Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome?

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is defined as the occurrence of multiple tumorous intraabdominal lesions, which are myomatous nodules. LPD is a rare disease with only about 100 cases reported. The usual course of LPD is benign with the majority of the patients being premenopausal females. Only two cases involving men have been reported, no syndrome or familial occurrence of LPD has been described. CASE PRESENTATION: We describe a Caucasian-American family in which six members (three men) are diagnosed with Leiomyomatosis peritonealis disseminata (LPD) and three deceased family members most likely had LPD (based on the autopsy reports). Furthermore we describe the association of LPD with Raynaud's syndrome and Prurigo nodularis. CONCLUSION: Familial clustering of Leiomyomatosis peritonealis disseminata (LPD) has not been reported so far. The etiology of LPD is unknown and no mode of inheritance is known. We discuss possible modes of inheritance in the presented case, taking into account the possibility of a genetic syndrome. Given the similarity to other genetic syndromes with leiomyomatosis and skin alterations, we describe possible similar genetic pathomechanisms

The Evolution of Surgical Treatment for Female Stress Urinary Incontinence: Era of Mid-Urethral Slings

Based on the integral theory, tension-free placement of a mid-urethral sling (MUS) for female stress urinary incontinence (SUI) has gained substantial popularity owing to the ease of the procedure and its effectiveness. Published series with long-term follow-up show continence rates after the MUS procedure ranging from 70% to 80%. Complication rates after MUS procedures are usually low. This review aimed to describe the historical change and the current use of the MUS. We discuss the efficacy and complications of various MUS procedures and the current strategies for managing failed slings

Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD

Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability

Hyperphosphatemia is common in patients with chronic kidney disease and is increasingly associated with poor clinical outcomes. Current management of hyperphosphatemia with dietary restriction and oral phosphate binders often proves inadequate. Tenapanor, a minimally absorbed, small-molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), acts locally in the gastrointestinal tract to inhibit sodium absorption. Because tenapanor also reduces intestinal phosphate absorption, it may have potential as a therapy for hyperphosphatemia. We investigated the mechanism by which tenapanor reduces gastrointestinal phosphate uptake, using in vivo studies in rodents and translational experiments on human small intestinal stem cell–derived enteroid monolayers to model ion transport physiology. We found that tenapanor produces its effect by modulating tight junctions, which increases transepithelial electrical resistance (TEER) and reduces permeability to phosphate, reducing paracellular phosphate absorption. NHE3-deficient monolayers mimicked the phosphate phenotype of tenapanor treatment, and tenapanor did not affect TEER or phosphate flux in the absence of NHE3. Tenapanor also prevents active transcellular phosphate absorption compensation by decreasing the expression of NaPi2b, the major active intestinal phosphate transporter. In healthy human volunteers, tenapanor (15 mg, given twice daily for 4 days) increased stool phosphorus and decreased urinary phosphorus excretion. We determined that tenapanor reduces intestinal phosphate absorption predominantly through reduction of passive paracellular phosphate flux, an effect mediated exclusively via on-target NHE3 inhibition

Risk factors for cataract subtypes waterclefts and retrodots: two case-control studies.

UNLABELLED: Waterclefts and retrodots are independently associated with visual impairment, yet a review identified no data on risk factors. PURPOSE: To investigate risk factors for these two human lens cataract subtypes. METHOD: Two nested case-control studies: The host study comprised 1078 subjects (55 years) attending the Somerset and Avon Eye Study (SAES). In total, 197 watercleft cases (Oxford grade 0.2 in either eye) and 199 retrodot cases (Oxford grade 1.0 in either eye) were individually age/gender matched to controls. Detailed ophthalmic and potential risk factor data were collected, including body mass index (BMI), smoking, alcohol, diabetes, hypertension, analgesics, vitamin supplementation, nutrition, sunlight exposure, dehydration, hormonal (women), blood lipids, glucose, urea, creatinine, uric acid, and vitamin levels. RESULTS: For waterclefts, univariable analysis identified BMI, alcohol intake, vitamin status, sunlight, urea, creatinine, and uric acid as possible risk factors. Multivariable analysis identified two independent associations. Total number of 'any' analgesics in the previous year: adjusted P<0.01 (U-shaped risk profile, unadjusted high vs medium use (=reference) OR 2.39, 95% CI 1.35-4.26 with medium use vs none (=reference) OR 0.43, 95% CI 0.26-0.72); total sunlight: adjusted P=0.03 (unadjusted highest exposure vs lowest (=reference) OR 3.25, 95% CI 1.11-9.50). For retrodots, univariable analysis identified alcohol, HRT, and lipids. Multivariable analysis identified two independent associations. Mean number of alcohol units consumed per month, adjusted P=0.02 and HDL cholesterol levels, adjusted P=0.02 (unadjusted ORs NS both). CONCLUSION: This is the first available published information on risk factors for the human cataractous lens features waterclefts and retrodots