High prevalence of muscular ventricular septal defect in neonates

Objectives.This study sought to use echocardiography to evaluate the prevalence of muscular ventricular septal defect in neonates.Background.Ventricular septal defect is usually asymptomatic and closes spontaneously. An increase in its prevalence has been noted recently. One reason is the improved detection of small defects, especially with the increased use of echocardiography. Therefore, one would expect a higher prevalence in neonates on the basis of echocardiographic screening.Methods.Color Doppler echocardiography was performed in 1,053 consecutive neonates 6 to 170 h old at Western Galilee Hospital, Israel. Data on the neonates, parents and family were obtained to analyze the influencing factors. The identified patients were followed up for 1 to 10 months or until ventricular septal defect closure.Results.Muscular ventricular septal defect was found in 56 (25 male, 31 female) of the 1,053 neonates, a prevalence of 53.2/1,000 live births. All neonates were asymptomatic. Six had a systolic murmur. Electrocardiographic findings were normal in 44 (97.8%) of 45 neonates followed up, and left ventricular hypertrophy occurred in 1 (2.2%). By echocardiography, 50 ventricular septal defects (89.3%) were single and 6 (10.7%) were multiple. The defects (range 1 to 5 mm in diameter, mean [±sd]2.3 ± 0.8) occurred anywhere along the muscular septum; 43 (76.8%) were detectable only on color Doppler imaging. The left atrium and left ventricle were mildly dilated. Of 45 neonates who were followed up for 6 to 10 months or until closure of the defects, 40 (88.9%) had defects that closed spontaneously. The risk of ventricular septal defect was not significantly associated with gestational age, birth weight, birth order, maternal age, diabetes, smoking, exposure to drugs or infection, paternal age, familial congenital heart disease, religion or consanguinity.Conclusions.There is a prevalence of muscular ventricular septal defect in neonates of 53.2/1,000 live births. The patients were asymptomatic, and 88.9% had defects that closed spontaneously within 1 to 10 months. These defects may be caused by environmental factors. In many cases, muscular ventricular septal defect may also result from delayed physiologic development

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Disseminated mycobacterium tuberculosis: Pulmonary and musculoskeletal infections in a previously healthy man

Chest wall masses are an uncommon result of Mycobacterium tuberculosis (MTB) infection especially in immune-competent patients. Herein, we report a case of 47-year-old previously healthy man who presented with an anterior chest wall mass, along with a swelling of the left fourth finger. MTB was recovered from the patient's sputum and from the aspirate of the chest wall mass. Four anti-tuberculous drugs for 2 months then 2 drugs for 7 months resulted in complete resolution of both masses with no need for surgical resection. Conclusion: MTB can present in disseminated form in a healthy man and treated with quadruple anti-tuberculous medications without surgical intervention

Experimental Approaches Towards Therapeutic Interventions for Fragile X-associated Tremor and Ataxia Syndrome

Fragile X-associated Tremor and Ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused a expanded CGG-repeat in the 5'-UTR region of the FMR1 gene. FXTAS is hypothesized to be caused by either an RNA gain-of-function where RNA binding proteins bind the CGG-repeat hairpin or by an protein gain-of-function caused by an alternative translation mechanism called repeat associated non-AUG (RAN) translation. The general aim of this manuscript is to advance our knowledge of FXTAS pathogenesis and neuropathology caused by the expression of FMRpolyG and the formation of intranuclear inclusions. We generated new mouse models that allowed us to study the role of intranuclear inclusions, FMRpolyG and the role of astrocytes in the brain. In addition, we generated a new relevant cellular model that allows us to test potential therapeutic interventions. We also developed a new sandwich-ELISA to detect soluble and insoluble FMRpolyG protein levels in post-mortem FXTAS brain tissue. This ELISA allows us to accurately measure FMRpolyG levels and hopefully aid in the search for reliable biomarkers for FXTAS. Finally, we propose a new small molecule therapeutic intervention that is capable of reducing FMRpolyG protein levels in our new in vitro model as well as in our ubiquitous inducible mouse model. The results in this thesis will hopefully contribute to our search for potential biomarkers and the future development of effective targeted therapeutic interventions

