Total Force Fitness: Making Holistic, Integrated Whole-Person Research a DoD Priority.

Total Force Fitness (TFF) was conceived as a holistic framework for building and sustaining Human Performance Optimization for Warfighters and their families. As such, TFF research must also be holistic in nature. During the research breakout, group barriers and challenges to TFF research were discussed, and critical research focus areas were prioritized. The top approaches discussed were (1) using big data to identify best practices and health trajectories; (2) applying community-based participatory research principles to military units; (3) focusing on "Whole-Person," integrative research (physical, behavioral, spiritual, and biological) across the Department of Defense; and, finally, (4) prioritizing key opportunities to advance TFF across the active duty and Reserve/Guard enterprises and their families. The research group noted that coordinated action would be needed to move the prioritized agenda forward. Finally, translating research into action is essential because TFF is a way of honoring our service members as whole persons with careers, goals, and families.

The Effect of Preoperative Behavioral Intervention on Pain, Anxiety, Opioid Use, and Function in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Study.

OBJECTIVE: To evaluate the efficacy of preoperative cognitive-behavioral psychoeducation (CBE) for improved pain, anxiety, opioid use, and postoperative function in total knee arthroplasty (TKA) patients. METHODS: A randomized controlled trial was conducted among 36 military health system beneficiaries attending preoperative education for TKA. The standard of care (SOC) group (n = 18) received information on home safety, rehabilitation, postoperative precautions, and pain management. In addition, the occupational therapy led CBE group (n = 16) received information on principles of holistic wellness (healing process, effects of stress on healing, heart-rate control through diaphragmatic breathing, anti-inflammatory nutrition, goal setting, and mental imagery). Outcomes of interest: knee active range of motion, pain (Defense and Veterans Pain Rating Scale), opioid medication use, heart-rate coherence (emwave2), anxiety (Generalized Anxiety Disorder Scale), and function (Knee Outcome Survey Activities of Daily Living [KOS-ADL], modified Functional Independence Measure, and Global Rate of Change). RESULTS: The CBE group demonstrated significantly greater decline in pain overall, with activity, and during sleep in relation to the SOC group when comparing visit 1 to visit 5. Opioid medication use was significantly lower for CBE versus SOC. Postoperative General Anxiety Disorder-7 scores decreased significantly among CBE participants with similar increase in high heart rate coherence. Function significantly improved postoperatively based on KOS-ADL and Global Rate of Change scores. Twice as many CBE participants had same-day discharge compared to SOC participants and most CBE participants continued with healthy lifestyle recommendations at the 3-month follow-up. CONCLUSION: A cognitive-behavioral approach to preoperative education may improve postoperative pain, anxiety, and function while decreasing opioid use among TKA patients. Findings from this pilot study support further research to examine similar interventions among distinct surgical populations and encourage further evaluation on the effects of CBE to enhance health and healthcare delivery.

Molecular mechanisms associated with microbial biostimulant-mediated growth enhancement, priming and drought stress tolerance in maize plants.

Microbial-based biostimulants are emerging as effective strategies to improve agricultural productivity; however, the modes of action of such formulations are still largely unknown. Thus, herein we report elucidated metabolic reconfigurations in maize (Zea mays) leaves associated with growth promotion and drought stress tolerance induced by a microbial-based biostimulant, a Bacillus consortium. Morphophysiological measurements revealed that the biostimulant induced a significant increase in biomass and enzymatic regulators of oxidative stress. Furthermore, the targeted metabolomics approach revealed differential quantitative profiles in amino acid-, phytohormone-, flavonoid- and phenolic acid levels in plants treated with the biostimulant under well-watered, mild, and severe drought stress conditions. These metabolic alterations were complemented with gene expression and global DNA methylation profiles. Thus, the postulated framework, describing biostimulant-induced metabolic events in maize plants, provides actionable knowledge necessary for industries and farmers to confidently and innovatively explore, design and fully implement microbial-based formulations and strategies into agronomic practices for sustainable agriculture and food production.

Engineering a Pseudo-26-kDa Schistosoma Glutathione Transferase from bovis/haematobium for Structure, Kinetics, and Ligandin Studies.

