CD8⁺ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung

The human lung T cell compartment contains many CD8⁺ T cells specific for respiratory viruses, suggesting that the lung is protected from recurring respiratory infections by a resident T cell pool. The entry site for respiratory viruses is the epithelium, in which a subset of lung CD8⁺ T cells expressing CD103 (αE integrin) resides. Here, we determined the specificity and function of CD103⁺CD8⁺ T cells in protecting human lung against viral infection. Mononuclear cells were isolated from human blood and lung resection samples. Variable numbers of CD103⁺CD8⁺ T cells were retrieved from the lung tissue. Interestingly, expression of CD103 was seen only in lung CD8⁺ T cells specific for influenza but not in those specific for EBV or CMV. CD103⁺ and influenza-reactive cells preferentially expressed NKG2A, an inhibitor of CD8⁺ T cell cytotoxic function. In contrast to CD103^–CD8⁺ T cells, most CD103⁺CD8⁺ cells did not contain perforin or granzyme B. However, they could quickly upregulate these cytotoxic mediators when exposed to a type I IFN milieu or via contact with their specific antigen. This mechanism may provide a rapid and efficient response to influenza infection, without inducing cytotoxic damage to the delicate epithelial barrier.     

Objectively Measured Sedentary Time May Predict Insulin Resistance Independent of Moderate- and Vigorous-Intensity Physical Activity

OBJECTIVE

To examine the prospective association between objectively measured time spent sedentary and insulin resistance and whether this association is independent of moderate- and vigorous-intensity physical activity (MVPA) and other relevant confounders.

RESEARCH DESIGN AND METHODS

This was a population-based study (Medical Research Council Ely study) in 376 middle-aged adults (166 men; 210 women) over 5.6 years of follow-up. Physical activity and sedentary time were measured objectively by individually calibrated minute-by-minute heart rate monitoring at both baseline and follow-up. Sedentary time was calculated as the heart rate observations (in minutes) below an individually predetermined threshold (flex heart rate) and expressed as a percentage of total monitored time during waking hours over 4 days. The percentage of time spent above 1.75 × resting heart rate represented MVPA. Fasting plasma insulin was used as a surrogate measure of insulin resistance.

RESULTS

Time spent sedentary at baseline was significantly and positively associated with log fasting insulin at follow-up (β = 0.003, 95% CI 0.0006–0.006, P = 0.015) independent of baseline age, sex, fat mass, fasting insulin, smoking status, and follow-up time. After further adjustment for MVPA, this association was somewhat strengthened (β = 0.004, 95% CI 0.0009–0.006, P = 0.009).

CONCLUSIONS

Time spent sedentary predicts higher levels of fasting insulin independent of the amount of time spent at moderate- and vigorous-intensity activity levels. This highlights the importance of reducing sedentary time in order to improve metabolic health, possibly in addition to the benefits associated with a physically active lifestyle.Insulin resistance is a precursor of type 2 diabetes and a major characteristic of the metabolic syndrome (1). Hyperinsulinemia and impaired insulin sensitivity are common clinical findings yielding independent health risks, including metabolic, cardiovascular, and neoplastic disorders (2–4).Several etiological factors have been identified for impaired insulin sensitivity, including genotype, body composition, inflammation, and lifestyle factors (5–7). Low levels of physical activity and lack of moderate- and vigorous-intensity physical activity (MVPA) are associated with insulin resistance (8,9).Sedentary time has been linked to various cardiometabolic health outcomes, sometimes independent of overall physical activity in cross-sectional analyses (10–12). Because the cardiometabolic consequences are suggested to be a unique feature in hazardous physical activity behavior, sedentary behavior should be considered distinctively from physical activity when examining associations with these health outcomes (13).A recent prospective analysis suggested that MVPA but not sedentary time was associated with insulin resistance in high-risk individuals over a 1-year follow-up period (14). Further prospective research is needed to examine these associations and the direction of causality in normal-risk populations with longer duration of follow-up. Therefore, the purpose of the present study was to 1) examine the prospective association between objectively measured sedentary time and fasting insulin, a marker of insulin resistance, in healthy middle-aged Caucasian subjects and 2) examine whether this association is independent of MVPA and other confounding variables.     

Limb deficiencies and chorion villus sampling

Amniocentesis of a fetus with a sonography diagnosis of nonimmune hydrops fetalis and bilateral clubfoot deformity at 16 weeks of gestation showed a chromosome constitution 49,XXXXY. © 1993 Wiley-Liss, Inc.     

Drug-induced sleep endoscopy changes snoring management plan very significantly compared to standard clinical evaluation

Drug-induced sleep endoscopy (DISE) is a new tool in the work-up of patients with sleep-disordered breathing (SDB). We assessed the impact of DISE on the treatment plan of snoring patients. This is a single institution prospective longitudinal clinical trial. The setting is a private teaching hospital. A consecutive series of 100 snoring patients prospectively underwent a standardised questionnaire, clinical examination, rhinomanometry, allergy skin prick testing, DISE and polysomnography. Management plan before and after DISE evaluation was compared. In 61 patients (excluding 16 patients sent for continuous positive airway pressure, three patients refused sleep endoscopy and 20 were lost to follow-up), we compared the treatment plans. DISE showed single level airway collapse in 13 and multilevel collapse in 48 patients. The site of flutter did not add additional information as compared to the pattern and the location of the collapse. After DISE, the initial management plan changed in 41 % of patients irrespective of the type of initial management plan. The only somewhat accurate initial treatment plan was uvulopalatopharyngoplasty (unchanged in 11/13 patients). Excluding moderate to severe obstructive sleep apnea patients DISE is an indispensable tool in treatment decision in all SDB patients. We suggest to simplify the protocol for DISE reporting.