Jervell and Lange-Nielsen syndrome: neurologic and cardiologic evaluation

Recurrent syncope, malignant ventricular arrhythmias, and sudden death are complications of the long QT syndrome (LQTS). Two well-known syndromes with long QT intervals are known. The Jervell and Lange-Nielsen syndrome (JLNS) is characterized by prolongation of the QT interval, deafness, and autosomal-recessive inheritance, and the Romano-Ward syndrome is characterized by a prolonged QT interval, autosomal-dominant inheritance, and no deafness. In the present study assessment was performed of the diagnostic importance of the ventricular derepolarization parameters, clinical features, and prevalence of JLNS among 132 children with congenital hearing loss (CHL). In the CHL group the mean QT, QTc, JT, and JTc intervals and the dispersion values (QT-d, JT-d, QTc-d, and JTc-d) were significantly longer than those of control subjects (n = 96) (P < 0.05). Patients with CHL and JLNS (n = 5) had significantly longer mean values of QT, QTc, JT, and JTc intervals and dispersion values than those of CHL without JLNS (n = 127) and control subjects (P < 0.05). The results suggest that assessment of ventricular derepolarization parameters in children with CHL will be helpful in the early detection of JLNS because infants with CHL cannot accurately describe the symptoms of syncope.     

Growth and diosgenin production by Dioscorea deltoidea cells in batch and continuous cultures

This paper reports the kinetics of growth and diosgenin production in batch cultures, and the application of the continuous culture (chemostat) technique to DIOSCOREA DELTOIDEA cells. In batch cultures, biomass production was dependent on the concentration (up to 60 g/liter) of the carbon source (sucrose); the cellular yield value obtained was 0.4 g cell dry wt/g sucrose utilized. Diosgenin was synthesized only after growth had ceased; its synthesis proceeded for about 18 days and a concentration of 1.8% (of cell dry wt.) was obtained. D. DELTOIDEA cells were grown at steady state conditions, at a constant growth rate in a chemostat. Only small amounts of diosgenin were produced by growing cells in the chemostat.     

Strategic,feasibility, economic,and cultural aspects of phase 0 approaches: Is it time to change the drug development process in order to increase productivity?

Research conducted over the past 2 decades has enhanced the validity and expanded the applications of microdosing and other phase 0 approaches in drug development. Phase 0 approaches can accelerate drug development timelines and reduce attrition in clinical development by increasing the quality of candidates entering clinical development and by reducing the time to “go‐no‐go” decisions. This can be done by adding clinical trial data (both healthy volunteers and patients) to preclinical candidate selection, and by applying methodological and operational advantages that phase 0 have over traditional approaches. The main feature of phase 0 approaches is the limited, subtherapeutic exposure to the test article. This means a reduced risk to research volunteers, and reduced regulatory requirements, timelines, and costs of first‐in‐human (FIH) testing. Whereas many operational aspects of phase 0 approaches are similar to those of other early phase clinical development programs, they have some unique strategic, regulatory, ethical, feasibility, economic, and cultural aspects. Here, we provide a guidance to these operational aspects and include case studies to highlight their potential impact in a range of clinical development scenarios.     

Cumulative Marijuana Use and Carotid Intima-Media Thickness at Middle Age: The CARDIA Study

BackgroundLong-term cardiovascular health effects of marijuana are understudied. Future cardiovascular disease is often indicated by subclinical atherosclerosis for which carotid intima-media thickness is an established parameter.MethodsUsing the data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 Black and white women and men at Year 20 visit, we studied the association between carotid intima-media thickness in midlife and lifetime exposure to marijuana (1 marijuana year = 365 days of use) and tobacco smoking (1 pack-year = 20 cigarettes/day for 365 days). We measured carotid intima-media thickness by ultrasound and defined high carotid intima-media thickness at the threshold of the 75th percentile of all examined participants. We fit logistic regression models stratified by tobacco smoking exposure, adjusting for demographics, cardiovascular risk factors, and other drug exposures.ResultsData was complete for 3257 participants; 2722 (84%) reported ever marijuana use; 374 (11%) were current users; 1539 (47%) reported ever tobacco smoking; 610 (19%) were current smokers. Multivariable adjusted models showed no association between cumulative marijuana exposure and high carotid intima-media thickness in never or ever tobacco smokers, odds ratio (OR) 0.87 (95% confidence interval [CI]: 0.63-1.21) at 1 marijuana-year among never smokers and OR 1.11 (95% CI: 0.85-1.45) among ever tobacco smokers. Cumulative exposure to tobacco was strongly associated with high carotid intima-media thickness, OR 1.88 (95%CI: 1.20-2.94) for 20 pack-years of exposure.ConclusionsThis study adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.     

Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile

Digestive Diseases and Sciences - Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT)...     

Does dystocia during labor pose a risk factor for another non-progressive labor during the subsequent delivery?

Objective: To establish whether failure to progress during labor poses a risk factor for another non-progressive labor (NPL) during the subsequent delivery.

Methods: A retrospective cohort study including singleton pregnancies that failed to progress during the previous labor and resulted in a cesarean section (CS) was conducted. Parturients were classified into three groups for both previous and subsequent labors: CS due to NPL stage I, stage II and an elective CS as a comparison group.

Results: Of 202?462 deliveries, 10?654 women met the inclusion criteria: 3068 women were operated due to NPL stage I and 1218 due to NPL stage II. The comparison group included 6368 women. Using a multivariable logistic regression models, NPL stage I during the previous delivery was found as an independent risk factor for another NPL stage I in the subsequent labor (adjusted odds ratio [OR]?=?2.9; 95% confidence interval [CI]?=?2.4–3.7; p?p?=?0.033; adjusted OR?=?5.3; 95% CI?=?3.7–7.5; p?Conclusion: A previous CS due to a NPL is an independent risk factor for another NPL in the subsequent pregnancy and for recurrent cesarean delivery.