Wilson disease and psychiatric symptoms: A brief case report

Wilson disease (WD) is an uncommon recessive genetic disorder affecting copper metabolism. Cardiac, neurological, hepatic and renal manifestations are well defined, nevertheless approximately 30% of patients debut with neuropsychiatric symptoms. These psychiatric alterations resulting from the accumulation of this heavy metal in the basal ganglia are some how less specific. We present a short review of psychiatric symptoms of WD and describe a case of a 37-year-old woman diagnosed with WD who presented neuropsychiatric symptoms and had a consequent delay in diagnosis and causal treatment. Patients who develop WD starting with a predominance of neuropsychiatric symptoms tend to manifest hepatic symptoms later, therefore have a longer delay of diagnosis and a poorer outcome than patients with hepatic symptoms. An early diagnosis of WD can avoid irreversible neurological damage

Sex Differences in Clinical Characteristics and Brain MRI Change in Patients With Wilson’s Disease in a Chinese Population

Background: Wilson’s disease (WD) is an inborn copper metabolism disease. Sex differences in clinical features of WD patients have been reported; however, the effect of sex on brain MRI is still unclear, especially for Chinese WD patients. Therefore, we aimed to examine sex differences in clinical correlates and brain MRI changes in WD patients in a Chinese Han population.Methods: 535 WD patients were enrolled and underwent MRI scanning. These patients were subdivided by the clinical symptoms, Kayser–Fleischer (K–F) rings, laboratory tests and sex. The mean age of onset and diagnosis, disease latency, localization of brain MRI lesions, and the level of copper metabolism were compared between male and female patients.Results: The neuropsychiatric form (452 and 84.5%) was the most common subtype. Compared to female patients, male patients had a higher percentage in three clinical forms: neuropsychiatric form (263 and 58.2%), hepatic form (41 and 59.4%), and presymptomatic form (10 and 71.4%). In the neuropsychiatric form, male patients had the earlier age of onset and definitive diagnosis, and shorter time of disease latency than female patients. Putamen was the most common site for lesions in brain MRI of three groups. In the hepatic form, more male patients showed the ventricular widening than female patients (14/41 vs. 3/28; p < 0.05). The level of serum ceruloplasmin and copper of WD patients with neuropsychiatric form was higher than that of male patients with hepatic or presymptomatic form. In women, however, patients of presymptomatic form have the highest level of the ceruloplasmin, and the level of serum copper in hepatic patients was highest.Conclusion: Our findings suggest sex differences in the percentage of three clinical forms. Meanwhile, the mean age of onset and diagnosis of female was higher than male, also happened in the disease latency. Only in the hepatic form, there was a sex difference in the ventricular widening

Design of a non-invasive sensing system for diagnosing gastric disorders

Gastric disorders are widely spread among the population of any age. At the moment, the diagnosis is made by using invasive systems that cause several side effects. The present manuscript proposes an innovative non-invasive sensing system for diagnosing gastric dysfunctions. The Electro-GastroGraphy (EGG) technique is used to record myoelectrical signals of stomach activities. Although EGG technique is well known for a long time, several issues concerning the signal processing and the definition of suitable diagnostic criteria are still unresolved. So, EGG is to this day a trial practice. The authors want to overcome the current limitations of the technique and improve its relevance. To this purpose, a smart EGG sensing system has been designed to non-invasively diagnose gastric disorders. In detail, the system records the gastric slow waves by means of skin surface electrodes placed in the epigastric area. Cutaneous myoelectrical signals are so acquired from the body surface in proximity of stomach. Electro-gastrographic record is then processed. According to the diagnostic model designed from the authors, the system estimates specific diagnostic parameters in time and frequency domains. It uses Discrete Wavelet Transform to obtain power spectral density diagrams. The frequency and power of the EGG waveform and the dominant frequency components are so analyzed. The defined diagnostic parameters are put in comparison with the reference values of a normal EGG in order to estimate the presence of gastric pathologies by the analysis of arrhythmias (tachygastria, bradygastria and irregular rhythm). The paper aims to describe the design of the system and of the arrhythmias detection algorithm. Prototype development and experimental data will be presented in future works. Preliminary results show an interesting relevance of the suggested technique so that it can be considered as a promising non-invasive tool for diagnosing gastrointestinal motility disorders

