Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

Extended-Spectrum-Beta-Lactamases, AmpC Beta-Lactamases and Plasmid Mediated Quinolone Resistance in Klebsiella spp. from Companion Animals in Italy

We report the genetic characterization of 15 Klebsiella pneumoniae (KP) and 4 isolates of K. oxytoca (KO) from clinical cases in dogs and cats and showing extended-spectrum cephalosporin (ESC) resistance. Extended spectrum beta-lactamase (ESBL) and AmpC genes, plasmid-mediated quinolone resistance (PMQR) and co-resistances were investigated. Among KP isolates, ST101 clone was predominant (8/15, 53%), followed by ST15 (4/15, 27%). ST11 and ST340, belonging to Clonal Complex (CC)11, were detected in 2012 (3/15, 20%). MLST on KP isolates corresponded well with PFGE results, with 11 different PFGE patterns observed, including two clusters of two (ST340) and four (ST101) indistinguishable isolates, respectively. All isolates harbored at least one ESBL or AmpC gene, all carried on transferable plasmids (IncR, IncFII, IncI1, IncN), and 16/19 were positive for PMQR genes (qnr family or aac(6')-Ib-cr). The most frequent ESBL was CTX-M-15 (11/19, 58%), detected in all KP ST101, in one KP ST15 and in both KP ST340. blaCTX-M-15 was carried on IncR plasmids in all but one KP isolate. All KP ST15 isolates harbored different ESC resistance genes and different plasmids, and presented the non-transferable blaSHV-28 gene, in association with blaCTX-M-15, blaCTX-M-1 (on IncR, or on IncN), blaSHV-2a (on IncR) or blaCMY-2 genes (on IncI1). KO isolates were positive for blaCTX-M-9 gene (on IncHI2), or for the blaSHV-12 and blaDHA-1 genes (on IncL/M). They were all positive for qnr genes, and one also for the aac(6')-Ib-cr gene. All Klebsiella isolates showed multiresistance towards aminoglycosides, sulfonamides, tetracyclines, trimethoprim and amphenicols, mediated by strA/B, aadA2, aadB, ant (2")-Ia, aac(6')-Ib, sul, tet, dfr and cat genes in various combinations. The emergence in pets of multidrug-resistant Klebsiella with ESBL, AmpC and PMQR determinants, poses further and serious challenges in companion animal therapy and raise concerns for possible bi-directional transmission between pets and humans, especially at household level

Salt intake and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project

Purpose: Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project. Methods: Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI). Results: Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25–2.03), always using table salt (aOR 1.33, 95% CI 1.16–1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01–1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82–1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics. Conclusion: Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.This study was funded by national funds from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020), by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Project no. 21378 (Investigator Grant), and the Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Grant 2017SGR723). AC and SM were funded under the scope of the project "NEON-PC—Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline" (POCI-01-0145-FEDER-032358; ref. PTDC/SAU-EPI/32358/2017). SM was also funded under EPIUnit—Junior Research—Prog Financing (UIDP/04750/2020). An individual grant attributed to NA (SFRH/BD/119390/2016) was funded by FCT and the ‘Programa Operacional Capital Humano’ (POCH/FSE). The authors thank the European Cancer Prevention (ECP) Organization for providing support for the project meetings, all MCC-Spain study collaborators (CIBERESP, ISCIII, ISGlobal, ICO, University of Huelva, University of Oviedo, University of Cantabria, University of León, ibs. Granada, Instituto Salud Pública de Navarra, FISABIO, Murcia Regional Health Authority and cols). The funding sources had no role in the study design; collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication

Gastric cancer is associated with NOS2 -954G/C polymorphism and environmental factors in a Brazilian population

<p>Abstract</p> <p>Background</p> <p>Gastric cancer can progress from a chronic inflammation of the gastric mucosa resulting from <it>Helicobacter pylori </it>infection that activates the inflammatory response of the host. Therefore, polymorphisms in genes involved in the inflammatory response, such as inducible nitric oxide synthase (<it>NOS2</it>), have been implicated in gastric carcinogenesis. The aim of this study was to evaluate the association of <it>NOS2 </it>polymorphisms Ser⁶⁰⁸Leu (rs2297518) in exon 16, -954G/C and -1173C/T, both in the promoter region, with gastric cancer and chronic gastritis and the association of cancer with risk factors such as smoking, alcohol intake and <it>H. pylori </it>infection.</p> <p>Methods</p> <p>We conducted a population-based case-control study in 474 Southeast Brazilian individuals (150 with gastric cancer, 160 with chronic gastritis, and 164 healthy individuals), in which we performed <it>NOS2 </it>genotyping by PCR-RFLP.</p> <p>Results</p> <p>SNP Ser⁶⁰⁸Leu was not associated with risk of chronic gastritis or gastric cancer. The polymorphic allele -1173T was not found in the studied population. However, the frequency of -954GC+CC genotypes was significantly higher (p < 0.01) in the cancer group (48.7%) than in both the gastritis (28.1%) and the control (29.9%) groups. Multivariate logistic regression showed that the <it>NOS2 </it>SNP -954G/C was associated with higher risk of gastric cancer (OR = 1.87; 95% CI = 1.12-3.13). We also observed an association with risk factors such as smoking and alcohol intake in both the gastric cancer (OR = 2.68; 95% CI = 1.58-4.53; OR = 3.60; 95% CI = 2.05-6.32, respectively) and the chronic gastritis (OR = 1.93; 95% CI = 1.19-3.13; OR = 2.79; 95% CI = 1.55-5.02, respectively) groups. This is the first report of increased risk of gastric cancer in association with the -954G/C polymorphism. These findings show that several polymorphisms in the promoter region of the <it>NOS2 </it>gene may contribute to the susceptibility to gastric cancer.</p> <p>Conclusions</p> <p>Polymorphism <it>NOS2 </it>-954 G/C, along with alcohol intake and tobacco smoking, is associated with gastric cancer. However, the <it>NOS2 </it>Ser⁶⁰⁸Leu polymorphism was not associated with gastric carcinogenesis. The <it>NOS2 </it>-1173C/T polymorphism was absent in the studied population.</p

