Role of DISC1 Interacting Proteins in Schizophrenia Risk from Genome‐Wide Analysis of Missense SNPs

A balanced translocation affecting DISC1 cosegregates with several psychiatric disorders, including schizophrenia, in a Scottish family. DISC1 is a hub protein of a network of protein–protein interactions involved in multiple developmental pathways within the brain. Gene set‐based analysis has been proposed as an alternative to individual analysis of single nucleotide polymorphisms (SNPs) to get information from genome‐wide association studies. In this work, we tested for an overrepresentation of the DISC1 interacting proteins within the top results of our ranked list of genes based on our previous genome‐wide association study of missense SNPs in schizophrenia. Our data set consisted of 5100 common missense SNPs genotyped in 476 schizophrenic patients and 447 control subjects from Galicia, NW Spain. We used a modification of the Gene Set Enrichment Analysis adapted for SNPs, as implemented in the GenGen software. The analysis detected an overrepresentation of the DISC1 interacting proteins (permuted P‐value = 0.0158), indicative of the role of this gene set in schizophrenia risk. We identified seven leading‐edge genes, MACF1, UTRN, DST, DISC1, KIF3A, SYNE1, and AKAP9, responsible for the overrepresentation. These genes are involved in neuronal cytoskeleton organization and intracellular transport through the microtubule cytoskeleton, suggesting that these processes may be impaired in schizophrenia.     

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4

Journal of Neurology - SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder...     

1324 prison suicides in 10 countries in South America: incidence,relative risks,and ecological factors

Purpose

Although suicide rates of prison populations and incidence factors have been reported for high-income countries, data from low- and middle-income regions are lacking. The purpose of the study was to estimate suicide rates among prison populations in South America, to examine prison-related factors, and to compare suicide rates between prison and general populations.

Methods

In this observational study, we collected the numbers of suicides in prison, rates of prison occupancy, and incarceration rates from primary sources in South America between 2000 and 2017. We compared suicide rates among prisoners with incidence rates in the general populations by calculating incidence rate ratios. We assessed the effect of gender, year, incarceration rates and occupancy on suicide rates in the prison populations using regression analyses.

Results

There were 1324 suicides reported during 4,437,591 person years of imprisonment between 2000 and 2017 in 10 South American countries. The mean suicide rate was 40 (95% CI 16–65) per 100,000 person years for male and female genders combined. The pooled incidence rate ratio of suicide between prison and general populations was 3.9 (95% CI 3.1–5.1) for both genders combined, 2.4 (95% CI 1.9–3.1) for men and a higher ratio in women (13.5, 95% CI 6.9–26.9). High occupancies of prisons were associated with lower incidence of suicide (β = − 58, 95% CI − 108.5 to − 7.1).

Conclusions

Suicides during imprisonment in South America are an important public health problem. Suicide prevention strategies need to target prison populations.

     

Clinical efficacy of amiodarone as an antiarrhythmic agent

Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 of 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued.     

Incontinence after lateral internal sphincterotomy

PURPOSE: This study was designed to evaluate the anatomic and functional consequences of lateral internal sphincterotomy in patients who developed anal incontinence and in matched controls. METHODS: The study includes 13 patients with anal incontinence after lateral internal sphincterotomy and 13 controls who underwent the same operation and were continent and satisfied with the results of the procedure. Patients underwent clinical evaluation, anorectal manometry, pudendal nerve terminal motor latency testing, and endoanal ultrasonography. RESULTS: Sphincterotomies were longer in incontinent patients (75vs. 57 percent), but the resting pressure and length of the high-pressure zone were not different between groups. Surprisingly, maximum voluntary contraction was higher in incontinent patients than in continent controls (136vs. 100 mmHg). Rectal sensation and pudendal nerve terminal motor latency were similar in both groups. The defect in the internal sphincter was wider in incontinent patients than in continent controls (17.3vs. 14.4 mm), but these differences were not statistically significant. The thickness of the internal sphincter measured by endoanal ultrasound was identical in both groups, but the external sphincter was thinner in incontinent patients both at the site of the sphincterotomy (6.8vs. 8.1 mm) and in the posterior midline (7.1vs. 8.6 mm). CONCLUSIONS: Anal incontinence after lateral internal sphincterotomy is directly related to the length of the sphincterotomy. Whether secondary to preoperative sphincter abnormality or the result of lateral internal sphincterotomy, the external sphincter is thinner in incontinent patients than in continent controls.Read at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.