Olfactory and cognitive decrements in 1991 Gulf War veterans with gulf war illness/chronic multisymptom illness.

BACKGROUND: Gulf War illness (GWI)/Chronic Multisymptom Illness (CMI) is a disorder related to military service in the 1991 Gulf War (GW). Prominent symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. Although anosmia is not a typical GWI/CMI symptom, anecdotally some GW veterans have reported losing their sense smell shortly after the war. Because olfactory deficit is a prodromal symptom of neurodegenerative diseases like Parkinson's and Alzheimer's disease, and because we previously reported suggestive evidence that deployed GW veterans may be at increased risk for Mild Cognitive Impairment (MCI) and dementia, the current study examined the relationship between olfactory and cognitive function in deployed GW veterans. METHODS: Eighty deployed GW veterans (mean age: 59.9 ±7.0; 4 female) were tested remotely with the University of Pennsylvania Smell Identification Test (UPSIT) and the Montreal Cognitive Assessment (MoCA). Veterans also completed self-report questionnaires about their health and deployment-related exposures and experiences. UPSIT and MoCA data from healthy control (HC) participants from the Parkinson's Progression Markers Initiative (PPMI) study were downloaded for comparison. RESULTS: GW veterans had a mean UPSIT score of 27.8 ± 6.3 (range 9-37) and a mean MoCA score of 25.3 ± 2.8 (range 19-30). According to age- and sex-specific normative data, 31% of GW veterans (vs. 8% PPMI HCs) had UPSIT scores below the 10th percentile. Nearly half (45%) of GW veterans (vs. 8% PPMI HCs) had MoCA scores below the cut-off for identifying MCI. Among GW veterans, but not PPMI HCs, there was a positive correlation between UPSIT and MoCA scores (Spearman's ρ = 0.39, p < 0.001). There were no significant differences in UPSIT or MoCA scores between GW veterans with and without history of COVID or between those with and without Kansas GWI exclusionary conditions. CONCLUSIONS: We found evidence of olfactory and cognitive deficits and a significant correlation between UPSIT and MoCA scores in a cohort of 80 deployed GW veterans, 99% of whom had CMI. Because impaired olfactory function has been associated with increased risk for MCI and dementia, it may be prudent to screen aging, deployed GW veterans with smell identification tests so that hypo- and anosmic veterans can be followed longitudinally and offered targeted neuroprotective therapies as they become available.

Rare, Atypical Mycobacterium Infection of the Hand in Immunocompetent Individuals.

We present two cases of immunocompetent individuals diagnosed with nontuberculous infections of the hand caused by organisms rarely seen in the clinical setting: Mycobacterium heckeshornense and Mycobacterium chelonae. In the first case, a 50-year-old male presented with tenosynovitis of left long finger. He was subsequently found to have a Mycobacterium heckeshornense infection that was resolved with multiple surgeries and a long-term regimen of several antibiotics. The second case was a 29-year-old female with a history of a trivial hand injury infected with Mycobacterium chelonae. She was successfully treated with surgical debridement and antibiotics over the course of eight months. It is important to recognize the increasing prevalence of these two species of bacteria as human pathogens that can result in infections of the extremities even in immunocompetent individuals. (Journal of Surgical Orthopaedic Advances 32(1):055-058, 2023).

Probiotics for paediatric functional abdominal pain disorders: A rapid review.

