ZDHHC15 as a candidate gene for autism spectrum disorder.

The phenotypic repercussion of ZDHHC15 haploinsufficiency is not well-known. This gene was initially suggested as a candidate for X-linked mental retardation, but such an association was later questioned. We studied a multiplex family with three members with autism spectrum disorder (ASD) by array CGH, karyotype, exome sequencing and X-chromosome inactivation patterns. Medical history interviews, cognitive and physical examinations, and sensory profiling were also assessed. The three family members with ASD (with normal cognitive abilities and an abnormal sensory profile) were the only carriers of a 1.7 Mb deletion in the long arm of chromosome X, involving: ZDHHC15, MAGEE2, PBDC1, MAGEE1, MIR384 and MIR325. The normal chromosome X was preferentially inactivated in female carriers, and the whole exome sequencing of an affected family member did not reveal any additional genetic variant that could explain the phenotype. Thus, in the present family, ASD segregates with a deletion on chromosome X that includes ZDHHC15. Considering our results together with gene data (regarding function, expression, conservation and animal/cellular models), ZDHHC15 is a candidate gene for ASD. Emerging evidence also suggests that this gene could be associated with other neurodevelopmental disorders, with incomplete penetrance and variable expressivity.

Differential regulation of insulin action and tumor necrosis factor alpha system activity by metformin.

BACKGROUND: Tumor necrosis factor alpha has a key role in insulin resistance. We study the effects of metformin on glucose tolerance, insulin resistance, beta cell function, and soluble tumor necrosis factor receptor (sTNFR) levels. METHODS: We performed a double-blind, randomized metformin-placebo study. Twenty-three subjects with impaired glucose tolerance or impaired fasting glucose were studied. Oral glucose tolerance, homeostasis model assessment, and continuous infusion of glucose with model assessment tests were used to evaluate glucose tolerance, insulin sensitivity, and beta cell function, respectively. Soluble tumor necrosis factor receptor levels were measured before and after therapy. Repeated measures analysis of variance was used for statistical analysis. RESULTS: After 12-week treatment, fasting glucose (110.1 +/- 9.9 to 98.9 +/- 15.7 mg/dl, P < .001), fasting insulin (11.6 +/- 5.4 to 8.8 +/- 3.5 mU/L, P = .05), fasting C-peptide (2.5 +/- 0.7 to 1.8 +/- 0.5 ng/mL, P < .05), and achieved C-peptide (5.2 +/- 1.2 to 4.2 +/- 1 ng/mL, P < .05) levels decreased in the metformin group. In addition, there was an improvement in insulin sensitivity (37.4% +/- 15.2% to 50.4% +/- 23.2%, P < .05) with unchanged sTNFR1 (2.0 +/- 0.8 to 2.3 +/- 1.2 microg/L, P = NS) and sTNFR2 (4.8 +/- 1.7 to 4.4 +/- 1.2 microg/L, P = NS) levels. CONCLUSIONS: Metformin is able to reverse insulin resistance and hyperglycemia in high-risk subjects for type 2 diabetes mellitus independently of the effects on tumor necrosis factor alpha system activity.

[Gender and ischemic heart disease]. / Género y cardiopatía isquémica.

Physiological and pathological processes differ in men and women, depending on factors such as sex and sociological and anthropological characteristics. However, many diseases are still approached from a masculine point of view. In this respect, ischemic heart disease is one of the diseases that most clearly reflects biological differences and social inequalities. In women, the disease presents at a more advanced age, and presentation is frequently atypical with a higher prevalence of comorbidities and greater severity. Consequently, treatment and outcome differ from those in men. Additionally, women differ in their knowledge, and beliefs regarding ischemic heart disease, as well as in their attitudes at symptom onset. Therefore, clinical practice should place significant emphasis on all these aspects in order to avoid inequalities between men and women in the correct diagnosis, treatment, prevention, and rehabilitation of ischemic heart disease.

A comparison of a triple-injection axillary brachial plexus block with the humeral approach.

BACKGROUND AND OBJECTIVES: This prospective, randomized, and single-blind study compared effectiveness, performance, onset, and total anesthetic time and complications of the multiple axillary block (median, radial, and musculocutaneous nerves) with the humeral approach. METHODS: One hundred patients were randomly assigned to 2 groups. In group A (axillary) median, radial, and musculocutaneus nerves were located by a nerve stimulator and injections were made. In group H (humeral) all 4 terminal nerves of the brachial plexus were located and injections were made. A total of 40 mL mepivacaine of 1% was used. RESULTS: Complete sensory block of all 6 peripheral nerves occurred in 94% and 79% of patients in groups A and H, respectively (P < .05). The time to perform the block was shorter in group A (8 +/- 4 minutes v 11 +/- 4 minutes; P < .001); onset time was shorter in group A (16 +/- 8 minutes v 21 +/- 9 minutes; P < .05); total anesthetic time was shorter in group A (24 +/- 8 minutes v 33 +/- 10 minutes; P < .0001). Complete motor block was greater in group A (88% v 66%; P < .05). More vascular punctures occurred in group A (22% v 8%, P < .05). CONCLUSION: The triple-injection axillary block was more effective than the humeral approach as it was associated with more cases of sensory and complete motor block and gave shorter performance and onset times.