Sleep-disordered breathing and oxidative stress in preclinical chronic mountain sickness (excessive erythrocytosis)

Chronic mountain sickness (CMS) is considered to be a loss of ventilatory acclimatization to high altitude (>2500 m) resulting in marked arterial hypoxemia and polycythemia. This case–control study explores the possibility that sleep-disordered breathing (SDB) and associated oxidative stress contribute to the etiology of CMS. Nocturnal respiratory and Sa_O2${\text{Sa}}_{{\text{O}}_2}$ patterns were measured using standard polysomnography techniques and compared between male high-altitude residents (aged 18–25) with preclinical CMS (excessive erythrocytosis (EE), n = 20) and controls (n = 19). Measures of oxidative stress and antioxidant status included isoprostanes (8-iso-PGF2_alpha), superoxide dismutase and ascorbic acid. EE cases had a greater apnea–hypopnea index, a higher frequency of apneas (central and obstructive) and hypopneas during REM sleep, and lower nocturnal Sa_O2${\text{Sa}}_{{\text{O}}_2}$ compared to controls. 8-iso-PGF2_alpha was greater in EE than controls, negatively associated with nocturnal Sa_O2${\text{Sa}}_{{\text{O}}_2}$, and positively associated with hemoglobin concentration. Mild sleep-disordered breathing and oxidative stress are evident in preclinical CMS, suggesting that the resolution of nocturnal hypoxemia or antioxidant treatment may prevent disease progression.     

Supporting Study Product Use and Accuracy in Self-Report in the iPrEx Study: Next Step Counseling and Neutral Assessment

The recent successes of biomedical HIV prevention approaches have sparked considerable debate over the scalability, feasibility, and acceptability of pre-exposure prophylaxis (PrEP) as a widespread prevention strategy for men who have sex with men and trans-gender. Anticipated difficulties with PrEP adherence and concerns about resources required to best support it have tempered enthusiasm of PrEP demonstration projects and roll-out. While no evidence-based approach for supporting PrEP use is presently available, a number of approaches have been developed in the context of double-blind, randomized, placebo-controlled trials of PrEP that can provide guidance in moving forward with real world support of open label PrEP use. We present the development, implementation and evaluation of feasibility and acceptability of next-step counseling (NSC) and neutral assessment (NA), the adherence support and promotion of accurate reporting approaches used in the late phases of the iPrEx study. Evaluation of the approach from the perspective of implementers of over 15,000 NSC sessions in seven different countries with almost 2,000 iPrEx participants provided support for NSC, its brevity (averaging ~14 min per follow-up session) and overall acceptability and feasibility. NA also was generally well supported, with a majority of study staff believing this approach was feasible and acceptable; however, lower acceptability for certain aspects of NA was noted amongst staff reporting NA was different from their previous interview approach. Quantitative and qualitative data gathered from implementers were used to make modifications for supporting PrEP use in the open-label extension of iPrEx.     

Functioning of Obese Individuals in Pre- and Postoperative Periods of Bariatric Surgery

Background

Obesity is a pathologic condition that causes functional incapacity, with reduction of quality of life and life expectancy and an increase in mortality. Bariatric surgery is indicated to alleviate associated comorbidities and increase physical capacity. The objective of this work was to evaluate the functional capacity of patients with morbid obesity before and after (3 months) bariatric surgery.

Methods

This was a cross-sectional study involving 67 patients, where 61 were women and six men, with a mean age of 38?±?10 years and mean BMI of 50.45?±?8.5 kg/m². All patients were assessed before surgery and 3 months afterwards. The following assessments were performed: 6-min walk test (6MWT), functional independence measure (FIM), and test for risk of falling and transfer capacity, called the timed up-and-go test.

Results

The study demonstrated a reduction in parameters evaluated in 6MWT with a statistically significant difference at two times (rest and final) when evaluated before and after bariatric surgery (p?<?0.001). In relation to the FIM and timed up-and-go test, the patients showed a statistically significant improvement (p?<?0.001) for both when comparing the tasks evaluated at the pre- and postoperative moments.

Conclusions

Obesity has an impact on the functioning and quality of life of patients. We observed an improvement in all instruments used for assessment before and after bariatric surgery, where a linear component was demonstrated in relation to diminution of body mass index and functioning.     

Microglial activation and expression of immune‐related genes in a rat ex vivo nervous system model after infection with Listeria monocytogenes

A wide variety of microorganisms has previously been identified as causes of brain infection. Among them, Listeria monocytogenes has a particular tropism for the central nervous system. To gain knowledge about the immune response elicited by L. monocytogenes in the brain, we used a rat ex vivo organotypic nervous system culture as a model for Listeria infection. Scanning electron microscopy (SEM) revealed that activated microglial cells showing a typical amoeboid morphology are quickly recruited to the surface of the explants after the infection. After bacterial engulfment, these cells appear to act as Trojan horses, releasing the engulfed bacteria inside the brain tissue. We describe cycles of microglial phagocytosis, necrotic cell death and the subsequent removal of cell debris for the first time. Furthermore, we used this ex vivo model to assess the expression profiles of immune relevant genes up to 24 h postinfection by means of q‐PCR‐arrays, finding that a number of inflammation‐promoting genes are upregulated. Shortly after infection by L. monocytogenes, upregulated genes were those that encoded molecules involved in Th1 responses, being the Ccl2 chemokine and members of the interleukin1‐β family the most abundant immunomodulatory signals expressed. After 5 h of infection, L. monocytogenes caused a substantial increase in the expression of TLR1 and TLR2 genes, as well as in several downstream genes of the TLR signaling pathways. © 2013 Wiley Periodicals, Inc.