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41.
D.A. Dyment E. Sell M.R. Vanstone A.C. Smith D. Garandeau V. Garcia S. Carpentier E. Le Trionnaire F. Sabourdy C.L. Beaulieu J.A. Schwartzentruber H.J. McMillan J. Majewski D.E. Bulman T. Levade K.M. Boycott 《Clinical genetics》2014,86(6):558-563
Spinal muscular atrophy with progressive myoclonic epilepsy (SMA‐PME) is a recently delineated, autosomal recessive condition caused by rare mutations in the N‐acylsphingosine amidohydrolase 1 (acid ceramidase) ASAH1 gene. It is characterized by motor neuron disease followed by progressive myoclonic seizures and eventual death due to respiratory insufficiency. Here we report an adolescent female who presented with atonic and absence seizures and myoclonic jerks and was later diagnosed as having myoclonic‐absence seizures. An extensive genetic and metabolic work‐up was unable to arrive at a molecular diagnosis. Whole exome sequencing (WES) identified two rare, deleterious mutations in the ASAH1 gene: c.850G>T;p.Gly284X and c.456A>C;p.Lys152Asn. These mutations were confirmed by Sanger sequencing in the patient and her parents. Functional studies in cultured fibroblasts showed that acid ceramidase was reduced in both overall amount and enzymatic activity. Ceramide level was doubled in the patient's fibroblasts as compared to control cells. The results of the WES and the functional studies prompted an electromyography (EMG) study that showed evidence of motor neuron disease despite only mild proximal muscle weakness. These findings expand the phenotypic spectrum of SMA‐PME caused by novel mutations in ASAH1 and highlight the clinical utility of WES for rare, intractable forms of epilepsy. 相似文献
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Lin Zhang Joseph JY Sung Jun Yu Siew C Ng Sunny H Wong Chi H Cho Simon SM Ng Francis KL Chan William KK Wu 《The Journal of pathology》2014,233(2):103-112
Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd 相似文献
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Kissinger P Kovacs S Anderson-Smits C Schmidt N Salinas O Hembling J Beaulieu A Longfellow L Liddon N Rice J Shedlin M 《AIDS and behavior》2012,16(1):199-213
The purpose of this study was to examine patterns and predictors of HIV/STI risk over time among Latino migrant men in a new receiving community. Latino men (N = 125) were interviewed quarterly for 18 months and HIV/STI tested annually. Selected individual, environmental and cultural factors by partner type and condom use were explored longitudinally and in a cross-section. Sex with female sex workers (FSWs) and multiple partners decreased, sex with main partners and abstinence increased, while the number of casual partners remained stable. Consistent condom use was highest with FSWs, lowest with main partners and midrange with casual partners with no trends over time. STI morbidity was low; no HIV was detected. Drug use and high mobility were associated with inconsistent condom use with FSW, whereas having family in the household was protective. HIV/STI prevention efforts should focus on drug using Latino migrants who are highly mobile and should foster healthy social connections. 相似文献
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Computed tomography (CT) images of patients having metallic implants or dental fillings exhibit severe streaking artifacts. These artifacts may disallow tumor and organ delineation and compromise dose calculation outcomes in radiotherapy. We used a sinogram interpolation metal streaking artifact correction algorithm on several phantoms of exact-known compositions and on a prostate patient with two hip prostheses. We compared original CT images and artifact-corrected images of both. To evaluate the effect of the artifact correction on dose calculations, we performed Monte Carlo dose calculation in the EGSnrc/DOSXYZnrc code. For the phantoms, we performed calculations in the exact geometry, in the original CT geometry and in the artifact-corrected geometry for photon and electron beams. The maximum errors in 6 MV photon beam dose calculation were found to exceed 25% in original CT images when the standard DOSXYZnrc/CTCREATE calibration is used but less than 2% in artifact-corrected images when an extended calibration is used. The extended calibration includes an extra calibration point for a metal. The patient dose volume histograms of a hypothetical target irradiated by five 18 MV photon beams in a hypothetical treatment differ significantly in the original CT geometry and in the artifact-corrected geometry. This was found to be mostly due to miss-assignment of tissue voxels to air due to metal artifacts. We also developed a simple Monte Carlo model for a CT scanner and we simulated the contribution of scatter and beam hardening to metal streaking artifacts. We found that whereas beam hardening has a minor effect on metal artifacts, scatter is an important cause of these artifacts. 相似文献
49.
Bianca?Lauria-HornerEmail authorView authors OrcID profile Tara?Beaulieu Stephanie?Knaak Rivian?Weinerman Helen?Campbell Scott?Patten 《BMC family practice》2018,19(1):183
Background
Depression affects over 400 million people globally. The majority are seen in primary care. Barriers in providing adequate care are not solely related to physicians’ knowledge/skills deficits, but also time constraints, lack of confidence/avoidance, which need to be addressed in mental health-care redesign. We hypothesized that family physician (FP) training in the Adult Mental Health Practice Support Program (AMHPSP) would lead to greater improvements in patient depressive symptom ratings (a priori primary outcome) compared to treatment as usual.Methods
From October 2013 to May 2015, in a controlled trial 77 FP practices were stratified on the total number of physicians/practice as well as urban/rural setting, and randomized to the British Columbia AMHPSP?a multi-component contact-based training to enhance FPs’ comfort/skills in treating mild-moderate depression (intervention), or no training (control) by an investigator not operationally involved in the trial. FPs with a valid license to practice in NS were eligible. FPs from both groups were asked to identify 3–4 consecutive patients >?18?years old, diagnosis of depression, Patient Health Questionnaire (PHQ-9) score ≥ 10, able to read English, intact cognitive functioning. Exclusion criteria: antidepressants within 5?weeks and psychotherapy within 3?months of enrollment, and clinically judged urgent/emergent medical/psychiatric condition. Patients were assigned to the same arm as their physician. Thirty-six practices recruited patients (intervention n =?23; control n =?13). The study was prematurely terminated at 6?months of enrollment start-date due to concomitant primary health-care transformation by health-system leaders which resulted in increased in-office demands, and recruitment failure. We used the PHQ-9 to assess between-group differences at baseline, 1, 2, 3, and 6?months follow-up. Outcome collectors and assessors were blind to group assignment.Results
One hundred-and-twenty-nine patients (intervention n =?72; control n =?57) were analysed. A significant improvement in depression scores among intervention group patients emerged between 3 and 6?months, time by treatment interaction, likelihood ratio test (LR) chi2(3)?=?7.96, p =?.047.Conclusions
This novel skill-based program shows promise in translating increased FP comfort and skills managing depressed patients into improved patient clinical outcomes?even in absence of mental health specialists availability.Trial registration
#NCT01975948.50.