Glutathione transferases (GSTs) are the main detoxification enzymes in schistosomes. These parasitic enzymes tend to be upregulated during drug treatment, with Schistosoma haematobium being one of the species that mainly affect humans. There is a lack of complete sequence information on the closely related bovis and haematobium 26-kDa GST isoforms in any database. Consequently, we engineered a pseudo-26-kDa S. bovis/haematobium GST (Sbh26GST) to understand structure-function relations and ligandin activity towards selected potential ligands. Sbh26GST was overexpressed in Escherichia coli as an MBP-fusion protein, purified to homogeneity and catalyzed 1-chloro-2,4-dinitrobenzene-glutathione (CDNB-GSH) conjugation activity, with a specific activity of 13 µmol/min/mg. This activity decreased by ~95% in the presence of bromosulfophthalein (BSP), which showed an IC50 of 27 µM. Additionally, enzyme kinetics revealed that BSP acts as a non-competitive inhibitor relative to GSH. Spectroscopic studies affirmed that Sbh26GST adopts the canonical GST structure, which is predominantly α-helical. Further extrinsic 8-anilino-1-naphthalenesulfonate (ANS) spectroscopy illustrated that BSP, praziquantel (PZQ), and artemisinin (ART) might preferentially bind at the dimer interface or in proximity to the hydrophobic substrate-binding site of the enzyme. The Sbh26GST-BSP interaction is both enthalpically and entropically driven, with a stoichiometry of one BSP molecule per Sbh26GST dimer. Enzyme stability appeared enhanced in the presence of BSP and GSH. Induced fit ligand docking affirmed the spectroscopic, thermodynamic, and molecular modelling results. In conclusion, BSP is a potent inhibitor of Sbh26GST and could potentially be rationalized as a treatment for schistosomiasis.

Plant Responses to Abiotic Stresses and Rhizobacterial Biostimulants: Metabolomics and Epigenetics Perspectives.

In response to abiotic stresses, plants mount comprehensive stress-specific responses which mediate signal transduction cascades, transcription of relevant responsive genes and the accumulation of numerous different stress-specific transcripts and metabolites, as well as coordinated stress-specific biochemical and physiological readjustments. These natural mechanisms employed by plants are however not always sufficient to ensure plant survival under abiotic stress conditions. Biostimulants such as plant growth-promoting rhizobacteria (PGPR) formulation are emerging as novel strategies for improving crop quality, yield and resilience against adverse environmental conditions. However, to successfully formulate these microbial-based biostimulants and design efficient application programs, the understanding of molecular and physiological mechanisms that govern biostimulant-plant interactions is imperatively required. Systems biology approaches, such as metabolomics, can unravel insights on the complex network of plant-PGPR interactions allowing for the identification of molecular targets responsible for improved growth and crop quality. Thus, this review highlights the current models on plant defence responses to abiotic stresses, from perception to the activation of cellular and molecular events. It further highlights the current knowledge on the application of microbial biostimulants and the use of epigenetics and metabolomics approaches to elucidate mechanisms of action of microbial biostimulants.

Vitamin D decreases silencer methylation to downregulate renin gene expression.

Renin, encoded by REN, is an essential enzyme in the renin-angiotensin aldosterone system (RAAS) which is responsible for the maintenance of blood pressure homeostasis. Transcriptional regulation of REN has been linked to enhancer-promoter crosstalk, cAMP response element-binding protein (CREB), the active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and a less well-characterized intronic silencer element. We hypothesized that in addition to these, differential DNA methylation is linked to REN expression and influenced by 1,25(OH)2D3. REN expressing cells (HEK293) were used to elucidate the effect of 1,25(OH)2D3 on REN methylation and expression as quantified by methylation-sensitive qPCR and RT-qPCR, respectively. In vitro 1,25(OH)2D3 supplementation (10 nM) induced significant hypomethylation of the REN silencer (P < 0.050), which was linked to a significant reduction in REN expression (P < 0.010) but had no effect on enhancer methylation. In addition, 1,25(OH)2D3 increased VDR (P < 0.05), as well as TET1 (P < 0.05) expression, suggesting an association between 1,25(OH)2D3 and DNA methylation. Thus, it appears that the silencer element, which is controlled by DNA methylation and influenced by 1,25(OH)2D3, plays an essential role in regulating REN expression.

Effect of Divalent Metal Ion on the Structure, Stability and Function of Klebsiella pneumoniae Nicotinate-Nucleotide Adenylyltransferase: Empirical and Computational Studies.