BACKGROUND: Functional abdominal pain disorders (FAPD) are prevalent in the paediatric population, however, there is currently no consensus regarding best practices for treatment. The use of probiotics is becoming popular to treat FAPD. The goal of this rapid review is to synthesize the best evidence on the use of probiotics in children with FAPD. METHODS: Searches were conducted on five main databases. Randomized controlled trials (RCTs) of probiotic use in children (0 to 18 years) with FAPD were searched. Populations of interest were patients with functional abdominal pain (FAP), irritable bowel syndrome (IBS), and functional dyspepsia (FD), recruited based on Rome criteria. Outcomes of interest were changes in abdominal pain severity, frequency, and duration. FINDINGS: Eleven RCTs with 829 participants with the diagnosis of FAP (n=400), IBS (n=329), FD (n=45), and mixed population (n=55) were included. Of six studies of children with FAP, two (n=103) used Lactobacillus rhamnosus GG (LGG) and reported no significant effects on pain, and four (n=281) used Lactobacillus (L) reuteri DSM 17938, of which three (n=229) reported significant positive effects on either severity or frequency of pain. Of six trials of children with IBS, four (n=219) used LGG, of which three (n=168) reported a positive effect. One (n=48) used bifidobacteria and one used VSL #3 (n=59), both demonstrating positive effects with probiotics. Two studies of FD reported no benefit. No adverse events were attributed to probiotics. CONCLUSIONS: There is preliminary evidence for use of probiotics, particularly LGG, in reducing abdominal pain in children with IBS. There are inconsistent positive effects of other probiotics, including L. reuteri DSM 17938, in reducing pain in patients with FAP, IBS, or FD. More RCTs with rigorous methodology using single or combination probiotics are warranted.

Association among anterior cingulate cortex volume, psychophysiological response, and PTSD diagnosis in a Veteran sample.

Posttraumatic stress disorder (PTSD) is associated with fear response system dysregulation. Research has shown that the anterior cingulate cortex (ACC) may modulate the fear response and that individuals with PTSD have abnormalities in ACC structure and functioning. Our objective was to assess whether ACC volume moderates the relationship between PTSD and fear-potentiated psychophysiological response in a sample of Gulf War Veterans. 142 Veteran participants who were associated with a larger study associated with Gulf War Illness were exposed to no threat, ambiguous threat, and high threat conditions in a fear conditioned startle response paradigm and also provided MRI imaging data. PTSD was assessed using the Clinician Administered PTSD Scale (CAPS). Decreased caudal ACC volume predicted greater psychophysiological responses with a slower habituation of psychophysiological magnitudes across trials (p < 0.001). PTSD diagnosis interacted significantly with both caudal and rostral ACC volumes on psychophysiological response magnitudes, where participants with PTSD and smaller rostral and caudal ACC volumes had greater psychophysiological magnitudes across trials (p < 0.05 and p < 0.001, respectively) and threat conditions (p < 0.05 and p < 0.005). Our results suggest that ACC volume may moderate both threat sensitivity and threat response via impaired habituation in individuals who have been exposed to traumatic events. More research is needed to assess whether ACC size and these associated response patterns are due to neurological processes resulting from trauma exposure or if they are indicative of a premorbid risk for PTSD subsequent to trauma exposure.

The role of carotid intima-media thickness in predicting longitudinal cognitive function in an older adult cohort.

BACKGROUND AND PURPOSE: Carotid atherosclerosis is a risk factor for cerebrovascular disease in older adults. Although age-related cognitive decline has been associated with cerebrovascular disease, not much is known about the consequences of carotid atherosclerosis on longitudinal cognitive function. This study examines the longitudinal relationship between atherosclerosis and cognition in a sample of non-demented older subjects using baseline measurements of carotid intima media thickness (CIMT) and annual cognitive measures of executive function (EXEC) and verbal memory (MEM). METHODS: Baseline measurements included CIMT derived from B-mode carotid artery ultrasound, structural T1-weighted images of white matter hypointensities (WMH), white matter lesions (WML), and cerebral infarct. Hypertension, low-density lipoprotein (LDL), diabetes, and waist to hip ratios (WHR) were included as covariates in our models to control for cerebrovascular risks and central adiposity. Annual composite scores of EXEC and MEM functions were derived from item response theory. Linear mixed models were used to model longitudinal cognitive change. RESULTS: A significant inverse relationship was found between baseline CIMT and annual EXEC score, but not annual MEM score. Subjects included in the highest 4th quartile of CIMT showed a rate of annual decline in EXEC score that was significant relative to subjects in lower quartile groups (p<0.01). The relationship between the 4th quartile of CIMT and annual EXEC score remained significant after independently adjusting for imaging measures of white matter injury and cerebral infarct. CONCLUSIONS: Older adult subjects with the highest index of CIMT showed an annual decline in EXEC scores that was significant relative to subjects with lower quartile measurements of CIMT, independent of our measures of white matter injury and cerebral infarct. Our findings suggest that elevated measures of CIMT may mark an atherosclerotic state, resulting in a decline in executive function and not memory in non-demented older adults.

