A document by Nina Wale, written on Authorea.

In this paper, we further Meirong Zhang, et al.’s work by computing the number of weighted eigenvalues for Sturm-Liouville equations, equipped with general integrable potentials and Dirac weights, under Dirichlet boundary condition. We show that, for a Sturm-Liouville equation with a general integrable potential, if its weight is a positive linear combination of $n$ Dirac Delta functions, then it has at most $n$ (may be less than $n$, or even be $0$) distinct real Dirichlet eigenvalues, or every complex number is a Dirichlet eigenvalue; in particular, under some sharp condition, the number of Dirichlet eigenvalues is exactly $n$. Our main method is to introduce the concepts of characteristics matrix and characteristics polynomial for Sturm-Liouville problem with Dirac weights, and put forward a general and direct algorithm used for computing eigenvalues. As an application, a class of inverse Dirichelt problems for Sturm-Liouville equations involving single Dirac distribution weights is studied.

Objective: The present study focused on the clinical pregnancy and cumulative live birth rate (CLBR) of female patients with X chromosome mosaicism (XM) after the first in-vitro-fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment, and the possible impact of different mosaic subtypes. Design: Retrospective cohort study Setting: Single Center study Population: Infertility couples Methods: In total, 76 couples with XM female partners and normal male partners were included (2014–2019) as the X group, with another 76 couples with normal karyotype included as the control group. Subgroup X1 included 41 45,X/46,XX cases, Subgroup X2 included 22 47,XXX/46,XX cases, and Subgroup X3 included 12 45,X/47,XXX/46,XX cases. Main Outcome Measures: The ovarian stimulation, embryo results and pregnancy outcomes were analyzed. Results: The X group presented similar CLBR but required a higher total gonadotropin (Gn) dosage than the control group (1800 IU vs. 1612 IU). Following subgroup analysis, the number of follicles during oocyte retrieval and average number of fertilized oocytes was lower in subgroup X1 than in X3. The clinical pregnancy rate and CLBR were similar in all groups. Conclusion: Females with XM may present a similar CLBR until one year after oocyte retrieval, but may require a higher total Gn dosage. Females with 45,X cells may recover fewer follicles during oocyte retrieval, resulting in fewer embryos. A higher 45,X cell ratio (over 5%) may lead to a lower CBLR. Funding: This study was supported by the Ministry of Science and Technology of China (2016YFC1000602). Keywords X chromosome mosaicism, IVF/ICSI outcome, cumulative live birth rate

We describe a case of Sporadic Creutzfeldt-Jakob disease (sCJD) and discuss our evidence-based diagnostic process.

Family-based treatment, the recommended treatment for adolescents and young adults with eating disorders, it is often not accessible for families. The aim of this case report is to describe outcomes of two patients treated virtually with an augmented team approach to provide preliminary evidence of feasibility and efficacy.

Background Ethanol infusion in the vein of Marshall (EIVM) has shown to be effective for treating atrial fibrillation (AF) and perimitral left atrial (LA) flutter (PMLAF). Aims To assess the persistence of LA lesions created by EIVM by electro-anatomical mapping (EAM) at repeated procedure for recurrent atrial tachycardia (AT) or AF. Methods We included consecutive patients who underwent EIVM then repeated CA for recurrent AT or AF with high-definition EAM in a single center. Acute and long term EIVM effect was assessed at the index and redo procedures by comparing the area of bipolar voltage <0.05 mV in the vein of Marshall (VOM) region before, immediately after and late after EIVM. Results 24 consecutive patients (mean age 68.6±6.1 years, 58% men) underwent redo procedure after previous successful EIVM for persistent AF (n=21; 88%) or PMLAF (n=5; 21%). In each case, EIVM had an acute effect, with a post-EIVM scar in the VOM (median 12.4 cm2 [interquartile range (IQR) 7.6–15.7]). Mitral isthmus (MI) bidirectional block was obtained in 20/24 patients (83%). In each patient, the EIVM-related lesion persisted, with a chronic scar in the VOM region (median 13.1 cm2 [IQR 8.1–15.9]). One quarter of patients (5/20) had late MI reconnection, which was located at the mitral annulus edge or in the coronary sinus. Conclusions Atrial lesions created by EIVM are durable, which reinforces the efficacy profile of EIVM. Reconduction sites in the MI are located at the edge of the mitral annulus and in the coronary sinus.

