Microbiota from human infants consuming secretors or non-secretors mothers' milk impacts the gut and immune system in mice.

Maternal secretor status is one of the determinants of human milk oligosaccharides (HMOs) composition, which, in turn, influences the gut microbiota composition of infants. To understand if this change in gut microbiota impacts immune cell composition, intestinal morphology, and gene expression, 21-day-old germ-free C57BL/6 mice were transplanted with fecal microbiota from infants whose mothers were either secretors (SMM) or non-secretors (NSM) or from infants consuming dairy-based formula (MFM). For each group, one set of mice was supplemented with HMOs. HMO supplementation did not significantly impact the microbiota diversity; however, SMM mice had a higher abundance of genus Bacteroides, Bifidobacterium, and Blautia, whereas, in the NSM group, there was a higher abundance of Akkermansia, Enterocloster, and Klebsiella. In MFM, gut microbiota was represented mainly by Parabacteroides, Ruminococcaceae_unclassified, and Clostrodium_sensu_stricto. In mesenteric lymph node, Foxp3+ T cells and innate lymphoid cells type 2 were increased in MFM mice supplemented with HMOs, while in the spleen, they were increased in SMM + HMOs mice. Similarly, serum immunoglobulin A was also elevated in MFM + HMOs group. Distinct global gene expression of the gut was observed in each microbiota group, which was enhanced with HMOs supplementation. Overall, our data show that distinct infant gut microbiota due to maternal secretor status or consumption of dairy-based formula and HMO supplementation impacts immune cell composition, antibody response, and intestinal gene expression in a mouse model. IMPORTANCE: Early life factors like neonatal diet modulate gut microbiota, which is important for the optimal gut and immune function. One such factor, human milk oligosaccharides (HMOs), the composition of which is determined by maternal secretor status, has a profound effect on infant gut microbiota. However, how the infant gut microbiota composition determined by maternal secretor status or consumption of infant formula devoid of HMOs impacts infant intestinal ammorphology, gene expression, and immune signature is not well explored. This study provides insights into the differential establishment of infant microbiota derived from infants fed by secretor or non-secretor mothers milk or those consuming infant formula and demonstrates that the secretor status of mothers promotes Bifidobacteria and Bacteroides sps. establishment. This study also shows that supplementation of pooled HMOs in mice changed immune cell composition in the spleen and mesenteric lymph nodes and immunoglobulins in circulation. Hence, this study highlights that maternal secretor status has a role in infant gut microbiota composition, and this, in turn, can impact host gut and immune system.

Colonic epithelial hypoxia remains constant during the progression of diabetes in male UC Davis type 2 diabetes mellitus rats.

INTRODUCTION: Colonocyte oxidation of bacterial-derived butyrate has been reported to maintain synergistic obligate anaerobe populations by reducing colonocyte oxygen levels; however, it is not known whether this process is disrupted during the progression of type 2 diabetes. Our aim was to determine whether diabetes influences colonocyte oxygen levels in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model. RESEARCH DESIGN AND METHODS: Age-matched male UCD-T2DM rats (174±4 days) prior to the onset of diabetes (PD, n=15), within 1 month post-onset (RD, n=12), and 3 months post-onset (D3M, n=12) were included in this study. Rats were administered an intraperitoneal injection of pimonidazole (60 mg/kg body weight) 1 hour prior to euthanasia and tissue collection to estimate colonic oxygen levels. Colon tissue was fixed in 10% formalin, embedded in paraffin, and processed for immunohistochemical detection of pimonidazole. The colonic microbiome was assessed by 16S gene rRNA amplicon sequencing and content of short-chain fatty acids was measured by liquid chromatography-mass spectrometry. RESULTS: HbA1c % increased linearly across the PD (5.9±0.1), RD (7.6±0.4), and D3M (11.5±0.6) groups, confirming the progression of diabetes in this cohort. D3M rats had a 2.5% increase in known facultative anaerobes, Escherichia-Shigella, and Streptococcus (false discovery rate <0.05) genera in colon contents. The intensity of pimonidazole staining of colonic epithelia did not differ across groups (p=0.37). Colon content concentrations of acetate and propionate also did not differ across UCD-T2DM groups; however, colonic butyric acid levels were higher in D3M rats relative to PD rats (p<0.01). CONCLUSIONS: The advancement of diabetes in UCD-T2DM rats was associated with an increase in facultative anaerobes; however, this was not explained by changes in colonocyte oxygen levels. The mechanisms underlying shifts in gut microbe populations associated with the progression of diabetes in the UCD-T2DM rat model remain to be identified.