Are hippocampal size differences in posttraumatic stress disorder mediated by sleep pathology?

Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume.

Current Health Status of Gulf War Deployed and Gulf War Era Veterans Who Use Veterans Affairs Health Care.

Background: Although some recent studies have examined the health of female Gulf War (GW) deployed and non-deployed GW era veterans, these all relied on self-report, which can be inaccurate and subject to recall bias. This study investigated the current health of GW deployed and non-deployed GW era female and male veterans using Veterans Health Administration (VHA) electronic health records (EHR). Methods: We performed a cohort study of deployed GW and non-deployed GW era veterans, identified from a list from the Defense Manpower Data Center (DMDC). We used the VA-Frailty Index (VA-FI), calculated with VHA administrative claims and EHR, as a proxy measure of current health. Results: We identified 402,869 veterans (351,496 GW deployed; 51,3373 non-deployed GW era; 38,555 female) in VHA databases. Deployed female veterans had the highest VA-FI (i.e., were frailest) despite being younger than deployed and non-deployed male veterans and non-deployed female veterans. Compared with deployed male veterans, deployed females were more likely to be pre-frail, mildly, and moderately frail. Health differences between deployed and non-deployed female veterans were more prominent among older (60+ years) than younger (<60 years) veterans. Conclusions: Mirroring reports from recent, smaller survey studies of users and non-users of VA health care, findings from this cohort study indicate that deployed female GW veterans who use VA health care are frailer and have more health deficits than non-deployed female GW era and deployed male GW veterans. Because deployed female GW veterans appear to have additional health care needs, this may warrant increased outreach from women's clinics at VA hospitals.

Biomechanical Comparison of Ulnar Collateral Ligament Reconstruction Between Palmaris Longus Autograft and Knee Medial Collateral Ligament Allograft.

Background: Medial ulnar collateral ligament (mUCL) injury can cause significant pain and alter throwing mechanics. Common autograft options for mUCL reconstruction (UCLR) include the palmaris longus (PL) and hamstring tendons. Allograft use may reduce donor site morbidity and decrease function related to PL autografts. Purpose: To compare varus stability and load to failure between a novel allograft for UCLR-knee medial collateral ligament (kMCL)-and a PL autograft in human donor elbow specimens. Study Design: Controlled laboratory study. Methods: A total of 24 fresh-frozen human elbows were dissected to expose the mUCL. Medial elbow stability was tested with the mUCL intact (native), deficient, and reconstructed utilizing the humeral single-docking technique with either a (1) kMCL allograft (n = 12) or (2) a PL autograft (n = 12). A 3-N·m valgus torque was applied to the elbow, and valgus rotation of the ulna was recorded via motion tracking cameras. The elbow was cycled through a full range of motion 5 times. After kinematic testing, specimens were loaded to failure at 70° of elbow flexion, and failure modes were recorded. Results: The mUCL-deficient elbows demonstrated significantly greater valgus rotation compared with the intact and reconstructed elbows at every flexion angle tested (10°-120°) (P <.001). Both kMCL- and PL-reconstructed elbows exhibited significantly higher mean valgus rotation compared with the intact state between 10° and 40° of flexion (P < .01). There were no significant differences in valgus rotation at any flexion angle between the kMCL and PL graft groups. When loaded to failure, elbows reconstructed with both kMCL and PL grafts failed at similar torque values (18.6 ± 4 and 18.1 ± 3.4 N·m, respectively; P = .765). Conclusion: Fresh-frozen and aseptically processed kMCL allografts demonstrated similar kinematic and failure properties to PL tendon autografts in UCL-reconstructed elbows, although neither graft fully restored kinematics between 10° and 40°. Clinical Relevance: Prepared kMCL ligament allografts may provide a viable graft material when reconstructing elbow ligaments while avoiding the potential complications related to PL autografts- including donor site morbidity.

