Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

Complex Pharmacology of Free Fatty Acid Receptors

G protein-coupled receptors (GPCRs) are historically the most successful family of drug targets. In recent times it has become clear that the pharmacology of these receptors is far more complex than previously imagined. Understanding of the pharmacological regulation of GPCRs now extends beyond simple competitive agonism or antagonism by ligands interacting with the orthosteric binding site of the receptor to incorporate concepts of allosteric agonism, allosteric modulation, signaling bias, constitutive activity, and inverse agonism. Herein, we consider how evolving concepts of GPCR pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or “free” fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets for the treatment of metabolic and inflammatory diseases. Further understanding of the complex pharmacology of these receptors will be critical to unlocking their ultimate therapeutic potential

A Case Report of Successful Kidney Donation After Brain Death Following Nicotine Intoxication

Nicotine intoxication is a rare cause of death and can lead to brain death after respiratory arrest and hypoxic-ischemic encephalopathy. To our knowledge, no previous reports regarding organ donation after nicotine intoxication have been described. We present a successful case of kidney donation after brain death caused by subcutaneous nicotine overdose from liquid nicotine from an e-cigarette cartridge in an attempted suicide. Both kidneys were transplanted successfully with immediate graft function, and both recipients were discharged at postoperative day 9 with normal plasma creatinine levels. Graft function has remained excellent in follow-up. This case suggests that kidneys from a donor with fatal nicotine intoxication may be successfully used for kidney transplantation in the absence of other contraindications for donation.Peer reviewe

The role of Probiotics in allergic diseases

Allergic disorders are very common in the pediatric age group. While the exact etiology is unclear, evidence is mounting to incriminate environmental factors and an aberrant gut microbiota with a shift of the Th1/Th2 balance towards a Th2 response. Probiotics have been shown to modulate the immune system back to a Th1 response. Several in vitro studies suggest a role for probiotics in treating allergic disorders. Human trials demonstrate a limited benefit for the use of probiotics in atopic dermatitis in a preventive as well as a therapeutic capacity. Data supporting their use in allergic rhinitis are less robust. Currently, there is no role for probiotic therapy in the treatment of bronchial asthma. Future studies will be critical in determining the exact role of probiotics in allergic disorders

Status of four-neutrino mass schemes: a global and unified approach to current neutrino oscillation data

We present a unified global analysis of neutrino oscillation data within the framework of the four-neutrino mass schemes (3+1) and (2+2). We include all data from solar and atmospheric neutrino experiments, as well as information from short-baseline experiments including LSND. If we combine only solar and atmospheric neutrino data, (3+1) schemes are clearly preferred, whereas short-baseline data in combination with atmospheric data prefers (2+2) models. When combining all data in a global analysis the (3+1) mass scheme gives a slightly better fit than the (2+2) case, though all four-neutrino schemes are presently acceptable. The LSND result disfavors the three-active neutrino scenario with only $\Delta m^2_{sol}$ and $\Delta m^2_{atm}$ at 99.9% CL with respect to the four-neutrino best fit model. We perform a detailed analysis of the goodness of fit to identify which sub-set of the data is in disagreement with the best fit solution in a given mass scheme.Comment: 32 pages, 8 Figures included, REVTeX4.Improved discussion in sec. XI, references added, version accepted by Phys. Rev.

The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota

The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease

Neutrinoless double beta decay within Self-consistent Renormalized Quasiparticle Random Phase Approximation and inclusion of induced nucleon currents

The first, to our knowledge, calculation of neutrinoless double beta decay ($0\nu\beta\beta$-decay) matrix elements within the self-consistent renormalised Quasiparticle Random Phase Approximation (SRQRPA) is presented. The contribution from the momentum-dependent induced nucleon currents to $0\nu\beta\beta$-decay amplitude is taken into account. A detailed nuclear structure study includes the discussion of the sensitivity of the obtained SRQRPA results for $0\nu\beta\beta$-decay of $^{76}$Ge to the parameters of nuclear Hamiltonian, two-nucleon short-range correlations and the truncation of the model space. A comparision with the standard and renormalized QRPA is presented. We have found a considerable reduction of the SRQRPA nuclear matrix elements, resulting in less stringent limits for the effective neutrino mass.Comment: 13 pages, 3 figures, 1 tabl

Lactobacillus rhamnosus HN001 Attenuates Allergy Development in a Pig Model

HN001 (HN001) supplementation decreased the prevalence of eczema and IgE associated eczema. However, the influence of HN001 on the incidence of wheeze, asthma, and/or other allergic manifestations has yet to be reported.This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model. allergen (ASA) during a six week time frame in post-weanling pigs supplemented daily with HN001, or without supplementation. One week following final sensitization intradermal skin tests and respiratory challenges were conducted.In response to intradermal and respiratory challenges, ASA-sensitized pigs fed HN001 had less severe skin flare reactions, smaller increases in pleural pressure, and trends towards lower changes in arterial oxygen and carbon dioxide partial pressure levels compared to control pigs. The frequency of ASA-specific IFN-γ-secreting peripheral blood mononuclear cells, as well as the amount of IL-10 produced by ASA-specific cells, was of greater magnitude in probiotic-fed pigs compared to control animals. These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression.Probiotic supplementation decreased the severity of allergic skin and lung responses in allergen-sensitized pigs with a corresponding increase in IFN-γ expression. A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans

Reconciling neutrino anomalies in a simple four-neutrino scheme with R-parity violation

We propose a simple extension of the MSSM based on extra compact dimensions which includes an $SU(2) \otimes U(1)$ singlet superfield. The fermion present in this superfield is the sterile neutrino, which combines with one linear combination of $\nu_e-\nu_{\mu}-\nu_{\tau}$ to form a Dirac pair whose mass accounts for the LSND anomaly. Its small mass can be ascribed to a volume suppression factor associated with extra compact dimensions. On the other hand the sterile neutrino scalar partner can trigger the spontaneous violation of R-parity, thereby inducing the necessary mass splittings to fit also the solar and atmospheric neutrino data. Thus the model can explain all neutrino oscillation data. It leads to four predictions for the neutrino oscillation parameters and implies that the atmospheric neutrino problem must include at least some $\nu_{\mu} \to \nu_s$ oscillations, which will be testable in the near future. Moreover it also predicts that the lightest supersymmetric particle (LSP) decays visibly via lepton number violating modes, which could be searched for at present and future accelerators.Comment: 15 pages, requires axodraw.sty and elsart.cl

Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease

Peer reviewe