Mcbridewhitehead8602
Schizophrenia (SCZ) is a debilitating disease with a complex genetic cause in which age at onset may reflect genetic vulnerability. Though there has been some association between genetic polymorphisms and age of onset, there has been little exploration of the role of epigenetic processes. We sought to explore the influence of DNA methylation, a key epigenetic mechanism, and its association with the age of onset of illness.
One hundred thirty-eight participants aged 18-75 years and previously diagnosed with SCZ spectrum disorders by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID DSM-5) were recruited. Venous blood was collected and genome-wide DNA methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array. Individual CpG sites and regions of differential methylation were explored by the age of onset; covariates included age, sex, as well as white blood cell composition.
Binary grouping (early vs. late onset) revealed four intergenic CpG sites on chromosome 2 that were above the expected P-value threshold, with hypermethylation of the CpG site cg10392614 most strongly associated with early-onset SCZ. The four most strongly associated CpG sites, including cg 10392614, were intergenic. Continuous analysis revealed the top CpG site to be cg11723066 , which is linked to the JAM3 gene, with hypomethylation associated with earlier onset; however, results were below the expected P-value threshold.
Studies on DNA methylation in the first-episode psychosis population may help further our understanding of the role of epigenetics in the age of onset of SCZ.
Studies on DNA methylation in the first-episode psychosis population may help further our understanding of the role of epigenetics in the age of onset of SCZ.
The complex structure of the chromosome 2q12.3-q13 region provides a high chance of recombination events between various low copy repeats (LCRs). Copy number variants (CNV) in this region are present in both healthy populations and individuals affected with developmental delay, autism and congenital anomalies. Variable expressivity, reduced penetrance and limited characterization of the affected genes have complicated the classification of the CNVs clinical significance.
Chromosomal microarray analysis data were reviewed for 10 298 patients with neurodevelopmental disorders referred to the UPMC Medical Genetics and Genomics Laboratories. A genotype-phenotype correlation was performed among the patients harboring the 2q12.3-q13 CNVs with overlapping genomic intervals.
We identified 17 (1 in ~600) individuals with rare CNVs in the 2q12.3-q13 region, including nine patients with deletions, seven individuals with duplications and one patient who had both a deletion and a duplication. Likely pathogenic CNVs with the breakpoints between LCRs encompassing the potential dosage-sensitive genes BCL2L11, BUB1, FBLN7 and TMEM87B were the most common. CNVs were also observed between LCRs surrounding the RANBP2 and LIMS1 genes.
Our study provides evidence for pathogenic CNV hotspots within the chromosome 2q12.3-q13 region. We suggest CNV classification based on the affected interval and the involvement of potential dosage-sensitive genes in these patients.
Our study provides evidence for pathogenic CNV hotspots within the chromosome 2q12.3-q13 region. We suggest CNV classification based on the affected interval and the involvement of potential dosage-sensitive genes in these patients.This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.
This study aimed to evaluate electrocardiographic and echocardiographic findings, Holter recordings of the multisystem inflammatory syndrome in children, and to identify prognostic factors for cardiac involvement.
We retrospectively reviewed demographic characteristics, medical data, laboratory findings, electrocardiogram and echocardiographic findings, 24-hour Holter recordings, need for an ICU, and extracorporeal membrane oxygenation in multisystem inflammatory syndrome in children. Acute left ventricular systolic dysfunction was defined as left ventricular ejection fraction (EF)≤%55 on echocardiography.
Sixty-seven children were included in the study. 24-hour Holters were recorded in 61.2% of the patients and 49.2% were normal. On echocardiographic examination, 14.9% of the patients had systolic dysfunction (EF ≤ 55%). While 32.8% of patients had mild mitral regurgitation, 3% had moderate mitral regurgitation, and 6% had mild aortic regurgitation. There was no statistically significant difference in igher in patients with systolic dysfunction. Also, the cut-off value of 1700 pg/ml for B-type natriuretic peptide was significantly effective. These parameters may indicate the severity of the disease but should be supported by prospective studies.Barrett's oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case-control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages and dietary scores, on risk of BE in over 20 000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990-1994) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007-2010). Logistic regression models were used to estimate OR and 95 % CI for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest v. lowest quartile OR = 0·59; CI 0·38, 0·94; P-trend = 0·02 and OR = 0·58; CI 0·37, 0·93; P-trend = 0·02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR = 1·54; CI 0·97, 2·44; P-trend = 0·04) and total fat intake (OR per 10 g/d = 1·11; CI 1·00, 1·23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy products or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.
Opioid use disorder (OUD) has become increasingly prevalent among hospitalized patients in the United States and globally. As its prevalence increases, this provides a valuable opportunity for clinicians in the hospital setting to engage and initiate management and treatment of OUD.
This article aims to provide hospitalists and other clinicians working in the hospital with a narrative review of the management of opioid withdrawal and the initiation of medications for opioid use disorder (MOUD) in the hospital and provide an update on a novel low dose approach to buprenorphine induction (also commonly referred to as the 'microinduction' method).
Authors performed a narrative review of the literature.
Management can initially include treating withdrawal symptoms with opioids as well as with a combination of non-opioid medications such as alpha 2 agonists, benzodiazepines, and/or antiemetics as needed. Besides simply managing withdrawal symptoms, clinicians can further improve the care of patients with Owith adequate and timely follow-up.
Proper management of opioid withdrawal and initiation of MOUD in the hospital can improve outcomes in patients with OUD.
Proper management of opioid withdrawal and initiation of MOUD in the hospital can improve outcomes in patients with OUD.The study aimed to evaluate the hypothesis that chewing is a mechanical and physiological contributor to swallowing, physiologic/pathologic processes of the gastrointestinal tract (GIT), and nutrition-related factors. A search strategy was applied to three different databases to investigate if chewing function in adults affects the swallowing, physiologic/pathologic processes of the GIT, and nutrition-related factors compared to controls with no exposure. The included studies were evaluated for methodological quality and risk of bias and certainty of evidence. The results showed 71 eligible studies. Overall, the results showed that 46 studies supported the hypothesis while 25 refuted it. However, the GRADE analysis showed low to very low certainty of the evidence to support the hypothesis that chewing is an important contributor in the swallowing process, and physiologic/pathologic processes in the GIT. The GRADE analysis also showed a moderate to very low certainty of the evidence to suggest that chewing function contributes to nutrition-related parameters. The overall results of the current study showed that a majority (64.7%) of the studies (46 out of 71) supported the hypothesis. However, robust studies with proper design, adequate sample size, and well-defined outcome parameters are needed to establish conclusive evidence.This research analyzed the effect of professional, organizational and care-unit identifications on both healthcare professionals' quality of professional life and mental health. This research was done in a local hospital in a region of northern Italy which was one of the first regions to be impacted by the first wave of the pandemic. Using a cross-sectional research, a web-based questionnaire was sent to the healthcare professionals. Professional quality of life, professional identifications as well as emotional maladjustment in terms of stress, anxiety and depression were measured. Results indicated that professional and care unit identification were positively linked to increased compassion satisfaction and reduced burnout. Professional identification was negatively associated with secondary traumatic stress as well, while care unit identification was positively associated with vicarious trauma. CX-5461 The negative dimension of the professional quality of life had positive relations with emotional maladjustment. Professional and care unit identifications appeared to have an indirect effect via professional quality of life on maladjustment.