Association between diabetes mellitus and active tuberculosis in Africa and the effect of HIV.

OBJECTIVE: To determine current evidence for the association between diabetes and active tuberculosis in Africa, and how HIV modifies, or not, any association between diabetes and active tuberculosis. METHODS: We conducted a systematic review by searching the EMBASE, Global Health and MEDLINE databases. Studies were eligible for inclusion if they explored the association between diabetes mellitus prevalence and active tuberculosis incidence or prevalence, used a comparison group, were conducted in an African population and adjusted the analysis for at least age. Study characteristics were compared, and risk of bias was assessed. The range of effect estimates was determined for the primary association and for effect modification by HIV. RESULTS: Three eligible studies were identified: two investigated the primary association and two investigated HIV as a potential effect modifier. All studies were case-control studies, including a combined total of 1958 tuberculosis cases and 2111 non-tuberculosis controls. Diabetes diagnostic methods and analysis strategies varied between studies. Individual study adjusted odds ratios of active tuberculosis for the effect of diabetes mellitus (unstratified) ranged from 0.88 (95% CI 0.17-4.58) to 10.7 (95% CI 4.5-26.0). Individual study P-values for HIV interaction ranged from 0.01 to 0.83. Quantitative synthesis of individual study data was not performed due to heterogeneity between studies. CONCLUSIONS: Few data currently exist on the association between diabetes and active tuberculosis in Africa, and on the effect of HIV on this association. Existing data are disparate. More regional research is needed to guide policy and practice on the care and control of tuberculosis and diabetes in Africa.

Measurement of the parity-violating asymmetry in inclusive electroproduction of π- near the Δ0 resonance.

The parity-violating (PV) asymmetry of inclusive π- production in electron scattering from a liquid deuterium target was measured at backward angles. The measurement was conducted as a part of the G0 experiment, at a beam energy of 360 MeV. The physics process dominating pion production for these kinematics is quasifree photoproduction off the neutron via the Δ0 resonance. In the context of heavy-baryon chiral perturbation theory, this asymmetry is related to a low-energy constant d(Δ)- that characterizes the parity-violating γNΔ coupling. Zhu et al. calculated d(Δ)- in a model benchmarked by the large asymmetries seen in hyperon weak radiative decays, and predicted potentially large asymmetries for this process, ranging from A(γ)-=-5.2 to +5.2 ppm. The measurement performed in this work leads to A(γ)-=-0.36±1.06±0.37±0.03 ppm (where sources of statistical, systematic and theoretical uncertainties are included), which would disfavor enchancements considered by Zhu et al. proportional to V(ud)/V(us). The measurement is part of a program of inelastic scattering measurements that were conducted by the G0 experiment, seeking to determine the N-Δ axial transition form factors using PV electron scattering.

Transverse beam spin asymmetries at backward angles in elastic electron-proton and quasielastic electron-deuteron scattering.

We have measured the beam-normal single-spin asymmetries in elastic scattering of transversely polarized electrons from the proton, and performed the first measurement in quasielastic scattering on the deuteron, at backward angles (lab scattering angle of 108°) for Q² = 0.22 GeV²/c² and 0.63 GeV²/c² at beam energies of 362 and 687 MeV, respectively. The asymmetry arises due to the imaginary part of the interference of the two-photon exchange amplitude with that of single-photon exchange. Results for the proton are consistent with a model calculation which includes inelastic intermediate hadronic (πN) states. An estimate of the beam-normal single-spin asymmetry for the scattering from the neutron is made using a quasistatic deuterium approximation, and is also in agreement with theory.

Strange quark contributions to parity-violating asymmetries in the backward angle G0 electron scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton and quasielastic electron-deuteron scattering at Q2=0.22 and 0.63 GeV2. They are sensitive to strange quark contributions to currents in the nucleon and the nucleon axial-vector current. The results indicate strange quark contributions of approximately < 10% of the charge and magnetic nucleon form factors at these four-momentum transfers. We also present the first measurement of anapole moment effects in the axial-vector current at these four-momentum transfers.

Acquisition of MDR-GNB in hospital settings: a systematic review and meta-analysis focusing on ESBL-E.