The continuous threat of drug-resistant Klebsiella pneumoniae justifies identifying novel targets and developing effective antibacterial agents. A potential target is nicotinate nucleotide adenylyltransferase (NNAT), an indispensable enzyme in the biosynthesis of the cell-dependent metabolite, NAD+. NNAT catalyses the adenylation of nicotinamide/nicotinate mononucleotide (NMN/NaMN), using ATP to form nicotinamide/nicotinate adenine dinucleotide (NAD+/NaAD). In addition, it employs divalent cations for co-substrate binding and catalysis and has a preference for different divalent cations. Here, the biophysical structure of NNAT from K. pneumoniae (KpNNAT) and the impact of divalent cations on its activity, conformational stability and substrate-binding are described using experimental and computational approaches. The experimental study was executed using an enzyme-coupled assay, far-UV circular dichroism, extrinsic fluorescence spectroscopy, and thermal shift assays, alongside homology modelling, molecular docking, and molecular dynamic simulation. The structure of KpNNAT revealed a predominately α-helical secondary structure content and a binding site that is partially hydrophobic. Its substrates ATP and NMN share the same binding pocket with similar affinity and exhibit an energetically favourable binding. KpNNAT showed maximum activity and minimal conformational changes with Mg2+ as a cofactor compared to Zn2+, Cu2+ and Ni2+. Overall, ATP binding affects KpNNAT dynamics, and the dynamics of ATP binding depend on the presence and type of divalent cation. The data obtained from this study would serve as a basis for further evaluation towards designing structure-based inhibitors with therapeutic potential.

Autophagy efficacy and vitamin D status: Population effects.

Toll-like receptor (TLR) 2/1 signalling is linked to autophagy through transcriptional actions of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-vitamin D receptor (VDR) complex. Population-specific effects have been reported for TLR2/1-VDR signalling. We hypothesized that population effects extend to autophagy and are influenced by vitamin D status. Serum 25(OH)D3 of healthy South Africans (Black individuals n = 10, White individuals n = 10) was quantified by LC-MS/MS. Primary monocytes-macrophages were supplemented in vitro with 1,25(OH)2D3 and stimulated with the lipoprotein Pam3CysSerLys4. TLR2, VDR, hCAP18, Beclin1, LC3-IIB, cytokines and CYP24A1 mRNA were quantified by flow cytometry and RT-qPCR, respectively. Black individuals showed significantly lower overall cumulative LC3-IIB (P < 0.010), but higher Beclin1, VDR, IL6 and TNFA (P < 0.050) than White individuals. 1,25(OH)2D3 enhanced autophagic flux in monocytes-macrophages from Black individuals upon TLR2/1 stimulation and strengthened autophagy in 25(OH)D3 deficient individuals (independent cohort, n = 20). These findings support population-directed vitamin D supplementation.

Brief Report: Higher Peripheral Monocyte Activation Markers Are Associated With Smaller Frontal and Temporal Cortical Volumes in Women With HIV.

BACKGROUND: Persistent inflammation is a life-long complication of HIV infection, even in virally suppressed individuals. Elevated plasma concentrations of soluble(s) CD14 and CD163 have been established as biomarkers of chronic inflammation, conferring higher risk for cognitive, neurovascular, and structural abnormalities. METHODS: Structural magnetic resonance imaging (frontal and temporal regions) as well as plasma inflammatory biomarkers of monocyte activation (sCD14 and sCD163), general inflammation (plasma C-reactive protein, interleukin[IL]-6), and gut microbial translocation (plasma intestinal fatty acid-binding protein) were available on 38 women (25 with HIV) from the Chicago Women's Interagency HIV Study site. Partial least-squares models adjusting for relevant covariates (eg, age, education, and race) were conducted to evaluate the relationship between inflammatory biomarkers and brain volume in the overall sample and among women with HIV (WWH). RESULTS: In the total sample, higher plasma sCD14 was associated with smaller volumes in multiple frontal and temporal lobe regions. In the WWH-only sample, sCD163 was associated with smaller volumes only in one region of the left frontal lobe. C-reactive protein, IL-6, and intestinal fatty acid-binding protein were not associated with brain volumes for either group of women. CONCLUSIONS: Of the inflammatory monocyte markers evaluated, sCD14 was associated with smaller frontal and temporal cortical volume in the overall and WWH-only samples, while plasma sCD163 was only associated with smaller left caudal middle frontal gyrus in the WWH-only group. Validating these monocyte proteins as neurological biomarkers of structural brain deficits in a larger sample is critical for understanding HIV-associated neurobiological complications.