Livestream, group movement program for people living with cognitive impairment and care partners: A randomized clinical trial.

INTRODUCTION: There are few widely-available, evidence-based options to support quality of life (QOL) for people living with Alzheimer's disease and related dementias. METHODS: We performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind-body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self-reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well-being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self-efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check-in surveys and collected qualitative data through evaluation surveys. Intention-to-treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs). RESULTS: Ninety-seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non-Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non-Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self-reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, p = 0.048) and CPs self-reported improved ability to manage stress (ES = 0.484, p = 0.021). Improvements in participant self-reported QOL were mediated by improvements in their self-reported well-being and CP-reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, p = 0.006; stress management ES = 0.742, p = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study-related serious adverse events. DISCUSSION: Online programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress. TRIAL REGISTRATION: ClinicalTrials.gov NCT04621448. Highlights: The approval of new medications that slow cognitive decline in people living with Alzheimer's disease and related disorders (ADRD) has raised hope and excitement. However, these medications do not appear to impact quality of life, which is often considered by patients and care partners to be the most important outcome.In this randomized clinical trial, we found that an evidence-based, online, livestream, mind-body, group movement program significantly and meaningfully improves self-rated quality of life in people with ADRD and helps care partners manage stress. Mediation analyses revealed that the key drivers of improvements in participants' quality of life were improvements in their feelings of well-being and care partners' ability to manage stress. Exploratory analyses also suggested a 30% reduction in falls.These results are important because they suggest that an online program, which is available now and can be performed by people from the comfort of home or other location of choice, could be recommended as a complement or alternative to new therapies to help maximize quality of life for people living with ADRD and their care partners.

Characterizing 1991 Gulf War women veterans from the Boston Biorepository and Integrative Network for Gulf War Illness: demographics, exposures, neuroimaging and cognitive outcomes.

Objective: Gulf War Illness (GWI) is a debilitating multisymptom condition that affects nearly a third of 1990-91 Gulf War (GW) veterans. Symptoms include pain, fatigue, gastrointestinal issues, and cognitive decrements. Our work has shown that GWI rates and potential causes for symptoms vary between men and women veterans. Studies have documented neuropsychological and neuroimaging findings mostly in men or combined sex datasets. Data are lacking for women veterans due to lack of power and repositories of women veteran samples. Methods: We characterized GW women veterans in terms of demographics, exposures, neuropsychological and neuroimaging outcomes from the newly collated Boston, Biorepository and Integrative Network (BBRAIN) for GWI. Results: BBRAIN women veterans are highly educated with an average age of 54 years. 81% met GWI criteria, 25% met criteria for current PTSD, 78% were white, and 81% served in the Army. Exposure to combined acetylcholinesterase inhibitors (AChEi) including skin pesticides, fogs/sprays and/or pyridostigmine bromide (PB) anti-nerve gas pill exposure resulted in slower processing speed on attentional tasks and a trend for executive impairment compared with non-exposed women. Brain imaging outcomes showed lower gray matter volumes and smaller caudate in exposed women. Conclusions: Although subtle and limited findings were present in this group of women veterans, it suggests that continued follow-up of GW women veterans is warranted. Future research should continue to evaluate differences between men and women in GW veteran samples. The BBRAIN women sub-repository is recruiting and these data are available to the research community for studies of women veterans.