Evaluation of a Plant-Based Infant Formula Containing Almonds and Buckwheat on Gut Microbiota Composition, Intestine Morphology, Metabolic and Immune Markers in a Neonatal Piglet Model.

A controlled-neonatal piglet trial was conducted to evaluate the impact of a plant-based infant formula containing buckwheat and almonds as the main source of protein compared to a commercially available dairy-based formula on the gut health parameters. Two day old piglets were fed either a plant-based or a dairy-based formula until day 21. Gut microbiome, cytokines, growth and metabolism related outcomes, and intestinal morphology were evaluated to determine the safety of the plant-based infant formula. This study reported that the plant-based formula-fed piglets had a similar intestinal microbiota composition relative to the dairy-based formula-fed group. However, differential abundance of specific microbiota species was detected within each diet group in the small and large intestinal regions and fecal samples. Lactobacillus delbrueckii, Lactobacillus crispatus, and Fusobacterium sp. had higher abundance in the small intestine of plant-based formula-fed piglets compared to the dairy-based group. Bacteroides nordii, Enterococcus sp., Lactobacillus crispatus, Prevotella sp., Ruminococcus lactaris, Bacteroides nordii, Eisenbergiella sp., Lactobacillus crispatus, Prevotella sp., and Akkermansia muciniphila had greater abundance in the large intestine of the plant based diet fed piglets relative to the dairy-based diet group. In the feces, Clostridiales, Bacteroides uniformis, Butyricimonasvirosa, Cloacibacillus porcorum, Clostridium clostridioforme, and Fusobacterium sp. were abundant in dairy-based group relative to the plant-based group. Lachnospiraceae, Clostridium scindens, Lactobacillus coleohominis, and Prevetolla sp. had greater abundance in the feces of the plant-based group in comparison to the dairy-based group. Gut morphology was similar between the plant and the dairy-based formula-fed piglets. Circulatory cytokines, magnesium, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), vitamin D, vitamin K, and IgE levels were similar among all piglets independent of dietary group. Overall, the present study demonstrated that a plant-based formula with buckwheat and almonds as the primary source of protein can support similar gut microbiota growth and health outcomes compared to a dairy-based infant formula.

Design and Implementation of the Pediatric Quality Measures Program 2.0.

The Pediatric Quality Measures Program (PQMP) was established in response to the Children's Health Insurance Program Reauthorization Act of 2009, aiming to measure and improve health care quality and outcomes for the nation's children. This brief report describes the PQMP 2.0 and its components. PQMP 2.0 established a priori research questions (Research Foci) and endeavored to assess usability and feasibility of measures through measure implementation and quality improvement initiatives. The Agency for Healthcare Research and Quality (AHRQ) and the Centers for Medicare and Medicaid Services (CMS) awarded 6 grants to Centers of Excellence (COEs), and a contract to facilitate collaboration and learning across the COEs. The 6 COEs partnered with stakeholders from multiple levels (eg, state, health plan, hospital, provider, family) to field test real-world implementation and refinement of pediatric quality measures and quality improvement initiatives. The PQMP Learning Collaborative (PQMP-LC) consisted of AHRQ, CMS, the 6 COEs, and L&M Policy Research, LLC. The PQMP-LC completed literature reviews, key informant interviews, and data collection to develop reports to address the Research Foci; aided with development of measure implementation and quality improvement toolkits; conceptualized an implementation science framework, analysis, and roadmap; and facilitated dissemination of learnings and products. The various products are intended to support the uptake of PQMP measures and inform future pediatric measurement and improvement work.

Progression of diabetes is associated with changes in the ileal transcriptome and ileal-colon morphology in the UC Davis Type 2 Diabetes Mellitus rat.

Deterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abundance, and transcript expression in the University of California Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model. Male UCD-T2DM rats (age ~170 days) were included if <1-month (n = 6, D1M) or 3-month (n = 6, D3M) post-onset of diabetes. Younger nondiabetic UCD-T2DM rats were included as a nondiabetic comparison (n = 6, ND, age ~70 days). Ileum villi height/crypt depths and colon crypt depths were assessed by histology. Microbial abundance of colon content was measured with 16S rRNA sequencing. Ileum and colon transcriptional abundances were analyzed using RNA sequencing. Ileum villi height and crypt depth were greater in D3M rats compared to ND. Colon crypt depth was greatest in D3M rats compared to both ND and D1M rats. Colon abundances of Akkermansia and Muribaculaceae were lower in D3M rats relative to D1M, while Oscillospirales, Phascolarctobacterium, and an unidentified genus of Lachnospiraceae were higher. Only two transcripts were altered by diabetes advancement within the colon; however, 2039 ileal transcripts were altered. Only colonic abundances of Sptlc3, Enpp7, Slc7a15, and Kctd14 had more than twofold changes between D1M and D3M rats. The advancement of diabetes in the UCD-T2DM rat results in a trophic effect on the mucosal epithelia and was associated with regulation of gastrointestinal tract RNA expression, which appears more pronounced in the ileum relative to the colon.

On the potential role of globins in brown adipose tissue: a novel conceptual model and studies in myoglobin knockout mice.

Myoglobin (Mb) regulates O2 bioavailability in muscle and heart as the partial pressure of O2 (Po2) drops with increased tissue workload. Globin proteins also modulate cellular NO pools, "scavenging" NO at higher Po2 and converting NO2- to NO as Po2 falls. Myoglobin binding of fatty acids may also signal a role in fat metabolism. Interestingly, Mb is expressed in brown adipose tissue (BAT), but its function is unknown. Herein, we present a new conceptual model that proposes links between BAT thermogenic activation, concurrently reduced Po2, and NO pools regulated by deoxy/oxy-globin toggling and xanthine oxidoreductase (XOR). We describe the effect of Mb knockout (Mb-/-) on BAT phenotype [lipid droplets, mitochondrial markers uncoupling protein 1 (UCP1) and cytochrome C oxidase 4 (Cox4), transcriptomics] in male and female mice fed a high-fat diet (HFD, 45% of energy, ∼13 wk), and examine Mb expression during brown adipocyte differentiation. Interscapular BAT weights did not differ by genotype, but there was a higher prevalence of mid-large sized droplets in Mb-/-. COX4 protein expression was significantly reduced in Mb-/- BAT, and a suite of metabolic/NO/stress/hypoxia transcripts were lower. All of these Mb-/--associated differences were most apparent in females. The new conceptual model, and results derived from Mb-/- mice, suggest a role for Mb in BAT metabolic regulation, in part through sexually dimorphic systems and NO signaling. This possibility requires further validation in light of significant mouse-to-mouse variability of BAT Mb mRNA and protein abundances in wild-type mice and lower expression relative to muscle and heart.NEW & NOTEWORTHY Myoglobin confers the distinct red color to muscle and heart, serving as an oxygen-binding protein in oxidative fibers. Less attention has been paid to brown fat, a thermogenic tissue that also expresses myoglobin. In a mouse knockout model lacking myoglobin, brown fat had larger fat droplets and lower markers of mitochondrial oxidative metabolism, especially in females. Gene expression patterns suggest a role for myoglobin as an oxygen/nitric oxide-sensor that regulates cellular metabolic and signaling pathways.

3,5-Di-bromo-4-carbamoyl-benzoic acid 2-propanol monosolvate.

In the title solvated crystal, C8H5Br2NO3·C3H8O, the acid mol-ecules form inversion dimers by pairwise N-H⋯O hydrogen bonds between carbamoyl groups and the carboxyl and carbamoyl groups link to form head-to-tail inversion dimers. The 2-propanol hydroxyl group inter-poses between adjacent head-tail pairs, resulting in C 3 3(10) chains of hydrogen bonds propagating along [100]. The mol-ecules of 2-propanol are disordered over two sets of sites in a 0.598 (8):0.402 (8) ratio. The best-fit planes of the carbamoyl group and benzene ring are inclined by 88.26 (11)°. This is a greater inclination than was previously reported with CH3, Cl, F or H in place of the Br atoms, although those analogues did not have a para carboxyl group.

