Identification of a novel MKS locus defined by TMEM107 mutation.

Meckel-Gruber syndrome (MKS) is a perinatally lethal disorder characterized by the triad of occipital encephalocele, polydactyly and polycystic kidneys. Typical of other disorders related to defective primary cilium (ciliopathies), MKS is genetically heterogeneous with mutations in a dozen genes to date known to cause the disease. In an ongoing effort to characterize MKS clinically and genetically, we implemented a gene panel and next-generation sequencing approach to identify the causal mutation in 25 MKS families. Of the three families that did not harbor an identifiable causal mutation by this approach, two mapped to a novel disease locus in which whole-exome sequencing revealed the likely causal mutation as a homozygous splicing variant in TMEM107, which we confirm leads to aberrant splicing and nonsense-mediated decay. TMEM107 had been independently identified in two mouse models as a cilia-related protein and mutant mice display typical ciliopathy phenotypes. Our analysis of patient fibroblasts shows marked ciliogenesis defect with an accompanying perturbation of sonic hedgehog signaling, highly concordant with the cellular phenotype in Tmem107 mutants. This study shows that known MKS loci account for the overwhelming majority of MKS cases but additional loci exist including MKS13 caused by TMEM107 mutation.

Complementary and alternative medicine for lowering blood lipid levels: A systematic review of systematic reviews.

BACKGROUND: The aim of this article is to summarize and critically evaluate the evidence from systematic reviews (SRs) of complementary and alternative medicine (CAM) for lowering blood lipid levels (BLL). METHODS: Eight electronic databases were searched until March 2016. Additionally, all the retrieved references were inspected manually for further relevant papers. Systematic reviews were considered eligible, if they included patients of any age and/or gender with elevated blood lipid levels using any type of CAM. We used the Oxman and AMSTAR criteria to critically appraise the methodological quality of the included SRs. RESULTS: Twenty-seven SRs were included in the analyses. The majority of the SRs were of high methodological quality (mean Oxman score=4.81, SD=4.88; and the mean AMSTAR score=7.22, SD=3.38). The majority of SRs (56%) arrived at equivocal conclusions (of these 8 were of high quality); 7 SRs (37%) arrived at positive conclusions (of these 6 were of high quality), and 2 (7%) arrived at negative conclusions (both were of high quality). There was conflicting evidence regarding the effectiveness of garlic; and promising evidence for yoga. CONCLUSIONS: To conclude, the evidence from SRs evaluating the effectiveness of CAM in lowering BLL is predominantly equivocal and confusing. Several limitations exist, such as variety of doses and preparations, confounding effects of diets and lifestyle factors, or heterogeneity of the primary trials among others.

De novo stress urinary incontinence after vaginal repair for pelvic organ prolapse: one-year follow-up.

OBJECTIVE: A few studies have reported a wide range (2-43%) in incidence of de novo stress urinary incontinence (SUI) following surgical repair of pelvic organ prolapse (POP) in previously continent women. The aim of this study was to re-examine this incidence up to one year following vaginal repair of prolapse. STUDY DESIGN: Retrospective review of a cohort of women who underwent reconstructive vaginal repair of POP without a concomitant anti-incontinence procedure between 2003 and 2007 at two tertiary referral centers. Women were considered eligible if they were stress continent by symptoms and objective assessment (including urodynamics testing) prior to surgical repair. All women who had had any anti-incontinence procedure previously were excluded. The endpoint was subjective SUI that prompted the patient to undergo any treatment within one year from their prolapse surgery. RESULTS: 64 women, with a mean age of 61 (±11) years, were eligible for the study: 26 (41%) had preoperative symptoms of overactive bladder. Fifty-four patients were available for analysis at the one-year visit. Seven women (13.5%) had symptoms of SUI but only one (2%) was found to have SUI objectively. Another patient underwent anti-incontinence surgery following her prolapse surgery. CONCLUSION: The incidence of de novo SUI requiring treatment in previously continent women who underwent vaginal repairs for POP without concomitant anti-incontinence surgery is low (4%). A large-scale prospective study is necessary to further evaluate this finding.

Potentiometric determination of ketotifen fumarate in pharmaceutical preparations and urine using carbon paste and PVC membrane selective electrodes.

This study compares between unmodified carbon paste (CPE; the paste has no ion pair) and polyvinyl chloride (PVC) membrane selective electrodes that were used in potentiometric determination of ketotifen fumarate (KTF), where sodium tetraphenylborate (NaTPB) was used as titrant. The performance characteristics of these sensors were evaluated according to IUPAC recommendations which reveal a fast, stable, and linear response for KTF over the concentration range of 10(-7) to 10(-2) mol L(-1). The electrodes show Nernstian slope value of 52.51 ± 0.20 and 51.51 ± 0.25 mV decade(-1) for CPE and PVC membrane electrodes at 30°C, respectively. The potential is nearly stable over the pH range 3.0-6.0 and 2.0-7.0 for CPE and PVC membrane electrodes, respectively. Selectivity coefficient values towards different inorganic cations, sugars, and amino acids reflect high selectivity of the prepared electrodes. The electrodes responses at different temperatures were also studied, and long operational lifetime of 12 and 5 weeks for CPE and PVC membrane electrodes, respectively, were found. These are used for determination of ketotifen fumarate using potentiometric titration, calibration, and standard addition methods in pure samples, its pharmaceutical preparations (Zaditen tablets), and biological fluid (urine). The direct potentiometric determination of KTF using the proposed sensors gave recoveries % of 98.97 ± 0.53 and 98.62 ± 0.74 with RSD 1.42 and 0.63% for CPE and PVC membrane selective electrodes, respectively. Validation of the method shows suitability of the proposed sensors for use in quality control assessment of KTF. The obtained results were in a good agreement with those obtained using the reported spectrophotometric method.

Evaluation of continuing medical education in Al-qasim, saudi arabia.

OBJECTIVE: To evaluate CME activities in Al-Qassim region in the Kingdom of Saudi Arabia METHODS: A study using a pre-structured questionnaire was conducted in Al-Qassim, targeting physicians working in the hospitals. The survey was conducted in two phases. The first phase was conducted at the inception of the department of professional education and the second one year later. Questionnaires were given to a sample of physicians working in the hospitals. RESULTS: Mean CME hours in the region increased from 5.5(±5.9) to 14.2(±19.7), p=0.0001. 50% said that the CME should be presented differently. There was a need for regular courses (61%), departmental and bedside activities (52%) and visiting speakers (45%). Only 47% of the physicians were using the Internet. CONCLUSION: There is a need to shift from credit counting to a process that can yield professional development through practical courses and departmental activities. The use of the Internet in CME activities should be encouraged.