Cellular context-dependent effects of H2ax and p53 deletion on the development of thymic lymphoma.

H2AX and Artemis each cooperate with p53 to suppress lymphoma. Germline H2ax(-/-)p53(-/-) mice die of T-cell receptor-ß(-) (TCR-ß(-)) thymic lymphomas with translocations and other lesions characteristic of human T-cell acute lymphoblastic leukemia. Here, we demonstrate that mice with inactivation of H2ax and p53 in thymocytes die at later ages to TCR-ß(-) or TCR-ß(+) thymic lymphomas containing a similar pattern of translocations as H2ax(-/-)p53(-/-) tumors. Germline Artemis(-/-) p53(-/-) mice die of lymphomas with antigen receptor locus translocations, whereas Artemis(-/-)H2ax(-/-)p53(-/-) mice die at earlier ages from multiple malignancies. We show here that Artemis(-/-) mice with p53 deletion in thymocytes die of TCR-ß(-) tumors containing Tcrα/δ translocations, other clonal translocations, or aneuploidy, as well as Notch1 mutations. Strikingly, Artemis(-/-) mice with H2ax and p53 deletion in thymocytes exhibited a lower rate of mortality from TCR-ß(-) tumors, which harbored significantly elevated levels of genomic instability. Our data reveal that the cellular origin of H2ax and p53 loss impacts the rate of mortality from and developmental stage of thymic lymphomas, and suggest that conditional deletion of tumor suppressor genes may provide more physiologic models for human lymphoid malignancies than germline inactivation.

Examining the current health of Gulf War veterans with the veterans affairs frailty index.

Introduction: Gulf War Illness (GWI) is a chronic, multisymptom (e.g., fatigue, muscle/joint pain, memory and concentration difficulties) condition estimated to affect 25-32% of Gulf War (GW) veterans. Longitudinal studies suggest that few veterans with GWI have recovered over time and that deployed GW veterans may be at increased risks for age-related conditions. Methods: We performed a retrospective cohort study to examine the current health status of 703 GW veterans who participated in research studies at the San Francisco VA Health Care System (SFVAHCS) between 2002 and 2018. We used the Veterans Affairs Frailty Index (VA-FI) as a proxy measure of current health and compared the VA-FIs of GW veterans to a group of randomly selected age- and sex-matched, non-GW veterans. We also examined GW veterans' VA-FIs as a function of different GWI case definitions and in relationship to deployment-related experiences and exposures. Results: Compared to matched, non-GW veterans, GW veterans had lower VA-FIs (0.10 ± 0.10 vs. 0.12 ± 0.11, p < 0.01). However, the subset of GW veterans who met criteria for severe Chronic Multisymptom Illness (CMI) at the time of the SFVAHCS studies had the highest VA-FI (0.13 ± 0.10, p < 0.001). GW veterans who had Kansas GWI exclusionary conditions had higher VA-FI (0.12 ± 0.12, p < 0.05) than veterans who were Kansas GWI cases (0.08 ± 0.08) and controls (i.e., veterans with little or no symptoms, 0.04 ± 0.06) at the time of the SFVAHCS research studies. The VA-FI was positively correlated with several GW deployment-related exposures, including the frequency of wearing flea collars. Discussion: Although GW veterans, as a group, were less frail than non-GW veterans, the subset of GW veterans who met criteria for severe CDC CMI and/or who had Kansas GWI exclusionary conditions at the time of the SFVAHCS research studies were frailest at index date. This suggests that many ongoing studies of GWI that use the Kansas GWI criteria may not be capturing the group of GW veterans who are most at risk for adverse chronic health outcomes.

The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study.

Introduction: Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding. Methods: We used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs). Results: We replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes. Discussion: Because MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration's recent approval of and the VA's decision to cover the cost for anti-amyloid ß (Aß) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aß in their brains.

