STATISTICS OF CANCER, 2020 IN INDIAN STATES: A REVIEW ON THE REPORT FROM NATIONAL CANCER REGISTRY PROGRAMME

The deliberate assortment of information on cancer growth was performed by different populace-based disease vaults (population-based cancer registries [PBCRs]) and clinic-based cancer growth libraries (hospital-based cancer registries [HBCRs]) across India under the National Cancer Registry Program–National Center for Disease Informatics and Research of Indian Council of Medical Research since 1982. This survey analyzed the malignant growth occurrence, designs, patterns, projections, and mortality from 28 PBCRs and furthermore the stage at introduction and kind of therapy of patients with disease from 58 HBCRs (n=667,666) from the pooled investigation for the composite time frame 2012–2016. Time patterns in cancer growth rate were created as yearly percent change from 16 PBCRs (those with at least 10 years of consistent great information accessible) utilizing Joinpoint relapse. Aizawl locale (269.4) and Papumpare region (219.8) had the most elevated age changed occurrence rates among guys and females, separately. The extended number of patients with disease in India is 1,392,179 for the year 2020, and the basic five driving destinations are cancer, lung, mouth, cervix uteri, and tongue. Patterns in disease frequency rate showed an expansion on the whole locales of cancer in both genders and were high in Kamrup Metropolitan (yearly percent change, 3.8%; p<0.05). Most of the patients with cancer were analyzed at the privately progressed stage for cancer (57.0%), cervix uteri (60.0%), head and neck (66.6%), and stomach (50.8%) disease, while in cellular breakdown in the lungs, far off metastasis was dominating among guys (44.0%) and females (47.6%). This audit gives a system to surveying the status and patterns of cancer growth in India. It will manage proper help for activity to fortify endeavors to improve cancer growth avoidance and control to accomplish the public non-communicable illness targets and the reasonable advancement objectives

MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice

Not all women infected with chlamydiae develop upper genital tract disease, but the reason(s) for this remains undefined. Host genetics and hormonal changes associated with the menstrual cycle are possible explanations for variable infection outcomes. It is also possible that disease severity depends on the virulence of the chlamydial inoculum. It is likely that the inoculum contains multiple genetic variants, differing in virulence. If the virulent variants dominate, then the individual is more likely to develop severe disease. Based on our previous studies, we hypothesized that the relative degree of virulence of a chlamydial population dictates the microRNA (miRNA) expression profile of the host, which, in turn, through regulation of the host inflammatory response, determines disease severity. Thus, we infected C57BL/6 mice with two populations of Chlamydia muridarum, each comprised of multiple genetic variants and differing in virulence: an attenuated strain (NiggA) and a virulent strain (NiggV). NiggA and NiggV elicited upper tract pathology in 54% and 91% of mice, respectively. miRNA expression analysis in NiggV-infected mice showed significant downregulation of miRNAs involved in dampening fibrosis (miR-200b, miR-200b-5p, and 200b-3p miR-200a-3p) and in transcriptional regulation of cytokine responses (miR-148a-3p, miR-152-3p, miR-132, and miR-212) and upregulation of profibrotic miRNAs (miR-142, and miR-147). Downregulated miRNAs were associated with increased expression of interleukin 8 (IL-8), CXCL2, IL-1β, tumor necrosis factor alpha (TNF-α), and IL-6. Infection with NiggV but not NiggA led to decreased expression of Dicer and Ago 2, suggesting that NiggV interaction with host cells inhibits expression of the miRNA biogenesis machinery, leading to increased cytokine expression and pathology

Managing the litter from hyperprolific sows

The practice of breeding from hyperprolific sows producing very large litters is becoming a normal occurrence in commercial pig production. However, the relationship between large litter size and piglet mortality is well established. In order to minimise the health and welfare challenges associated with large litters and maximise the economic potential of increased numbers born, various genetic, nutritional and management interventions are required. This chapter outlines the different challenges associated with hyperprolificacy before focusing on management strategies adopted over the farrowing and lactation period to tackle those challenges. These include early interventions to assist vulnerable piglets, such as those suffering from intrauterine growth retardation, as well as strategies involving whole litter interventions (e.g. use of nurse sows, artificial rearing) to help rear supernumerary piglets

