Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term proton pump inhibitors use and risk of gastric cancer: a meta-analysis of 926 386 participants

We read with interest the study by Cheung et al 1 reporting that long-term use of proton pump inhibitors (PPIs) was associated with an increased risk of gastric cancer (GC) in participants after Helicobacter pylori eradication. Considering PPIs were widely used for the treatment of acid-related disorders, and previous studies about PPIs use and risk of GC did not have a consistent result. To better understand this issue, we conducted this meta-analysis that investigated the associations between long-term PPIs use and risk of GC. We searched the PubMed, Embase and Web of Science for potential studies published before March 2018. …
A Study on Safe Injection Practices of Nursing Personnel in a Tertiary Care Hospital of Kolkata, West Bengal, India -

AIM: Although a safe injection does not harm to patient, unsafe injection practices may leads some health problems. The most affected category of health care providers are the nursing personnel. METHOD: This hospital based cross sectional observational study was conducted among 80 nurses involved in patient care to assess their knowledge regarding safe injection practices and to assess certain aspects of their practice while administering injection and disposal of the disposables. RESULTS: About 52.5% subjects were protected by hepatitis B vaccination. During the last 6 months, 6.3% nurses got accidental needle stick injury three or more times. About 12.5% study subjects washed their hands with soap and water before administering injection. About 60% of the nursing personnel maintained correct procedure during giving injection; while sterile gloves were used only by 3.7% nurses. During disposal of used needles, in 57.5% cases hub cutters were used, while needles were recapped in 42.5% of cases. Used syringes were disposed off correctly in 41.2% of cases. CONCLUSION: There is a need to educate, train and motivate service providers in proper method of handling injection equipments. A local policy and surveillance programme based on the WHO guidelines might be helpful in this situation.
Authors’ response: Association between IBD and Parkinson’s disease: seek and you shall find?

Dr Weimers and colleagues have drawn attention1 to the possibility that our recently published observation of an association between IBD and Parkinson’s disease (PD) in a nationwide Danish cohort study2 may reflect surveillance bias. In a recently published Swedish cohort study, Dr Weimers and colleagues found that adjusting for number of healthcare visits during follow-up of patients with IBD attenuated the risk of developing PD markedly.3 They also found that the risk of future PD was …
Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures

Objective Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. Design We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. Results The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. Conclusions The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.
Genome‐wide DNA methylation analysis in alcohol dependence

Genetic, epigenetic, and environmental factors influence the development of alcohol dependence (AD). Recent studies have shown that DNA methylation markers in peripheral blood may serve as risk markers for AD. Yet a genome‐wide epigenomic approach investigating the role of DNA methylation in AD has yet to be performed. We conducted a population‐based, case‐control study of genome‐wide DNA methylation to determine if alterations in gene‐specific methylation were associated with AD in a Chinese population. Using the Illumina Infinium Human Methylation27 BeadChip, we assessed gene‐specific methylation in over 27 000 CpG sites from DNA isolated from lymphocytes in 63 male AD in‐patients and 65 male healthy controls. Using a multi‐factorial statistical model, we observed differential methylation between cases and controls at multiple CpG sites with the majority of the methylated CpG sites being hypomethylated. Analyses with the online gene set analysis toolkit WebGestalt revealed that the genes of interest were enriched in multiple biological processes involved in AD development. Gene Ontology function annotation showed that stress, immune response and signal transduction were highly associated with AD. Further analysis by the Kyoto Encyclopedia of Genes and Genomes revealed associations with multiple pathways involved in metabolism through cytochrome P450, cytokine–cytokine receptor interaction and calcium signaling. Associations with canonical pathways previously shown to be involved in AD were also observed, such as dehydrogenases 1A (ADH1A), ADH7, aldehyde dehydrogenases 3B2 (ALDH3B2) and cytochrome P450 2A13. We present evidence that alterations in DNA methylation may be associated with AD, which is consistent with epigenetic theory.
Polyploidy spectrum: a new marker in HCC classification

