Peripheral inflammation and depressed mood independently predict neurocognitive worsening over 12 years.

Background: Neurocognitive (NC) impairment in people with HIV (PWH) is associated with important adverse outcomes, but no markers exist to predict long-term NC decline. We evaluated depressed mood and markers of persistent inflammation, oxidative stress and altered amyloid processing (all common in PWH) as predictors of NC worsening over 12 years. Methods: PWH were enrolled and followed longitudinally in the CNS HIV Antiretroviral Effects Research (CHARTER) study at six US sites. At entry we quantified biomarkers in blood of inflammation: (interleukin-6 [IL-6], C-reactive protein [CRP], monocyte chemoattractant protein type 1 [MCP-1], D-dimer, soluble sCD14 (sCD14), soluble tumor necrosis factor receptor - type II [sTNFR-II], neopterin, and soluble CD40 ligand [sCD40L], oxidative stress (protein carbonyls, 8-oxo-2'-deoxyguanosine [8-oxo-dG]) and altered amyloid processing [amyloid beta (Aß)-42, soluble amyloid precursor protein-α (sAPPα)] using commercial immunoassays. The Beck Depression Inventory-II (BDI-II) assessed depressed mood at entry. NC decline over 12 years was evaluated using the published and validated summary (global) regression-based change score (sRBCS). A factor analysis reduced dimensionality of the biomarkers. Univariable and multiple regression models tested the relationship between baseline predictors and the outcome of neurocognitive decline. Results: Participants were 191 PWH, 37 (19.4%) women, 46.6% African American, 43.5% non-Hispanic white, 8.83% Hispanic, 15.7% white, 1.6% other; at study entry mean (SD) age 43.6 (8.06) years, estimated duration of HIV infection (median, IQR) 9.82 [4.44, 14.5] years, nadir CD4 104/µL (19,205), current CD4 568/µL (356, 817), and 80.1% had plasma HIV RNA <50 c/mL. Participants were enrolled between 2003 and 2007; median (IQR) duration of follow-up 12.4 [9.69, 16.2] years. Three biomarker factors were identified: Factor (F)1 (IL-6, CRP), F2 (sTNFR-II, neopterin) and F3 (sCD40L, sAPPα). Participants with higher F1, reflecting worse systemic inflammation at baseline, and higher F3, had greater decline in global neurocognition (r â€‹= â€‹-0.168, p â€‹= â€‹0.0205 and r â€‹= â€‹-0.156, p â€‹= â€‹0.0309, respectively). Of the F1 components, higher CRP levels were associated with worse decline (r â€‹= â€‹-0.154, p â€‹= â€‹0.0332), while IL-6 did not (r â€‹= â€‹-0.109, p â€‹= â€‹0.135). NC change was not significantly related to F2, nor to demographics, nadir and current CD4, viral suppression or baseline NC comorbidity ratings. Individuals with worse depressed mood at entry also experienced more NC decline (r â€‹= â€‹-0.1734, p â€‹= â€‹0.0006). Together BDI-II (p â€‹= â€‹0.0290), F1 (p â€‹= â€‹0.0484) and F3 (p â€‹= â€‹0.0309) contributed independently to NC decline (p â€‹= â€‹0.0028); their interactions were not significant. Neither CRP nor IL-6 correlated significantly with depression. Conclusions: PWH with greater systemic inflammation and more depression at entry had greater NC decline over 12 years. Understanding the basis of this inflammatory state might be particularly important. These findings raise the possibility that targeted anti-inflammatory or antidepressant therapies may help prevent NC worsening in PWH with depression and inflammation.

A Place to Live and to Die: A Qualitative Exploration of the Social Practices and Rituals of Death in Residential Aged Care.

In many countries, an increasing proportion of deaths occur in residential aged care (RAC) (nursing homes) meaning that these have become both a place to live - a home- and a place to die. This paper reports on death practices and rituals in 49 RAC facilities in Aotearoa/New Zealand narrated in semi-structured interviews with staff. Themes coalesced around 'good death'. Dying alone was not seen as a good death and the demands of trying to prevent this caused tension for staff. Meeting family wishes, post death decision-making, after death practices and rituals, including communicating and remembrance of the death, were explored as part of good death. Overall, death rituals in RAC were limited. Balancing the needs of the living, the dying and the dead created tension. The rituals and practices facilities are currently enacting in death/post-death require attention, since more people will die in RAC with increasingly diverse needs.

Divergent roles for KLF4 and TFCP2L1 in naive ground state pluripotency and human primordial germ cell development.

