Obesity is a chronic disease that is strongly associated with an increase in mortality and morbidity including, certain types of cancer, cardiovascular disease, disability, diabetes mellitus, hypertension, osteoarthritis, and stroke. In adults, overweight is defined as a body mass index (BMI) of 25 kg/m(2) to 29 kg/m(2) and obesity as a BMI of greater than 30 kg/m(2). If current trends continue, it is estimated that, by the year 2030, 38% of the world's adult population will be overweight and another 20% obese. Significant global health strategies must reduce the morbidity and mortality associated with the obesity epidemic.
Exertional heat stroke (EHS) is one of the most common causes of sudden death in athletes. It also represents a unique medical challenge to the prehospital healthcare provider due to the time sensitive nature of treatment. In cases of EHS, when cooling is delayed, there is a significant increase in organ damage, morbidity, and mortality after 30 minutes, faster than the average EMS transport and ED evaluation window. The purpose of this document is to present a paradigm for prehospital healthcare systems to minimize the risk of morbidity and mortality for EHS patients. With proper planning, EHS can be managed successfully by the prehospital healthcare provider.
Fibronectin (FN) assembly into a fibrillar extracellular matrix is a stepwise process requiring participation from multiple FN domains. Fibril formation is regulated in part by segments within the first seven type III repeats (III1–7). To define the specific function(s) of this region, recombinant FNs (recFNs) containing an overlapping set of deletions were tested for the ability to assemble into fibrils. Surprisingly, recFN lacking type III repeat III1 (FNΔIII1), which contains a cryptic FN binding site and has been suggested to be essential for fibril assembly, formed a matrix identical in all respects to a native FN matrix. Similarly, displacement of the cell binding domain in repeats III9–10 to a position close to the NH2-terminal assembly domain, as well as a large deletion spanning repeats III4–7, had no effect on assembly. In contrast, two deletions that included repeat III2, ΔIII1–2 and ΔIII2–5, caused significant reductions in fibril elongation, although binding of FN to the cell surface and initiation of assembly still proceeded. Using individual repeats in binding assays, we show that III2 but not III1 contains an FN binding site. Thus, these results pinpoint repeat III2 as an important module for FN–FN interactions during fibril growth.
Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.
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