A Novel Truncating FLAD1 Variant, Causing Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) in an 8-Year-Old Boy.

Multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) is a clinically heterogeneous disorder affecting fatty acid and amino acid metabolism. Presentations range from a severe neonatal form with hypoglycemia, metabolic acidosis, and hepatomegaly with or without congenital anomalies to later-onset lipid storage myopathy. Genetic testing for MADD traditionally comprises analysis of ETFA, ETFB, and ETFDH. Patients may respond to pharmacological doses of riboflavin, particularly those with late-onset MADD due to variants in ETFDH. Increasingly other genes involved in riboflavin transport and flavoprotein biosynthesis are recognized as causing a MADD phenotype. Flavin adenine dinucleotide synthase (FADS) deficiency caused by biallelic variants in FLAD1 has been identified in nine previous cases of MADD. FLAD1 missense mutations have been associated with a riboflavin-responsive phenotype; however the effect of riboflavin with biallelic loss of function FLAD1 mutations required further investigation. Herein we describe a novel, truncating variant in FLAD1 causing MADD in an 8-year-old boy. Fibroblast studies showed a dramatic reduction in FADS protein with corresponding reduction in the FAD synthesis rate and FAD cellular content, beyond that previously documented in FLAD1-related MADD. There was apparent biochemical and clinical response to riboflavin treatment, beyond that previously reported in cases of biallelic loss of function variants in FLAD1. Early riboflavin treatment may have attenuated an otherwise severe phenotype.

Fumarase Deficiency: A Safe and Potentially Disease Modifying Effect of High Fat/Low Carbohydrate Diet.

Fumarate hydratase deficiency (FHD) caused by biallelic alterations of the FH (fumarate hydratase) gene is a rare disorder of the tricarboxylic acid cycle, classically characterized by encephalopathy, profound psychomotor retardation, seizures, a spectrum of brain abnormalities and early death in childhood. Less common milder phenotypes with moderate cognitive impairment and long-term survival have been reported. In addition, heterozygous mutations of the FH gene are responsible for hereditary leiomyomatosis and renal cell cancer (HLRCC). There is currently no recommended disease modifying treatment for FHD and only isolated reports of unsuccessful dietary modifications. Herein, we describe the safe and possibly disease modifying effect of a high fat, low carbohydrate diet in a 14-year-old female with severe FHD.

Intervention-related increases in preoperative physical activity are maintained 6-months after Bariatric surgery: results from the bari-active trial.

Higher preoperative physical activity (PA) strongly predicts higher post-operative PA in bariatric surgery (BS) patients, providing rationale for preoperative PA interventions (PAIs). However, whether PAI-related increases can be maintained post-operatively has not been examined. This study compared PA changes across pre- (baseline, post-intervention) and post-operative (6-month follow up) periods in participants randomized to 6 weeks of preoperative PAI or standard care control (SC). Of 75 participants initially randomized, 36 (PAI n=22; SC n=14) underwent BS. Changes in daily bout-related (⩾10-min bouts) moderate-to-vigorous PA (MVPA) and steps were assessed via the SenseWear Armband monitor. PAI received weekly counseling to increase walking exercise. Retention (86%) at post-operative follow up was similar between groups. Intent-to-treat analyses showed that PAI vs SC had greater increases across time (baseline, post-intervention, follow up) in bout-related MVPA minutes/day (4.3±5.1, 26.3±21.3, 28.7±26.3 vs 10.4±22.9, 11.4±16.0, 18.5±28.2; P=0.013) and steps/day (5163±2901, 7950±3286, 7870±3936 vs 5163±2901, 5601±3368, 5087±2603; P<0.001). PAI differed from SC on bout-related MVPA at post-intervention (P=0.016; d=0.91), but not follow up (P=0.15; d=0.41), and steps at post-intervention (P=0.031; d=0.78) and follow up (P=0.024; d=0.84). PAI participants maintained preoperative PA increases post-operatively. Findings support preoperative PAIs and research to test whether PA changes can be sustained and influence surgical outcomes beyond the initial post-operative period.

Medical student clerkship performance and career selection after a junior medical student surgical mentorship program.

BACKGROUND: The impact of early medical school mentorship in students' clerkships performance and career selection is unknown. METHODS: We administered Introduction to Surgery, a resident-directed, semester-long, preclinical elective to junior medical students who answered a Likert-type survey after residency application. Elective participants (EPs) were compared with nonparticipant applicants (EAs), medical school class (MS), and national match outcomes (USA). RESULTS: All 18 EPs (7 M1's, 11 M2's) completed the elective and survey. EP reported more confidence and improved surgical skills, especially attributed to resident mentorship (F(13,237) = 2.3, P = 8*10(-3)). EP "honored" the clerkship more than MS (P = .05); 55.6% of EP, 37.5% of EA, and 27.7% of MS chose surgical fields, yielding a relative risk of 2.0 for EP vs MS (95% confidence interval: 1.3 to 3.2, P = 4*10(-3)). EP "strongly agree" with future mentorship programs (4.6/5), and 1 EP reported the course to be the "main reason" for applying to general surgery. CONCLUSIONS: Introduction to Surgery provides a model for a multifaceted junior medical student mentorship program, which has the potential to retain interested students for surgical career selection.

Natural family planning in the 1990s.

PIP: Natural family planning (NFP) tends to be considered as a matter of chance resulting in unplanned pregnancies and large families. A World Health Organization (WHO) multicenter trial of the ovulation method of NFP was undertaken during 1975-79 with the primary objective of determining what proportion of women of many different cultures could be taught to recognize changes in the cervical mucus around the time of ovulation. The conclusions were that: a) irrespective of cultural, educational, or economic background, over 95% of fertile women could recognize the mucus signs of fertility; b) the fertility rate was 22.6 pregnancies per 100 woman years; c) the preovulatory and postovulatory days designated by the ovulation method of NFP rules as infertile were indeed infertile, as the pregnancies in this phase were 4 per 1000 acts of intercourse. The knowledge gained through the WHO trial and subsequent experience has given NFP organizations and teachers a much greater understanding of the fertile and infertile phases, so that total pregnancy rates have been steadily falling. Of the 11 NFP studies so far reported in the 1990s, the 3 that had total pregnancy rates greater than 5 per 100 woman years were trials of atypical NFP approaches or teaching methods. The results can be compared with reported pregnancy rates of between 0.18 and 3.6 for artificial contraceptive methods in well-motivated couples. One criticism of NFP is that the necessary periods of abstinence may be detrimental to the marital relationship. It is suggested that the sexual revolution of the last 20-30 years has caused marital and family breakdown on a massive scale, thus NFP might be the antidote. Since women are potentially fertile for no more than 6-8 days in the cycle, these easily recognized symptoms empower women through the knowledge they impart regarding their state of fertility. All women are entitled to this simple and fundamental information.^ieng