During embryo development, human primordial germ cells (hPGCs) express a naive gene expression program with similarities to pre-implantation naive epiblast (EPI) cells and naive human embryonic stem cells (hESCs). Previous studies have shown that TFAP2C is required for establishing naive gene expression in these cell types, however the role of additional naive transcription factors in hPGC biology is not known. Here, we show that unlike TFAP2C, the naive transcription factors KLF4 and TFCP2L1 are not required for induction of hPGC-like cells (hPGCLCs) from hESCs, and they have no role in establishing and maintaining a naive-like gene expression program in hPGCLCs with extended time in culture. Taken together, our results suggest a model whereby the molecular mechanisms that drive naive gene expression in hPGCs/hPGCLCs are distinct from those in the naive EPI/hESCs.

Topical lotions utilized in outpatient rehabilitation clinics as a potential source of bacterial contamination.

Soft tissue mobilization and massage requiring lotions or creams are commonly used interventions in outpatient rehabilitation clinics. For at least 50 years hand creams used in healthcare settings have been found to be contaminated by bacteria. The purpose of this study was to determine the current state of bacterial contamination of lotions used in clinics and to determine the efficacy of lotion preservatives to kill bacteria. Unopened containers of lotions were studied, along with 81 lotion containers used in 22 outpatient clinics in southeast Tennessee and northwest Georgia. Three sites on each container were sampled using sterile swabs. At a microbiology lab, bacterial growth media was inoculated and incubated. Of the 81 containers sampled, 16 supported bacterial growth (19.8%). Container threads displayed the highest contamination compared with other container locations (p < 0.01). No bacteria were found in unopened lotion containers, although when challenged with live bacterial cultures lotion preservatives did not kill bacteria tested. Enrichment cultures using lotions studied here supported the growth of several bacterial species. These findings suggest the need for standardized protocols to help reduce potential healthcare-associated infections due to use of lotions. Improved efficacy of preservatives added to lotions should be a priority.

Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.

Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder.

Diagnosis of gestational diabetes: a 'teachable moment'.

AIMS: Research regarding the determinants of concordance with gestational diabetes mellitus (GDM) treatment is limited. Here, we test whether the psychosocial changes outlined in the teachable moments model, as proposed by McBride et al. (McBride CM, Emmons KM, Lipkus IM. Understanding the potential of teachable moments: the case of smoking cessation. Health Educ Res 2003; 18: 156-170) are associated with following GDM treatment recommendations. METHODS: Fifty-nine women completed a baseline questionnaire (1 week after GDM diagnosis) in which they reported risk perception, social support, emotional response, the importance of their maternal identity and self-efficacy. One month later, participants reported their concordance with instructions regarding glucose monitoring, diet and, if applicable, medication. We used regression analysis to test for associations between the psychosocial factors measured at baseline and concordance at 1-month follow-up. RESULTS: Those who perceived their risk as higher or felt supported by family or friends were more likely to report a high level of concordance with GDM treatment. Emotional response, identity salience and self-efficacy were not related to concordance. CONCLUSIONS: Future interventions designed to increase concordance could benefit from a focus on risk perception and social support, as these factors appear to be most strongly associated with following GDM treatment recommendations.

Dose-response between frequency of interruption of sedentary time and fasting glucose, the dawn phenomenon and night-time glucose in Type 2 diabetes.

AIM: To explore the dose-response between frequency of interruption of sedentary time and basal glucose (fasting glucose, the dawn phenomenon and night-time glucose) in Type 2 diabetes. METHODS: In a randomized three-treatment, two-period balanced incomplete block trial, 12 people with Type 2 diabetes (age, 60.0 ± 3.2 years; BMI, 30.2 ± 1.4 kg/m2 ) completed two of three conditions: sitting for 7 h interrupted every 60 min (Condition 1), 30 min (Condition 2), and 15 min (Condition 3) by 3-min light-intensity walking breaks. The activPAL3 and FreeStyle Libre were used to assess physical activity/sedentary behaviour and continuous glucose profile. Standardized meals were provided, and changes in basal glucose of the nights and early mornings before and after treatment conditions were calculated (mean ± SE). RESULTS: After treatment conditions, fasting glucose and duration of the dawn phenomenon were lower for Condition 3 (-1.0 ± 0.2 mmol/l, P < 0.02; -3.1 ± 1.3 h, P = 0.004) compared with Condition 1 (-0.1 ± 0.2 mmol/l; 1.9 ± 1.2 h). The magnitude of the dawn phenomenon was reduced in Condition 3 (-0.6 ± 0.4 mmol/l, P = 0.041) compared with Condition 2 (0.6 ± 0.3 mmol/l). Night-time glycaemic variability (coefficient of variation) was reduced in Condition 3 (-9.7 ± 3.9%) relative to Condition 2 (6.1 ± 4.8%, P < 0.03) and Condition 1 (2.5 ± 1.8%, P = 0.02). There was no change in night-time mean glucose. CONCLUSIONS: Frequent interruptions of prolonged sitting with 3 min of light-intensity walking breaks every 15 min improves fasting glucose, the dawn phenomenon and night-time glycaemic variability, and this might be a simple therapeutic intervention to improve glucose control. Clinicaltrials.gov Identifier: NCT02738996.

