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Inflammation is a crucial driver of host damage in patients with C. difficile colitis. We examined the potential for the intestinal microbiome to modify inflammation in patients with C. difficile colitis via the effects of gut-derived endotoxin on cytokine production.

Endotoxin from E. coli and P. aeruginosa as well as stool-derived endotoxin was tested for their ability to enhance IL-1β and TNFα- production by toxin B-stimulated peripheral blood mononuclear cells. Inflammasome and TLR-4 blocking studies were done to discern the importance of these pathways, while metagenomic studies were done to characterize predominant organisms from stool samples.

Endotoxin significantly enhanced the ability of C. difficile toxin B to promote IL-1β production but not TNF- α. The magnitude of this effect varied by endotoxin type and was dependent on combined inflammasome and TLR-4 activation. Stool-derived endotoxin exhibited a similar synergistic effect on IL-1 β production with less synergy observed for stools that contained a high proportion of gamma-proteobacteria.

The ability of endotoxin to enhance IL-1 β production highlights a manner by which the microbiome can modify inflammation and severity of C. difficile disease. This information may be useful in devising new therapies for severe C. difficile colitis.

The ability of endotoxin to enhance IL-1 β production highlights a manner by which the microbiome can modify inflammation and severity of C. difficile disease. This information may be useful in devising new therapies for severe C. difficile colitis.

Central congenital hypothyroidism (CH) requires lifelong medical treatment. The majority of children with central CH have multiple pituitary hormone deficiencies (MPHD), but in some cases central CH is isolated. Most pituitary hormone deficiencies are associated with impaired health-related quality of life (HRQoL). However, studies on HRQoL in central CH are lacking.

to evaluate HRQoL and fatigue in children and young adults with central CH, as well as parent perspectives.

nationwide cross-sectional study comparing HRQoL between early-detected central CH patients and unaffected siblings with the Pediatric Quality of Life inventory (PedsQL™) and PedsQL Multidimensional Fatigue Scale. Participants ≥8 years old filled in self-reports; parents of participants aged 3-18 years filled in parent-reports. Isolated central CH patients, MPHD patients and siblings were compared using a linear mixed model and Tukey's post hoc test.

Eighty-eight patients and 52 siblings participated, yielding 98 self-reports and 11rents.

In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bone quality other than BMD are affected in PHPT as well.

To evaluate bone material properties using impact microindentation (IMI) in PHPT patients.

In this cross-sectional study, the Bone Material Strength index (BMSi) was measured by IMI at the midshaft of the tibia in 37 patients with PHPT (28 women), 11 of whom had prevalent fragility fractures, and 37 euparathyroid controls (28 women) matched for age, gender, and fragility fracture status.

Mean age of PHPT patients and controls was 61.8 ± 13.3 and 61.0 ± 11.8 years, respectively, P = .77. Calcium and PTH levels were significantly higher in PHPT patients but BMD at the lumbar spine (0.92 ± 0.15 vs 0.89 ± 0.11, P = .37) and the femoral neck (0.70 ± 0.11 vs 0.67 ± 0.07, P = .15) were comparable between groups. BMSi however was significantly lower in PHPT patients than in controls (78.2 ± 5.7 vs 82.8 ± 4.5, P < .001). In addition, BMSi was significantly lower in 11 PHPT patients with fragility fractures than in the 26 PHPT patients without fragility fractures (74.7 ± 6.0 vs 79.6 ± 5.0, P = .015).

Our data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT.

Our data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT.

U.S. hospitals are required by CMS to publicly report CLABSI, CAUTI, C.diffficile, MRSA bacteremia, and selected SSIs for benchmarking and pay-for-performance programs. It is unclear, however, to what extent these conditions capture the full breadth of serious healthcare-associated infections (HAIs). CDC's hospital-onset Adult Sepsis Event (HO-ASE) definition could facilitate more comprehensive and efficient surveillance for serious HAIs, but the overlap between HO-ASE and currently reportable HAIs is unknown.

We retrospectively assessed the overlap between HO-ASEs and reportable HAIs among adults hospitalized between June 2015-June 2018 in 3 hospitals. Medical record reviews were conducted for 110 randomly selected HO-ASE cases to determine clinical correlates.

Amongst 282,441 hospitalized patients, 2,301 (0.8%) met HO-ASE criteria and 1,260 (0.4%) had reportable HAIs. In-hospital mortality rates were higher with HO-ASEs than reportable HAIs (28.6% vs 12.9%). Mortality rates for HO-ASE missed by reportcal significance of surveillance while identifying new targets for prevention.This study reports the impact of HIV and antiretroviral therapy (cART) on immune activation during pregnancy in a Zambian cohort of HIV exposed but uninfected children followed from birth. Activated CD8+ T-cells (CD38+ and HLA-DR+) were compared among HIV- (N=95), HIV+/cART experienced (N=111) and HIV+/cART naïve (N=21) pregnant women. Immune activation was highest among HIV+/cART naïve women but decreased during pregnancy. HIV+ women who started cART during pregnancy reduced immune activation but not to levels similar to HIV- women. The effects of elevated maternal immune activation in pregnancy on subsequent infant health and immunity remain to be determined.