Adult ADHD Medications and Their Cardiovascular Implications

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobiological disorder exhibited by difficulty maintaining attention, as well as hyperactivity and impulsive behavior. Central nervous system (CNS) stimulants are the first line of treatment for ADHD. With the increase in number of adults on CNS stimulants, the question that arises is how well do we understand the long-term cardiovascular effects of these drugs. There has been increasing concern that adults with ADHD are at greater risk for developing adverse cardiovascular events such as sudden death, myocardial infarction, and stroke as compared to pediatric population. Cardiovascular response attributed to ADHD medication has mainly been observed in heart rate and blood pressure elevations, while less is known about the etiology of rare cardiovascular events like acute myocardial infarction (AMI), arrhythmia, and cardiomyopathy and its long-term sequelae. We present a unique case of AMI in an adult taking Adderall (mixed amphetamine salts) and briefly discuss the literature relevant to the cardiovascular safety of CNS stimulants for adult ADHD

Environmental enteropathy in undernourished Pakistani children: Clinical and histomorphometric analyses

Despite nutrition interventions, stunting thought to be secondary to underlying environmental enteropathy (EE) remains pervasive among infants residing in resource-poor countries and remains poorly characterized. From a birth cohort of 380 children, 65 malnourished infants received 12 weeks of nutritional supplementation with ready-to-use therapeutic food (RUTF). Eleven children with insufficient response to RUTF underwent upper endoscopy with duodenal biopsies, which were compared with U.S., age-matched specimens for healthy, celiac disease, non-celiac villous atrophy, non-celiac intraepithelial lymphocytosis, and graft-versus-host disease patients. Of the 11 children biopsied, EE was found in 10 (91%) with one subject with celiac disease. Morphometry demonstrated decreased villus-to-crypt (V:C) ratios in EE relative to healthy and non-celiac lymphocytosis patients. Environmental enteropathy villus volumes were significantly decreased relative to healthy controls. In EE, average CD3+ cells per 100 epithelial cells and per 1,000 µm2 of lamina propria and the number of lamina propria CD20+ B-cell aggregates were increased relative to all other groups. Our results indicate that V:C ratios are reduced in EE but are less severe than in celiac disease. Environmental enteropathy intraepithelial and lamina propria T lymphocytosis is of greater magnitude than that in celiac disease. The increases in lamina propria B and T lymphocytes suggest that non-cytolytic lymphocytic activation may be a more prominent feature of EE relative to celiac disease. These results provide new insights into shared yet distinct histological and immunological features of EE and celiac disease in children

Associations between maternal microbiome, metabolome and incidence of low-birth weight in Guatemalan participants from the Women First Trial

BackgroundLow birth weight (LBW; <2,500 g) affects approximately 15 to 20 percent of global births annually and is associated with suboptimal child development. Recent studies suggest a link between the maternal gut microbiome and poor obstetric and perinatal outcomes. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings.MethodsThis was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 weeks were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine.ResultsNo differences in β-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 weeks was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers (p < 0.05) were observed at 12 weeks with increasing abundances of Barnesiella, Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance.ConclusionCollectively, the findings indicate that alterations in the maternal microbiome and metabolome were associated with LBW. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight

NF-κB-dependent synergistic regulation of CXCL10 gene expression by IL-1β and IFN-γ in human intestinal epithelial cell lines