Introduction: The approach to thyroid hormone replacement varies across centres but the extent and determinants of variation is unclear. We evaluated geographical variation in levothyroxine (LT4) and liothyronine (LT3) prescribing across General Practices in England and analysed the relationship of prescribing patterns to clinical and socioeconomic factors. Methods: Data was downloaded from the NHS monthly General Practice Prescribing Data in England for the period 2011-2020. Results Overall, 0.5% of levothyroxine treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019-20. Factors strongly influencing more levothyroxine prescribing (model accounted for 62% of variance) were the CCG to which the practice belonged and the proportion of people with diabetes registered on the practice list plus antidepressant prescribing, with socioeconomic disadvantage associated with less levothyroxine prescribing. For liothyronine prescribing (model accounted for 17% of variance), factors that were associated with increased levels of liothyronine prescribing were antidepressant prescribing and % of type 2 diabetes mellitus individuals achieving HbA1c control of 58mmol/mol or less. Factors that were associated with reduced levels of liothyronine prescribing included smoking and higher obesity rates. Conclusion: In spite of strenuous attempts to limit prescribing of liothyronine in general practice a significant number of patients continue to receive this therapy, although there is significant geographical variation in the prescribing of this as for levothyroxine, with specific general practice and CCG related factors influencing prescribing of both levothyroxine and liothyronine.

Aim To demonstrate the best home care of children with diarrhea in our community by investigating certain knowledge deficiencies, specific inappropriate attitudes, and particular improper practice toward children diarrhea and its management, this study was conducted to evaluate knowledge, attitude and practice of Saudi mothers towards diarrhea in their children and its management at home. Methods Online cross-sectional validated online survey targeting Saudi mothers who are living in Saudi Arabia was used to collect data from the beginning of March to the end of April 2019. Results A total of 1140 mothers (52.1% of them are housewives) participated in the study. About of 40.3 % of participating mothers believed that childhood diarrhea is major problem in Saudi community; however, Almost 23% of the participants were unable to identify any critical sign of sever diarrhea, and around 66% falsely stated that diarrhea is caused by teething. Although of 62 % of our participating mothers knew about the oral rehydration therapy (ORS), only 23.5 % of them used it for their children. Conclusion Adequate knowledge of mothers about the critical sings, causes, transmission, prevention, and management of childhood diarrhea should be applied in simple language to communicate the health-related information in clear manner.

Aim: This study aimed to determine the approaches of family physicians in Turkey on the fasting of diabetic patients and whether they use international treatment guidelines when making recommendations. In addition, this study aimed to increase the awareness of family physicians on this issue before Ramadan, which is the fasting month. Material and Method: The study herein comprised cross-sectional observational research. Before Ramadan 2018, a structured questionnaire form, which was unique to this study, was prepared by considering the guidelines of the International Diabetes Federation (IDF) and the American Diabetes Association (ADA), through platforms where family physicians gathered via social media and mail groups, and sent to the family physicians in Turkey via a link created using an electronic questionnaire preparation and application program. Moreover, the total knowledge level, attitude, and approach score were calculated through the questions prepared from the relevant guidelines. Results: Participating in the survey were 262 family physicians. Only 22% of family physicians said that they were aware that there were international guidelines for Ramadan and diabetes management, and only 10% said that they had read the relevant guidelines. The mean knowledge level, attitude, and approach scores were found to be lower than expected, and a significant difference was found between their scores and their academic titles. Conclusion: The lack of knowledge of international guidelines on the subject and lack of knowledge and experience about diabetes mellitus patient management in the fasting month stood out as the biggest problems. This study revealed that the awareness and competence of family physicians in disease management should be increased in addition to fasting before, during, and after Ramadan in diabetic patients.

