Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia

Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22⁺ TCRβ⁺ cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection.     

Comparison of Perpetration Characteristics Between Male Juvenile and Adult Sexual Offenders: Preliminary Results

This study investigated the characteristics of the sexual abuse perpetrated by 16 juvenile (JSO) and 19 adult sexual offenders (ASO). Data were collected from a randomly selected group of males who received psychotherapy services at a community agency. The results revealed significant differences between the JSOs and the ASOs on the number of committed offenses, length of sexual relationships maintained with victims, quality of these relationships, nature of the sexual acts committed, and presence of force during abuse incidents. The results show similarities and differences in the sexual abuse characteristics perpetrated by juveniles and adults.     

Bartonella species as a cause of culture-negative endocarditis in South Africa

European Journal of Clinical Microbiology & Infectious Diseases - Previous reports have highlighted the high prevalence of blood culture negative endocarditis (BCNE) in South Africa. The...     

Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: Results from the randomized Optima study

AimTo compare continuous glucose monitoring (CGM) profiles on vildagliptin versus sitagliptin in addition to metformin, in patients with inadequately controlled type 2 diabetes mellitus (HbA_1c 6.5–8.0%).MethodsA multicenter, prospective, randomised, open-label study with blinded endpoint analysis. CGM data acquired over three days – firstly on metformin alone and then 8 weeks after the addition of either vildagliptin (n = 14) or sitagliptin (n = 16) –were blinded and analyzed centrally.ResultsIn comparable populations with a mean baseline HbA_1c of 7.1%, 24-hour glucose variability – measured by mean amplitude of glucose excursions and standard deviation of mean glucose concentration – showed similar improvement on both drugs versus metformin alone. In contrast, a series of predefined parameters reflecting daily glycaemic control – mean 24-hour blood glucose concentration, and the times spent in the optimal glycaemic range (70–140 mg/dL) and above the hyperglycaemic thresholds of 140 and 180 mg/dL together with the corresponding AUC values – were significantly improved from baseline only in the vildagliptin arm. In addition, overall hyperglycaemia (AUC[24 h] >100 mg/dL) significantly dropped from baseline on vildagliptin [–37%] but not on sitagliptin [–9%], while postprandial hyperglycaemia (AUC[0–4 h] × 3) was significantly reduced on both, and basal hyperglycaemia (overall – postprandial hyperglycaemia was reduced only on vildagliptin [–41%; P = 0.04]).ConclusionsThe addition of a DPP-4 inhibitor significantly reduced glycaemic variability with no difference between the two drugs. However, vildagliptin induced better circadian glycaemic control than sitagliptin with a significant decrease on overall hyperglycemia, mainly driven by reduction on basal hyperglycaemia.     

The glycemic triumvirate and diabetic complications: is the whole greater than the sum of its component parts?

The dysglycemia of diabetes mellitus can be depicted as the glycemic triumvirate with its 3 main components: the sustained chronic (ambient) hyperglycemia, glucose variability and hypoglycemic episodes. The respective contributions of these glycemic disorders to the overall risk for diabetic complications remain a subject of debate. At present, there is cogent evidence for the direct deleterious effect of ambient hyperglycemia while the roles exerted by glucose variability and hypoglycemia remain less documented and only based on observational and pathophysiological studies. In addition, these 3 glycemic disorders could be regarded as components of either an additive or an initiator/accelerator model according to whether each disorder exerts an independent or inter-dependent effect on the development and progression of diabetes-related complications, respectively. In the present review, pros and cons arguments for each model are debated. However it is highly likely that these 3 glycemic disorders have both direct (spoke in a wheel) and indirect (link in a chain) causal effects on clinical cardiovascular outcomes. As a consequence, the relationship between the so-called glycemic triumvirate and diabetic complications might be summarized by the famous Aristotle's aphorism: "the whole is greater than the sum of its parts".