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Aim The treatment of transsphincteric anal fistula requires a balance between eradication of the disease and preservation of faecal control. A cutting seton is an old tool that is now out of vogue for many surgeons. We hypothesized that the concept remains reliable and safe with results that exceed those reported for many of the more recently described methods. Method A retrospective review was conducted of real-time electronic health records (single institution, single surgeon) of patients presenting during the 14 years between 2001 and 2014 with a transsphincteric anal fistula who were treated with a cutting seton. Excluded were patients with Crohn's disease, fistulae related to malignancy or a previous anastomosis and patients whose fistula was treated by another method including a loose draining seton. Data collection included demographics, duration of the disease, duration of the treatment, outcome and continence. Results In all, 121 patients (80 men) of mean age 40.2 ± 12.2 years (range 18-76) with a mean follow-up of 5.1 ± 3.3 (1-24) months were included in the analysis. The median duration of symptoms was 6 (1-84) months; 36% had failed other fistula surgery, 12% had a complex fistula with more than one track and 35% had some form of comorbidity. The median time to healing was 3 (1-18) months; 7.4% required further surgery, but eventually 98% had complete fistula healing. The incontinence rate decreased postoperatively to 11.6% from 19% before treatment with 17/121 with pre-existing incontinence resolved and 8/107 new cases developing. Conclusion Despite its retrospective non-comparative design, the study has demonstrated that a cutting seton is a safe, well tolerated and highly successful treatment for transsphincteric anal fistula and is followed overall by improved continence. The results compare very favourably with other techniques. [ABSTRACT FROM AUTHOR]

Presents an obituary for Frank N. McMillan, a psychoanalyst.

Keloids are an abnormal response to wound healing distinguished by an overproduction of collagen. Thickened bundles of collagen in the reticular dermis oriented haphazardly in relation to the overlying epithelium are found in keloids, in contrast to thinner collagen fibers in a more orderly arrangement that are found in normal scars. Previous clinical trials of intralesional interferon-gamma (IFN-G) injections by Larrabee et al. and Granstein et al. showed a decrease in lesion size. These findings led to a conclusion that IFN-G would be a useful adjunct to surgical excision of keloids to aid in preventing recurrence. We performed a double-blind, placebo-controlled trial in patients with two or more keloids treated with excision and subsequent local injections of IFN-G or placebo. [ABSTRACT FROM AUTHOR]

In variance component quantitative trait loci (QTL) analysis, a mixed model is used to detect the most likely chromosome position of a QTL. The putative QTL is included as a random effect and a method is needed to estimate the QTL variance. The standard estimation method used is an iterative method based on the restricted maximum likelihood (REML). In this paper, we present a novel non-iterative variance component estimation method. This method is based on Henderson's method 3, but relaxes the condition of unbiasedness. Two similar estimators were compared, which were developed from two different partitions of the sum of squares in Henderson's method 3. The approach was compared with REML on data from a European wild boar × domestic pig intercross. A meat quality trait was studied on chromosome 6 where a functional gene was known to be located. Both partitions resulted in estimated QTL variances close to the REML estimates. From the non-iterative estimates, we could also compute good approximations of the likelihood ratio curve on the studied chromosome. [ABSTRACT FROM AUTHOR]

Kenya established intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) for malaria in pregnancy as national policy in 1998. We assessed the coverage of IPT among women who had recently delivered in a rural area of western Kenya with perennial malaria transmission and high coverage with insecticide treated nets (ITNs) through a cross-sectional, community-based survey in December 2002. Antenatal clinic (ANC) attendance was high (89.9% of the 635 participating women); 77.5% of attendees visited an ANC before the third trimester and 91.9% made more than one visit. Delivery of SP by the ANC was reported by 19.1% of all women but only 6.8% reported receiving more than one dose. Given the high rate of use of ANC services, if SP were given at each visit after the first trimester, the potential coverage of IPT (two doses of SP) would be 80.3% in this study population. ITNs were used by 82.4% of women during pregnancy, and almost all mothers (98.5%) who slept under an ITN shared the nets with their newborns after delivery. Women who thought malaria in pregnancy caused foetal problems were more likely to have used an ITN (adjusted odds ratio [AOR] 1.6, 95% confidence interval [CI] 1.0–2.4), and to have visited ANC more than once (AOR 2.4, 95% CI 1.2–4.7) compared to women who thought malaria in pregnancy was either not a problem or caused problems for the mother only. These findings illustrate the need for improved IPT coverage in this rural area. Identification and removal of the barriers to provision of IPT during ANC visits can help to increase coverage. In this area of Kenya, health messages stressing that foetal complications of malaria in pregnancy may occur in the absence of maternal illness may improve the demand for IPT. [ABSTRACT FROM AUTHOR]

This article summarizes the proceedings of the RSA 2004 Combined Basic Research Satellite Meeting convened at the Westin Bayshore Resort and Marina, Vancouver, CA. One of the sessions 'Alcohol and mitochondrial metabolism: At the crossroads of life and death' featured five speakers and was chaired by Drs. Jan Hoek and Sam Zakhari. The presentations were 1) Introduction: Alcohol and cellular energy metabolism by Jan Hoek, 2) Ethanol-dependent dysfunction of mitochondrial energy metabolism: the role of NO by Victor Darley-Usmar, 3) Ethanol and apoptosis in the heart by Gyorgy Hajnoczky, 4) Alcohol and mitochondrial biogenesis in development by Thomas Knudsen, and 5) Alcohol, mitochondrial function and cardiac preconditioning by Daria Mochly-Rosen. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding amyotrophic lateral sclerosis.

Objective: To monitor the effectiveness of intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) for the control of malaria in pregnancy at delivery in the Provincial Hospital in Kisumu, Kenya, and to assess the effect of IPT in participants in a cohort study.Methods: Between June 1999 and June 2000, information on IPT and birth outcome was collected in 2302 consecutive deliveries. A group of 889 women, who were enrolled in a cohort to assess the interaction between malaria and HIV, were analysed separately because of the enrollment criteria and different access to health care.Results: The prevalence of placental malaria was 13.8% and of low birthweight (LBW) was 12.2%. In multivariable analysis, IPT (> or =1 dose of SP) was associated with a reduction in placental malaria and LBW [adjusted odds ratio (OR) 0.56, 95% confidence interval (CI) 0.39-0.83 and OR 0.65, 95% CI 0.45-0.95, respectively]. An adjusted mean increase in birthweight of 61 g was seen (95% CI 22-101 g) for each increment in number of SP doses (> or =2 doses grouped together). IPT was associated with a reduction in placental malaria in HIV-seronegative women (OR 0.49, 95% CI 0.28-0.86) but this was not significant among HIV-seropositive women (OR 0.45, 95% CI 0.20-1.05). A significant effect on birthweight could not be detected among participants in the HIV-cohort.Conclusions: This evaluation confirms that IPT with SP is effective in reducing placental malaria and LBW. It will be important to increase coverage of IPT and to extend IPT to antenatal clinics in peri-urban and rural areas. [ABSTRACT FROM AUTHOR]

This paper focuses on the Singer-Loomis Type Deployment Inventory (SL-TDI), which is an alternative to the Myers-Briggs Type Indicator (MBTI). The SL-TDI utilizes a continuous, non-forced choice format and therefore is a more accurate representation of Jung's personality theory of psychological types. The purpose of the study reported here is to evaluate the reliability and validity of scores from the SL-TDI. Specifically, the goals were to (a) provide estimates of the internal consistency of SL-TDI scores; (b) evaluate the divergent validity of SL-TDI scores by examination of their relationships with the scores on a social desirability responding measure; and (c) examine the test-retest stability of scores from the SL-TDI. Strong support was found for both the reliability and validity of SL-TDI scores. [ABSTRACT FROM AUTHOR]