Aims/Introduction: Insulin Degludec/Aspart (IDegAsp) and Insulin Glargine U300 (IGlarU300) have recently emerged as popular new-generation insulin analogs. The aim of this real-life study was to investigate the patient profiles in which IGlarU300 and IDegAsp were preferred and the insulin combinations after which each of them were mostly used, and also to analyze the effect of these two insulin analogs on blood glucose regulation and hypoglycemia. Materials and Methods: The retrospective study included 174 patients that were switched from basal insulin, basal+bolus insulin, or premixed insulin to IGlarU300 or IDegAsp due to uncontrolled blood glucose levels or history of hypoglycemia. Hypoglycemia, body weight, body mass index (BMI), fasting blood glucose (FBG), and HbA1c levels over three-month periods were evaluated for each patient. Results: There were 84 and 90 patients in the IGlarU300 and IDegAsp groups, respectively. Body weight was similar in both groups. Baseline FBG and HbA1c levels in the IGlarU300 and IDegAsp groups were 9.0%, 175.5 mg/dl and 9.4%, 193.5 mg/dl, respectively. A significant decrease was found in FBG and HbA1c levels in both groups (138.5, 7.8 vs. 141.5, 8.2; p<0.001 for all). Moreover, a significant weight gain was observed in both groups (p<0.05 for both). The prevalence of hypoglycemia in both groups decreased significantly and consistently between month 1 and 9 (p<0.001). At month 12, although this decrease continued in the IGlarU300 group (p=0.013), no significant decrease was observed in the IDegAsp group(p=0.057). Conclusion: Both twice-daily IDegAsp±bolus insulin and IGlarU300+bolus insulin therapies are effective and safe treatment modalities.

Reconstructing the geographic origins of invasive species is critical for establishing effective management strategies. Frequently, molecular investigations are undertaken when the source population is not known, however; these analyses are constrained both by the amount of diversity present in the native region and by changes in the genetic background of the invading population following bottlenecks and/or hybridization events. Here we explore the geographical origins of the invasive winter moth (Operopthera brumata L.) that has caused widespread defoliation to forests, orchards, and crops in four discrete regions: Nova Scotia, British Columbia, Oregon, and the northeastern United States. It is not known whether these represent independent introductions to North America, or “stepping stone” spread among regions. Using a combination of Bayesian assignment and approximate Bayesian computation methods, we analyzed a population genetic dataset of 24 polymorphic microsatellite loci. We estimate that winter moth was introduced to North America on at least four occasions, with the Nova Scotian and British Columbian populations likely being introduced from France and Sweden, respectively; the Oregonian population likely being introduced from either the British Isles or northern Fennoscandia; and the population in the northeastern United States likely being introduced from somewhere in Central Europe. To our surprise, we found that hybridization has not played a large role in the establishment of winter moth populations even though previous reports have documented widespread hybridization between winter moth and a native congener. We discuss the impact of genetic bottlenecks on analyses meant to determine region of origin.

Bioequivalence (BE) is established between the brand drug and the generic drug to allow the linking of preclinical and clinical testing conducted on the reference listed drug. Regulatory agencies around the globe have come up with the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches. The prime intent of the present article is to compare approaches of different international regulatory authorities such as Health Canada, European Medicines Agency and the US Food and Drug Administration that have published guidance related to locally acting OIDPs. Moreover, the Central Drugs Standard Control Organisation, India, has published guidelines for bioavailability and bioequivalence studies. BE recommendations from global regulatory agencies were based on comparison for different parameters, namely inhaler device, formulation, reference product’s selection, in-vitro as well as in-vivo studies (pharmacokinetics, pharmacodynamics, and clinical studies). In the case of in-vivo studies, details about study design, dose choices, inclusion/ exclusion criteria of the subject, study period, endpoint study, and equivalence acceptance criteria were discussed in the present review article.