INTRODUCTION: Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and other multi-drug-resistant Gram-negative bacteria (MDR-GNB) have disseminated globally since their discovery in the late 20th century. Various infection prevention and control measures are in place to prevent nosocomial transmission of these organisms, but their efficacy remains disputed. New literature has emerged in recent years providing further evidence which can be used to formulate effective strategies to tackle this issue in the future. METHODS: A systematic review was performed to characterize the prevalence of colonization of multi-drug-resistant organisms and subsequent acquisition of these organisms within hospital settings. A meta-analysis was performed to characterize the prevalence and acquisition of ESBL-E in Europe and North America. RESULTS: Twenty-eight studies fulfilled the inclusion criteria. Escherichia coli formed the main burden of MDR-GNB colonization worldwide. Patient-to-patient transmission of ESBL-E was found to be rare, but increased transmissibility of Klebsiella pneumoniae was described over E. coli. Within European and North American healthcare settings, a meta-analysis of eight studies identified a pooled prevalence of ESBL-E on admission to hospital of 7.91% and an acquisition rate of 3.73%. DISCUSSION: Low prevalence at the point of hospital admission and insufficient evidence of patient-to-patient transmission suggests that infection prevention and control measures such as universal surveillance screening and single-room isolation are unlikely to be practical or effective interventions in reducing the overall burden of ESBL-E in hospitals, in line with current European guidelines. Instead, it is argued that efforts should be placed on controlling the spread of these organisms and other MDR-GNB in the community, predominantly long-term care facilities.

The sensitivity of the QuantiFERON®-TB Gold Plus assay in Zambian adults with active tuberculosis.

SETTING AND OBJECTIVE: To investigate the sensitivity of the new interferon-gamma release assay (IGRA), QuantiFERON®-TB Gold Plus (QFT-Plus), for active TB (used as a surrogate for latent tuberculous infection) in a Zambian TB clinic. DESIGN: Consecutive smear or Xpert® MTB/RIF-positive adult (age 18 years) pulmonary TB patients were recruited between June 2015 and March 2016. Venous blood was tested using QFT-Plus. The sensitivity was defined as the number positive divided by the total number tested. Using logistic regression, factors associated with positive QFT-Plus results were explored. RESULTS: Of 108 patients (median age 32 years, interquartile range 27-38; 73% male; 63% human immunodeficiency virus [HIV] positive), 90 were QFT-Plus-positive, 11 were negative and seven had indeterminate results; sensitivity was 83% (95%CI 75-90). There was no difference in sensitivity by HIV status (HIV-positive 85%, 95%CI 75-93; n = 68 vs. HIV-negative 80%, 95%CI 64-91; n = 40; P = 0.59). In models adjusted for age alone, CD4 cell count <100 cells/µl (OR 0.15, 95%CI 0.02-0.96; P = 0.05) and body mass index <18.5 kg/m2 (OR 0.27, 95%CI 0.08-0.91; P = 0.02) were associated with decreased odds of positive QFT-Plus results. CONCLUSION: Overall, the sensitivity of QFT-Plus is similar to that of the tuberculin skin test and other IGRAs. While overall sensitivity is not affected by HIV status, QFT-Plus sensitivity was lower among people living with HIV/acquired immune-deficiency syndrome with severe immunosuppression.

Levels of methyleugenol in a subset of adults in the general U.S. population as determined by high resolution mass spectrometry.

We developed a sensitive and accurate analytical method for quantifying methyleugenol (ME) in human serum. Our method uses a simple solid-phase extraction followed by a highly specific analysis using isotope dilution gas chromatography-high resolution mass spectrometry. Our method is very accurate; its limit of detection is 3.1 pg/g and its average coefficient of variation is 14% over a 200-pg/g range. We applied this method to measure serum ME concentrations in adults in the general U.S. population. ME was detected in 98% of our samples, with a mean ME concentration of 24 pg/g (range < 3.1-390 pg/g). Lipid adjustment of the data did not alter the distribution. Bivariate and multivariate analyses using selected demographic variables showed only marginal relationships between race/ethnicity and sex/fasting status with serum ME concentrations. Although no demographic variable was a good predictor of ME exposure or dose, our data indicate prevalent exposure of U.S. adults to ME. Detailed pharmacokinetic studies are required to determine the relationship between ME intake and human serum ME concentrations.