Diabetes, malignancy and age as predictors of Candida glabrata bloodstream infection: A re-evaluation of the risk factors.

OBJECTIVE: Echinocandins and azoles are widely used in the treatment of candidaemia. Guidelines of the Infectious Diseases Society of America recommend commencing treatment with an echinocandin in candidaemic patients with risk factors for Candida glabrata i.e. patients who are elderly, or who have diabetes or malignancy, or those with recent prescription of azoles. We attempted to validate whether age, diabetes and malignancy are associated with C. glabrata candidaemia. PATIENTS, MATERIALS AND METHODS: Information in relation to demographics, patient associated risk factors, and laboratory parameters were collected from the casenotes and the laboratory information system. We then analysed the distribution of the risk factors (age, diabetes, and malignancy) in candidaemic patients with C. glabrata and patients with species other than C. glabrata (excluding Candida krusei). RESULTS: Over a 42-month period (April 2011-September 2017), 124 patients had candidaemia. We analysed data for 119 patients of whom 33 (27.7%) had C. glabrata and the remaining 86 (72.2%) were infected with other species. Sixty-five patients were elderly (age≥65), 40 had some form of malignancy, 34 had diabetes, and 4 patients were prescribed azoles in the 30 days prior to candidaemia (many patients had multiple risk factors). Comparing patients with C. glabrata to patients infected with other species, we found no association with diabetes (39.3% vs. 24.4%, P=0.1), malignancy (36.3 vs. 32.5%, P=0.69), and age (54.5% vs. 54.6%, P=0.99). CONCLUSIONS: Diabetes, malignancy and age are not reliable predictors of candidaemia due to C. glabrata.

Virtually optimized insoles for offloading the diabetic foot: A randomized crossover study.

Integration of objective biomechanical measures of foot function into the design process for insoles has been shown to provide enhanced plantar tissue protection for individuals at-risk of plantar ulceration. The use of virtual simulations utilizing numerical modeling techniques offers a potential approach to further optimize these devices. In a patient population at-risk of foot ulceration, we aimed to compare the pressure offloading performance of insoles that were optimized via numerical simulation techniques against shape-based devices. Twenty participants with diabetes and at-risk feet were enrolled in this study. Three pairs of personalized insoles: one based on shape data and subsequently manufactured via direct milling; and two were based on a design derived from shape, pressure, and ultrasound data which underwent a finite element analysis-based virtual optimization procedure. For the latter set of insole designs, one pair was manufactured via direct milling, and a second pair was manufactured through 3D printing. The offloading performance of the insoles was analyzed for forefoot regions identified as having elevated plantar pressures. In 88% of the regions of interest, the use of virtually optimized insoles resulted in lower peak plantar pressures compared to the shape-based devices. Overall, the virtually optimized insoles significantly reduced peak pressures by a mean of 41.3kPa (p<0.001, 95% CI [31.1, 51.5]) for milled and 40.5kPa (p<0.001, 95% CI [26.4, 54.5]) for printed devices compared to shape-based insoles. The integration of virtual optimization into the insole design process resulted in improved offloading performance compared to standard, shape-based devices. CLINICAL TRIAL REGISTRATION: ISRCTN19805071, www.ISRCTN.org.

Methamphetamine, smoking, and gestational hypertension affect norepinephrine levels in umbilical cord tissues.