Cdx-2 polymorphism in the vitamin D receptor gene (VDR) marks VDR expression in monocyte/macrophages through VDR promoter methylation.

Caudal-type homeobox protein 2 (CDX-2) is an intestine-specific transcription factor (TF), with a polymorphic binding site (Cdx-2, rs11568820, A/G) in the vitamin D receptor gene (VDR). The molecular mechanism underlying Cdx-2 association with conditions like osteoporosis, which depends on intestinal VDR expression and calcium absorption, is believed to be due to higher affinity of CDX-2 for the ancestral A allele compared to the G allele. However, it is unclear why the polymorphism is associated with diseases like tuberculosis, which is dependent on VDR expression in immune cells that do not express CDX-2. This study aimed to explain Cdx-2 variant association with immune-related conditions. We hypothesised that the effect of Cdx-2 polymorphism on VDR expression in monocytes/macrophages, devoid of the CDX-2 TF, is indirect and dependent on circulating 25(OH)D3 and VDR methylation. Primary monocyte/macrophages from healthy donors (n = 100) were activated though TLR2/1 elicitation. VDR mRNA and 25(OH)D3 were quantified by RT-qPCR and LC-MS/MS, respectively. Genotyping and methylation analysis were done by pyrosequencing. AA vs. AG/GG showed reduced levels of 25(OH)D3 (P < 0.010), higher VDR promoter methylation (P < 0.050) and lower VDR mRNA induction (P < 0.050). Analysis of covariance confirmed that the effect of Cdx-2 variants depends primarily on VDR methylation. Thus, VDR methylation may confound association studies linking VDR polymorphisms to disease.

Sport Psychology for the Soldier Athlete: A Paradigm Shift.

Background: Competitive athletes train body and mind in preparation for competition with mental fortitude often providing the "winning edge." Similarly, the current-day warfighter faces significant physical and psychological challenges and must be prepared to respond to life-threatening danger with mental and physical agility. Sport Psychology for the Soldier Athlete recognizes the soldier as an elite athlete and provides training required to perform at the highest caliber. Through this curriculum, mental skills coaching in goal setting, imagery, positive self-talk, and heart rate control is integrated into routine physical fitness training. These skills commonly used by professional and Olympic athletes for optimal performance provide soldiers with the ability to manage every day military stressors. Sport Psychology for the Soldier Athlete supports GEN Milley's top priority of readiness and decreases the cost of Army Physical Fitness Test (APFT) failures. Procedures: Soldiers from a large military treatment facility participated in a 6-wk sport psychology mental skills training program led by an Army occupational therapist. The training that was integrated into regularly scheduled physical training consisted of 10 min of physical readiness training, 10 min of mental skills coaching followed by push-up, sit-up, and running drills focusing on the mental skills learned. Semi-annual APFT scores following the sport psychology training were compared with the five previous semi-APFT scores for the same company using analysis of variance. Findings: Results comparing company APFT scores to the previous five semi-annual tests showed statistical significance of 0.001 with the intervention group achieving an average 13- to 14-point improvement. Post-training survey showed 91% of participants recognizing the benefit of these "life skills" in other Army tasks such as weapons qualification, combat medic tasks, and career planning. Soldiers acknowledged this curriculum as quality hands-on training with the suggestion for further development. Discussion: A proactive approach to incorporating mental skills training into the military culture, Sport Psychology for the Soldier Athlete, is in direct alignment with The Army Human Dimension Strategy of developing mental and physical proficiency. This paradigm shift is both timely and necessary for answering readiness and resilience needs of U.S troops and provides additional tools for attaining optimal physical and mental endurance.

Methylation of the Vitamin D Receptor (VDR) Gene, Together with Genetic Variation, Race, and Environment Influence the Signaling Efficacy of the Toll-Like Receptor 2/1-VDR Pathway.

