cycling trials at moderate (60% [Formula: see text]O2MAX; 27 min, MOD) and high (80% [Formula: see text]O2MAX; 20 min, HIGH) intensities, and a low-volume high-intensity interval training trial (10 × 1 min 90% [Formula: see text]O2MAX, LV-HIIT). Peripheral blood mononuclear cells were assessed for TRX-1 and over-oxidised PRDX (isoforms I-IV) protein expression before, during, and 30 min following exercise (post + 30). The activities of TRX reductase (TRX-R) and the nuclear factor kappa B (NF-κB) p65 subunit were also assessed. RESULTS: TRX-1 increased during exercise in all trials (MOD, + 84.5%; HIGH, + 64.1%; LV-HIIT, + 205.7%; p < 05), whereas over-oxidised PRDX increased during HIGH only (MOD, - 28.7%; HIGH, + 202.9%; LV-HIIT, - 22.7%; p < .05). TRX-R and NF-κB p65 activity increased during exercise in all trials, with the greatest response in TRX-R activity seen in HIGH (p < 0.05). DISCUSSION: All trials stimulated a transient increase in TRX-1 protein expression during exercise. Only HIGH induced a transient over-oxidation of PRDX, alongside the greatest change in TRX-R activity. Future studies are needed to clarify the significance of heightened peroxide exposure during continuous high-intensity exercise and the mechanisms of PRDX-regulatory control.

TNF haplotypes in a Southern African population resemble those seen in Caucasians and Asians.

Haplotypes spanning the tumor necrosis factor (TNF) gene block in the central major histocompatibility complex were defined in a Southern African population using 31 single-nucleotide polymorphisms. Twenty haplotypes accounted for 91.8% of the cohort. The haplotypes matched those described previously in Caucasian and Asian populations, supporting the hypothesis that TNF block haplotypes are ancient and highly conserved. They are presented here as a tool for disease-association studies.

A polymorphism in IL4 may associate with sensory neuropathy in African HIV patients.

INTRODUCTION: Animal and in vitro models of HIV-associated sensory neuropathy suggest an inflammatory etiology. Previous genetic association studies of HIV-SN have been in small Caucasian or Asian cohorts. We assessed cytokine single nucleotide polymorphisms (SNPs) in a Black Southern African cohort. METHOD: 342 black HIV-positive Southern Africans were recruited. 190 individuals had HIV-associated sensory neuropathy and 152 did not. DNA samples from all participants were genotyped for cytokine SNPs identified in studies of HIV disease and/or neuropathy. RESULTS: IL4-590*T associated with an increased prevalence of HIV-SN including following correction for age, height and CD4 T-cell count. No other cytokine SNPs assessed displayed an association. DISCUSSION: We identified a novel association between IL4-590*T and HIV-SN in African HIV-positive patients which warrants further investigation.

Hepatitis C seropositivity is not a risk factor for sensory neuropathy among patients with HIV.

BACKGROUND: Sensory neuropathy (SN) is common in patients with HIV. Hepatitis C (HCV) coinfection is often cited as an HIV-SN risk factor, but data to support this are lacking. This collaboration aimed to examine the association between HCV serostatus and SN risk among ambulatory HIV-positive patients. METHODS: Patients with HIV were assessed in cross-sectional studies in Baltimore, Jakarta, Johannesburg, Kuala Lumpur, Melbourne, and Sydney for SN (defined by both supportive symptoms and signs). HCV seropositivity was assessed as an SN risk using a chi(2) test, followed by logistic regression modeling to correct for treatment exposures and demographics. RESULTS: A total of 837 patients of African, Asian, and Caucasian descent were studied. HCV seroprevalence varied by site (Baltimore n = 104, 61% HCV+; Jakarta 96, 51%; Johannesburg 300, 1%; Kuala Lumpur 97, 10%; Melbourne 206, 16%; Sydney 34, 18%). HCV seropositivity was not associated with increased SN risk at any site, but was associated with reduced SN risk in Melbourne (p = 0.003). On multivariate analyses, the independent associations with SN were increasing age, height, and stavudine exposure. HCV seropositivity was not independently associated with an increased SN risk at any site, but associated independently with reduced SN risk in Baltimore (p = 0.04) and Melbourne (p = 0.06). CONCLUSIONS: Hepatitis C (HCV) seropositivity was not associated with increased sensory neuropathy risk among HIV-positive patients at any site. While we were unable to assess HCV RNA or liver damage, the data suggest that HCV coinfection is not a major contributor to HIV-SN. HCV = hepatitis C; SN = sensory neuropathy.