Psychosocial Factors Associated with Healthy and Unhealthy Interpregnancy Intervals.

Purpose: To examine the influence of psychosocial factors, including anxiety, depression, social support, maternal substance abuse, and intimate partner violence (IPV) on interpregnancy intervals (IPIs). Methods: B'more for Healthy Babies-Upton/Druid Heights is part of a citywide initiative to improve the health of at-risk pregnant women and their children. Participants with at least one prior birth completed baseline, postpartum, and 3-month follow-up surveys with questions about pregnancy, medical, and psychosocial history. Associations between IPI and the independent variables were assessed using chi-square analysis and analysis of variance. Multivariable multinomial logistic regression models examined significant associations while controlling for other independent variables and potential confounders. Results: Participants with current IPV were more likely to have a short IPI (odds ratio [OR]=13.1; 95% confidence interval [CI]=1.07-158.9; p=0.04) than healthy IPI. Women with family social support were more likely to have a healthy IPI (OR=5.88, 95% CI=1.02-31.25, p=0.05) than those without family social support. Maternal anxiety and depression did not significantly influence IPI. Conclusion: IPV increased the likelihood of having an unhealthy IPI among this population and family social support increased the likelihood of having a healthy IPI. Additional efforts to address IPV and enhance family social support may lead to improved pregnancy outcomes.

Implementation of Local Wellness Policies in Schools: Role of School Systems, School Health Councils, and Health Disparities.

BACKGROUND: Written local wellness policies (LWPs) are mandated in school systems to enhance opportunities for healthy eating/activity. LWP effectiveness relies on school-level implementation. We examined factors associated with school-level LWP implementation. Hypothesized associations included system support for school-level implementation and having a school-level wellness team/school health council (SHC), with stronger associations among schools without disparity enrollment (majority African-American/Hispanic or low-income students). METHODS: Online surveys were administered: 24 systems (support), 1349 schools (LWP implementation, perceived system support, SHC). The state provided school demographics. Analyses included multilevel multinomial logistic regression. RESULTS: Response rates were 100% (systems)/55.2% (schools). Among schools, 44.0% had SHCs, 22.6% majority (≥75%) African-American/Hispanic students, and 25.5% majority (≥75%) low-income (receiving free/reduced-price meals). LWP implementation (17-items) categorized as none = 36.3%, low (1-5 items) = 36.3%, high (6+ items) = 27.4%. In adjusted models, greater likelihood of LWP implementation was observed among schools with perceived system support (high versus none relative risk ratio, RRR = 1.63, CI: 1.49, 1.78; low versus none RRR = 1.26, CI: 1.18, 1.36) and SHCs (high versus none RRR = 6.8, CI: 4.07, 11.37; low versus none RRR = 2.24, CI: 1.48, 3.39). Disparity enrollment did not moderate associations (p > .05). CONCLUSIONS: Schools with perceived system support and SHCs had greater likelihood of LWP implementation, with no moderating effect of disparity enrollment. SHCs/support may overcome LWP implementation obstacles related to disparities.

Convalescent care of infants in the neonatal intensive care unit in community hospitals: risk or benefit?

OBJECTIVE: To compare very low birth weight (VLBW) infants transported to a community hospital (CH) before discharge with infants who received convalescent care in a regional-referral NICU (RR-NICU) on 4 parameters: health indicators at the time of hospital discharge, health care use during the 4 months after discharge to home, parent satisfaction with hospital care, and cost of hospitalization. PATIENTS AND METHODS: VLBW infants cared for in 2 RR-NICUs during 2004-2006 were enrolled in the study. One RR-NICU transfers infants to a CH for convalescent care and the other discharges infants directly home. Infants were followed prospectively. Information was gathered from medical charts, parent interviews, and hospital business offices. RESULTS: A total of 255 VLBW infants were enrolled in the study, and 148 were transferred to 15 CHs. Nineteen percent of transferred infants were readmitted to a higher level of care before discharge from the hospital. Preventative health measures and screening examinations were more frequently missed, readmission within 2 weeks of discharge from the hospital was more frequent, parents were less satisfied with hospital care, and duration of hospitalization was 12 days longer, although not statistically different, if infants were transferred to a CH for convalescence rather than discharged from the RR-NICU. Total hospital charges did not differ significantly between the groups. CONCLUSION: Transfer of infants to a CH from an RR-NICU for convalescent care has become routine but may place infants at risk. Our study indicates room for improvement by both CHs and RR-NICUs in the care of transferred VLBW infants.