BACKGROUND: These studies were undertaken to determine methamphetamine (METH) and smoking effects on umbilical vascular dynamics and pregnancy outcomes. MATERIALS AND METHODS: Umbilical cords (54) were collected prospectively at birth, washed of blood, and stored at -80°C. Cords were thawed and lysates prepared, then catecholamine levels quantified with enzyme-linked immunosorbent assay (ELISA). RESULTS: Catecholamine levels in umbilical cords were not associated with maternal or gestational age, gravidity, parity, neonatal or placental weight. Neither smoking nor METH affected dopamine or epinephrine. However, smoking (two-fold) and METH (four-fold) decreased norepinephrine and together a 60-fold reduction occurred (p = 0.025). Cesarean section and hypertension were both associated with lower norepinephrine levels (p < 0.001) regardless of drug status. In normotensive pregnancies, smoking and METH significantly decreased norepinephrine levels (two-fold and 3.5-fold each, respectively) with a 40-fold decrease for METH/smoking together. DISCUSSION: Depletion of norephinephrine by METH and smoking likely contributes to pregnancy complications, including the higher incidence of respiratory distress and postpartum hemorrhage in cesarean section.

Observation of intrinsically bright terrestrial gamma ray flashes from the Mediterranean basin.

We present three terrestrial gamma ray flashes (TGFs) observed over the Mediterranean basin by the Reuven Ramaty High Energy Solar Spectroscope Imager (RHESSI) satellite. Since the occurrence of these events in the Mediterranean region is quite rare, the characterization of the events was optimized by combining different approaches in order to better define the cloud of origin. The TGFs on 7 November 2004 and 16 October 2006 came from clouds with cloud top higher than 10-12 km where often a strong penetration into the stratosphere is found. This kind of cloud is usually associated with heavy precipitation and intense lightning activity. Nevertheless, the analysis of the cloud type based on satellite retrievals shows that the TGF on 27 May 2004 was produced by an unusual shallow convection. This result appears to be supported by the model simulation of the particle distribution and phase in the upper troposphere. The TGF on 7 November 2004 is among the brightest ever measured by RHESSI. The analysis of the energy spectrum of this event is consistent with a production altitude ≤12 km, which is in the upper part of the cloud, as found by the meteorological analysis of the TGF-producing thunderstorm. This event must be unusually bright at the source in order to produce such a strong signal in RHESSI. We estimate that this TGF must contain ∼3 × 1018 initial photons with energy >1 MeV. This is 1 order of magnitude brighter than earlier estimations of an average RHESSI TGF.

Impact of socioeconomic status and gender on glycaemic control, cardiovascular risk factors and diabetes complications in type 1 and 2 diabetes: a population based analysis from a Scottish region.

AIMS: In this cross-sectional study, the aims were to investigate the association of the socioeconomic status and gender on the prevalence of type 1 and 2 diabetes, glycaemic control, cardiovascular risk factors plus the complications of diabetes in a population-based analysis in the county of Ayrshire and Arran, Scotland. METHODS: Quality Outcome Framework data was obtained from General Practices in Ayrshire and Arran, Scotland (n=15,351 patients). RESULTS: In type 1 diabetes, there was an increasing linear trend in HbA1c across deprivation levels (P<0.01). In type 1 diabetes, obesity in women (P<0.01) and increased non-fasting triglyceride levels in both men and women were associated with deprivation (P<0.05). In type 2 diabetes, there was a significant prevalence trend with deprivation for women (P<0.01) but not with glycaemic control (P=0.12). Smoking, ischaemic heart disease and neuropathy (P<0.01) were all associated with increasing deprivation with gender differences. In type 2 diabetes, reduced HDL cholesterol (P<0.01 both genders), and percentage of people on lipid lowering therapy (men P<0.05; women P<0.01) were associated with deprivation. Smoking, ischaemic heart disease, peripheral vascular disease and neuropathy plus foot ulcers (P<0.05) were all associated with increasing deprivation with gender differences. CONCLUSIONS: Socioeconomic status and gender are associated with changes in glycaemic control and cardiovascular risk factors plus complication development in both type 1 and 2 diabetes. The mechanisms are unclear but follow-up of these patients should allow greater understanding.

Gender differences and patterns of cardiovascular risk factors in Type 1 and Type 2 diabetes: a population-based analysis from a Scottish region.

