Relationship between HIV Stigma and Self-Isolation among People Living with HIV in Tennessee

Introduction

HIV stigma is a contributing factor to poor patient outcomes. Although HIV stigma has been documented, its impact on patient well-being in the southern US is not well understood.

Methods

Thirty-two adults participated in cognitive interviews after completing the Berger HIV or the Van Rie stigma scale. Participant responses were probed to ensure the scales accurately measured stigma and to assess the impact stigma had on behavior.

Results

Three main themes emerged regarding HIV stigma: (1) negative attitudes, fear of contagion, and misperceptions about transmission; (2) acts of discrimination by families, friends, health care providers, and within the workplace; and (3) participants’ use of self-isolation as a coping mechanism. Overwhelming reluctance to disclose a person’s HIV status made identifying enacted stigma with a quantitative scale difficult.

Discussion

Fear of discrimination resulted in participants isolating themselves from friends or experiences to avoid disclosure. Participant unwillingness to disclose their HIV status to friends and family could lead to an underestimation of enacted HIV stigma in quantitative scales.     

Kinematic and kinetic synergies of the lower extremities during the pull in olympic weightlifting

The purpose of this study was to identify multijoint lower extremity kinematic and kinetic synergies in weightlifting and compare these synergies between joints and across different external loads. Subjects completed sets of the clean exercise at loads equal to 65, 75, and 85% of their estimated 1-RM. Functional data analysis was used to extract principal component functions (PCF's) for hip, knee, and ankle joint angles and moments of force during the pull phase of the clean at all loads. The PCF scores were then compared between joints and across loads to determine how much of each PCF was present at each joint and how it differed across loads. The analyses extracted two kinematic and four kinetic PCF's. The statistical comparisons indicated that all kinematic and two of the four kinetic PCF's did not differ across load, but scaled according to joint function. The PCF's captured a set of joint- and load-specific synergies that quantified biomechanical function of the lower extremity during Olympic weightlifting and revealed important technical characteristics that should be considered in sports training and future research.     

Evidence for an essential histidine residue in the ascorbate-binding site of cytochrome b561

Cytochrome b(561) mediates equilibration of the ascorbate/semidehydroascorbate redox couple across the membranes of secretory vesicles. The cytochrome is reduced by ascorbic acid and oxidized by semidehydroascorbate on either side of the membrane. Treatment with diethyl pyrocarbonate (DEPC) inhibits reduction of the cytochrome by ascorbate, but this activity can be restored by subsequent treatment with hydroxylamine, suggesting the involvement of an essential histidine residue. Moreover, DEPC inactivates cytochrome b(561) more rapidly at alkaline pH, consistent with modification of a histidine residue. DEPC does not affect the absorption spectrum of cytochrome b(561) nor does it change the midpoint reduction potential, confirming that histidine modification does not affect the heme. Ascorbate protects the cytochrome from inactivation by DEPC, indicating that the essential histidine is in the ascorbate-binding site. Further evidence for this is that DEPC treatment inhibits oxidation of the cytochrome by semidehydroascorbate but not by ferricyanide. This supports a reaction mechanism in which ascorbate loses a hydrogen atom by donating a proton to histidine and transferring an electron to the heme.     

Long-term cerebral cortex protection and behavioral stabilization by gonadal steroid hormones after transient focal hypoxia

Sex steroids are neuroprotective following traumatic brain injury or during neurodegenerative processes. In a recent short-term study, we have shown that 17β-estradiol (E) and progesterone (P) applied directly after ischemia reduced the infarct volume by more than 70%. This protection might primarily result from the anti-inflammatory effects of steroids. Here, we focus on the long-term neuroprotection by both steroids with respect to the infarct volume, functional recovery, and vessel density in the penumbra. The application of E/P during the first 48h after stroke (transient middle cerebral artery occlusion, tMCAO) revealed neuroprotection after two weeks. The infarct area was reduced by 70% and motor activity was preserved compared to placebo-treated animals. Blood vessel density in the penumbra using immunohistochemistry for von Willebrand factor showed increased vessel density after tMCAO which was not affected by hormones. Expression of vascular endothelial growth factor (VEGF) and its receptor (R1) was increased at 24h after tMCAO and up-regulated by E/P but not changed 14 days after stroke. These findings suggest that the neuroprotective potency of both steroids is sustained and persists for at least two weeks. Besides anti-inflammatory and anti-apoptotic actions, angiogenesis in the damaged area appears to be initially affected early after ischemia and is manifested up to two weeks. This article is part of a Special Issue entitled 'Neurosteroids'.     