Associations among vascular risk factors, carotid atherosclerosis, and cortical volume and thickness in older adults.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate whether the Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness are associated with cortical volume and thickness. METHODS: Consecutive subjects participating in a prospective cohort study of aging and mild cognitive impairment enriched for vascular risk factors for atherosclerosis underwent structural MRI scans at 3-T and 4-T MRI at 3 sites. Freesurfer (Version 5.1) was used to obtain regional measures of neocortical volumes (mm3) and thickness (mm). Multiple linear regression was used to determine the association of Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness with cortical volume and thickness. RESULTS: One hundred fifty-two subjects (82 men) were aged 78 (±7) years, 94 had a clinical dementia rating of 0, 58 had a clinical dementia rating of 0.5, and the mean Mini-Mental State Examination was 28±2. Framingham Cardiovascular Risk Profile score was inversely associated with total gray matter volume and parietal and temporal gray matter volume (adjusted P<0.04). Framingham Cardiovascular Risk Profile was inversely associated with parietal and total cerebral gray matter thickness (adjusted P<0.03). Carotid artery intima-media thickness was inversely associated with thickness of parietal gray matter only (adjusted P=0.04). Including history of myocardial infarction or stroke and radiological evidence of brain infarction, or apolipoprotein E genotype did not alter relationships with Framingham Cardiovascular Risk Profile or carotid artery intima-media thickness. CONCLUSIONS: Increased cardiovascular risk was associated with reduced gray matter volume and thickness in regions also affected by Alzheimer disease independent of infarcts and apolipoprotein E genotype. These results suggest a "double hit" toward developing dementia when someone with incipient Alzheimer disease also has high cardiovascular risk.

Patient Risk Factors Associated With Postoperative Complications After Common Hand Procedures.

BACKGROUND: Carpal tunnel syndrome (CTS), trigger finger (TF), and De Quervain tenosynovitis (DQ) are 3 common pathologies of the hand often treated with relatively simple surgical procedures. However, outcomes from these procedures can be compromised by postoperative complications. The aim of this study was to evaluate the association between diabetes, tobacco use, and obesity and the incidence of postoperative complications. METHODS: We reviewed 597 patients treated surgically for CTS, TF, or DQ from 2010 to 2015. We used bivariate and multivariate analyses to assess independent associations between diabetes, tobacco use, obesity, and surgical complications and compared the incidences with healthier patients without these comorbidities. We also looked at patients with overlapping diagnoses of these comorbidities. RESULTS: Bivariate analysis showed that patients with diabetes and smokers were more likely to have a surgical complication. Multivariate analysis showed diabetes and tobacco use as independent predictors of complications. The disease states or combinations placing patients at the highest risk of a postoperative complication were the diabetic-smoker-obese, diabetic-smoker, diabetic-obese, diabetic, and smoker-obese groups. The diabetic-smoker-obese patient population had a 42.02% predicted rate of postoperative complications. CONCLUSIONS: Diabetes and tobacco use are independent risk factors for complications after operative treatment of CTS, TF, and DQ. Obesity when coexisting with diabetes mellitus (DM) and/or tobacco use increased the risk of complications. When the 3 patient factors evaluated, DM, obesity, and tobacco use, were present, the rate of complications was 42.02%. Careful assessment and discussion should occur before proceeding with operative treatment for simple hand conditions in patients with the risk factors studied.

Assembled DJ beta complexes influence TCR beta chain selection and peripheral V beta repertoire.

TCRbeta chain repertoire of peripheral alphabeta T cells is generated through the stepwise assembly and subsequent selection of TCRbeta V region exons during thymocyte development. To evaluate the influence of a two-step recombination process on Vbeta rearrangement and selection, we generated mice with a preassembled Dbeta1Jbeta1.1 complex on the Jbeta1(omega) allele, an endogenous TCRbeta allele that lacks the Dbeta2-Jbeta2 cluster, creating the Jbeta1(DJbeta) allele. As compared with Jbeta1(omega/omega) mice, both Jbeta1(DJbeta/omega) and Jbeta1(DJbeta/DJbeta) mice exhibited grossly normal thymocyte development and TCRbeta allelic exclusion. In addition, Vbeta rearrangements on Jbeta1(DJbeta) and Jbeta1(omega) alleles were similarly regulated by TCRbeta-mediated feedback regulation. However, in-frame VbetaDJbeta rearrangements were present at a higher level on the Jbeta1(DJbeta) alleles of Jbeta1(DJbeta/omega) alphabeta T cell hybridomas, as compared with on the Jbeta1(omega) alleles. This bias was most likely due to both an increased frequency of Vbeta-to-DJbeta rearrangements on Jbeta1(DJbeta) alleles and a preferential selection of cells with in-frame VbetaDJbeta exons assembled on Jbeta1(DJbeta) alleles during the development of Jbeta1(DJbeta/omega) alphabeta T cells. Consistent with the differential selection of in-frame VbetaDJbeta rearrangements on Jbeta1(DJbeta) alleles, the Vbeta repertoire of alphabeta T cells was significantly altered during alphabeta TCR selection in Jbeta1(DJbeta/omega) and Jbeta1(DJbeta/DJbeta) mice, as compared with in Jbeta1(omega/omega) mice. Our data indicate that the diversity of DJbeta complexes assembled during thymocyte development influences TCRbeta chain selection and peripheral Vbeta repertoire.

Preventing Loss of Independence through Exercise (PLIÉ): A Pilot Trial in Older Adults with Subjective Memory Decline and Mild Cognitive Impairment.

BACKGROUND: Preventing Loss of Independence through Exercise (PLIÉ) is a group movement program initially developed for people with mild-to-moderate dementia that integrates principles from several well-established traditions to specifically address the needs of people with cognitive impairment. OBJECTIVE: To investigate whether PLIÉ would benefit cognitive and behavioral outcomes and functional brain connectivity in older adults with milder forms of cognitive impairment. METHODS: Participants (≥55 y) with subjective memory decline (SMD) or mild cognitive impairment (MCI) were assessed with tests of cognitive and physical function, self-report questionnaires, and resting state functional magnetic resonance imaging (rs-fMRI) on a 3 Tesla scanner before and after participating in twice weekly PLIÉ classes for 12 weeks at the San Francisco Veterans Affairs Medical Center. RESULTS: Eighteen participants completed the pre-post intervention pilot trial. We observed significant improvements on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog; effect size 0.34, p = 0.002) and enhanced functional connections between the medial prefrontal cortex (mPFC) and other nodes of the default mode network (DMN) after PLIÉ. Improvements (i.e., lower scores) on ADAS-cog were significantly correlated with enhanced functional connectivity between the mPFC and left lateral parietal cortex (Spearman's ρ= -0.74, p = 0.001) and between the mPFC and right hippocampus (Spearman's ρ= -0.83, p = 0.001). After completing PLIÉ, participants reported significant reductions in feelings of social isolation and improvements in well-being and interoceptive self-regulation. CONCLUSION: These preliminary findings of post-PLIÉ improvements in DMN functional connectivity, cognition, interoceptive self-regulation, well-being and reduced feelings of social isolation warrant larger randomized, controlled trials of PLIÉ in older adults with SMD and MCI.

Cognitive behavioral therapy for insomnia in veterans with gulf war illness: Results from a randomized controlled trial.

