Microbiome changes associated with acute and chronic pancreatitis: A systematic review.

BACKGROUND: Altered intestinal microbiota has been reported in pancreatic disorders, however, it remains unclear whether these changes alter the course of disease in patients with acute (AP) and chronic pancreatitis (CP), or whether these disease states alter the environment to enable pathogenic microbial composition changes to occur. We undertook a systematic review to characterize the gut microbiome in pancreatitis patients. METHODS: MEDLINE and EMBASE were searched for studies on microbiota in pancreatitis published from January 1, 2000 to June 5, 2020. Animal studies, reviews, case reports, and non-English articles were excluded. A frequency analysis was performed for outcomes reported in ≥2 studies and studies were analyzed for risk of bias and quality of evidence. RESULTS: 22 papers met inclusion criteria; 15 included AP, 7 included CP. No studies were appropriately designed to assess whether alterations in the gut microbiome exacerbate pancreatitis or develop as a result of pancreatitis. We did identify several patterns of microbiome changes that are associated with pancreatitis. The gut microbiome demonstrated decreased alpha diversity in 3/3 A P studies and 3/3 C P studies. Beta diversity analysis revealed differences in bacterial community composition in the gut microbiome in 2/2 A P studies and 3/3 C P studies. Functionally, gut microbiome changes were associated with infectious pathways in AP and CP. Several studies suffered from high risk of bias and inadequate quality. CONCLUSIONS: Detecting differences in microbial composition associated with AP and CP may represent a diagnostic tool. Appropriately controlled longitudinal studies are needed to determine whether microbiome changes are causative or reactive in pancreatitis.

Stokes phenomena in discrete Painlevé II.

We consider the asymptotic behaviour of the second discrete Painlevé equation in the limit as the independent variable becomes large. Using asymptotic power series, we find solutions that are asymptotically pole-free within some region of the complex plane. These asymptotic solutions exhibit Stokes phenomena, which is typically invisible to classical power series methods. We subsequently apply exponential asymptotic techniques to investigate such phenomena, and obtain mathematical descriptions of the rapid switching behaviour associated with Stokes curves. Through this analysis, we determine the regions of the complex plane in which the asymptotic behaviour is described by a power series expression, and find that the behaviour of these asymptotic solutions shares a number of features with the tronquée and tri-tronquée solutions of the second continuous Painlevé equation.

The role of copper in the thermal conductivity of thermoelectric oxychalcogenides: do lone pairs matter?

Understanding the underlying mechanisms that suppress thermal conduction in solids is of paramount importance for the targeted design of materials for thermal management and thermoelectric energy conversion applications. Bismuth copper oxychalcogenides, BiOCuQ (Q = Se, Te), are highly crystalline thermoelectric materials with an unusually low lattice thermal conductivity of ∼0.5 Wm(-1) K(-1), a value normally found in amorphous materials. Here we unveil the origin of the unusual thermal transport properties of these phases. First principles calculations of the vibrational properties combined with analysis of in-situ neutron diffraction data, demonstrate that weak bonding of copper atoms within the structure leads to an unexpected vibrational mode at low frequencies, which is likely to be a major contributor to the low thermal conductivity of these materials. In addition, we show that anharmonicity and the large Grüneisen parameter in these oxychalcogenides are mainly related to the low frequency copper vibrations, rather than to the Bi(3+) lone pairs.

Novel GMP-compatible protocol employing an allogeneic B cell bank for clonal expansion of allospecific natural regulatory T cells.

The adoptive transfer of natural regulatory T cells (nTreg) is a new option to reshape undesired immune reactivity in autoimmunity and transplantation toward "tolerance." The first clinical trials using adoptive transfer of polyclonal nTreg demonstrated safety and hints of efficacy. However, the low frequencies of antigen-specific cells among the pool of polyclonal nTreg and their broad antigen nonspecific suppression are limitations of this approach regarding efficacy and safety. Recently, the isolation and expansion of (allo)antigen-specific nTreg have successfully been achieved by using Treg-specific activation markers but the yield is relatively low. Here, we describe a novel good manufacturing practice (GMP)-compatible expansion protocol of alloantigen-specific nTreg based on the stimulation of nTreg by allogeneic activated B cells. Their functionality and specificity are superior compared to polyclonal nTreg both in vitro and in vivo. Employing an allogeneic B cell bank, designed to cover the majority of HLA types, allows fast GMP-compliant manufacturing for donor-specific nTreg for clinical application in organ and stem cell transplantation. TCR repertoire analyses by next generation sequencing revealed impressive expansion by several log-steps of even very low-abundance alloantigen-specific nTreg clones. This novel method offers a simple approach for expanding antigen-specific nTreg and is characterized by high replicability and easy transferability to full GMP standards.