AIM: To explore the gender differences, along with the relationships between BMI, glycaemic control, cardiovascular risk factors and the prevalence of diabetes complications, in a representative population-based group of people with Type 1 and Type 2 diabetes. METHODS: Data were obtained from general practices in Ayrshire and Arran, Scotland for 15 351 patients. RESULTS: In the cohort with Type 1 diabetes, after adjustment for age, men had a significantly lower BMI (P = 0.007) and significantly lower total cholesterol (P = 0.005), HDL-cholesterol (P = 2.5*10(-17)) and HbA1c levels (P = 0.003) than women. By contrast, men had higher blood pressure, both systolic (P = 0.034) and diastolic (P = 0.0003), and higher non-fasting triglyceride levels (P = 0.001). Men with Type 1 diabetes had a higher prevalence of neuropathy (P = 0.021). Among people with Type 2 diabetes, men had a significantly lower BMI (P = 4.26*10(-37)), and significantly lower total cholesterol (P = 2.96*10(-62)) and HDL-cholesterol levels (P = 8.25*10(-141)) but higher non-fasting triglyceride levels (P = 0.0002). In Type 2 diabetes, men had a higher prevalence of ischaemic heart disease (P = 1.66*10(-25)), stroke (P = 0.002) and peripheral vascular disease (P = 1.68*10(-12)), while women were older (P = 4.83*10(-23)), heavier and had a higher prevalence of hypertension (P = 5.32*10(-12)). More people with Type 2 diabetes were on lipid-lowering treatment (84.7 vs 52.4%; P = 5.51*10(-8)) than were those with Type 1 diabetes. The prevalence of retinopathy was higher among non-smokers thank smokers in people with both Type 1 and Type 2 diabetes (Type 1, P = 0.016; Type 2, P = 0.001). CONCLUSIONS: The study shows gender differences between Type 1 and 2 diabetes that are of clinical significance and require further investigation. Follow-up of the patients included in the present study should give us much greater understanding of the importance of gender in the development of metabolic abnormalities and diabetes complications.

Brain morphometric correlates of metabolic variables in HIV: the CHARTER study.

Obesity and other metabolic variables are associated with abnormal brain structural volumes and cognitive dysfunction in HIV-uninfected populations. Since individuals with HIV infection on combined antiretroviral therapy (CART) often have systemic metabolic abnormalities and changes in brain morphology and function, we examined associations among brain volumes and metabolic factors in the multisite CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort, cross-sectional study of 222 HIV-infected individuals. Metabolic variables included body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure, random blood glucose, and diabetes. MRI measured volumes of cerebral white matter, abnormal white matter, cortical and subcortical gray matter, and ventricular and sulcal CSF. Multiple linear regression models allowed us to examine metabolic variables separately and in combination to predict each regional volume. Greater BMI was associated with smaller cortical gray and larger white matter volumes. Higher total cholesterol (C) levels were associated with smaller cortex volumes; higher LDL-C was associated with larger cerebral white matter volumes, while higher HDL-C levels were associated with larger sulci. Higher blood glucose levels and diabetes were associated with more abnormal white matter. Multiple atherogenic metabolic factors contribute to regional brain volumes in HIV-infected, CART-treated patients, reflecting associations similar to those found in HIV-uninfected individuals. These risk factors may accelerate cerebral atherosclerosis and consequent brain alterations and cognitive dysfunction.

Characterizing HIV medication adherence for virologic success among individuals living with HIV/AIDS: Experience with the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.

Antiretroviral therapy (ART) has changed HIV related illness from terminal to chronic by suppressing viral load which results in immunologic and clinical improvement. Success with ART is dependent on optimal adherence, commonly categorized as >95%. As medication type, class and frequency of use continue to evolve, we assessed adherence levels related to viral suppression. Using a cross-sectional analysis with secondary data (n = 381) from an ongoing multi-site study on impact of ART on the Central Nervous System (CNS), we compared self-reported adherence rates with biological outcomes of HIV-RNA copies/ml, and CD4 cell/mm3. Adherence to ART measures included taking all prescribed medication as directed on schedule and following dietary restrictions. While depression was a barrier to adherence, undetectable viral suppression was achieved at pill adherence percentages lower than 95%. Practice, research and policy implications are discussed in the context of patient-, provider-, and system-level factors influencing adherence to ART.

Is Clostridium difficile associated with the '4C' antibiotics? A retrospective observational study in diabetic foot ulcer patients.