AIMS: To examine whether cognitive behavioral therapy for insomnia (CBT-I), delivered by telephone, improves sleep and non-sleep symptoms of Gulf War Illness (GWI). MAIN METHODS: Eighty-five Gulf War veterans (21 women, mean age: 54 years, range 46-72 years) who met the Kansas GWI case definition, the Centers for Disease Control and Prevention (CDC) case definition for Chronic Multisymptom Illness (CMI), and research diagnostic criteria for insomnia disorder were randomly assigned to CBT-I or monitor-only wait list control. Eight weekly sessions of individual CBT-I were administered via telephone by Ph.D. level psychologists to study participants. Outcome measures included pre-, mid-, and post-treatment assessments of GWI and insomnia symptoms, subjective sleep quality, and continuous sleep monitoring with diary. Outcomes were re-assessed 6-months post-treatment in participants randomized to CBT-I. KEY FINDINGS: Compared to wait list, CBT-I produced significant improvements in overall GWI symptom severity, individual measures of fatigue, cognitive dysfunction, depression and anxiety, insomnia severity, subjective sleep quality, and sleep diary outcome measures. The beneficial effects of CBT-I on overall GWI symptom severity and most individual GWI symptom measures were maintained 6-months after treatment. SIGNIFICANCE: GWI symptoms have historically been difficult to treat. Because CBT-I, which is associated with low stigma and is increasingly readily available to veterans, improved both sleep and non-sleep symptoms of GWI, these results suggest that a comprehensive approach to the treatment of GWI should include behavioral sleep interventions.

Ventromedial and insular cortical volume moderates the relationship between BDNF Val66Met and threat sensitivity.

While the BDNF Val66Met polymorphism has been linked to various trauma and anxiety - related psychiatric disorders, limited focus has been on the neural structures that might modulate its relationship with objective measures of threat sensitivity. Therefore, we assessed whether there was an interaction of Val66Met polymorphism with brain area volumes previously associated with anxiety and PTSD, such as the ventromedial prefrontal cortex (vmPFC), insular cortex (IC), and dorsal and ventral anterior cingulate cortices (dACC and vACC), in predicting fear-potentiated psychophysiological response in a clinical sample of Veterans. 110 participants engaged in a fear-potentiated acoustic startle paradigm and provided genetic and imaging data. Fear conditions included no, ambiguous, and high threat conditions (shock). Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate (HR). PTSD status, trauma history, and demographics were also assessed. There was an interaction of Met allele carrier status with vmPFC, IC, dACC, and vACC volumes for predicting SCR (p < 0.001 for all regions). However, only vmPFC and IC significantly moderated the relationship between Val66Met and psychophysiological response (SCR). The Val66met polymorphism may increase susceptibility to PTSD and anxiety disorders via an interaction with reduced vmPFC and IC volume. Future research should examine whether these relationships might be associated with a differential course of illness longitudinally or response to treatments.

Regional gray matter oligodendrocyte- and myelin-related measures are associated with differential susceptibility to stress-induced behavior in rats and humans.

Individual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies demonstrate the surprising plasticity of oligodendrocytes and myelin with stress and experience, providing a potential mechanism by which trauma induces aberrant structural and functional changes in the adult brain. In this study, we utilized a translational approach to test the hypothesis that gray matter oligodendrocytes contribute to traumatic-stress-induced behavioral variation in both rats and humans. We exposed adult, male rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior, as well as oligodendrocyte and myelin basic protein (MBP) content in multiple brain areas. We found that oligodendrocyte cell density and MBP were correlated with behavioral outcomes in a region-specific manner. Specifically, stress-induced avoidance positively correlated with hippocampal dentate gyrus oligodendrocytes and MBP. Viral overexpression of the oligodendrogenic factor Olig1 in the dentate gyrus was sufficient to induce an anxiety-like behavioral phenotype. In contrast, contextual fear learning positively correlated with MBP in the amygdala and spatial-processing regions of the hippocampus. In a group of trauma-exposed US veterans, T1-/T2-weighted magnetic resonance imaging estimates of hippocampal and amygdala myelin associated with symptom profiles in a region-specific manner that mirrored the findings in rats. These results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and differential behavioral phenotypes following traumatic stress exposure. This study suggests a novel mechanism for brain plasticity that underlies individual variance in sensitivity to traumatic stress.