Functional endoscopic sinus surgery (FESS) has gained widespread support as the treatment of choice for chronic sinusitis in children. Seven developmentally delayed children were evaluated for chronic sinusitis with symptoms of cough, chronic rhinorrhea, and head banging because of pain. All seven were nonresponsive to repeated courses of oral and sometimes intravenous antibiotics; computed tomography scans on all revealed sinus disease. FESS was performed on all of them. Three children had marked respiratory difficulty at the end of the procedure, with two requiring reintubation. Two children were not able to take oral feedings postoperatively. Because of the complicated postoperative course, a second-look procedure was performed in only two children. We believe that FESS for developmentally delayed children should be tailored accordingly and that a second-look procedure should not be a routine. [ABSTRACT FROM AUTHOR]

Abstract Parthenogenesis-inducing intracellular bacteria of the genus Wolbachia are found in a variety of parasitoid wasp genera. The presence of Wolbachia in the uniparental Aphytis species A. fingnanensis Compere, A. diaspidis (Howard), A. chilensis Howard, and A. chrysomphali (Mercet) was tested using primers specific for the ftsZ gene. The symbiont was detected in all of these species. Wolbachia ftsZ genes that were sequenced from the four hosts show a high degree of similarity. Both the PCR with specific primers for group ‘A’ and phylogenetic analysis place these Wolbachia in group ‘A’. The fact that the tested Aphytis species belong to different phylogenetic groups and harbour what seem to be almost identical Wolbachia , lends credence to the horizontal transmission hypothesis. [ABSTRACT FROM AUTHOR]

- Of 478 patients treated at a single institution for prostate cancer, 29 developed spinal cord or cauda equina compression. In 5 patients, spinal cord compression was the first evidence of malignancy. Clinical features were predominantly pain, weakness, sensory and sphincter disturbance. The median duration of symptoms was 2 weeks, although the diagnosis was made rapidly at presentation. Clinical diagnosis correlated well with myelographic findings. Only 1 patient suffered neurological deterioration as a consequence of myelography. The functional outcome was dependent on the ability to walk prior to treatment. The median survival in those who were bedridden following treatment was 6 weeks (range 3.5-13) and 21 weeks (range 7-110+) in those who were ambulant following therapy. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis is an inflammatory disease of the thyroid gland with autoimmune etiology. Patients afflicted with Hashimoto's have a higher risk of thyroid malignancies such as papillary thyroid carcinoma. In the present study, we investigated the frequency of papillary thyroid carcinoma specific genes in patients diagnosed with Hashimoto's disease. The newly identified oncogenes RET/PTC1 and RET/PTC3 provide useful and specific markers of the early stages of papillary carcinoma as they are highly specific for malignant cells. Using a sensitive and specific reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we found messenger RNA (mRNA) expression for the RET/PTC1 and RET/PTC3 oncogenes in 95% of the Hashimoto's patients studied. All Hashimoto's patients presenting without histopathologic evidence of papillary thyroid cancer showed molecular genetic evidence of cancer. These data suggest that multiple, independent occult tumors exist in these patients at high frequency. [ABSTRACT FROM AUTHOR]

Aphis citricola was first recorded in Israel in 1970. The distinguishing characteristics of this species are discussed and a list of its host plants in Israel is presented. A quantitative sampling method for estimating its population is described, consisting of a 5- grade logarithmic scale of tree infestation (based on most infested leaf), from which the grove infestation index is calculated. Infestation trends observed in an orange grove in Israel in 1982-1984 are described. The main population rise was in spring, originating from a large number of colonies founded by immigrating alates, possibly also by alates produced on other host plants within the grove. The production of alates on citrus itself started later in spring. Of meteorological factors, only hot dry desert winds (khamsin) were found to cause sudden, massive death of the aphids. Zusammenfassung Populationsentwicklung von Aphis citricola van der Goot in einer Zitrus-Plantage in Israel Aphis citricola wurde in Israel 1970 erstmals entdeckt. Es werden die Erkennungsmerkmale dieser Art und eine Auflistung der Wirtspflanzen in Israel angegeben. Zur Bestimmung der Populationsdichte wurde eine quantitative Sammelmethode auf der Basis einer 5stufigen logarithmischen Skala der Befallsintensität (Grundlage sind die am stärksten befallenen Blätter) entwickelt, woraus sich der Befallsindex der Plantage berechnen läßt. Es wird die Befallsentwicklung in einer israelischen Orangenplantage von 1982 bis 1984 beschrieben. Der stärkste Populationsanstieg war im Frühjahr zu beobachten und ist auf die große Anzahl Kolonien, die von der Exil-Alata-Generation gegründet wurden, zurückzuführen und möglicherweise auch von Alata-Generationen, die von anderen Wirtspflanzen in der Plantage stammten. Auf der Zitruspflanze selbst setzte die Entwicklung der Alatae erst im späteren Frühjahr ein. Von den Witterungsfaktoren bewirkten lediglich die heißen und trockenen Wüstenwinde (khamsin) eine plötzliche und hohe Mortalität der Läuse. [ABSTRACT FROM AUTHOR]