Objectives Polyploidy is a fascinating characteristic of liver parenchyma. Hepatocyte polyploidy depends on the DNA content of each nucleus (nuclear ploidy) and the number of nuclei per cell (cellular ploidy). Which role can be assigned to polyploidy during human hepatocellular carcinoma (HCC) development is still an open question. Here, we investigated whether a specific ploidy spectrum is associated with clinical and molecular features of HCC. Design Ploidy spectra were determined on surgically resected tissues from patients with HCC as well as healthy control tissues. To define ploidy profiles, a quantitative and qualitative in situ imaging approach was used on paraffin tissue liver sections. Results We first demonstrated that polyploid hepatocytes are the major components of human liver parenchyma, polyploidy being mainly cellular (binuclear hepatocytes). Across liver lobules, polyploid hepatocytes do not exhibit a specific zonation pattern. During liver tumorigenesis, cellular ploidy is drastically reduced; binuclear polyploid hepatocytes are barely present in HCC tumours. Remarkably, nuclear ploidy is specifically amplified in HCC tumours. In fact, nuclear ploidy is amplified in HCCs harbouring a low degree of differentiation and TP53 mutations. Finally, our results demonstrated that highly polyploid tumours are associated with a poor prognosis. Conclusions Our results underline the importance of quantification of cellular and nuclear ploidy spectra during HCC tumorigenesis.
The efficacy of pregabalin in patients with moderate and severe pain due to diabetic peripheral neuropathy

Abstract Objective To compare the therapeutic response to pregabalin in patients with moderate or severe painful diabetic peripheral neuropathy (pDPN). Research design and methods Data were pooled from 11 placebo-controlled trials to evaluate the efficacy of pregabalin flexible or fixed dose (150, 300 or 600 mg/day) in pDPN patients with mean baseline pain scores of ≥4 to <7 (moderate) or ≥7 to ≤10 (severe). Last observation carried forward imputation was used. Study number/ClinicalTrials.gov identifier 1008-014/-, 1008-029/-, 1008-040/-, 1008-131/-, 1008-149/-, 1008-000-155/-, A0081030/NCT00156078, A0081060/NCT00159679, A0081071/NCT00143156, A0081081/NCT00301223, A0081163/NCT00553475. Main outcome measures Pregabalin-mediated change in pain, pain-related sleep interference (PRSI) and patient global impression of change (PGIC) were compared versus placebo and between moderate and severe pain cohorts. Adverse events (AEs) were reported. Results At baseline, 1816 patients had moderate pain (pregabalin, n = 1189) and 1119 patients had severe pain (pregabalin, n = 720). Pregabalin significantly reduced pain scores at endpoint compared with placebo when patients of all pain levels were combined (all doses; p < 0.05). In the moderate and severe pain cohorts, pregabalin treatment (300, 600 mg/day or flexible) significantly reduced mean pain scores at endpoint compared with placebo (p < 0.01). Pain reduction was greatest in patients with severe baseline pain compared with moderate baseline pain (pregabalin 300, 600 mg/day or flexible; p < 0.0001). Pregabalin improved PRSI and PGIC in the moderate and severe cohorts compared with placebo. The greatest improvement in PRSI also occurred in the severe cohort. Treatment-emergent AEs, most commonly dizziness, somnolence and peripheral edema, occurred more frequently in patients treated with pregabalin compared with placebo. Conclusions Pregabalin was effective in pDPN patients with both moderate and severe baseline pain. Patients with severe pain exhibited greater improvements in pain and PRSI than patients with moderate pain. Pain severity may, in part, predict therapeutic response to pregabalin.
Myeloid cells in liver and bone marrow acquire a functionally distinct inflammatory phenotype during obesity-related steatohepatitis

Objective Bone marrow-derived myeloid cells accumulate in the liver as monocytes and macrophages during the progression of obesity-related non-alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH). Myeloid cells comprise heterogeneous subsets, and dietary overnutrition may affect macrophages in the liver and bone marrow. We therefore aimed at characterising in depth the functional adaptations of myeloid cells in fatty liver. Design We employed single-cell RNA sequencing to comprehensively assess the heterogeneity of myeloid cells in the liver and bone marrow during NAFLD, by analysing C57BL/6 mice fed with a high-fat, high-sugar, high-cholesterol ‘Western diet’ for 16 weeks. We also characterised NAFLD-driven functional adaptations of macrophages in vitro and their functional relevance during steatohepatitis in vivo. Results Single-cell RNA sequencing identified distinct myeloid cell clusters in the liver and bone marrow. In both compartments, monocyte-derived populations were largely expanded in NASH-affected mice. Importantly, the liver myeloid compartment adapted a unique inflammatory phenotype during NAFLD progression, exemplarily characterised by downregulated inflammatory calprotectin (S100A8/A9) in macrophage and dendritic cell subsets. This distinctive gene signature was also found in their bone marrow precursors. The NASH myeloid phenotype was principally recapitulated by in vitro exposure of bone marrow-derived macrophages with fatty acids, depended on toll-like receptor 4 signalling and defined a characteristic response pattern to lipopolysaccharide stimulation. This imprinted and stable NASH myeloid immune phenotype functionally determined inflammatory responses following acute liver injury (acetaminophen poisoning) in vivo. Conclusion Liver myeloid leucocytes and their bone marrow precursors adapt a common and functionally relevant inflammatory signature during NAFLD progression.
Tuberculosis in Children