Assessment of hindfoot deformity by three-dimensional MRI in infant club foot.

In 12 infants aged under 16 months with unilateral club foot we used MRI in association with multiplanar reconstruction to calculate the volume and principal axes of inertia of the bone and cartilaginous structures of the hindfoot. The volume of these structures in the club foot is about 20% smaller than that in the normal foot. The reduction in volume of the ossification centre of the talus (40%) is greater than that of the calcaneus (20%). The long axes of both the ossification centre and the cartilaginous anlage of the calcaneus are identical in normal and club feet. The long axis of the osseous nucleus of the talus of normal and club feet is medially rotated relative to the cartilaginous anlage, but the angle is greater in club feet (10 degrees v 14 degrees). The cartilaginous structure of the calcaneus is significantly medially rotated in club feet (15 degrees) relative to the bimalleolar axis. The cartilaginous anlage of the talus is medially rotated in both normal and club feet, but with a smaller angle for club feet (28 degrees v 38 degrees). This objective technique of measurement of the deformity may be of value preoperatively.

Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians.

There is a functional polymorphism of the mitochondrial aldehyde dehydrogenase (ALDH2) gene with the variant allele (ALDH2*2) encoding a protein subunit that confers low activity to the tetrameric enzyme. Genetic epidemiologic studies have strongly suggested that homozygosity for the allele ALDH2*2 is sufficient in completely inhibiting the development of alcoholism in Asians. To study the pathophysiology of this unique pharmacogenetic effect, we recruited a total of eighteen adult Han Chinese men, matched by age, body-mass index, nutritional state and homozygosity at the alcohol dehydrogenase gene loci from a population base of 273 men. Six individuals were chosen for each of the three ALDH2 allelotypes: homozygous ALDH2*2/*2, heterozygous ALDH2*1/*2, and homozygous ALDH2*1/*1. Following a low dose of ethanol (0.2 g/kg body weight), blood ethanol/acetaldehyde concentrations, cardiac and extracranial/intracranial arterial hemodynamic parameters, as well as self-rated subjective sensations, were measured for 130 min. Homozygous ALDH2*2 individuals were found to be strikingly responsive to the small amount of alcohol, as evidenced by the pronounced cardiovascular hemodynamic effects as well as subjective perception of general discomfort for as long as 2 h following ingestion. This low-dose alcohol hypersensitivity, accompanied by a prolonged and large accumulation of acetaldehyde in blood, provides an explanation for the strong protection against heavy drinking and alcoholism in individuals homozygous for the ALDH2*2 gene allele.

Ethanol and acetaldehyde metabolism in chinese with different aldehyde dehydrogenase-2 genotypes.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for ethanol metabolism in humans. Both enzymes exhibit genetic polymorphisms among racial populations. About half of the Chinese population lack mitochondrial ALDH2 activity and such a deficiency has been believed to be a negative risk factor for the development of alcoholism. To assess ethanol and acetaldehyde metabolism in Chinese with different ALDH2 genotypes, we genotyped 273 male adults at the ADH2, ADH3, and ALDH2 loci by using polymerase chain reaction-directed mutagenesis and restriction fragment length polymorphisms. Of the 143 individuals homozygous for both the ADH2*2 and the ADH3*1 alleles, 80, 55, and 8 were identified as ALDH2*1/*1, ALDH2*1/*2, and ALDH2*/*2, respectively. Five each from the above three ALDH2 genotypic subjects underwent alcohol elimination testing. Blood ethanol and acetaldehyde levels were determined at various times up to 130 min after intaking a low dose of ethanol (0.2 g/kg body weight) by using head-space gas chromatography and high-performance liquid chromatography with fluorescence detection, respectively. The mutant homozygotes of ALDH2*2/*2 and the heterozygotes exhibited significantly higher peak acetaldehyde concentrations and also greater areas under the blood concentrations-time curve (AUC) than did the normal homozygotes of ALDH2*1/*1, with the mutant homozygotes both being the largest. The mutant homozygotes displayed significantly higher peak ethanol levels and AUC compared to the normal homozygotes. Of the 17 subjective feeling items tested, palpitation, facial warming, effects of alcohol, and dizziness were found to be most pronounced among the mutant homozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)