Pseudohypoparathyroidism (PHP) is a group of disorders characterized by hypocalcemia, hyperphosphatemia and elevated PTH levels, as a result of end-organ resistance to PTH.

To describe a cohort of 26 patients with PHP, followed in a single tertiary center.

Clinical, biochemical, radiological and genetic analysis of the GNAS gene were collected in 26 patients recruited since 2002.

Ten patients harbored a GNAS mutation, 15 epigenetic abnormalities at the GNAS locus and one was negative. According to clinical, biochemical and genetic features, patients were classified as PHP1A, PHP1B and PPHP.

with PHP1A had an earlier diagnosis and more cases with family history, Albright hereditary osteodystrophy features (AHO), hormonal resistance and hypertension. Obesity was a common feature. No difference in biochemical values was present among PHP1A and PHP1B. Intracerebral calcification occurred in 72% of patients with no difference among PHP1A and PHP1B subgroups. No significant difference was observed between patients with and without intracerebral calcification for the time-weighted average values of total serum calcium, phosphate, calcium-phosphate product and PTH fold increase. A borderline association between cerebral calcification and age at the time of diagnosis (P =0.04) was found in the whole cohort of patients.No renal calcifications were found in the overall cohort.

Patients with PHP1A more frequently have AHO features as well as hypertension compared to PHP1B. PHP patients presented a high rate of intracerebral calcification with no significant difference between subgroups. No increased risk of renal calcifications was also found in the entire cohort.

Patients with PHP1A more frequently have AHO features as well as hypertension compared to PHP1B. PHP patients presented a high rate of intracerebral calcification with no significant difference between subgroups. No increased risk of renal calcifications was also found in the entire cohort.

This study aims to describe the relationships between physical activity (PA), body composition and multimorbidity over 10 years.

Participants (N=373; 49% women; average age 61.3±6.7 years) were followed for 10 years. Multimorbidity was defined by self-report as the presence of two or more of 12 listed chronic conditions. PA (steps-per-day) at baseline was assessed by pedometer, handgrip strength (HGS) by dynamometer and appendicular lean mass (ALM) and total body fat mass by dual x-ray absorptiometry . Relative HGS and ALM were calculated by dividing each body mass index (BMI). Regression cubic splines were used to assess evidence for a non-linear relationship.

After 10 years, 45% participants had multimorbidity. There was a non-linear relationship between PA and multimorbidity - PA was associated with lower multimorbidity risk among individuals who engaged in <10,000 steps-per-day (RR=0.91, 95% CI 0.85, 0.97, per 1000 steps-per-day), but not among those who participated in ≥10,000 steps-per-day (RR=1.04, 95% CI 0.93, 1.09, per 1000 steps-per-day). Higher BMI (RR=1.05, 95% CI 1.02, 1.08, per kg/m 2) and fat mass (RR=1.03, 95% CI 1.01, 1.04, per kg), and lower relative HGS (RR=0.85, 95% CI 0.77, 0.94, per 0.1 psi/kg/m 2) and ALM (RR=0.93, 95% CI 0.88, 0.98, per 0.1kg/kg/m 2) were linearly associated with a higher risk of multimorbidity. Absolute HGS and ALM were not significantly associated with multimorbidity.

These findings highlight the potential clinical importance of maintaining adequate levels of PA and of reducing adiposity and maintaining muscle function for minimising the risk of multimorbidity in older adults.

These findings highlight the potential clinical importance of maintaining adequate levels of PA and of reducing adiposity and maintaining muscle function for minimising the risk of multimorbidity in older adults.Intrauterine stress impairs growth and metabolism in the fetus and offspring. We recently found that sustained maternofetal inflammation resulted in intrauterine growth-restricted (MI-IUGR) fetuses with asymmetric body composition, impaired muscle glucose metabolism, and β-cell dysfunction near term. 3,4-Dichlorophenyl isothiocyanate These fetuses also exhibited heightened inflammatory tone, which we postulated was a fetal programming mechanism for the IUGR phenotype. Thus, the objective of this study was to determine whether poor growth and metabolism persisted in MI-IUGR lambs after birth. Polypay ewes received serial lipopolysaccharide or saline injections in the first 2 wk of the third trimester of pregnancy to produce MI-IUGR (n = 13) and control (n = 12) lambs, respectively. Lambs were catheterized at 25 d of age. β-Cell function was assessed at 29 d, hindlimb glucose metabolism at 30 d, and daily blood parameters from day 26 to 31. Glucose metabolism was also assessed in flexor digitorum superficialis (FDS) muscle isolated at necropsy locyte concentrations were greater (P less then 0.05) in MI-IUGR lambs, plasma tumor necrosis factor α (TNFα) was reduced (P less then 0.05). FDS muscle contained greater (P less then 0.05) TNF receptor 1 (TNFR1) and IκBα protein content. These findings indicate that maternofetal inflammation in late pregnancy results in fetal programming that impairs growth capacity, muscle glucose oxidation, and lipid homeostasis in offspring. Inflammatory indicators measured in this study appear to reflect heightened cytokine sensitivity in muscle and compensatory systemic responses to it.