Tuberculosis (TB) in children is a neglected aspect of the TB epidemic despite it constituting 20% or more of all TB cases in many countries with high TB incidence. Childhood TB is a direct consequence of adult TB but remains overshadowed by adult TB because it is usually smear-negative. Infants and young children are more likely to develop life-threatening forms of TB than older children and adults due to their immature immune systems. Therefore, prompt diagnoses are extremely important although difficult since clinical and radiological signs of TB can be non-specific and variable in children. Despite undeniable advances in identifying definite, probable, or possible TB markers, pediatricians still face many problems when diagnosing TB diagnosis. Moreover, curing TB can be difficult when treatment is delayed and when multi-drug resistant (MDR) pathogens are the cause of the disease. In these cases, the prognosis in children is particularly poor because MDR-TB treatment and treatment duration remain unclear. New studies of diagnostic tests and optimal treatment in children are urgently needed with the final goal of developing an effective anti-TB vaccine.
Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease

Objective Following ileal resection for Crohn’s disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence. Patients and methods Ileal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France. Results Ileal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors. Conclusion Surgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.
Thompson & Thompson Genetics in Medicine

This latest edition of Thompson and Thompson's Genetics in Medicine has been updated by more recent information and is larger than the fourth edition, which was published in 1986. This 1991 volume has the advantage of being produced by three very knowledgeable and literate authors with input by multiple acknowledged leaders in the field of genetics. In this instance, "more is better. " The areas of expansion include additions to multiple chapters such as single-gene inheritance, with discussions of fragile X syndrome, phenotypic expressions of various disorders, mitochondrial genetics, genetic imprinting, and uniparental disomies. The authors have added superb coverage of the newer methods and tools used in gene linkage and mapping. Further, there is considerably more information on the clinical aspects of chromosome abnormalities and on molecular and biochemical genetic disorders. The sections on cancer genetics and gene therapy are also new in this volume. Previous brief, incomplete discussions of
Chronic intermittent alcohol disrupts the GluN2B‐associated proteome and specifically regulates group I mGlu receptor‐dependent long‐term depression

N‐Methyl‐d‐aspartate receptors (NMDARs) are major targets of both acute and chronic alcohol, as well as regulators of plasticity in a number of brain regions. Aberrant plasticity may contribute to the treatment resistance and high relapse rates observed in alcoholics. Recent work suggests that chronic alcohol treatment preferentially modulates both the expression and subcellular localization of NMDARs containing the GluN2B subunit. Signaling through synaptic and extrasynaptic GluN2B‐NMDARs has already been implicated in the pathophysiology of various other neurological disorders. NMDARs interact with a large number of proteins at the glutamate synapse, and a better understanding of how alcohol modulates this proteome is needed. We employed a discovery‐based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)‐exposed C57Bl/6J mice to gain insight into alcohol‐induced changes in GluN2B signaling complexes. Protein enrichment analyses revealed changes in the association of post‐synaptic proteins, including scaffolding, glutamate receptor and PDZ‐domain binding proteins with GluN2B. In particular, GluN2B interaction with metabotropic glutamate (mGlu)1/5 receptor‐dependent long‐term depression (LTD)‐associated proteins such as Arc and Homer 1 was increased, while GluA2 was decreased. Accordingly, we found a lack of mGlu1/5‐induced LTD while α1‐adrenergic receptor‐induced LTD remained intact in hippocampal CA1 following CIE. These data suggest that CIE specifically disrupts mGlu1/5‐LTD, representing a possible connection between NMDAR and mGlu receptor signaling. These studies not only demonstrate a new way in which alcohol can modulate plasticity in the hippocampus but also emphasize the utility of this discovery‐based proteomic approach to generate new hypotheses regarding alcohol‐related mechanisms.
Normal echocardiographic mitral and aortic valve thickness in children

