Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

ANALISIS MEMBACA PERMULAAN DI KELAS III SEKOLAH DASAR (Studi Kasus di Sekolah Dasar Negeri Nyantong)

Penelitian ini dilatar belakangi karena masih terdapat beberapa peserta didik yang masih kesulitan dalam membaca permulaan di kelas III SDN Nyantong. Faktor tersebut terjadi dikarenakan tidak efektifnya pembelajaran dilakukan secara tatap maya, faktor pendukung dari orang tua serta masa peralihan dari pandemi Covid-19. Penelitian ini bertujuan untuk mendeskripsikan kemampuan membaca permulaan, kesulitan yang dihadapi, serta solusi yang diberikan guru perihal kesulitan yang dihadapi dalam membaca permulaan. Proses analisis data dilakukan dengan menganalisi berupa data hasil observasi, wawancara dan studi dokumentasi di kelas III SDN Nyantong. Adapun subjek dalam penelitian ini yaitu subjek pada penelitian ini yaitu keseluruhan siswa kelas III sekolah dasar, kemudian fokus kajiannya pada siswa yang mengalami kesulitan dalam membaca permulaan, guru dan kepala sekolah SDN Nyatong. Hasil menunjukan bahwa kemampuan membaca permulaan di kelas III hanya dikuasi oleh 32 peserta didik yakni; kemampuan mengidentifikasi huruf (vocal, konsonan dan diftong), mengidentifikasi kata, merangkai susunan kata, membaca kata yang tidak mempunyai arti, membaca dengan nyaring serta pemahaman membaca. Kesulitan yang dihadapi; : (1) mengidentifikasi huruf abjad, vocal, konsonan dan diftong, , (2) membaca kata dengan indicator (mengidentifikasi kata dan merangkai susunan kata), (3) kata yang tidak mempunyai arti dan (4) tidak lancar dalam membaca nyaring dan tidak memahami isi bacaan yang telah dibaca. Solusi yang diberikan guru, yakni; jam tambahan khusus, menggunakan media yang menarik dan efektif, memberikan perhatian khusus serta menggunakan buku khusus. This research is motivated because there are still some students who still have difficulty in reading the beginning in grade III SDN Nyantong. This factor occurred due to the ineffectiveness of virtual face-to-face learning, supporting factors from parents and the transition period from the Covid-19 pandemic. This study aims to describe the ability to read the beginning, the difficulties faced, and the solutions given by teachers regarding the difficulties faced in reading the beginning. The data analysis process was carried out by analyzing data from observations, interviews and documentation studies in grade III SDN Nyantong. The subjects in this study are the subjects in this study, namely all grade III elementary school students, then the focus of the study is on students who have difficulty in reading the beginning, teachers and principals of SDN Nyatong. The results showed that the initial reading ability in grade III was only mastered by 32 students, namely; Ability to identify letters (vowels, consonants and diphthongs), identify words, string words, read meaningless words, read aloud and reading comprehension. Difficulties encountered;(1) identify letters of the alphabet, vowels, consonants and diphthongs, (2) read words with indicators (identify words and string together word arrangements), (3) words that have no meaning and (4) are not fluent in reading aloud and do not understand the content of the reading that has been read. The solutions provided by the teacher, namely; special extra hours, using interesting and effective media, paying special attention as well as using special books. Keywords: difficulty, reading the beginnin

Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan:the PROMIS study

Background: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians. Methods: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure. Results: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 x 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P-interaction = 0.014), CADM2 rs13078960 (P-interaction = 0.037) and GALNT10 rs7715256 (P-interaction = 0.048) with physical activity, and PTBP2 rs11165643 (P-interaction = 0.045), HIP1 rs1167827 (P-interaction = 0.015), C6orf106 rs205262 (P-interaction = 0.032) and GRID1 rs7899106 (P-interaction = 0.043) with smoking on BMI. Conclusions: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity

Structure of a nucleosome-bound MuvB transcription factor complex reveals DNA remodelling.

Genes encoding the core cell cycle machinery are transcriptionally regulated by the MuvB family of protein complexes in a cell cycle-specific manner. Complexes of MuvB with the transcription factors B-MYB and FOXM1 activate mitotic genes during cell proliferation. The mechanisms of transcriptional regulation by these complexes are still poorly characterised. Here, we combine biochemical analysis and in vitro reconstitution, with structural analysis by cryo-electron microscopy and cross-linking mass spectrometry, to functionally examine these complexes. We find that the MuvB:B-MYB complex binds and remodels nucleosomes, thereby exposing nucleosomal DNA. This remodelling activity is supported by B-MYB which directly binds the remodelled DNA. Given the remodelling activity on the nucleosome, we propose that the MuvB:B-MYB complex functions as a pioneer transcription factor complex. In this work, we rationalise prior biochemical and cellular studies and provide a molecular framework of interactions on a protein complex that is key for cell cycle regulation

Gasdermin D Hypermethylation Inhibits Pyroptosis And LPS-Induced IL-1β Release From NK92 Cells