BACKGROUND: The disparity in prevalence of infectious diseases across the globe is common knowledge. Vitamin D receptor (VDR)-mediated toll-like receptor (TLR) 2/1 signaling produces antimicrobial peptides, which is critical as a first line of defense in innate immunity. Numerous studies disclosed the independent role of genetic polymorphisms in this pathway, vitamin D status or season and more recently epigenetics, as factors contributing to infectious disease predisposition. Few studies address the interaction between environment, genetics, and epigenetics. Here, we hypothesized that VDR-mediated TLR2/1 signaling is influenced by a combination of environment, epigenetics and genetics, collectively influencing differential innate immunity. METHODS: Healthy Black and White South Africans (n = 100) donated blood, while ultraviolet index (UVI) was recorded for the duration of the study. LC-MS/MS supported 25(OH)D3 quantification. Monocyte/macrophage cultures, supplemented with/without 1,25(OH)2D3, were activated with the TLR2/1 elicitor, Pam3CSK4. VDR, cathelicidin antimicrobial peptide, hCAP-18, and 25-hydroxyvitamin D3-24-hydroxylase expression were quantified by RT-qPCR or flow cytometry. Pyrosequencing facilitated VDR methylation analysis and single-nucleotide polymorphism (SNP) genotyping in regions pinpointed through a bioinformatics workflow. RESULTS: Season interacted with race showing 25(OH)D3 deficiency in Blacks. UVI correlated with 25(OH)D3 and VDR methylation, likely influencing race differences in the latter. Regarding the TLR2/1 pathway, race differences in SNP genotype distribution were confirmed and functional analysis of VDR-mediated signaling showed interaction between race, season, and 25(OH)D3 status. Multivariate OPLS-DA mirrored several interactions between UVI, 25(OH)D3 status, DNA sequence, and methylation variants. Methylation of the third cytosine-phosphate-guanine dinucleotide (CpG) in the promoter CpG island (CGI) 1062, CGI 1062 CpG 3, significantly discriminated a 5.7-fold above average mean in VDR protein level upon TLR2/1 elicitation, the variation of which was further influenced by 25(OH)D3 status and the VDR SNP TaqI. CONCLUSION: Regulation of VDR-mediated TLR2/1 signaling is multifactorial, involving interaction between environment [UVI and consequent 25(OH)D3 status], epigenetics (VDR methylation at key regulatory sites), and genetics (TLR1, TIRAP, and VDR SNPs).

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress.

Laboratory stress tasks such as the Trier Social Stress Test (TSST) have provided a key piece to the puzzle for how psychosocial stress impacts the hypothalamic-pituitary-adrenal axis, other stress-responsive biomarkers, and ultimately wellbeing. These tasks are thought to work through biopsychosocial processes, specifically social evaluative threat and the uncontrollability heighten situational demands. The present study integrated an experimental modification to the design of the TSST to probe whether additional social evaluative threat, via negative verbal feedback about speech performance, can further alter stress reactivity in 63 men and women. This TSST study confirmed previous findings related to stress reactivity and stress recovery but extended this literature in several ways. First, we showed that additional social evaluative threat components, mid-task following the speech portion of the TSST, were still capable of enhancing the psychosocial stressor. Second, we considered stress-reactive hormones beyond cortisol to include dehydroepiandrosterone (DHEA) and testosterone, and found these hormones were also stress-responsive, and their release was coupled with one another. Third, we explored whether gain- and loss-framing incentive instructions, meant to influence performance motivation by enhancing the personal relevance of task performance, impacted hormonal reactivity. Results showed that each hormone was stress reactive and further had different responses to the modified TSST compared to the original TSST. Beyond the utility of showing how the TSST can be modified with heightened social evaluative threat and incentive-framing instructions, this study informs about how these three stress-responsive hormones have differential responses to the demands of a challenge and a stressor.

Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth.

The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging.

Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV.

HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (perceived stress scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p < 0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher vs. lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p < 0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p = 0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory.

Prefrontal cortical volume loss is associated with stress-related deficits in verbal learning and memory in HIV-infected women.