Current roles of artificial intelligence in ophthalmology

Artificial intelligence (AI) studies are increasingly reporting successful results in the diagnosis and prognosis prediction of ophthalmological diseases as well as systemic disorders. The goal of this review is to detail how AI can be utilized in making diagnostic predictions to enhance the clinical setting. It is crucial to keep improving methods that emphasize clarity in AI models. This makes it possible to evaluate the information obtained from ocular imaging and easily incorporate it into therapeutic decision-making procedures. This will contribute to the wider acceptance and adoption of AI-based ocular imaging in healthcare settings combining advanced machine learning and deep learning techniques with new developments. Multiple studies were reviewed and evaluated, including AI-based algorithms, retinal images, fundus and optic nerve head (ONH) photographs, and extensive expert reviews. In these studies, carried out in various countries and laboratories of the world, it is seen those complex diagnoses, which can be detected systemic diseases from ophthalmological images, can be made much faster and with higher predictability, accuracy, sensitivity, and specificity, in addition to ophthalmological diseases, by comparing large numbers of images and teaching them to the computer. It is now clear that it can be taken advantage of AI to achieve diagnostic certainty. Collaboration between the fields of medicine and engineering foresees promising advances in improving the predictive accuracy and precision of future medical diagnoses achieved by training machines with this information. However, it is important to keep in mind that each new development requires new additions or updates to various social, psychological, ethical, and legal regulations

Experimental approaches and clinical opportunities in metabolic liver diseases

Metabolic liver diseases are uncommon individually, however, collectively they represent significant cause of morbidity and mortality globally. The liver has many diverse functions, such as; detoxification from hazardous compounds, either ingested or produced by the body, and production of vital proteins, e.g. coagulation factors and acute phase proteins. Liver disease manifestations are therefore immensely diverse and may present both in a strictly hepatic or extra-hepatic manner. Metabolic liver diseases are usually monogenic, meaning a single point mutation is causing the propagation of the disease. Orthotopic liver transplantation has been employed for the treatment of a broad range of metabolic liver diseases and is indeed a curative method in most instances. In this thesis, we focused on alpha 1-antitrypsin deficiency–one of the monogenetic liver diseases with both hepatic and pulmonary manifestations. In Study I, we examined and showed that alpha 1-antitrypsin replacement therapy may also have an impact on hepatocytes and the propagation of liver disease. Replacement therapy is currently only reserved for pulmonary manifestation of alpha 1-antitrypsin deficiency. Addition of exogenous alpha 1- antitrypsin protein reduced alpha 1-antitrypsin (SERPINA1) mRNA expression in primary human hepatocytes from both deficient and proficient patients. Furthermore, similar results were seen in lung tissue samples from deficient patients. Altogether, the results may indicate a feedback mechanism where adequate circulating alpha 1-antitrypsin causes a reduction in its own production and replacement therapy may be beneficial for the reduction of hepatic damage caused by mutant alpha 1-antitrypsin. Study II focused on investigating the novel promising mRNA-based therapies for protein replacement in alpha 1-antitrypsin deficiency. Modified mRNA encoding alpha 1-antitrypsin protein was delivered in vitro to primary human hepatocytes from both deficient and proficient patients. Subsequently in vivo delivery of modified mRNA was conducted in wild type mice and the NSG-PiZ AATd mouse model. Translated and functional AAT protein was detected both in vitro and in vivo. At time of liver transplantation, explanted livers from metabolic liver disease patients may be recovered and used as a graft for another patient with chronic liver disease in a procedure called domino liver transplantation. In Study III, we evaluated the domino liver transplant program at Karolinska University Hospital, Huddinge from 2007–2017. Patients undergoing domino liver transplant had similar survival rate and time spent on waiting list as age and diagnosis matched patients undergoing deceased donor liver transplantation. To conclude, we have shown hepatic benefits of replacement therapy in alpha 1-antitrypsin deficiency and explored mRNA therapy as a novel way to replace the missing protein. We have further evaluated the domino liver transplant program, in which livers from metabolic liver disease patients are used as donor grafts and concluded that the program has enabled additional transplantations without affecting patients’ waiting time or survival

Evaluation of the prevalence of minimal hepatic encephalopathy in patients with compensated cirrhosis