INTRODUCTION: Although natural killer (NK) are major cells used to treat cancer patients, recent clinical trials showed that NK92 cells can be also used for the same purpose due to their high anti-tumor activity. Here, we examined whether these cells might be inflammatory due to the release of interleukin-1β (IL-1β), and whether the anti-inflammatory molecules dimethyl fumarate (DMF), or monomethyl fumarate (MMF) impair this activity. METHODS: NK92 cells were examined for the synthesis and release of IL-1β utilizing RT-PCR and ELISA assay, respectively. The expression of hydroxy-carboxylic acid receptors (HCA)1, HCA2 and HCA3 was detected by immunoblotting, flow cytometry, immunofluorescence and RT-PCR assays. The activation of caspase-1 and Gasdermin D (GSDMD) was evaluated by immunoblot assay. Pyroptosis was demonstrated by immunofluorescence imaging. Expression of DNA methyltransferases (DNMTs) mRNA was determined by whole transcriptome and immunoblot analyses. RESULTS: LPS-induced the release of IL-1β from NK92 cells, whereas DMF or MMF inhibited this induction. The effect of these drugs was due to inhibiting the conversion of procaspase-1 into active caspase-1. NK92 cells highly expressed GSDMD, a pyroptotic-mediated molecule. However, LPS induced the distribution of GSDMD into the cell membranes, corroborated with the presence of pyroptotic bodies, an activity that was inhibited by DMF or MMF. These molecule also inhibited the generation of GSDMD through DNMT-mediated hypermethylation of the promoter region of GSDMD gene. These results were supported by increased expression of DNMTs mRNA as determined by whole transcriptome analysis. DISCUSSION: Our results are the first to show that NK92 cells utilize GSDMD pathway to release IL-1β. Further, DMF and MMF which were previously shown to enhance NK cell cytotoxicity, also inhibit the inflammatory effects of these cells, making them most suitable for treating cancer patients

APLIKASI PUPUK KOMPOS ECENG GONDOK DAN MIKORIZA BERPENGARUH TERHADAP PERTUMBUHAN TANAMAN TEMBAKAU DELI (Nicotiana tabaccum L.)

Penelitian dilaksanakan pada bulan Februari 2016 sampai dengan bulan April 2016 di kebun percobaan BPTD PTP Nusantara II Jl. Kesuma No. 6 Sampali Kabupaten Deli Serdang dengan ketinggian tempat + 25 mdpl. Metoda penelitian ini menggunakan Rancangan Acak Kelompok (RAK) Faktorial dengan dua faktor, faktor pertama yaitu pemberian pupuk kompos eceng gondok (P) terdiri dari tiga taraf, yaitu P1 = 300 g/polibeg, P2 = 600 g/polibeg dan P3 = 900 g/polibeg. Faktor kedua yaitu pupuk Mikoriza (M), terdiri dari tiga taraf, yaitu M0 = tanpa pupuk Mikoriza (Kontrol), M1 = 7,5 g/polibeg dan M2 = 15 g/polibeg. Hasil penelitian menunjukkan bahwa aplikasi pupuk kompos eceng gondok memberikan pengaruh yang nyata terhadap tanaman tembakau Deli pada umur 8 MSPT pada parameter tinggi tanaman tertinggi 68,43 cm, jumlah daun terbanyak 13,30 helai, luas daun terluas 172,24 cm2, diameter batang 0,92 mm, panjang akar 26,58 cm, berat basah tanaman 125,61 g dan berat kering tanaman 19,66 g. Aplikasi pupuk Mikoriza dan interaksi memberikan pengaruh yang tidak nyata terhadap semua parameter pengamatan yang diukur

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Penegakan Hukum Pidana Terhadap Pelaku Penambangan Pasir Secara Ilegal

Mining activities has grown very much, a given result is very given an advantage for the miners. Nevertheless, activities which promise this also also bring an adverse impact on man and the environment when this activity was undertaken not based on the regulation that has been set. Mining illegally also occurred at the sandbanks Parangtritis, sandbanks I know about the Parangtritis are unique and useful for maintained because it is being very specific with the form of a crescent or bacon and is the one and only sandbanks found in the southeast Asia. Arrangement about mining activities that environmentally sound has set out in various regulation, but this appears to have not run as expected, so may is still needed law enforcement tighter and clear to mining sand conducted an illegal. The research was conducted by juridical normative is the approach that was undertaken based on material law by means of reviewing the theory, the concept, a normative law and the regulatory legislation that deals with this research. This approach is known the approach literature, namely by studying books, regulation and other documents related to this research. Criminal law enforcement of the mining sand illegally in sandbanks Parangtritis has started to walk but not yet optimal .The laws governing about mining sand has been is in a few rules, but the law enforcement not is the responsibility of law enforcement officials just, law enforcement is also a responsibility community in an effort to ahead and recover crimes sand mining illegally. Obstacles faced by law enforcement in dealing with crimes sand mining illegal in sandbanks Parangtritis are the lack of legal awareness to the community, economic factors, the lack of knowledge of the community towards the impact of mining sand illegally and factors law enforcement. Key word: Criminal law; Sand Mining; Illega