The lowest dose of corticosteroids, which stops the episodes of PFAPA syndrome

Background The episodes of PFAPA syndrome with their exhausting periodic fever, annoying oral aphthae and sore throat, warrant treatment. Corticosteroids are the most efficacious. Aims Providing evidence that a weight-independent minimal dose of betamethasone the least ever used can resolve symptoms of PFAPA syndrome within few hours. Methods In a retrospective case-series analysis study, approved by the relevant ethical committees of Clalit Health Organization, we collected analysed and interpreted data from medical files of children who suffered from PFAPA syndrome, during 1998 until 2015, concerning the lowest effective betamethasone dose, they received and which had abated fever within few hours. Results We had diagnosed 132 children of our 2300 children community, as suffering from PFAPA syndrome (rate 6 per cent). Ninety eight per cent of the patients satisfactorily responded, within two-to-twelve hours, to treatment with a minimal one-time weight-independent dose of betamethasone in every flare. The rest of patients (2 per cent) needed an equal second dose to end their first flare during the following twelve hours. Three patients who were four to five-months-old at time of diagnosis, had received 0.1mg dose. Conclusion A dose of 0.5mg of betamethasone for children under 5 years of age and a dose of 1.0mg was prescribed for children >5, were effective for prompt resolution of PFAPA flares. We believe that as long as there is an effective lowest dose for treating PFAPA episodes, a great reduction of corticosteroid consumption will be exercisable globally

The lowest dose of corticosteroids, which stops the episodes of PFAPA syndrome

BackgroundThe episodes of PFAPA syndrome with their exhausting periodic fever, annoying oral aphthae and sore throat, warrant treatment. Corticosteroids are the most efficacious.AimsProviding evidence that a weight-independent, minimal dose of betamethasone, the least ever used, can resolve symptoms of PFAPA syndrome, within few hours.Methods In a retrospective case-series analysis study, approved by the relevant ethical committees of Clalit Health Organization, we collected analysed and interpreted data from medical files of children who suffered from PFAPA syndrome, during 1998 until 2015, concerning the lowest effective betamethasone dose, they received and which had abated fever within few hours.Results We had diagnosed 132 children of our 2300 children community, as suffering from PFAPA syndrome (rate 6 per cent). Ninety eight per cent of the patients satisfactorily responded, within two-to-twelve hours, to treatment with a minimal one-time weight-independent dose of betamethasone in every flare. The rest of patients (2 per cent) needed an equal second dose to end their first flare during the following twelve hours. Three patients who were four to five-months-old at time of diagnosis, had received 0.1mg dose.ConclusionA dose of 0.5mg of betamethasone for children under 5 years of age and a dose of 1.0mg was prescribed for children >5, were effective for prompt resolution of PFAPA flares. We believe that as long as there is an effective lowest dose for treating PFAPA episodes, a great reduction of corticosteroid consumption will be exercisable globally

A tandem array of CBF/DREB1 genes is located in a major freezing tolerance QTL region on Medicago truncatula chromosome 6.

Freezing provokes severe yield losses to different fall-sown annual legumes. Understanding the molecular bases of freezing tolerance is of great interest for breeding programs. Medicago truncatula Gaertn. is an annual temperate forage legume that has been chosen as a model species for agronomically and economically important legume crops. The present study aimed to identify positional candidate genes for a major freezing tolerance quantitative trait locus that was previously mapped to M. truncatula chromosome 6 (Mt-FTQTL6) using the LR3 population derived from a cross between the freezing-tolerant accession F83005-5 and the freezing-sensitive accession DZA045-5. The confidence interval of Mt-FTQTL6 was narrowed down to the region comprised between markers MTIC153 and NT6054 using recombinant F7 and F8 lines. A bacterial-artificial chromosome (BAC) clone contig map was constructed in an attempt to close the residual assembly gap existing therein. Twenty positional candidate genes including twelve C-repeat binding factor (CBF)/dehydration-responsive element binding factor 1 (DREB1) genes were identified from BAC-derived sequences and whole-genome shotgun sequences (WGS). CBF/DREB1 genes are organized in a tandem array within an approximately 296-Kb region. Eleven CBF/DREB1 genes were isolated and sequenced from F83005-5 and DZA045-5 which revealed high polymorphism among these accessions. Unique features characterizing CBF/DREB1 genes from M. truncatula, such as alternative splicing and large tandem duplication, are elucidated for the first time. Overall, twenty genes were identified as potential candidates to explain Mt-FTQTL6 effect. Their future functional characterization will uncover the gene(s) involved in freezing tolerance difference observed between F83005-5 and DZA045-5. Knowledge transfer for breeding improvement of crop legumes is expected. Furthermore, CBF/DREB1 related data will certainly have a large impact on research studies targeting this group of transcriptional activators in M. truncatula and other legume species