Grandparental genotyping enhances exome variant interpretation

Trio exome sequencing is a powerful tool in the molecular investigation of monogenic disorders and provides an incremental diagnostic yield over proband‐only sequencing, mainly due to the rapid identification of de novo disease‐causing variants. However, heterozygous variants inherited from unaffected parents may be inadvertently dismissed, although multiple explanations are available for such scenarios including mosaicism in the parent, incomplete penetrance, imprinting, or skewed X‐inactivation. We report three probands, in which a pathogenic or likely pathogenic variant was identified upon exome sequencing, yet was inherited from an unaffected parent. Segregation of the variants (in NOTCH1, PHF6, and SOX10) in the grandparent generation revealed that the variant was de novo in each case. Additionally, one proband had skewed X‐inactivation. We discuss the possible genetic mechanism in each case, and urge caution in data interpretation of exome sequencing data. We illustrate the utility of expanding segregation studies to the grandparent generation and demonstrate the impact on exome interpretation strategies, by showing that objective genotype data can overcome subjective parental report of lack of symptoms.     

Potential repair of rat spinal cord injuries using stimulated homologous macrophages

The failure of the adult mammalian central nervous system (CNS) to regenerate after injury has long been viewed as a unique phenomenon resulting from the specific nature of this system. The finding that some CNS axons could be induced to regrow if provided with a permissive environment suggested that this failure is a result, at least in part, of the nature of the postinjury neuronal environment. It was further shown that the involvement of inflammatory cells, particularly macrophages, in postinjury processes in the CNS is limited. We have suggested that, to achieve recovery after injury, the adult mammalian CNS may require the assistance of the same postinjury factors as those involved in the recovery of spontaneously regenerating systems but that its accessibility to such assistance is restricted. Accordingly, we proposed that it might be possible to circumvent the restriction, allowing regeneration to occur. We showed that the implantation of autologous macrophages, which had been prestimulated by exposure to a regenerative (sciatic) nerve, into completely transected spinal cords of adult rats led to partial motor recovery. This treatment intervenes in the postinjury process by simulating in the axotomized CNS the events that occur naturally in spontaneously regenerating systems.     

Is there really a decrease in sperm parameters among healthy young men? A survey of sperm donations during 15 years

Purpose: Our purpose was to measure changes in semen quality and quantity in young healthy sperm donors in Jerusalem over time. Methods: A retrospective analysis of semen parameters over 15 years using linear regression analysis, in a single sperm bank in a tertiary university center. Study population consisted of 188 young, healthy medical students, aged 20 to 30 years, who donated sperm samples for Artificial insemination between 1980 and 1995. Results: There were no statistically significant changes in semen concentration and motility during the study period. The mean semen volume increased by 0.1 ml (5.1%) per year (P < 0.0001), with a concomitant mean rise of 5.8 × 10⁶ (7.7%) per year in total motile sperm count. The percentage normal morphology decreased by a mean of 1.04% per year during the entire period (P < 0.0001). Conclusions: During the past 15 years, there has been an increase in total motile sperm count, secondary to an increase in semen volume, and a decline in normal morphology that are independent of the age and the duration of abstinence in fertile men.     

Are cognitive–behavioral interventions effective in reducing occupational stress among nurses?

Despite the growing evidence regarding the effectiveness of cognitive–behavioral interventions in reducing occupational stress, very few studies have examined its effectiveness among nurses. This study investigated the impact of a cognitive–behavioral (CB) course on the nurses' well-being. The study compared the sense of coherence (SOC), perceived stress (PSS), and mood states of 20 nurses who had participated in the CB course to that of 16 control participants using a pre–post test design. At baseline (t1), no significant differences were found between the two groups in SOC, PSS, and mood states. The effects within each group controlling for t1 were examined by analysis of covariance. At t2, a significant increase in SOC and the mood state of vigor and a significant decrease in PSS and fatigue were found only among participants in the CB course. The results are discussed in relation to the conceptual framework of stress and coping theory.     

Non-imaging-guided fine-needle aspiration of liver lesions: a retrospective study of 279 patients

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Fatal ventricular arrhythmia as a complication of transesophageal echocardiography.

AIM: To report a case of serious ventricular arrhythmia during transesophageal echocardiography. METHODS AND RESULTS: A 58-year-old woman with previous mitral and tricuspid valve replacement and permanent pacemaker implantation suffered from recurrent fever and Staphylococcus aureus bacteremia. Transesophageal echocardiography was performed as part of the assessment for infective endocarditis. During this procedure the patient developed sustained ventricular tachycardia and subsequently ventricular flutter. She was successfully resuscitated. Subsequently the procedure was undertaken under general anesthesia with no complications. CONCLUSION: The increasing use of TEE in a wider spectrum of patients, many of whom are seriously ill, may result in serious side-effects.