Hypercapnic arousal responses in Prader-Willi syndrome.

STUDY OBJECTIVE: Prader-Willi syndrome (PWS) is characterized by a number of abnormalities of hypothalamic function, such as hyperphagia, short stature, temperature instability, hypogonadotropic hypogonadism, and neurosecretory growth hormone deficiency. Patients with PWS are reported to have sleep-disordered breathing and have blunted hypercapnic ventilatory responses secondary to abnormal peripheral chemoreceptor function. Thus, we hypothesized that hypercapnic arousal responses would be abnormal in PWS. DESIGN: Hypercapnic arousal responses were tested in ten nonobese children and adults with PWS, aged 17.7 +/- 2.5 (SEM) years, 70% female, and nine control subjects, aged 14.2 +/- 2.6 years, 67% female. Hypercapnic challenges were performed during stage 3/4 non-rapid eye movement sleep. RESULTS: The PWS subjects had a significantly higher arousal threshold to hypercapnia compared with the controls (53 +/- 1.0 vs 46 +/- 1.7 mm Hg; p < 0.01). The PWS subjects had significantly higher baseline end-tidal CO2 levels (42 +/- 0.8 vs 38 +/- 1.1 mm Hg; p < 0.01) and more central apneas greater than 15 s/h of sleep (1.5 +/- 0.3 vs 0.1 +/- 0.1; p < 0.01). CONCLUSIONS: Elevated hypercapnic arousal thresholds during sleep are found in PWS subjects; these may be a manifestation of abnormal peripheral chemoreceptor function and may further contribute to sleep-disordered breathing in PWS patients.

Restorative effects of GDNF on striatal dopamine release in rats treated with neurotoxic doses of methamphetamine.

Repeated methamphetamine (METH) administration to animals can result in long-lasting decreases in striatal dopamine (DA) release and content. Glial cell line-derived neurotrophic factor (GDNF) has pronounced effects on dopaminergic systems in vivo, including neuroprotective effects against METH. The present experiments were designed to examine the ability of GDNF to reverse, or accelerate recovery from, METH-induced alterations in striatal DA release. Male Fischer-344 rats were administered METH (5 mg/kg, s.c.) or saline 4 times in one day at 2-hour intervals. Seven days later the animals were anesthetized and given a single injection of 10 microg GDNF, or vehicle, into the right striatum. Three weeks later microdialysis experiments were carried out in both the right and left striata to examine basal and evoked levels of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). In animals treated with METH followed by vehicle 7 days later, there were significant reductions in potassium- and amphetamine-evoked overflow of DA, and in basal levels of DOPAC and HVA, compared to control animals. In rats treated with METH followed 7 days later with GDNF, there were significant increases in potassium- and amphetamine-evoked overflow of DA on the right, GDNF-treated, side of the brain compared to the left side. Basal levels of DOPAC and HVA were also elevated on the GDNF-treated side of the brain. These results suggest that GDNF can accelerate recovery of dopaminergic release processes in the striatum of rats treated with neurotoxic doses of METH.

Evolution of pulmonary function during an acute exacerbation in hospitalized patients with cystic fibrosis.

Few objective criteria have been validated for serial clinical monitoring in patients with cystic fibrosis (CF) during pulmonary exacerbations. While pulmonary function tests (PFT) are often used to monitor clinical improvement, it is not known which test correlates most closely with clinical improvement. To answer this, we measured routine PFT in 58 patients with CF before, during, and at discharge after 2-3 week hospital admission in 71 episodes of pulmonary exacerbation. Patients with CF were discharged based on clinical, radiological, and laboratory criteria. In general, all PFTs improved at midadmission and improved further by discharge, at which time forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75), vital capacity (VC), maximal voluntary ventilation (MVV), and oxygen saturation by pulse oximetry (SPO2) increased. The residual volume to total capacity ratio (RV/TLC) and the slope of phase 3 in the single breath N2 washout curve (SP3 N2) decreased. The change in SP3 N2 was significantly greater than in any other PFT (P < 0.01 vs. VC and FEV1; P < 0.02 vs. RV and P < 0.001 vs. SPO2). A calculated optimal cut-off value for SP3 N2 improvement was significantly more sensitive in identifying patient improvement at discharge than any other pulmonary function test (P = 0.005). We speculate that clinical improvement in patients with CF is closely linked to improved distribution of ventilation.

Morningness-eveningness and early-morning salivary cortisol levels.

The purposes of this exploratory study were: (1) to describe a 2-h segment of the early-morning salivary cortisol levels of morning (M) and evening (E) types of healthy, day-active adults on one morning; and (2) to compare selected demographic and sleep characteristics. The sample consisted of 20 subjects, aged 23-39 years, 10 of each type. Measures included: morningness-eveningness questionnaire score, demographic information, self-report sleep characteristics, and self-report of well-being. Beginning with time of arising, seven salivary samples were collected at approximately 20-min intervals. Among the sleep variables, bedtime (p = 0.005), time of mid-sleep (p = 0.002), and arising time (p = 0.043) were later in the E group as compared to the M group. Six M and one E subject awoke spontaneously on the morning of sampling without an awakening aid (p = 0.018). Even though total hours of sleep were comparable between groups, E subjects reported feeling less rested in the morning (p = 0.019). Although mean M group salivary cortisol levels were greater than mean E group levels for each sampling time, there were no significant group differences. Eight M subjects reached a sampling period salivary cortisol peak by 50 min after arising, contrasted with six E subjects who reached their peak at that time. These preliminary findings suggest that E types demonstrate lower morning arousal and a delay in their early-morning peak of salivary cortisol relative to M types. Further study is needed to explore the relationship between M and E types, their sleep-wake patterns, and cortisol secretion patterns.

Strength of the quadriceps femoris muscle and functional recovery after reconstruction of the anterior cruciate ligament. A prospective, randomized clinical trial of electrical stimulation.

Immediately after reconstruction of the anterior cruciate ligament, 110 patients were randomly assigned to treatment with high-intensity neuromuscular electrical stimulation (thirty-one patients), high-level volitional exercise (thirty-four patients), low-intensity neuromuscular electrical stimulation (twenty-five patients), or combined high and low-intensity neuromuscular electrical stimulation (twenty patients). All treatment was performed isometrically with the knee in 65 degrees of flexion. All of the patients participated in an intensive program of closed-kinetic-chain exercise. After four weeks of treatment, the strength of the quadriceps femoris muscle and the kinematics of the knee during stance phase were measured. Quadriceps strength averaged 70 per cent or more of the strength on the uninvolved side in the two groups that were treated with high-intensity electrical stimulation (either alone or combined with low-intensity electrical stimulation), 57 per cent in the group that was treated with high-level volitional exercise, and 51 per cent in the group that was treated with low-intensity electrical stimulation. The kinematics of the knee joint were directly and significantly (p < 0.05) correlated with the strength of the quadriceps. There was a clinically and statistically significant (p < 0.05) difference in the recovery of the quadriceps and the gait parameters according to the type of operation that had been performed: the patients who had had reconstruction of the anterior cruciate ligament with use of an autologous patellar-ligament graft did poorly compared with the other patients.

Cardiovascular recovery from laboratory stress: biopsychosocial concomitants in older adults.

Although cardiovascular recovery may be important to long term cardiovascular health, its biopsychosocial correlates have received much less attention than the correlates of cardiovascular reactivity. Of the few studies that have examined recovery, fewer still have examined men and women over 60 yr of age. This study examined relationships of psychosocial factors (e.g. state anxiety, anger, avoidance coping, Type A behavior, etc.) with recovery in 186 older married men (n = 63) and women (n = 123) (mean age = 69.7 +/- 6.1 yr). Regressions were performed to explain recovery variability in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in response to emotional and cognitive tasks. In each analysis, we controlled for the effects of gender, type of task, reactivity to the task, and other important covariates. Individuals with slower recovery had higher scores on anxiety (for SBP, p < 0.03 and DBP, p < 0.01), higher scores on avoidance coping (for DBP and HR, p < 0.01), and lower scores on anger held in (for DBP, p < 0.01). Psychosocial factors may be important in explaining recovery in older adults.

Circadian rhythmicity of cortisol and body temperature: morningness-eveningness effects.

The purpose of this study was to describe and compare the circadian rhythm of body temperature and cortisol, as well as self-reported clock times of sleep onset and offset on weekdays and weekends in 19 healthy adult "larks" (morning chronotypes) and "owls" (evening chronotypes), defined by the Home and Ostberg questionnaire. Day-active subjects entered the General Clinical Research Center, where blood was sampled every 2 h over 38 h for later analysis for cortisol concentration by enzyme immunoassay. Rectal body temperature was measured continuously. Lights were turned off at 22:30 for sleep and turned on at 06:00, when subjects were awakened. The acrophases (peak times) of the cortisol and temperature rhythms occurred 55 minutes (P < or = .05) and 68 minutes (P < .01), respectively, earlier in the morningness group. The amplitude of the cortisol rhythm was lower in the eveningness than in the morningness group (P = n.s.). Subject groups differed on all indices of habitual and preferred timing of sleep and work weekdays and weekends (P = .05-.001).

Sleep impairments in healthy seniors: roles of stress, cortisol, and interleukin-1 beta.

STUDY OBJECTIVES: Increased stress responsivity and a longer-lasting glucocorticoid increase are common findings in aging studies. Increased cortisol levels at the circadian nadir also accompany aging. We used 24 h free urine cortisol to assess these age changes in healthy seniors. We hypothesized that free cortisol levels would explain individual differences in age-related sleep impairments. DESIGN: The study compared sleep, cortisol, and sleep-cortisol correlations under baseline and "stress" conditions in men and women. SETTING: Subjects were studied in the General Clinical Research Center under baseline conditions and a mildly stressful procedure (24 h indwelling intravenous catheter placement). PARTICIPANTS: Eighty-eight healthy, nonobese subjects (60 women and 28 men) from a large study of successful aging participated in the study. Mean ages were 70.6 (+/-6.2) and 72.3 (+/-5.7) years for women and men, respectively. MEASUREMENTS: The 24 h urines were collected for cortisol assay (radioimmunoassay [RIA]); blood was sampled at three diurnal time points for assay (enzyme-linked immunosorbent assay [ELISA]) of interleukin-1 (IL-1) beta; sleep architecture and sleep electroencephalograms (EEGs) were analyzed (after an adaptation and screening night) on baseline and stress nights via polysomnography and EEG power spectral analysis. RESULTS: Healthy older women and men with higher levels of free cortisol (24 h urine level) under a mild stress condition had impaired sleep (lower sleep efficiency; fewer minutes of stages 2, 3, and 4 sleep; more EEG beta activity during non-rapid eye movement sleep [NREM] sleep). Similar results were obtained when stress reactivity measures were used (cortisol and sleep values adjusted for baseline values), but not when baseline values alone were used. Gender differences were apparent: Men had higher levels of free urine cortisol in both baseline and mild stress conditions. Cortisol and sleep correlated most strongly in men; cortisol stress response levels explained 36% of the variance in NREM sleep stress responses. In women, but not men, higher cortisol was also associated with earlier time of arising and less REM sleep. Higher cortisol response to stress was associated with increased circulating levels of IL-1beta, explaining 24% of the variance in a subset of women. CONCLUSION: These results indicate that free cortisol (as indexed by 24 h urine values) can index responses to mild stress in healthy senior adults, revealing functional correlations (impaired sleep, earlier times of arising, more EEG beta activity during sleep, more IL-1beta) and gender differences.

Characteristics of students who bring weapons to school.