The anatomy of the syconia and flowers in the sycomore fig (Ficus sycomorus) has been studied. The developmental course of the ovules and pollen grains and their ultimate structure found to be normal. No difference was detected between short- and long-styled flowers. In the Mediterranean area, Sycophaga sycomori is the principal sycophilous wasp developing within the ovaries of the sycomore. The wasp inserts its egg into the embryo sac via the style. Inhabited but unfertilized syconia which do not contain plant embryos persist on the tree and continue to develop, while the unoccupied syconia drop within a few days. Inhabitation by the wasp has a decisive effect on the subsequent development of the syconia and flowers. Oviposition induces sclerification of the pericarp and proliferation of the nucellus, which serves as `feeding' tissue for the insect larva. Inhabitation by Sycophaga is indispensable for the maturation of the male flowers. Uninucleate pollen grains were the final stage attained in uninhabited syconia. [ABSTRACT FROM AUTHOR]

Odontogenic infections may spread to the orbit by one or more of several paths. Such extension is potentially dangerous and may lead to loss of vision. A case of infection from a primary tooth, which extended to the retrobulbar area is presented in this report. Treatment included surgical drainage of the resulting subperiosteal orbital abscess through a Caldwell-Luc approach as well as aggressive antibiotic therapy. The importance of early suspicion of this entity and its potential sequelae are discussed. [ABSTRACT FROM AUTHOR]

Two toddlers with scald injuries of the pharynx and larynx following hot liquid aspiration that rapidly progressed to life-threatening upper airway obstruction requiring endotracheal intubation are described. Conclusions: Toddlers presenting with scald burns of the face, especially of the perioral area, should be suspected of having aspirated hot liquid with potentially lethal laryngeal edema an impending complication that must be ruled out. Stridor, hoarseness, profuse drooling, changes of the voice or cry of the child scald victim are among the early signs heralding impending upper airway obstruction and requiring immediate life-saving measures. [ABSTRACT FROM AUTHOR]

Rationale: Clinical Practice Guidelines (CPGs) represent evidence-based tools designed to assist healthcare practitioners and patients in decisions in clinical practice. Evidence supports the clinical benefits of adhering to CPGs. However, their successful implementation and adherence in clinical settings often encounter challenges., Aims and Objectives: This systematic review aimed to explore barriers and facilitators influencing adherence to CPGs in Germany., Method: The protocol of this study was registered in the Open Science Framework (OSF) registry (DOI: 10.17605/OSF. IO/GMFUB). In November 2022 we searched on PubMed and Embase for primary studies employing qualitative, quantitative and mixed-methods approaches that focus on barriers or facilitators to CPGs adherence in the Germany. Two reviewers independently screened articles, extracted data, and evaluated the quality of the studies. The collected data on barriers and facilitators of CPG adherence were systematically categorized and analyzed using the Theoretical Domains Framework (TDF)., Results: A total of 24 studies were included, mainly focusing on adherence to national CPGs. This review introduces a new domain, guideline characteristics, reflecting the need to address barriers and facilitators to CPG development, implementation, dissemination and format, which couldn't be encompassed within the existing 14 domains of TDF framework. Among healthcare professionals, the most frequently reported influencing factors were related to the environmental context and resources (encompassing aspects such as employer support for CPG utilization), the CPG development and dissemination process (including layout, wording, and interactive tools) and beliefs about consequences (such as contradictions with practical experience). Knowledge (knowledge about the content of CPGs, awareness about published CPGs), primarily as a barrier, and reinforcement facilitators (notably financial support), were also frequently reported., Conclusion: The findings revealed multilevel factors contributing to CPG adherence, with environmental context and resources emerging as the most frequently reported considerations. This systematic review offer holistic insights into the barriers and facilitators of CPG adherence in Germany. The results contribute to a better understanding of the topic and serve as a resource for developing targeted strategies to enhance CPG adherence and implementation within the German healthcare system., (© 2024 The Author(s). Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Background: Laparoscopic reverse submucosal dissection (LRSD) is a standardised surgical technique for removal of rectosigmoid endometriosis which optimises the anatomical dissection plane for excision of endometriotic nodules., Aim: This cohort study assesses the outcomes of the first cohort of women treated by LRSD, for deeply infiltrating rectosigmoid endometriosis., Materials and Methods: Primary outcomes assessed were complication rate as defined by the Clavien-Dindo system, and completion of the planned LRSD. Secondary outcomes include mucosal breach, specimen margin involvement, length of hospital admission, and a comparison of pre-operative and post-operative pain, bowel function and quality of life surveys. These included the Endometriosis Health Profile Questionnaire (EHP-30), the Knowles-Eccersley-Scott Symptom Questionnaire (KESS) and the Wexner scale., Results: Of 19 patients treated, one required a segmental resection. The median length of hospital admission was two days (range 1-5) and no post-operative complications occurred. Median pain visual analogue scales (scale 0-10) were higher prior to surgery (dysmenorrhoea 9.0, dyspareunia 7.5, dyschezia 9.0, pelvic pain 6.0) compared to post-surgical median scores (dysmenorrhoea 5.0, dyspareunia 4.0, dyschezia 2.0, pelvic pain 4.0) at a median of six months (range 4-32). Quality of life studies suggested improvement following surgery with pre-operative median EHP-30 and KESS scores (EHP-30: 85 (5-106), KESS score 9 (0-20)) higher than post-operative scores (EHP-30: 48.5 (0-80), KESS score: 3 (0-19))., Conclusion: This series highlights the feasibility of LRSD with low associated morbidity as a progression of partial thickness discoid excision (rectal shaving) for the treatment of rectosigmoid deep infiltrating endometriosis., (© 2023 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background Mortality prediction in critically ill patients with cardiogenic shock can guide triage and selection of potentially high-risk treatment options. Methods and Results We developed and externally validated a checklist risk score to predict in-hospital mortality among adults admitted to the cardiac intensive care unit with Society for Cardiovascular Angiography & Interventions Shock Stage C or greater cardiogenic shock using 2 real-world data sets and Risk-Calibrated Super-sparse Linear Integer Modeling (RiskSLIM). We compared this model to those developed using conventional penalized logistic regression and published cardiogenic shock and intensive care unit mortality prediction models. There were 8815 patients in our training cohort (in-hospital mortality 13.4%) and 2237 patients in our validation cohort (in-hospital mortality 22.8%), and there were 39 candidate predictor variables. The final risk score (termed BOS,MA 2 ) included maximum blood urea nitrogen ≥25 mg/dL, minimum oxygen saturation <88%, minimum systolic blood pressure <80 mm Hg, use of mechanical ventilation, age ≥60 years, and maximum anion gap ≥14 mmol/L, based on values recorded during the first 24 hours of intensive care unit stay. Predicted in-hospital mortality ranged from 0.5% for a score of 0 to 70.2% for a score of 6. The area under the receiver operating curve was 0.83 (0.82-0.84) in training and 0.76 (0.73-0.78) in validation, and the expected calibration error was 0.9% in training and 2.6% in validation. Conclusions Developed using a novel machine learning method and the largest cardiogenic shock cohorts among published models, BOS,MA 2 is a simple, clinically interpretable risk score that has improved performance compared with existing cardiogenic-shock risk scores and better calibration than general intensive care unit risk scores.

