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ucose in the hyper- or hypoglycemic concentrations range and challenge the clinical importance of short-term glucose fluctuations for gastric emptying in patients with type 1 diabetes. Rather, chronic hyperglycemia is associated with slowed gastric emptying.

To identify the core gut microbial features associated with type 2 diabetes risk and potential demographic, adiposity, and dietary factors associated with these features.

We used an interpretable machine learning framework to identify the type 2 diabetes-related gut microbiome features in the cross-sectional analyses of three Chinese cohorts one discovery cohort (

= 1,832, 270 cases of type 2 diabetes) and two validation cohorts (cohort 1

= 203, 48 cases; cohort 2

= 7,009, 608 cases). We constructed a microbiome risk score (MRS) with the identified features. We examined the prospective association of the MRS with glucose increment in 249 participants without type 2 diabetes and assessed the correlation between the MRS and host blood metabolites (

= 1,016). We transferred human fecal samples with different MRS levels to germ-free mice to confirm the MRS-type 2 diabetes relationship. We then examined the prospective association of demographic, adiposity, and dietary factors with the MRS (

= 1,832).

The MRS (including 14 microbial features) consistently associated with type 2 diabetes, with risk ratio for per 1-unit change in MRS 1.28 (95% CI 1.23-1.33), 1.23 (1.13-1.34), and 1.12 (1.06-1.18) across three cohorts. The MRS was positively associated with future glucose increment (

< 0.05) and was correlated with a variety of gut microbiota-derived blood metabolites. Animal study further confirmed the MRS-type 2 diabetes relationship. Body fat distribution was found to be a key factor modulating the gut microbiome-type 2 diabetes relationship.

Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment.

Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment.

The aim of this study was to compare the University of Texas (UT) and Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) foot ulcer scores in predicting ulcer outcome within a routine diabetes foot clinic.

From 2006 to 2018, data were collected from all patients attending an outpatient diabetes foot clinic with an active ulcer not healed within 4 weeks. UT and SINBAD were compared in predicting ulcer outcome. A unified numerical score for UT was constructed and compared with UT grade (depth) and stage scores. Outcomes included death, a healed ulcer, or a nonhealed ulcer, which included major or minor amputation and nonhealing chronic ulcers.

Outcomes were available from 1,645 ulcer outcomes in 1,068 patients (mean [SD] age 65.4 [4] years, 72% male), of which 1,108 (67%) healed. With exclusion of death as an adverse outcome, the c-statistic (area under operator curve) was 0.67 (95% CI 0.65-0.71) for UT grade/depth and 0.64 (0.61-0.67) for UT stage. The new unified UT score had an improved c-statistic of 0.71 (0.68-0.74). The c-statistic was 0.72 (0.69-0.75) for SINBAD. There was a stepwise decrease in the proportion of ulcers healed for each increased score on ulcer grading for both grading schemes.

This large and independent observational comparison, in a real-world clinical setting, demonstrated that the UT and SINBAD diabetes foot ulcer grading schemes had similar prognostic ability for predicting foot ulcer outcomes. We have devised and validated a unified numerical scoring system for UT.

This large and independent observational comparison, in a real-world clinical setting, demonstrated that the UT and SINBAD diabetes foot ulcer grading schemes had similar prognostic ability for predicting foot ulcer outcomes. We have devised and validated a unified numerical scoring system for UT.Cutibacterium acnes is the third most common cause of cerebrospinal fluid (CSF) shunt infection and is likely underdiagnosed due to the difficulty in culturing this pathogen. Shunt infections lead to grave neurologic morbidity for patients especially when there is a delay in diagnosis. Currently, the gold standard for identifying CSF shunt infections is microbiologic culture. However, C. acnes infection often results in falsely negative cultures; therefore, new diagnostic methods are needed. To investigate potential CSF biomarkers of C. acnes CSF shunt infection we adapted a rat model of CSF catheter infection to C. acnes. We found elevated levels of interleukin-1β (IL-1β), IL-6, chemokine ligand 2, and IL-10 in the CSF and brain tissues of animals implanted with C. acnes-infected catheters compared to sterile controls at day 1 postinfection. This coincided with modest increases in neutrophils in the CSF and, to a greater extent, in the brain tissues of animals with C. acnes infection, which closely mirrors the clinical findings in patients with C. acnes shunt infection. Mass spectrometry revealed that the CSF proteome is altered during C. acnes shunt infection and changes over the course of disease, typified at day 1 postinfection by an acute-phase and pathogen neutralization response evolving to a response consistent with wound resolution at day 28 compared to a sterile catheter placement. selleck chemical Collectively, these results demonstrate that it is possible to distinguish C. acnes infection from sterile postoperative inflammation and that CSF proteins could be useful in a diagnostic strategy for this pathogen that is difficult to diagnose.Enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrheal illness in the military, travelers, and children living in low- to middle-income countries. Increased antibiotic resistance, the absence of a licensed vaccine, and the lack of broadly practical therapeutics perpetuate the significant health and financial burden resulting from ETEC infection. A critical step in the evaluation of vaccines and therapeutics is preclinical screening in a relevant animal disease model that closely replicates human disease. We previously developed a diarrheal model of class 5a colonization factor (CF) CFA/I-expressing ETEC in the New World owl monkey species Aotus nancymaae using ETEC strain H10407. In order to broaden the use of the model, we report here on the development of A. nancymaae models of ETEC expressing the class 5b CFs CS17 and CS19 with strains LSN03-016011/A and WS0115A, respectively. For both models, we observed diarrheal attack rates of ≥80% after oral inoculation with 5 × 1011 CFU of bacteria. These models will aid in assessing the efficacy of future ETEC vaccine candidates and therapeutics.

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