Apoptotic cleavage of scaffold attachment factor A (SAF-A) by caspase-3 occurs at a noncanonical cleavage site

Members of the caspase family of cysteine proteases play essential roles in the disintegration of cellular architecture during apoptosis. Caspases have been grouped into subfamilies according to their preferred cleavage sites, with the "apoptotic executioner" caspase-3 as the prototype of DEXD-dependent proteases. We show here that caspase-3 is more tolerant to variations of the cleavage site than previously anticipated and present an example of a noncanonical recognition site that is efficiently cleaved by caspase-3 in vitro and in vivo. The new cleavage site was identified in human scaffold attachment factor A, one of the major scaffold attachment region DNA-binding proteins of human cells thought to be involved in nuclear architecture by fastening chromatin loops to a proteinaceous nuclear skeleton, the so-called nuclear matrix or scaffold. Using an amino-terminal recombinant construct of scaffold attachment factor A and recombinant caspase-3, we have mapped the cleavage site by matrix-assisted laser desorption ionization/time of flight mass spectrometry and Edman sequencing. We find that cleavage occurs after Asp-100 in a sequence context (SALD) that does not conform to the hitherto accepted DEXD consensus sequence of caspase-3. A point mutation, D100A, abrogates cleavage by recombinant caspase-3 in vitro and during apoptosis in vivo, confirming SALD as a novel caspase-3 cleavage site.     

Re-Validation of the Van Rie HIV/AIDS-Related Stigma Scale for Use with People Living with HIV in the United States

There is little consensus about which of the many validated human immunodeficiency virus (HIV) stigma scales should be regularly used, with few being re-validated in different contexts or evaluated for how they compare to other, existing HIV stigma scales. The purpose of this exploratory study was to re-validate the Van Rie HIV/AIDS-Related Stigma Scale, originally validated in Thailand and using a third-person wording structure, for use with people living with HIV in the United States. Adult HIV clinic patients completed a survey including the Berger and Van Rie scales, and measures of social support and depression. Eighty-five of 211 (40%) eligible participants provided data for both stigma scales. Exploratory factor analyses identified three factors to the Van Rie scale: Loss of Social Relationships (new subscale), Managing HIV Concealment (new subscale), and Perceived Community Stigma (original subscale). These subscales were moderately inter-related (r = 0.51 to 0.58) with acceptable to excellent reliability (Cronbach’s alpha = 0.69 to 0.90). The Van Rie subscales were also moderately inter-correlated with the Berger subscales (r = 0.44 to 0.76), had similar construct validity, and tended to have higher mean stigma scores when compared with Berger subscales that were conceptually most similar. The revised Van Rie HIV-related Stigma Scale demonstrates good validity and internal consistency, offering a valid measure of HIV stigma with a three-factor structure. The third-person wording may be particularly suitable for measuring stigmatizing attitudes during an individual’s transition from at-risk and undergoing HIV testing to newly diagnosed, a time when experiences of discrimination and processing issues of disclosure have not yet occurred. The stigma mechanisms for individuals making this transition have not been well explored. These scenarios, combined with the observed non-response to the Berger Enacted Stigma subscale items (a surprise finding), highlight gaps in our understanding of HIV stigma and how best to measure it.     