In this study 50 cases of compensated cirrhotics were evaluated for presence of Minimal Hepatic Encephalopathy. • In this study we defined minimal hepatic encephalopathy based on psychometric analysis,13 by way of the Number Connection Test, since earlier studies have proved that the abnormal psychometric test as one of the earliest manifestation of minimal hepatic encephalopathy. Based on the NCT this study found a prevalence of 38% MHE amongst the compensated cirrhotics studied • Minimal hepatic encephalopathy was defined in our study based on the prolonged time taken to complete the NCT and/or Electroencephalography changes/ or a combination of electroencephalography and serum ammonia rise/ or a combination of serum ammonia and number connection test. • High serum ammonia alone was not taken as indicative of minimal hepatic encephalopathy as it was found by many studies not to correlate with the presence of Minimal hepatic encephalopathy. • The total percentage of cases diagnosed as having minimal hepatic encephalopathy in our study using the above criteria was 38% • Out of the 19 patients tested positive for minimal hepatic encephalopathy 16 were males and 3 were females • In a study conducted by Quero et.al in Holland13 about MHE in cirrhotics with NCT and EEG, showed a prevalence of 24%. Correlation was done using arterial ammonia and PET scan. Magnetic Resonance Spectroscopy was also used for correlation. • In a German study47 published in the Journal of Hepatology in 1998 July, pages 45 to 49 volume 28 No.1 the prevalence of MHE was estimated to be 45% by various psychometric tests including the Number Connection Test thus establishing it as a simple bedside tool for assessment of the presence of MHE in the cirrhotics • In a study conducted by Amodio et al in Italy46 it was found that using the NCT and Line tract test the prevalence of Minimal Hepatic encephalopathy was estimated to be 28% but estimates by spectral EEG was only 10% • In comparison, our study shows a prevalence of minimal hepatic encephalopathy in the group by number connection test to be 34% and that by electroencephalogram to be 6%. CONCLUSIONS : The prevalence of Minimal Hepatic Encephalopathy in compensated cirrhotics in our study is 38%. There is no significant difference in the prevalence rate between males and females. (38% Vs 37%) Number Connection Test and other psychometric tests are useful as bedside tools in estimating Minimal Hepatic Encephalopathy. Psychometric test positivity does not correlate well with Electro-encephalographic changes in the diagnosis of Minimal Hepatic Encephalopathy. Evaluating a cirrhotic patient for MHE is essential for its impact on day to day functionality like driving, operating machineries and social interaction apart from other activities like driving

216 Jewish Hospital of St. Louis

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Endoscopic Procedures in Colon and Rectum

Endoscopic procedures in colon and rectum presents nine chapters which start with introductory ones like screening by colonoscopy as the preparation and monitoring for this exam. In addition to these approaches the book aims in the last four chapters to explain endoscopic diagnostic and therapeutic aspects in the colon and rectum. The description of each text is very comprehensive, instructive and easy to understand and presents the most current practices on the topics described. This book is recommended for general and colorectal surgeons as it presents guidelines for diagnosis and treatment which are very well established

Gene expression and metabolism in malignant hyperthermia susceptible and normal skeletal muscle

Malignant hyperthermia (MH) is an autosomal dominant, pharmacogenetic disorder primarily caused by RYR1 mutations which result in calcium dysregulation within skeletal muscle. Genetically susceptible individuals are at risk of potentially fatal hypermetabolic reactions when exposed to volatile anaesthetics and the muscle relaxant succinylcholine. MH susceptibility is diagnosed through the in vitro contracture test (IVCT) by challenging muscle biopsies with triggering agents, or by genetic screening for known familial mutations. Genome-wide gene expression was compared before and after IVCT, from MH-susceptible (MHS) and non-susceptible (MHN) skeletal muscle by RNA sequencing. A downregulation of genes related to oxidative phosphorylation (OXPHOS) was observed in MHS samples at baseline, suggesting a metabolic defect. Mitochondrial function was assessed by high resolution respirometry, measuring oxygen consumption rates in permeabilised muscle fibres. Results showed evidence of reduced OXPHOS capacity, complex II deficiency and increased mitochondrial content in MHS muscle at baseline. Exposure to halothane triggered a hypermetabolic response in MHS mitochondria which significantly increased oxygen consumption rates in several respiratory states, whilst MHN samples were unaltered. Genome-wide gene expression and mitochondrial function was also studied at baseline and after halothane challenge, using transgenic mouse models of MH to investigate RYR1 variant-specific effects. At baseline, fatty acid oxidation and mitochondria-related gene expression was downregulated in mice homozygous (HOM) for G2435R-RYR1 and heterozygous (HET) for T4826I-RYR1. In comparison to wild-type, mitochondria from G2435R-RYR1 HOM mice showed an increase in complex I-facilitated OXPHOS and reduced mitochondrial content at baseline. Mitochondria from transgenic mice also showed evidence of increased sensitivity to both halothane and calcium in comparison to wild-type. This study presents evidence of mitochondrial dysfunction in human and mouse MHS skeletal muscle, which is correlated with gene expression changes associated with oxidative metabolism. Functional defects in mitochondria are therefore potential contributors to phenotypic variability observed in MH

Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies