Management of Severe and Severe/Complicated Clostridoides difficile Infection Using Sequential Fecal Microbiota Transplant by Retention Enema.

We evaluated serial fecal microbiota transplant (FMT) by retention enema in patients with severe or severe/complicated Clostridoides difficile infection (CDI) unresponsive to at least 48 hours of standard antibiotic therapy. Of the 15 patients included, despite initial improvement in most patients, only 5 patients sustained cure at 30 days, and serious adverse events occurred in 4 patients.

Effects of Gabra2 Point Mutations on Alcohol Intake: Increased Binge-Like and Blunted Chronic Drinking by Mice.

BACKGROUND: Alcohol use disorders are associated with single-nucleotide polymorphisms in GABRA2, the gene encoding the GABAA receptor α2-subunit in humans. Deficient GABAergic functioning is linked to impulse control disorders, intermittent explosive disorder, and to drug abuse and dependence, yet it remains unclear whether α2-containing GABAA receptor sensitivity to endogenous ligands is involved in excessive alcohol drinking. METHODS: Male wild-type (Wt) C57BL/6J and point-mutated mice rendered insensitive to GABAergic modulation by benzodiazepines (BZD; H101R), allopregnanolone (ALLO) or tetrahydrodeoxycorticosterone (THDOC; Q241M), or high concentrations of ethanol (EtOH) (S270H/L277A) at α2-containing GABAA receptors were assessed for their binge-like, moderate, or escalated chronic drinking using drinking in the dark, continuous access (CA) and intermittent access (IA) to alcohol protocols, respectively. Social approach by mutant and Wt mice in forced alcohol abstinence was compared to approach by EtOH-naïve controls. Social deficits in forced abstinence were treated with allopregnanolone (0, 3.0, 10.0 mg/kg, intraperitoneal [i.p.]) or midazolam (0, 0.56, 1.0 mg/kg, i.p.). RESULTS: Mice with BZD-insensitive α2-containing GABAA receptors (H101R) escalated their binge-like drinking. Mutants harboring the Q241M point substitution in Gabra2 showed blunted chronic intake in the CA and IA protocols. S270H/L277A mutants consumed excessive amounts of alcohol but, unlike wild-types, they did not show forced abstinence-induced social deficits. CONCLUSIONS: These findings suggest a role for: (i) H101 in species-typical binge-like drinking, (ii) Q241 in escalated chronic drinking, and (iii) S270 and/or L277 in the development of forced abstinence-associated social deficits. Clinical findings report reduced BZD-binding sites in the cortex of dependent patients; the present findings suggest a specific role for BZD-sensitive α2-containing receptors. In addition, amino acid residue 241 in Gabra2 is necessary for positive modulation and activation of GABAA receptors by ALLO and THDOC; we postulate that neurosteroid action on α2-containing receptor may be necessary for escalated chronic EtOH intake.

Association of PNC, BC, and PM2.5 measured at a central monitoring site with blood pressure in a predominantly near highway population.

Elevated blood pressure is an indicator of cardiovascular stress and increased risk of cardiovascular-related morbidity and mortality. There is emerging evidence suggesting air pollutants, including particulate matter (PM), could promote hypertension, thereby increasing cardiovascular disease risk. Repeated measurement analyses were conducted to examine the associations of three types of PM with systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) in 220 participants, (mean age=58.5 years) from the Community Assessment of Freeway Exposure and Health study (CAFEH), most of whom live near a major highway. Ambient levels of air pollutants including particle number concentration (PNC; a measure of ultrafine particle (UFP) concentration), fine PM (PM2.5, Particle diameter<2.5 µm), and black carbon (BC) were measured at a central site<7 km from the study areas. Central sites are good at capturing short-term temporal trends in pollution associated with meteorological changes over regional areas. Linear mixed-effect models that accounted for repeated measures within one person were used to examine the associations between blood pressure variables and daily average of ambient PNC, PM2.5, or BC, controlling for demographic characteristics and major confounders including temperature. Our PNC model predicted that a higher PNC of 10,000 particles/cm3 was associated with higher DBP of 2.40 mmHg (p=0.03), independent of other factors in the model. There were no significant associations for PM2.5 or BC. Post hoc subgroup analyses by obesity status showed that positive associations of DBP with PNC were more pronounced among obese individuals than non-obese individuals. These results suggested that PNC levels are associated with increased blood pressure, which may contribute to cardiovascular disease risk. More research is needed to assess the relationship between PNC and blood pressure and to address possible residual confounding.