Background: There is no consensus regarding the optimal anesthetic approach to rigid bronchoscopy in children suffering from tracheobronchial FBA. We performed this meta-analysis to assess the efficacy and safety of the different anesthesia agents and ventilation modes for tracheobronchial foreign body removal via rigid bronchoscopy in young children. Methods: A systematic search of three major databases for all relevant articles. A meta-analysis was performed to analyze the data. Results: Four trials for evaluating different anesthetics and six trials for evaluating two kinds of ventilation modes were found. Compared with the sevoflurane-based volatile anesthesia group , the rate of perioperative complications included hypoxemia (OR, 2.07; 95% CI, 1.38–3.11; P=0.0004; I2 = 0%), apnea (OR, 2.74; 95% CI, 1.11–6.78; P = 0.03; I2 = 60%), laryngospasm (OR, 2.89; 95% CI, 1.67–4.98; P=0.0001; I2 = 0%), cough/bucking (OR, 2.93; 95% CI, 1.86–4.63; P<0.00001; I2 = 0%), and body movement (OR, 3.51; 95% CI, 2.03–6.09; P<0.00001; I2 = 0%) were significantly increased in the propofol-based total intravenous anesthesia and the duration of operation were longer in the Group Prop. Compared with the control ventilation group , the incidences of laryngospasm (OR, 0.16; 95% CI, 0.05–0.56; P=0.004; I2 = 54%), apnea (OR, 0.21; 95% CI, 0.09–0.50; P=0.0004; I2 = 0%), and cough/bucking (OR, 0.03; 95% CI, 0.01–0.10; P<0.00001; I2 = 41%) increased in the spontaneous ventilation group and the duration of operationand emergence from anesthesia significantly prolonged in the Group SV. Conclusions: Our meta-analysis suggests that sevoflurane-based volatile anesthesia was superior to propofol-based total intravenous anesthesia for the management of foreign body aspiration in children. There is still no strong evidence indicated that one ventilation technique was superio

This article aims to provide a comprehensive review of the clinical features and genetics basis of multi-system pseudohypoaldosteronism type 1 caused by SCNN1B gene mutations.

Doege Potter syndrome is a rare paraneoplastic clinical entity. A 31-year-old woman consulted with a right indurated malar mass and hypoglycemia. Blood test showed a non-insulin-mediated hypoglycemia. CT scan revealed a solid tumor from the right temporal region with liver metastasis. The histopathological diagnosis revealed a solitary fibrous tumor.

We described an atypical presentation of papillary thyroid cancer metastasized to left finger. This case highlights the importance of an early and effective engagement of multidisciplinary team approach with family in order to optimize patient care.

Maxillary sinus grafting is a well-know procedure with high predictability used to to correct vertical bone defects in the posterior region of the maxilla.The presence of a sinus osteoma adds to its difficulty and may recquire a more specific case management depending on the lesion's extent.

Blue discoloration of the skin and cartilage, or ochronosis, is a rare physical examination finding. Here are two cases of childhood onset ochronosis, one exogenous and one endogenous in etiology.

We report a case of P. yeei CAPD-peritonitis in a patient experiencing repeated episodes of peritonitis. P. yeei, an emerging opportunistic pathogen, takes advantage of specific virulence factors and peculiar circumstances. We discuss the exogenous or endogenous microbial source of the peritonitis and guidelines to decrease its occurrence.

Background: The weekend effect is a phenomenon characterized by increased early all-cause mortality among patients hospitalized or undergoing surgery over the weekend for emergencies. Objectives: With this meta-analysis we aimed to determine whether weekend hospitalization/surgery due to acute aortic syndromes (AAS) is associated with increased early all-cause mortality. Methods：Major electronic databases were searched for studies published up to October 2020 reporting early all-cause mortality rates for admissions/operations on weekends versus weekdays. Data were pooled using fixed- and random-effects models. The primary outcome of the study was early all-cause mortality after weekend versus weekday. Results: All the included studies were retrospective, comparative or cohort studies enrolling patients admitted or underwent surgery for AAS and reported early all-cause mortality after weekend (including holiday) versus weekday. A total of 18 studies including a total of 252807 patients were identified. This meta-analysis showed a significant increase in the early all-cause mortality for patients admitted/conducted surgery for AAS on weekends compare with weekdays (fixed-effect: OR 1.1;95% CI 1.06-1.14;P＜0.00001). Conclusion: Weekend admission/surgery for AAS is associated with a increased risk of early all-cause mortality.