Deficits in verbal learning and memory are a prominent feature of neurocognitive function in HIV-infected women, and are associated with high levels of perceived stress. To understand the neurobiological factors contributing to this stress-related memory impairment, we examined the association between stress, verbal memory, and brain volumes in HIV-infected women. Participants included 38 HIV-infected women (Mean age=43.9years) from the Chicago Consortium of the Women's Interagency HIV Study (WIHS). Participants underwent structural magnetic resonance imaging (MRI) and completed standardized measures of verbal learning and memory and stress (Perceived Stress Scale-10; PSS-10). Brain volumes were evaluated in a priori regions of interest, including the medial temporal lobe (MTL) and prefrontal cortex (PFC). Compared to HIV-infected women with lower stress (PSS-10 scores in lower two tertiles), HIV-infected women with higher stress (scores in the top tertile), performed worse on measures of verbal learning and memory and showed smaller volumes bilaterally in the parahippocampal gyrus, superior frontal gyrus, middle frontal gyrus, and inferior frontal gyrus (p's<0.05). Reduced volumes in the inferior frontal gyrus, middle frontal gyrus, and superior frontal gyrus (all right hemisphere) were negatively associated with verbal learning and memory performance. Prefrontal cortical atrophy is associated with stress-related deficits in verbal learning and memory in HIV-infected women. The time course of these volume losses in relation to memory deficits has yet to be elucidated, but the magnitude of the volumetric differences between women with higher versus lower stress suggests a prolonged vulnerability due to chronic stress and/or early life trauma.

Vitamin D Status in South Africa and Tuberculosis.

According to the World Health Organisation South Africa has the third highest tuberculosis (TB) incidence in the world, with an estimated 60 % incident cases having both TB and HIV. The South African National Tuberculosis Association (SANTA) recognized the importance of nutrition in the prevention and management of TB by including feeding schemes in community outreach programs. Vitamin D enhances innate immunity against mycobacterial infection through the antimicrobial peptide, cathelicidin. We reviewed studies on vitamin D status, its link with TB, and potential use in therapy in multiethnic South Africa with sunlight as primary source of vitamin D. Ethnicity, season, disease state, latitude, and urbanization are critical factors to be considered in vitamin D supplementation for prevention and treatment of TB.

Multiplanar wrist joint proprioception: The effect of anesthetic blockade of the posterior interosseous nerve or skin envelope surrounding the joint.

STUDY DESIGN: Randomized clinical trial. PURPOSE: Contribution of the posterior interosseous nerve (PIN) and surrounding skin envelope to wrist proprioception is a topic of debate and the primary focus of this research. METHODS: We performed a double-blinded, placebo control study in which subjects underwent baseline multiplanar testing of wrist proprioception. They were randomized to receive either anesthetic blockade of the PIN within the fourth dorsal compartment, or circumferential topical anesthetic blockade of skin surrounding the wrist. Corresponding opposite wrists underwent placebo intervention with saline injection or inert ultrasound gel. Subjects repeated proprioceptive testing. RESULTS: Eighty subjects, 45 male and 35 female, mean age 33 years (range, 19-64 years), completed testing. The percentage of measurements falling outside a ±18° range did not differ between pre-treatment and post-treatment PIN blockade or for circumferential skin anesthesia. CONCLUSIONS: Wrist proprioception appears to be a multifactorial phenomenon. Surgeons may sacrifice the PIN without concern for effect on joint proprioception. LEVEL OF EVIDENCE: Level I.

Experience, cortisol reactivity, and the coordination of emotional responses to skydiving.

Physiological habituation to laboratory stressors has previously been demonstrated, although the literature remains equivocal. Previous studies have found skydiving to be a salient naturalistic stressor that elicits a robust subjective and physiological stress response. However, it is uncertain whether (or how) stress reactivity habituates to this stressor given that skydiving remains a risky, life-threatening challenge with every jump despite experience. While multiple components of the stress response have been documented, it is unclear whether an individual's subjective emotions are related to their physiological responses. Documenting coordinated responsivity would lend insight into shared underlying mechanisms for the nature of habituation of both subjective (emotion) and objective (cortisol) stress responses. Therefore, we examined subjective emotion and cortisol responses in first-time compared to experienced skydivers in a predominantly male sample (total n = 44; males = 32, females = 12). Hierarchical linear modeling (HLM) revealed that experienced skydivers showed less reactivity and faster recovery compared to first-time skydivers. Subjective emotions were coordinated with physiological responses primarily within first-time skydivers. Pre-jump anxiety predicted cortisol reactivity within first-time, but not experienced, skydivers. Higher post-jump happiness predicted faster cortisol recovery after jumping although this effect overlapped somewhat with the effect of experience. Results suggest that experience may modulate the coordination of emotional response with cortisol reactivity to skydiving. Prior experience does not appear to extinguish the stress response but rather alters the individual's engagement of the HPA axis.

Genetic predictor of working memory and prefrontal function in women with HIV.

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.