AIMS: Clostridium difficile is an anaerobic cytotoxin-producing bacterium that can cause infectious diarrhoea, pseudomembranous colitis and toxic megacolon. The major risk factors for developing C. difficile infection include recent or current antimicrobial use, diabetes, age over 65, proton pump inhibitor use, immunosuppression and previous infection with C. difficile. Most diabetic foot ulcers are polymicrobial. METHODS: As a result guidelines advise treatment with broad spectrum antibiotics which include the '4C's' (clindamycin, cephalosporins, co-amoxiclav and ciprofloxacin) which are associated with a higher risk of C. difficile infection. Retrospective observational data (June 2008 to January 2012) for the diabetes foot ulcers were gathered from the Diabetes/Podiatry Clinic database in NHS Ayrshire and Arran and cross-matched with the NHS Ayrshire and Arran Microbiology database. There were 111 patients with mean age 59 years (range 24-94 years), 33 type 1 patients, 78 type 2 patients, mean duration of diabetes 16 years (6 months-37 years) and mean HbA1c 67 mmol/mol (54-108 mmol/mol) [8.3% (7.1-12%)]. RESULTS: The total number of days antimicrobials prescribed for all patients was 7938 (mean number of antimicrobial days per patient = 71.5 days). There was one case of C. difficile infection of 111 patients giving an incidence of 1.25 cases per 10,000 patient-days of antibiotics/1 case per 209 foot ulcers. CONCLUSIONS: Large doses, numbers and greater duration of antibiotic therapy all result in a greater degree of normal gut flora depletion. It is possible that the alterations in gut flora in diabetic foot ulcer patients protect them from antibiotic-induced C. difficile overgrowth.

A comparison of the functional difficulties in staged and simultaneous open carpal tunnel decompression.

There is no agreement about whether patients with bilateral carpal tunnel syndrome should undergo staged or simultaneous open decompression. The purpose of this study was to quantify and compare the functional difficulties during the recovery from surgery for patients undergoing staged or simultaneous decompressions. Sixty-three patients had surgery; 33 had staged decompression (Group 1) and 30 simultaneous decompressions (Group 2). Functional difficulties were recorded using the Levine and Quick-DASH scores along with a visual analogue score for pain. There were no complications in either group. There was no significant difference in terms of pain or satisfaction. Functional difficulties were greater in the simultaneous group; however, there was no difference in completing simple tasks. Patients reported high satisfaction with either management approach. However, significantly fewer would consider undergoing simultaneous decompression again.

An altitude and distance correction to the source fluence distribution of TGFs.

The source fluence distribution of terrestrial gamma ray flashes (TGFs) has been extensively discussed in recent years, but few have considered how the TGF fluence distribution at the source, as estimated from satellite measurements, depends on the distance from satellite foot point and assumed production altitude. As the absorption of the TGF photons increases significantly with lower source altitude and larger distance between the source and the observing satellite, these might be important factors. We have addressed the issue by using the tropopause pressure distribution as an approximation of the TGF production altitude distribution and World Wide Lightning Location Network spheric measurements to determine the distance. The study is made possible by the increased number of Ramaty High Energy Solar Spectroscopic Imager (RHESSI) TGFs found in the second catalog of the RHESSI data. One find is that the TGF/lightning ratio for the tropics probably has an annual variability due to an annual variability in the Dobson-Brewer circulation. The main result is an indication that the altitude distribution and distance should be considered when investigating the source fluence distribution of TGFs, as this leads to a softening of the inferred distribution of source brightness.

Neurocognitive impairment in HIV-infected individuals with previous syphilis.

Cognitive impairment is common in HIV-infected individuals, as is syphilis. Treponema pallidum, the bacterium that causes syphilis, invades the central nervous system early in disease. We hypothesized that HIV-infected patients with a history of syphilis or neurosyphilis would have more cognitive impairment than HIV-infected individuals without these infections. Eighty-two of 1574 enrollees in CHARTER, a prospective, observational study, had reactive serum rapid plasma reagin (RPR) tests. They were matched to 84 controls with non-reactive RPR by age, gender, ethnicity and HIV risk factor. Participants underwent comprehensive neuropsychological (NP) evaluations. RPR results were confirmed and serum fluorescent treponemal antibody absorption (FTA-ABS) test reactivity determined at a central laboratory. Sera from 101 of 166 participants were FTA-ABS reactive, indicating past or current syphilis. Among the 136 individuals without confounding conditions, compared with patients who had never had syphilis, those with prior syphilis had a greater number of impaired NP test domains (1.90 SD [1.77] versus 1.25 [1.52], P = 0.03), a higher global deficit score (0.47 [0.46] versus 0.31 [0.33], P = 0.03), and more were impaired in the NP learning domain (36 [42.9%] of 84 versus 13 [25.0%] of 52, P = 0.04). These effects of prior syphilis remained after controlling for education and premorbid intelligence.

Apolipoprotein E4 genotype does not increase risk of HIV-associated neurocognitive disorders.

This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid.