Sensory afferent and hypoxia-mediated activation of nucleus tractus solitarius neurons that project to the rostral ventrolateral medulla

The nucleus tractus solitarius (nTS) of the brainstem receives sensory afferent inputs, processes that information, and sends projections to a variety of brain regions responsible for influencing autonomic and respiratory output. The nTS sends direct projections to the rostral ventrolateral medulla (RVLM), an area important for cardiorespiratory reflexes and homeostasis. Since the net reflex effect of nTS processing ultimately depends on the properties of output neurons, we determined the characteristics of these RVLM-projecting nTS neurons using electrophysiological and immunohistochemical techniques. RVLM-projecting nTS neurons were identified by retrograde tracers. Patch clamp analysis in the horizontal brainstem nTS slice demonstrated that RVLM-projecting nTS cells exhibit constant latency solitary tract evoked excitatory postsynaptic currents (EPSCs), suggesting they receive strong monosynaptic contacts from visceral afferents. Three distinct patterns of action potential firing, associated with different underlying potassium currents, were observed in RVLM-projecting cells. Following activation of the chemoreflex in conscious animals by 3 h of acute hypoxia, 11.2±1.9% of the RVLM-projecting nTS neurons were activated, as indicated by positive Fos-immunoreactivity. Very few RVLM-projecting nTS cells were catecholaminergic. Taken together, these data suggest that RVLM projecting nTS neurons receive strong monosynaptic inputs from sensory afferents and a subpopulation participates in the chemoreflex pathway.     

Prompt initiation of ART With therapeutic food is associated with improved outcomes in HIV-infected Malawian children with malnutrition

This retrospective observational study of 140 HIV-infected children with uncomplicated malnutrition in urban Malawi tested the hypothesis that initiation of antiretroviral therapy (ART) within 21 days of outpatient therapeutic feeding (prompt ART) improved clinical outcomes. Children receiving prompt ART were more likely to recover nutritionally (86% vs. 60%, P < 0.01) and had higher rates of weight gain (3.6 vs. 1.6 g/k/day; P = 0.02). Logistic regression modeling found prompt ART was associated with increased likelihood of nutritional recovery (odds ratio: 5.4, 95% confidence interval: 2.0 to 14.5). This suggests that prompt ART is associated with improved outcomes in HIV-infected Malawian children with uncomplicated malnutrition.     

Smoking, alcohol and caffeine in relation to ovarian age during the reproductive years

BACKGROUND: We sought to determine whether smoking, alcohol and caffeine are related to four indicators of ovarian age: antral follicle count (AFC), follicle stimulating hormone (FSH), inhibin B and estradiol. METHODS: Analyses drew on ultrasound scans and sera from 188 women, aged 22-49. We used least squares regression to estimate differences in AFC and hormone levels for women who smoke cigarettes or who drink alcohol or caffeine. RESULTS: Current smoking is related to elevated FSH (beta for ln(FSH) = 0.21, 95% CI 0.04, 0.39), but not to AFC, inhibin B or estradiol. Neither alcohol nor caffeine is related to any ovarian age indicator. Exploratory analyses suggest that the association of current smoking with FSH varies with age: comparing current with never smokers, at ages 30, 35, 40 and 45, estimated differences in mean FSH are 0.3, 1.3, 3.2 and 6.9 mIU/ml. CONCLUSIONS: The association of current smoking with FSH may reflect accelerated oocyte atresia, impaired follicle quality or dysregulation of the hypothalamic-pituitary-ovarian axis. Identification of the causal mechanism has implications for prevention or treatment of conception delay, infertility and morbidity associated with early menopause.     

The failed repressor: EEG asymmetry as a moderator of the relation between defensiveness and depressive symptoms

This study assessed the joint effects of defensiveness and frontal asymmetry in predicting symptoms of depression and anxiety. Depression symptoms were measured with the Beck Depression Inventory (BDI) and anxiety symptoms with the Taylor Manifest Anxiety Scale (TMAS). Defensiveness was assessed with both the Marlowe Crowne Social Desirability Scale (MCSD) and the Eysenck Personality Questionnaire L scale (EPQL). Participants completed two EEG recording sessions 3 weeks apart. Six baselines, three eyes open and three eyes closed, were recorded in each session. Alpha power (8–13 Hz) was computed and log transformed. R–L asymmetry was computed at eight pairs of homologous sites for aggregated data. Defensiveness (EPQL and MCSD scores) and depression symptoms (BDI) were assessed at the beginning of the first session. L and MCSD correlated positively with anterior R–L asymmetries. For both scales, the highest correlations were observed at F8–F7. L interacted with F8–F7 asymmetry to predict depressive symptoms. Among left frontally active individuals, there was trend toward a negative correlation between L and BDI. Among the right frontally active individuals, the correlation between L and the BDI was positive. MCSD did not moderate the relation between F8–F7 asymmetry and BDI. The results are consistent with the hypothesis that defensiveness protects against symptoms of depression in the context of left frontal activity, and serves as a diathesis for depression in the context of right frontal activity. High-defensive individuals who are right frontally active may represent “failed repressors,” i.e. individuals for whom defensiveness does not protect against depression, and may even exacerbate it.     

Streptozocin-induced diabetic mouse model of urinary tract infection

Diabetics have a higher incidence of urinary tract infection (UTI), are infected with a broader range of uropathogens, and more commonly develop serious UTI sequelae than nondiabetics. To better study UTI in the diabetic host, we created and characterized a murine model of diabetic UTI using the pancreatic islet beta-cell toxin streptozocin in C3H/HeN, C3H/HeJ, and C57BL/6 mouse backgrounds. Intraperitoneal injections of streptozocin were used to initiate diabetes in healthy mouse backgrounds, as defined by consecutive blood glucose levels of >250 mg/dl. UTIs caused by uropathogenic Escherichia coli (UTI89), Klebsiella pneumoniae (TOP52 1721), and Enterococcus faecalis (0852) were studied, and diabetic mice were found to be considerably more susceptible to infection. All three uropathogens produced significantly higher bladder and kidney titers than buffer-treated controls. Uropathogens did not have as large an advantage in the Toll-like receptor 4-defective C3H/HeJ diabetic mouse, arguing that the dramatic increase in colonization seen in C3H/HeN diabetic mice may partially be due to diabetic-induced defects in innate immunity. Competition experiments demonstrated that E. coli had a significant advantage over K. pneumoniae in the bladders of healthy mice and less of an advantage in diabetic bladders. In the kidneys, K. pneumoniae outcompeted E. coli in healthy mice but in diabetic mice E. coli outcompeted K. pneumoniae and caused severe pyelonephritis. Diabetic kidneys contained renal tubules laden with communities of E. coli UTI89 bacteria within an extracellular-matrix material. Diabetic mice also had glucosuria, which may enhance bacterial replication in the urinary tract. These data support that this murine diabetic UTI model is consistent with known characteristics of human diabetic UTI and can provide a powerful tool for dissecting this infection in the multifactorial setting of diabetes.     

Vaccine-derived poliomyelitis 12 years after infection in Minnesota

A 44-year-old woman with long-standing common variable immunodeficiency who was receiving intravenous immune globulin suddenly had paralysis of all four limbs and the respiratory muscles, resulting in death. Type 2 vaccine-derived poliovirus was isolated from stool. The viral capsid protein VP1 region had diverged from the vaccine strain at 12.3% of nucleotide positions, and the two attenuating substitutions had reverted to the wild-type sequence. Infection probably occurred 11.9 years earlier (95% confidence interval [CI], 10.9 to 13.2), when her child received the oral poliovirus vaccine. No secondary cases were identified among close contacts or 2038 screened health care workers. Patients with common variable immunodeficiency can be chronically infected with poliovirus, and poliomyelitis can develop despite treatment with intravenous immune globulin.     

Exercise during early pregnancy is associated with greater sleep continuity

Objectives/background: Pregnant women report disturbed sleep beginning in early pregnancy. Among nonpregnant populations, exercise has been associated with improved sleep; however, research in pregnant samples has been equivocal. We examined whether varying degrees of exercise were associated with better nocturnal sleep among pregnant women during early gestation. Participants: 172 pregnant women. Methods: Self-reported sleep and exercise and objective sleep were collected during early gestation: T1 (10–12 weeks), T2 (14–16 weeks), and T3 (18–20 weeks) from 172 pregnant women. Exercise was categorized into three time-varying groups: 0 metabolic equivalent minutes per week (MET-min/week), 1 to < 500 MET-min/week, or ≥ 500 MET-min/week. Linear mixed-effects models were employed to test hypotheses. Results: A significant main effect for Time (F[2,254] = 9.77, p < 0.0001) and Time*Exercise group interaction were observed for actigraphic sleep efficiency (aSE) (F[4,569] = 2.73, p = 0.0285). At T2, women who reported ≥ 500 MET-min/week had higher aSE than those who reported 0 MET-min/week. Significant main effects for Exercise Group and Time were observed for actigraphic wake after sleep onset (aWASO; F[2,694] = 3.04, p = 0.0483 and F[2,260] = 3.21, p = 0.0419). aWASO was lowest for those reporting 1 to < 500 MET-min/week (t[701] = 2.35, adjusted p = .0489) and aWASO decreased from T1 to T3 (t[258] = 2.53, adjusted p value = 0.036). Lastly, there was a main effect for Time for the PSQI (F[2,689] = 52.11, p < 0.0001), indicating that sleep quality improved over time. Conclusions: Some level of exercise among pregnant women appears to be more advantageous than no exercise at all. Moderate exercise, while still unclearly defined, may be a worthwhile adjunct treatment to combat sleep disturbances during pregnancy.