Background: The negative media attention surrounding vaginal mesh procedures has seen a rise in demand for minimally invasive non-mesh options for the treatment of stress urinary incontinence (SUI). The laparoscopic Burch colposuspension (LBC) is a non-mesh alternative to synthetic midurethral slings (MUS) with similar short-term outcomes. However, long-term outcomes are not well established., Aims: To evaluate the long-term outcomes of LBC for treatment of SUI in women., Material and Methods: One hundred and fifty-one cases of LBC were performed by a single surgeon over two private hospital settings between January 2010 and January 2016. Follow-up subjective outcomes were obtained in 137 cases (90.7%) utilising standardised questionnaires. Primary outcome was successful treatment of SUI, defined as subjective cure or significant improvement of stress incontinence symptoms. Secondary outcomes included new-onset or worsened symptoms of overactive bladder (OAB), voiding dysfunction, prolapse, and perioperative complications., Results: One hundred and thirty-seven patients were analysed with a mean follow-up of 50.6 months (range: 13-89 months). Primary outcome of successful treatment was achieved in 90.5% of women. New-onset or worsened symptoms of OAB was reported in 10.2%, with a further 8.8% of women experiencing symptomatic voiding dysfunction. Sixteen patients (11.7%) reported new-onset or worsening symptoms of prolapse. There were no major surgical complications., Conclusions: LBC is a safe and effective long-term treatment for SUI, with low failure rates and minimal adverse outcomes. It is a suitable alternative for women with contraindications to mesh or those having concomitant laparoscopic procedures., (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Bioenergetic failure and oxidative stress are common pathological hallmarks of amyotrophic lateral sclerosis (ALS), but whether these could be targeted effectively for novel therapeutic intervention needs to be determined. One of the reported contributors to ALS pathology is mitochondrial dysfunction associated with excessive mitochondrial fission and fragmentation, which is predominantly mediated by Drp1 hyperactivation. Here, we determined whether inhibition of excessive fission by inhibiting Drp1/Fis1 interaction affects disease progression. We observed mitochondrial excessive fragmentation and dysfunction in several familial forms of ALS patient-derived fibroblasts as well as in cultured motor neurons expressing SOD1 mutant. In both cell models, inhibition of Drp1/Fis1 interaction by a selective peptide inhibitor, P110, led to a significant reduction in reactive oxygen species levels, and to improvement in mitochondrial structure and functions. Sustained treatment of mice expressing G93A SOD1 mutation with P110, beginning at the onset of disease symptoms at day 90, produced an improvement in motor performance and survival, suggesting that Drp1 hyperactivation may be an attractive target in the treatment of ALS patients., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Obstructive sleep apnea (OSA) occurs at a high prevalence in patients with Down syndrome (DS). A polysomnogram, which is often cumbersome and challenging, remains the gold standard method of diagnosing OSA. OSA in patients with DS is often attributed to skeletal and soft-tissue structural alterations that are characteristic of the DS phenotype; as such, we hypothesized that assessing anthropometric facial measurements may be predictive of OSA in patients with DS. We used the 3dMDface sterophotography system to capture and create 3D facial images, and we subsequently identified facial landmarks using a single, experienced investigator and utilizing proprietary software to calculate inter-landmark distances and angles. We compared our findings with similar data for neurotypically developing participants. We further compared the findings in participants with DS with and without OSA. Participants with DS had maxillomandibular hypoplasia with smaller ear, nose, and eye measurements compared to neurotypically developing peers. We found no statistically significant differences in 3D photogrammetric measurements between participants with DS with or without OSA., (© 2017 Wiley Periodicals, Inc.)