Objective We aimed to define the normal range of aortic and mitral valve thickness in healthy schoolchildren from a high prevalence rheumatic heart disease (RHD) region, using a standardised protocol for imaging and measurement. Methods Measurements were performed in 288 children without RHD. Anterior mitral valve leaflet (AMVL) thickness measurements were performed at the midpoint and tip of the leaflet in the parasternal long axis (PSLA) in diastole, when the AMVL was approximately parallel to the ventricular septum. Thickness of the aortic valve was measured from PSLA imaging in systole when the leaflets were at maximum excursion. The right coronary and non-coronary closure lines of the aortic valve were measured in diastole in parasternal short axis (PSSA) imaging. Results were compared with 51 children with RHD classified by World Heart Federation diagnostic criteria. Results In normal children, median AMVL tip thickness was 2.0 mm (IQR 1.7–2.4) and median AMVL midpoint thickness 2.0 mm (IQR 1.7–2.4). The median aortic valve thickness was 1.5 mm (IQR 1.3–1.6) in the PSLA view and 1.4 mm (IQR 1.2–1.6) in the PSSA view. The interclass correlation coefficient for the AMVL tip was 0.85 (0.71 to 0.92) and for the AMVL midpoint was 0.77 (0.54 to 0.87). Conclusions We have described a standardised method for mitral and aortic valve measurement in children which is objective and reproducible. Normal ranges of left heart valve thickness in a high prevalence RHD population are established. These results provide a reference range for school-age children in high prevalence RHD regions undergoing echocardiographic screening.
Reduced activity in functional networks during reward processing is modulated by abstinence in cocaine addicts

Cocaine addiction is characterized by alterations in motivational and cognitive processes. Recent studies have shown that some alterations present in cocaine users may be related to the activity of large functional networks. The aim of this study was to investigate how these functional networks are modulated by non‐drug rewarding stimuli in cocaine‐dependent individuals. Twenty abstinent cocaine‐dependent and 21 healthy matched male controls viewed erotic and neutral pictures while undergoing a functional magnetic resonance imaging scan. Group independent component analysis was then performed in order to investigate how functional networks were modulated by reward in cocaine addicts. The results showed that cocaine addicts, compared with healthy controls, displayed diminished modulation of the left frontoparietal network in response to erotic pictures, specifically when they were unpredicted. Additionally, a positive correlation between the length of cocaine abstinence and the modulation of the left frontoparietal network by unpredicted erotic images was found. In agreement with current addiction models, our results suggest that cocaine addiction contributes to reduce sensitivity to rewarding stimuli and that abstinence may mitigate this effect.
Limited role for ivabradine in the treatment of chronic heart failure

Objective To quantify the proportion of patients attending a community heart failure clinic with left ventricular systolic impairment who might be suitable for ivabradine therapy. Background High resting heart rate is an important and potentially modifiable risk factor in patients with heart failure. The SHIFT study suggested that ivabradine was beneficial when added to conventional treatment including a β-blocker in heart failure patients in sinus rhythm whose resting heart rates remained 70 beats per minute (bpm) or greater and who had worse than moderate left ventricular impairment. Methods and Results The primary cohort included 2211 patients with a left ventricular ejection fraction (LVEF) of 50% or less. Patients were seen at baseline, then reviewed at 4 and 12 months. ‘Suitability’ for ivabradine was assessed as: LVEF 35% or less, sinus rhythm and a resting heart rate of 70 bpm or greater. The proportion of patients who were ‘suitable’ for ivabradine therapy fell from 19.4% (n=429) at baseline, to 14.1% (n=185) at 4 months and finally 9% (n=82) by the 12-month clinic visit. The proportion fell to 5.3% (n=48) if only patients with New York Heart Association class I symptoms and/or no β-blocker therapy were excluded. Conclusions After uptitration of heart failure medications, the number of patients ‘suitable’ for ivabradine therapy was small. First and foremost, β-blocker therapy should be commenced and titrated. The decision to add ivabradine should be made after allowing adequate time to uptitrate conventional medical therapy.