PURPOSE: This study explores the relationships between social, demographic, and behavioral characteristics and self-reported carrying of a weapon to school among middle school students. The results provide a statistical profile of youth most likely to bring weapons to school and help to identify characteristics that are only spuriously related to this behavior. METHODS: Study respondents were part of an ongoing randomized evaluation of a school-based drug use prevention program in Illinois. Self-administered questionnaires were completed by 1,503 seventh and eighth graders in the spring of 1992. RESULTS: Fifteen percent of respondents brought some type of weapon to school in the past month. In a multivariate logistic regression model, being male, not living with both parents, not feeling close to parents, drinking heavily, participating in fights, damaging school property, and perceiving that at least a few other students brought weapons to school, were significantly associated with weapon carrying. Victimization and fear for safety in school were not significantly associated with weapon carrying in the multivariate model. CONCLUSIONS: Study results suggest that both the structure and the dynamics of the family play an important role in weapon carrying behavior. Weapon carrying also appears to cluster with other deviant behaviors. Furthermore, the findings suggest that weapons are not brought to school because of a heightened need for protection, but rather may be in response to normative influences in school.

Substance use and risky sexual behavior among homeless and runaway youth.

PURPOSE: To (a) characterize human immunodeficiency virus (HIV)-related risk behaviors of homeless youth; (b) determine whether substance use is associated with risky sexual behavior in this population; and, if so, (c) explore explanations for this relationship. METHODS: A purposive sample of 327 homeless youth (ages 14-21 years) in Washington, DC, were surveyed in 1995 and 1996. Survey items were adapted from items used in a national study of adult substance use and sexual behavior and measured global (lifetime) and event-specific (most recent sexual encounter) behaviors. RESULTS: Sexual activity with many partners, "survival" sex, and substance use were common. However, needle use was rare, and consistent condom use was evident in half the sample. Nearly all correlations between global measures of substance use and risky sex were statistically significant, but only a few of the event-specific correlations were significant. Marijuana use during the most recent sexual encounter was associated with nonuse of condoms, but this relationship disappeared in the multivariate model. However, crack use during the last encounter was associated with condom use; this relationship remained significant in the multivariate model. Lack of motivation to use condoms, longer histories of sexual activity and homelessness, symptoms of drug dependency, not discussing HIV risks with partner, and being female were also associated with nonuse of condoms. CONCLUSIONS: Homeless youth do use condoms, even within the context of substance use and casual sex. Results suggest that prevention and targeted intervention efforts have had some positive effect on this population, but young homeless women are in need of targeted prevention. Finally, additional research is needed to investigate the observed relationship between crack use and condom use in this sample.

Risky sexual behaviors among adolescents with alcohol use disorders.

Little is known about risky sexual activity among adolescents with alcohol use disorders. This study of 371 adolescent drinkers found that those with alcohol disorders were more likely than other drinkers to be sexually active, to have greater numbers of partners, and to initiate sexual activity at slightly younger ages. Independent of alcohol group, females were more likely than males to have unprotected sexual encounters.

HIV-risk behaviors associated with homelessness characteristics in youth.

PURPOSE: To examine characteristics of youth homelessness associated with engaging in risk behaviors for human immunodeficiency virus (HIV). METHODS: The sample included 288 currently homeless or runaway Washington, DC youth aged 14-21 years. Measures were self-reported homelessness characteristics, unsafe sexual behavior, injection drug use, and background characteristics. Bivariate and multivariable analyses of the relationships between homelessness characteristics and HIV risk behaviors were conducted. RESULTS: Both male (n = 140) and female (n = 148) participants reported high rates of unsafe sexual behaviors, but low rates of injection drug use. HIV risk was significantly associated in bivariate analyses with severity of homelessness circumstances (i.e., spending the night in public place or with strangers, going hungry, and participating in the street economy), the duration of homelessness (i.e., greater number of episodes of homelessness, longer time length of current episode), and specific reasons for being homeless (i.e., thrown out). In addition, sexual victimization and older age were associated with increased HIV risk. In multivariable models, a smaller set of these homelessness characteristics remained significant independent correlates and explained a substantial amount of the variation in the HIV risk indices for both males and females. CONCLUSIONS: The results contribute to greater theoretical understanding of the characteristics of homelessness associated with increased risk of HIV infection within this vulnerable population of youth. The associations between homelessness characteristics and HIV risk suggest the need for HIV prevention efforts to focus directly on ameliorating the homelessness circumstances of youth.