Cataloguing functionally relevant polymorphisms in gene DNA ligase I: a computational approach

A computational approach for identifying functionally relevant SNPs in gene LIG1 has been proposed. LIG1 is a crucial gene which is involved in excision repair pathways and mutations in this gene may lead to increase sensitivity towards DNA damaging agents. A total of 792 SNPs were reported to be associated with gene LIG1 in dbSNP. Different web server namely SIFT, PolyPhen, CUPSAT, FASTSNP, MAPPER and dbSMR were used to identify potentially functional SNPs in gene LIG1. SIFT, PolyPhen and CUPSAT servers predicted eleven nsSNPs to be intolerant, thirteen nsSNP to be damaging and two nsSNPs have the potential to destabilize protein structure. The nsSNP rs11666150 was predicted to be damaging by all three servers and its mutant structure showed significant increase in overall energy. FASTSNP predicted twenty SNPs to be present in splicing modifier binding sites while rSNP module from MAPPER server predicted nine SNPs to influence the binding of transcription factors. The results from the study may provide vital clues in establishing affect of polymorphism on phenotype and in elucidating drug response

Detecting Instability in Animal Social Networks: Genetic Fragmentation Is Associated with Social Instability in Rhesus Macaques

The persistence of biological systems requires evolved mechanisms which promote stability. Cohesive primate social groups are one example of stable biological systems, which persist in spite of regular conflict. We suggest that genetic relatedness and its associated kinship structure are a potential source of stability in primate social groups as kinship structure is an important organizing principle in many animal societies. We investigated the effect of average genetic relatedness per matrilineal family on the stability of matrilineal grooming and agonistic interactions in 48 matrilines from seven captive groups of rhesus macaques. Matrilines with low average genetic relatedness show increased family-level instability such as: more sub-grouping in their matrilineal groom network, more frequent fighting with kin, and higher rates of wounding. Family-level instability in multiple matrilines within a group is further associated with group-level instability such as increased wounding. Stability appears to arise from the presence of clear matrilineal structure in the rhesus macaque group hierarchy, which is derived from cohesion among kin in their affiliative and agonistic interactions with each other. We conclude that genetic relatedness and kinship structure are an important source of group stability in animal societies, particularly when dominance and/or affilative interactions are typically governed by kinship

Taking two to tango:fMRI analysis of improvised joint action with physical contact

<div><p>Many forms of joint action involve physical coupling between the participants, such as when moving a sofa together or dancing a tango. We report the results of a novel two-person functional MRI study in which trained couple dancers engaged in bimanual contact with an experimenter standing next to the bore of the magnet, and in which the two alternated between being the leader and the follower of joint improvised movements. Leading showed a general pattern of self-orientation, being associated with brain areas involved in motor planning, navigation, sequencing, action monitoring, and error correction. In contrast, following showed a far more sensory, externally-oriented pattern, revealing areas involved in somatosensation, proprioception, motion tracking, social cognition, and outcome monitoring. We also had participants perform a “mutual” condition in which the movement patterns were pre-learned and the roles were symmetric, thereby minimizing any tendency toward either leading or following. The mutual condition showed greater activity in brain areas involved in mentalizing and social reward than did leading or following. Finally, the analysis of improvisation revealed the dual importance of motor-planning and working-memory areas. We discuss these results in terms of theories of both joint action and improvisation.</p></div

A network linking scene perception and spatial memory systems in posterior cerebral cortex

The neural systems supporting scene-perception and spatial-memory systems of the human brain are well-described. But how do these neural systems interact? Here, using fine-grained individual-subject fMRI, we report three cortical areas of the human brain, each lying immediately anterior to a region of the scene perception network in posterior cerebral cortex, that selectively activate when recalling familiar real-world locations. Despite their close proximity to the scene-perception areas, network analyses show that these regions constitute a distinct functional network that interfaces with spatial memory systems during naturalistic scene understanding. These “place-memory areas” offer a new framework for understanding how the brain implements memory-guided visual behaviors, including navigation

Nature meets nurture: molecular genetics of gastric cancer

The immensity of genes and molecules implicated in gastric carcinogenesis is overwhelming and the relevant importance of some of these molecules is too often unclear. This review serves to bring us up-to-date with the latest findings as well as to look at the larger picture in terms of how to tackle the problem of solving this multi-piece puzzle. In this review, the environmental nurturing of intestinal cancer is discussed, beginning with epidemiology (known causative factors for inducing molecular change), an update of H. pylori research, including the role of inflammation and stem cells in premalignant lesions. The role of E-cadherin in the nature (genotype) of diffuse gastric cancer is highlighted, and finally the ever growing discipline of SNP analysis (including IL1B) is discussed