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

ABSTRACT: BackroundNeuroprotective strategies after cardiopulmonary resuscitation are currently the focus of experimental and clinical research. Levosimendan has been proposed as a promising drug candidate because of its cardioprotective properties, improved haemodynamic effects in vivo and reduced traumatic brain injury in vitro. The effects of levosimendan on brain metabolism during and after ischaemia/hypoxia are unknown. METHODS: Transient cerebral ischaemia/hypoxia was induced in 30 male Wistar rats by bilateral common carotid artery clamping for 15 min and concomitant ventilation with 6 % O2 during general anaesthesia with urethane. After 10 min of global ischaemia/hypoxia, the rats were treated with an i.v. bolus of 24 mug kg-1 levosimendan followed by a continuous infusion of 0.2 mug kg-1 min-1. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glutamate were monitored by microdialysis. In addition, the effects on global haemodynamics, cerebral perfusion and autoregulation, oedema and expression of proinflammatory genes in the neocortex were assessed. RESULTS: Levosimendan reduced blood pressure during initial reperfusion (72 [PLUS-MINUS SIGN] 14 vs. 109 [PLUS-MINUS SIGN] 2 mmHg, p = 0.03) and delayed flow maximum by 5 minutes (p = 0.002). Whereas no effects on time course of lactate, glucose, pyruvate and glutamate concentrations in the dialysate could be observed, the lactate/pyruvate ratio during initial reperfusion (144 [PLUS-MINUS SIGN] 31 vs. 77 [PLUS-MINUS SIGN] 8, p = 0.017) and the glutamate release during 90 minutes of reperfusion (75 [PLUS-MINUS SIGN] 19 vs. 24 [PLUS-MINUS SIGN] 28 mumol[MIDDLE DOT]L-1) were higher in the levosimendan group. The increased expression of IL-6, IL-1ss TNFalpha and ICAM-1, extend of cerebral edema and cerebral autoregulation was not influenced by levosimendan. CONCLUSION: Although levosimendan has neuroprotective actions in vitro and on the spinal cord in vivo and has been shown to cross the blood--brain barrier, the present results showed that levosimendan did not reduce the initial neuronal injury after transient ischaemia/hypoxia.     

Organic Osmolyte Channels in the Renal Medulla: Their Properties and Regulation

In the mammalian kidney renal medullary cells use organic osmolytessuch as sorbitol, myo-inositol, glycerophosphorylcholine, betaine,and taurine to adjust their intracellular osmolarity (and therebytheir volume) to rapid and drastic changes in extracellularosmolarity. Using an immortalized cell line derived from rabbitthick ascending limb of Henle's loop (TALH cells) and primarycultures of rat inner medullary collecting duct (IMCD cells)the membrane transport systems activated during exposure tohypotonicity were investigated. In TALH cells an increase insorbitol permeability of the (luminal) plasma membrane occursby activation of a channel-like transporter involving a calcium/calmodulin-dependentprotein kinase. A similar system seems to operate in IMCD cells.In addition, the latter cells possess a swelling-activated anionchannel that is also permeable for taurine and myo-inositoland inhibited by "anion channel" blockers, such as NPPB andDIDS. The sorbitol permeability of the plasma membrane appearsto be furthermore regulated by a transient insertion of activetransporters into the basolateral cell surface by a membranerecycling mechanism.     

Evidence of independent gene duplications during the evolution of archaeal and eukaryotic family B DNA polymerases

Eukaryotes and archaea both possess multiple genes coding for family B DNA polymerases. In animals and fungi, three family B DNA polymerases, alpha, delta, and epsilon, are responsible for replication of nuclear DNA. We used a PCR-based approach to amplify and sequence phylogenetically conserved regions of these three DNA polymerases from Giardia intestinalis and Trichomonas vaginalis, representatives of early-diverging eukaryotic lineages. Phylogenetic analysis of eukaryotic and archaeal paralogs suggests that the gene duplications that gave rise to the three replicative paralogs occurred before the divergence of the earliest eukaryotic lineages, and that all eukaryotes are likely to possess these paralogs. One eukaryotic paralog, epsilon, consistently branches within archaeal sequences to the exclusion of other eukaryotic paralogs, suggesting that an epsilon-like family B DNA polymerase was ancestral to both archaea and eukaryotes. Because crenarchaeote and euryarchaeote paralogs do not form monophyletic groups in phylogenetic analysis, it is possible that archaeal family B paralogs themselves evolved by a series of gene duplications independent of the gene duplications that gave rise to eukaryotic paralogs.