Background and aims Little is known about the intestinal epithelial expression and secretion of CXCL10 (IP-10), a chemokine involved in recruiting T cells and monocytes. We aimed to study CXCL10 gene expression and regulation by the pro-inflammatory cytokines interleukin (IL)-1 beta, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in intestinal epithelial cell lines. Materials and methods CXCL10 expression and secretion kinetics were assessed in Caco-2, HT-29 and DLD1 human colon epithelial cells, treated with IL-1 beta, TNF-alpha, IFN-gamma alone or in combination with each other by real-time polymerase chain reaction (PCR), Northern blotting and enzyme-linked immunoabsorbent assay (ELISA). Transient transfections with TGL-IP10 (CXCL10 promoter) and TGL-IP10-kappa B2 mutant promoter and gelshifts and supershifts for nuclear factor (NF)-kappa B were also performed. Results Real-time PCRs and ELISA experiments revealed that IL-1 beta was the strongest and earliest inducer of CXCL10 messenger ribonucleic acid (mRNA) expression and protein secretion in Caco-2 cell line, whereas INF-gamma had a delayed kinetics. There was a strong synergistic effect of either TNF-alpha or IL-1 beta with IFN-gamma both on CXCL10 mRNA expression and protein secretion in all three cell lines. Real-time PCR and ELISA experiments using a specific NF-kappa B inhibitor and transfection experiments with a NF-kappa B-binding defective CXCL10 promoter construct revealed that the induction of CXCL10 by IL-1 beta and its synergism with IFN-gamma is NF-kappa B dependent. Conclusion These data demonstrate that in colonic epithelial cells, depending on the cellular context and utilizing the NF-kappa B pathway, IL-1 beta alone and/or in synergism with IFN-gamma may play a major role in the induction of CXCL10

GO Explorer: A gene-ontology tool to aid in the interpretation of shotgun proteomics data

<p>Abstract</p> <p>Background</p> <p>Spectral counting is a shotgun proteomics approach comprising the identification and relative quantitation of thousands of proteins in complex mixtures. However, this strategy generates bewildering amounts of data whose biological interpretation is a challenge.</p> <p>Results</p> <p>Here we present a new algorithm, termed GO Explorer (GOEx), that leverages the gene ontology (GO) to aid in the interpretation of proteomic data. GOEx stands out because it combines data from protein fold changes with GO over-representation statistics to help draw conclusions. Moreover, it is tightly integrated within the PatternLab for Proteomics project and, thus, lies within a complete computational environment that provides parsers and pattern recognition tools designed for spectral counting. GOEx offers three independent methods to query data: an interactive directed acyclic graph, a specialist mode where key words can be searched, and an automatic search. Its usefulness is demonstrated by applying it to help interpret the effects of perillyl alcohol, a natural chemotherapeutic agent, on glioblastoma multiform cell lines (A172). We used a new multi-surfactant shotgun proteomic strategy and identified more than 2600 proteins; GOEx pinpointed key sets of differentially expressed proteins related to cell cycle, alcohol catabolism, the Ras pathway, apoptosis, and stress response, to name a few.</p> <p>Conclusion</p> <p>GOEx facilitates organism-specific studies by leveraging GO and providing a rich graphical user interface. It is a simple to use tool, specialized for biologists who wish to analyze spectral counting data from shotgun proteomics. GOEx is available at <url>http://pcarvalho.com/patternlab</url>.</p

Lsr2 of Mycobacterium tuberculosis is a DNA-bridging protein

Lsr2 is a small, basic protein present in Mycobacterium and related actinomycetes. Recent studies suggest that Lsr2 is a regulatory protein involved in multiple cellular processes including cell wall biosynthesis and antibiotic resistance. However, the underlying molecular mechanisms remain unknown. In this article, we performed biochemical studies of Lsr2–DNA interactions and structure–function analysis of Lsr2. Analysis by atomic force microscopy revealed that Lsr2 has the ability to bridge distant DNA segments, suggesting that Lsr2 plays a role in the overall organization and compactness of the nucleoid. Mutational analysis identified critical residues and selection of dominant negative mutants demonstrated that both DNA binding and protein oligomerization are essential for the normal functions of Lsr2 in vivo. These results provide strong evidence that Lsr2 is a DNA bridging protein, which represents the first identification of such proteins in bacteria phylogenetically distant from the Enterobacteriaceae. DNA bridging by Lsr2 also provides a mechanism of transcriptional regulation by Lsr2