"Nationals" and "expatriates": challenges of fulfilling "sans frontières" ("without borders") ideals in international humanitarian action.

The international humanitarian organization, Médecins Sans Frontières (MSF), is strongly committed to principles of universalism, egalitarianism, and equity, in both its internal and external relations. Nevertheless, the organization distinguishes between so-called "national" staff members (those who are indigenous to the countries where MSF projects are located), and "expatriate" staff (those who are involved in projects outside their countries of residence), in certain ways that it has self-critically termed "discriminatory", "colonialist", and even "racist". It has resolved to remedy such practices. Through a first-hand case study of MSF activities in Russia, this article demonstrates that the dynamics of the "nationals"/ "expatriates" divide is a more complex phenomenon than MSF's self-accusatory diagnosis implies; that a fuller recognition and utilization of nationals' local knowledge would mitigate some of the conditions of inequality and inequity that they experience; but that it would not necessarily be desirable to expunge all differences between the two groups of staff Furthermore, because they are intrinsic to the structure and conditions of international humanitarian action, some of these differences could not easily be elminated by MSF, or by any other organization engaged in this kind of action.

Meeting threats to global health: a call for American leadership.

Although the application of major biomedical advances has yielded spectacular results for individual health, there has been little improvement in the health of whole populations. There is a "back to the future" irony in the fact that at the inception of the 21st century, the eruption and spread of a multitude of "old" and "new" infectious diseases has become the most serious global threat to the health of humankind. At this historical juncture, the United States is the country with the most potential for favorably influencing global health and health care. Although there are historical, cultural, economic, and political factors that impede the United States from rising to this challenge, there is both a moral imperative and a rational long-term self-interest basis for the U.S. medical profession and government to exercise leadership in facing the health challenges of tragic and genocidal proportions that threaten everyone in an increasingly interdependent world.

Remembering the "golden years" of patient-oriented clinical research: a collective conversation.

The period from the end of World War II to the early 1960s has been characterized as the "golden years" of patient-oriented clinical research in the United States, a period catalyzed and fostered by advances in biology and medicine, changes in the organization and financing of research units, and strong moral and political convictions growing out of the war about the importance and possibilities of the scientific enterprise. This account of some of the salient themes, phenomena, and issues in clinical research during that era draws primarily on the proceedings of an oral history conference whose core participants were a number of emeritus physician-investigators who had played major roles in shaping patient-oriented research. The topics that they and the other conferees discussed included the factors that had led the emeritus physician-investigators into clinical research; the organizational attributes of the units where they had trained and worked, focusing particularly on Boston's Peter Bent Brigham Hospital; the vital role played by private and federal funding for research and training; and some of the changes in the nature of clinical research, research training, and their relationships to the care of the sick in the decades since the golden years.

"He knows that machine is his mortality": old and new social and cultural patterns in the clinical trial of the AbioCor artificial heart.

The clinical trial of the AbioCor artificial heart, initiated in July 2001 and still in process, has taken place within a matrix of social and cultural patterns that are both "old" and new. The old patterns--those that have accompanied previous clinical trials of other vital artificial organs and transplantation in the United States--include "experiment perilous," and courage, heroism, and pioneering themes; "right stuff" motifs; "Americana" symbols; allusions to the meaning of the human heart; connections with a for-profit corporation; and the occurrence of moratoriums. New patterns--those more particular and distinctive to the AbioCor trial--involve the restrictions imposed on releasing information about the post-operative clinical status of the implant recipients; the quasi-institutionalization of a patient advocacy system to represent patient-subjects and their families; and the "crises of success" that were encountered when several of the AbioCor recipients survived longer than expected. In certain instances, old and new patterns have been combined--for example, in some of the idiosyncratic features of the AbioCor-associated lawsuit that has resulted in part from the problem of the "therapeutic misconception," the belief that an experimental intervention is actually intended to be a treatment.