Obstructive sleep apnea (OSA) occurs frequently in people with Down syndrome (DS) with reported prevalences ranging between 55% and 97%, compared to 1-4% in the neurotypical pediatric population. Sleep studies are often uncomfortable, costly, and poorly tolerated by individuals with DS. The objective of this study was to construct a tool to identify individuals with DS unlikely to have moderate or severe sleep OSA and in whom sleep studies might offer little benefit. An observational, prospective cohort study was performed in an outpatient clinic and overnight sleep study center with 130 DS patients, ages 3-24 years. Exclusion criteria included previous adenoid and/or tonsil removal, a sleep study within the past 6 months, or being treated for apnea with continuous positive airway pressure. This study involved a physical examination/medical history, lateral cephalogram, 3D photograph, validated sleep questionnaires, an overnight polysomnogram, and urine samples. The main outcome measure was the apnea-hypopnea index. Using a Logic Learning Machine, the best model had a cross-validated negative predictive value of 73% for mild obstructive sleep apnea and 90% for moderate or severe obstructive sleep apnea; positive predictive values were 55% and 25%, respectively. The model included variables from survey questions, medication history, anthropometric measurements, vital signs, patient's age, and physical examination findings. With simple procedures that can be collected at minimal cost, the proposed model could predict which patients with DS were unlikely to have moderate to severe obstructive sleep apnea and thus may not need a diagnostic sleep study., (© 2017 Wiley Periodicals, Inc.)

Background: The transient receptor potential vanilloid 1 (TRPV1) mediates cellular responses to pain, heat, or noxious stimuli by calcium influx; however, the cellular localization and function of TRPV1 in the cardiomyocyte is largely unknown. We studied whether myocardial injury is regulated by TRPV1 and whether we could mitigate reperfusion injury by limiting the calcineurin interaction with TRPV1., Methods and Results: In primary cardiomyocytes, confocal and electron microscopy demonstrates that TRPV1 is localized to the mitochondria. Capsaicin, the specific TRPV1 agonist, dose-dependently reduced mitochondrial membrane potential and was blocked by the TRPV1 antagonist capsazepine or the calcineurin inhibitor cyclosporine. Using in silico analysis, we discovered an interaction site for TRPV1 with calcineurin. We synthesized a peptide, V1-cal, to inhibit the interaction between TRPV1 and calcineurin. In an in vivo rat myocardial infarction model, V1-cal given just prior to reperfusion substantially mitigated myocardial infarct size compared with vehicle, capsaicin, or cyclosporine (24±3% versus 61±2%, 45±1%, and 49±2%, respectively; n=6 per group; P<0.01 versus all groups). Infarct size reduction by V1-cal was also not seen in TRPV1 knockout rats., Conclusions: TRPV1 is localized at the mitochondria in cardiomyocytes and regulates mitochondrial membrane potential through an interaction with calcineurin. We developed a novel therapeutic, V1-cal, that substantially reduces reperfusion injury by inhibiting the interaction of calcineurin with TRPV1. These data suggest that TRPV1 is an end-effector of cardioprotection and that modulating the TRPV1 protein interaction with calcineurin limits reperfusion injury., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Mitochondrial dysfunction is implicated in multiple neurodegenerative diseases. In order to maintain a healthy population of functional mitochondria in cells, defective mitochondria must be properly eliminated by lysosomal machinery in a process referred to as mitophagy. Here, we uncover a new molecular mechanism underlying mitophagy driven by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) under the pathological condition of Huntington's disease (HD) caused by expansion of polyglutamine repeats. Expression of expanded polyglutamine tracts catalytically inactivates GAPDH (iGAPDH), which triggers its selective association with damaged mitochondria in several cell culture models of HD. Through this mechanism, iGAPDH serves as a signaling molecule to induce direct engulfment of damaged mitochondria into lysosomes (micro-mitophagy). However, abnormal interaction of mitochondrial GAPDH with long polyglutamine tracts stalled GAPDH-mediated mitophagy, leading to accumulation of damaged mitochondria, and increased cell death. We further demonstrated that overexpression of inactive GAPDH rescues this blunted process and enhances mitochondrial function and cell survival, indicating a role for GAPDH-driven mitophagy in the pathology of HD., (© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)