Rationale: Noninvasive ventilation (NIV) is the first-line therapy in infants with bronchiolitis-related acute respiratory failure. However, there is a lack of data regarding weaning from NIV in this setting. Working hypothesis: This study aims to evaluate a nurse-driven weaning protocol in this homogenous population. Study design: A retrospective single-center study with pre-versus-post comparative design in a tertiary center. Methodology: Data from all infants aged ≤ 6 months admitted to the PICU during 2 seasons with a clinical diagnosis of bronchiolitis and requiring any type of noninvasive ventilatory support on admission, were analyzed. Main results: In total, 187 infants (95 with standard and 92 with nurse-driven protocols) were included; the median age was 47 (IQR 24-75) and 31 days (19-58) in patients at baseline and after the protocol implementation, respectively. There was no difference in terms of weaning failure between the two periods (11 (12%) versus 14 (15%), p=0.46). At baseline, the ventilatory support duration was 70 hours (IQR 54-104) versus 56 hours (IQR 29-83) during the nurse-driven protocol period (p=0.29). The PICU and hospital lengths of stay did not differ between the two periods. No complication related to NIV occurred in the two periods. Conclusions: In patients with bronchiolitis supported by NIV, the nurse-driven weaning management - as opposed to physician-driven - was not associated with a significantly higher proportion of weaning failure cases.

Gear contact fatigue is becoming a primary limitation for the growing demand of power density and service life in gear-driven equipment. The unchecked surface fatigue crack could further cause premature failure and put a serious risk to the safety and reliability of mechanical systems. In this work, an attempt is made to investigate the effects of rolling-sliding and mild wear on contact fatigue behavior. A comprehensive contact model is developed to capture the variation instantaneous pressure and stress field is calculated with the transient mixed EHL approach. Rolling-sliding contact is simulated with the time-varying roughness topography updated by Archard wear equation. The stress cycles are extracted and the relative contact fatigue life is obtained by using Zaretsky criterion. Results suggest that in rolling-sliding contact the contact fatigue life is obviously lower compared with pure rolling. The increases in the number and amplitude of stress micro-cycles is found to be the main contributors to the reduction of fatigue life. Mild wear tends to smooth the surface, subsequently mitigates the stress concentration and reduces stress cycles, then decrease the risk of surface contact fatigue.

Commentary:When Starting a MICS Program, Don’t Assume Excellence: Prove It!Rachel Eikelboom MD1,2, Rashmi Nedadur MD3,Roberto Vanin Pinto Ribeiro MD3, Bobby Yanagawa MD PhD31 Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada2 Division of Cardiac Surgery, McMaster University, Hamilton, Ontario, Canada3 Division of Cardiac Surgery, St Michael’s Hospital, University of Toronto, Toronto, Ontario, CanadaCorresponding author:Bobby Yanagawa MD, PhD, FRCSC Program Director, Division of Cardiac Surgery, University of Toronto Assistant Professor, Division of Cardiac Surgery, St. Michael’s Hospital  30 Bond Street, 8th Floor, Bond Wing Toronto, ON M5B 1W8 Canada Tel: 416 864 5706 Fax: 416 864 5031 Email: yanagawab@smh.caWord count: 430Conflict of interest: The authors have no conflict of interest and have not received any funding.Central Figure:

Background and Purpose: Amyotrophic lateral sclerosis with associated frontotemporal dementia, Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease are the major neurodegenerative disorders that afflict more than 7 million people worldwide. There are no disease-modifying or disease-retarding therapeutic agents currently available on the market. All four conditions feature several seemingly-disparate pathological and genetic lesions, which, however, converge into calcium dyshomeostasis and a disturbed function of the axis of the endoplasmic reticulum (ER) and mitochondria. Experimental Approach: Incretin mimetics – traditionally anti-diabetic therapeutic agents – have been repeatedly shown to exert neurotrophic effects in neuroblastoma cells, rodent primary neurones, and murine models of neurodegeneration. Herein, for the very first time, we assess the pharmacological effects of Liraglutide and the dual incretin DA-CH3 in terminally differentiated human neurones under conditions of calcium-dependent chronic ER stress and additionally assess their efficacy in one of the most critical regulatory point for neurones, the mitochondrial respiration and dynamics. Key Results: Liraglutide and DA-CH3 rescue the arrested oxidative phosphorylation and glycolysis. They mitigate the suppressed mitochondrial biogenesis and hyper-polarisation of the mitochondrial membrane, all, to re-establish normalcy of cellular bioenergetics under conditions of chronic ER stress. These effects correlate with a resolution of the unfolded protein response and the autophagic arrest to halt the excessive synaptic and neuronal death, with the dual incretin displaying a superior anti-apoptotic effect. Conclusions: Our findings pave the way for a therapeutic strategy for disorders with a considerable social-economic burden and deepen our understanding of the spectrum of the incretin-signalling functions.