Neuropsychological function in borderline personality disorder.

To evaluate the possibility of an underlying dimension of organicity in borderline personality disorder (BPD), a carefully diagnosed group of borderline patients was assessed across a wide range of neuropsychological functions and then was compared to an age- and education-matched non-patient control group. The BPD group had significantly lower Verbal, Performance, and Full Scale IQ scores on the WAIS-R. The BPD group also was impaired significantly on motor skills, figural memory, complex visuomotor integration, social or interpersonal intelligence, and on a measure of susceptibility to interference. This pattern of deficits localized to the fronto-temporal regions and became more pronounced when a subgroup analysis was performed. This study suggests that subtle organic factors may be operative in some, but not all, BPD patients.

Effect of fasting, branched-chain amino acids, and glucocorticoids on histone H1 extractability from rat skeletal muscle.

The effect of 72 h fasting, nutritional therapy of fasted rats, and acute and chronic glucocorticoid treatment on the yield of histone H1 from rat hind limb muscles was determined. Fasting significantly enhanced the extractability of muscle H1. The effect of treating starved rats with glucose alone, or with glucose supplemented with branched-chain amino acids (BCAA), or with two commercial preparations of mixtures of essential and non-essential amino acids was evaluated. Treatment of starved rats with glucose alone significantly decreased H1 extractability from muscles, but isocaloric treatment with glucose supplemented with BCAA or two commercial preparations of amino acid mixtures was more effective. Glucocorticoid treatment for 5 days enhanced the yield of H1 from muscles less than starvation. The enhanced H1 extractability from muscles noted in starved rats is similar to that reported in rats with insulinopenic diabetes and may reflect changes in nuclear fragility.

Effect of parvalbumin and S-100 protein on protein synthesis in rabbit reticulocyte lysate.

The effect of two high affinity Ca+ binding acidic proteins, parvalbumin and S-100 protein on protein synthesis in rabbit reticulocyte lysates (RRL), was investigated. Nuclease-treated RRL, supplemented with yeast mRNA, and 3H-leucine were incubated at 37 degrees C, and incorporation of 3H-leucine into protein was determined for 24 min. At 20 micrograms/100 microliters lysate concentration, both parvalbumin and S-100 protein caused a marked inhibition of protein synthesis compared with the control lysate. At a lower concentration parvalbumin was less inhibitory than histone H1; the effect of S-100 protein was not significant. The combined inhibitory effect of parvalbumin and H1 was not additive probably due to strong interaction between them as was evidenced by the enhanced absorbance of parvalbumin-H1 mixture. Spectrophotometric profiles of parvalbumin-tRNA mixture indicated that, unlike H1, parvalbumin did not inhibit protein synthesis by binding with nucleic acids. These results suggest an important role for parvalbumin in translational regulation.

Sex differences and handedness in hemispheric lateralization of tactile-spatial functions.

Sex differences in spatial processing and handedness were studied with a tactile-spatial task in 27 male and 29 female right-handed undergraduate students in psychology. Subjects were asked to identify amorphous shapes to investigate possible male right-hemisphere specialization for spatial functions and bilateral representation among the women. The Annett handedness questionnaire estimated extent of right-handedness. Subjects were classified by major, and women by phase of menstrual cycle. Analysis shows significantly more right-handedness in women and ambidexterity in men. Over-all, men do not perform significantly better than women, although men outperform women with their left hands when handedness is covaried. Within sex, no difference is seen between left and right hand scores for men, but women perform significantly better with right than left hands. Further analyses suggest men appear right-hemisphere dominant for this task whereas women show left-hemisphere dominance. Analyses of hormonal data support recent research, in that for women on the pill there is a trend to perform worse than all other groups. Engineering students perform significantly better than all other majors.