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The Canadian Neuromuscular Disease Registry (CNDR) is a pan-neuromuscular disease registry that prospectively collects spinal muscular atrophy (SMA)-specific data in 32 clinics across Canada. The CNDR captures a comprehensive SMA dataset to evaluate long-term real-world experience with available and emerging therapies. The objective of this study is to describe real-world data from the CNDR-SMA patient population. The CNDR has 417 SMA patients registered, 207 adult patients (170 with clinical data) and 198 pediatric patients (181 with clinical data). This represents a large percentage of expected Canadians with SMA. Of those with complete data, Median age is 37 (18-80) for adults, and 9 (1-17) for pediatric patients. 243 (66%) patients have SNM2 copy number reported, 69 (28%) have 2 copies, 134 (55%) have 3 copies, 38 (16%) have 4 copies, and 119 are unknown/not reported. 93 (26%) patients are ambulatory. There are three disease modifying therapies (DMTs) approved for the treatment of SMA: risdiplam, nusinersen, and onasemnogene abeparvovec that all showed efficacy in clinical trials. Real-world effectiveness must be assessed across a broader range of patients presenting with variable comorbidities and disease severity. The CNDR collects DMT-specific real-world data to contextualize the effects of DMTs and to further access to treatment options in Canada. DMT's are differentially accessible across Canada, based on reimbursement recommendations of provincial payers. DMT use has been reported in 222 CNDR SMA patients: 184 on nusinersen, 41 on risdiplam, 36 on zolgensma (152 pediatric, and 71 adult), and 75 with no DMT use. In conclusion, the CNDR captures a comprehensive SMA dataset that prospectively evaluates real-world data, supporting post-marketing surveillance of novel therapies in Canada. Analysis is ongoing and available longitudinal follow-up data will be presented with descriptive statistics for both naive and DMT patients. [ABSTRACT FROM AUTHOR]

Background: This study describes the efficacy of a new protamine zinc recombinant human insulin (PZIR) preparation for treating diabetic cats. Objective: To evaluate effects of PZIR on control of glycemia in cats with newly diagnosed or poorly controlled diabetes mellitus. Animals: One hundred and thirty-three diabetic cats 120 newly diagnosed and 13 previously treated. Methods: Prospective, uncontrolled clinical trial. Cats were treated with PZIR twice daily for 45 days. Control of glycemia was assessed on days 7, 14, 30, and 45 by evaluation of change in water consumption, frequency of urination, appetite, and body weight, serum fructosamine concentration, and blood glucose concentrations determined 1, 3, 5, 7, and 9 hours after administration of PZIR. Adjustments in dosage of PZIR were made as needed to control glycemia. Results: PZIR administration resulted in a significant decrease in 9-hour mean blood glucose (199 ± 114 versus 417 ± 83 mg/dL, X± SD, P < .001) and serum fructosamine (375 ± 117 versus 505 ± 96 μmol/L, P < .001) concentration and a significant increase in mean body weight (5.9 ± 1.4 versus 5.4 ± 1.5 kg, P= .017) in 133 diabetic cats at day 45 compared with day 0, respectively. By day 45, polyuria and polydipsia had improved in 79% (105 of 133), 89% (118 of 133) had a good body condition, and 9-hour mean blood glucose concentration, serum fructosamine concentration, or both had improved in 84% (112 of 133) of the cats compared with day 0. Hypoglycemia (<80 mg/dL) was identified in 151 of 678, 9-hour serial blood glucose determinations and in 85 of 133 diabetic cats. Hypoglycemia causing clinical signs was confirmed in 2 diabetic cats. Conclusions and Clinical Relevance: PZIR is effective for controlling glycemia in diabetic cats and can be used as an initial treatment or as an alternative treatment in diabetic cats that do not respond to treatment with other insulin preparations. [ABSTRACT FROM AUTHOR]

The chronic inflammatory component of asthma is propagated by granulocytes, including neutrophils and eosinophils, in the peripheral circulation and airway. Previous studies have suggested that these cells have an altered expression of adhesion-related molecules and a propensity for the release of granule contents that may contribute to tissue damage and enhance inflammatory complications in patients with status asthmaticus. The goal of this prospective cohort study at a tertiary care pediatric hospital with a large population of asthma patients was to assess the role of granulocyte-based inflammation in the development of asthma exacerbation. Subjects were enrolled from two patient populations: those with mild-to-moderate asthma exacerbations seen in the emergency department and those with severe asthma admitted to the intensive care unit (PICU). Clinical data were collected, and blood was drawn. Granulocytes were immediately purified, and the phenotype was assessed, including the expression of cell surface markers, elastase release, and cytokine production. Severe asthmatics admitted to the PICU displayed a significantly higher total neutrophil count when compared with healthy donors. Moreover, little to no eosinophils were found in granulocyte preparations from severe asthmatics. Circulating neutrophils from severe asthmatics admitted to the PICU displayed significantly increased elastase release ex vivo when compared with the PMN from healthy donors. These data suggest that the neutrophil-based activation and release of inflammatory products displayed by severe asthmatics may contribute to the propagation of asthma exacerbations.

Background: Using an experimental study, we examined the link between state moral elevation and stigmatic beliefs surrounding male veterans with military sexual trauma (MST)., Methods: Undergraduate students were presented with a video or written narrative of a male veteran self-disclosing how they struggled with and overcame MST (n = 292). Participants completed measures regarding trait and demographic characteristics at baseline, then measures immediately after the disclosure stimulus to assess immediate elevation and stigma-related reactions., Results: Results suggest state-level elevation in response to a veteran self-disclosing their experience with MST was negatively correlated with harmful stigmatic beliefs about MST. A greater predisposition to experience elevation and PTSD symptoms were linked with stronger elevation responses to the stimulus., Conclusion: Findings support the need for further exploration of elevation and its potential to impact public stigma for male veterans with MST., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The spread of COVID-19 acutely challenges and affects not just economic markets, demographic statistics and healthcare systems, but indeed also the politics of organizing and becoming in a new everyday life of academia emerging in our homes. Through a collage of stories, snapshots, vignettes, photos and other reflections of everyday life, this collective contribution is catching a glimpse of corona-life and its micro-politics of multiple, often contradicting claims on practices as many of us live, work and care at home. It embodies concerns, dreams, anger, hope, numbness, passion and much more emerging amongst academics from across the world in response to the crisis. As such, this piece manifests a shared need to - together, apart - enact and explore constitutive relations of resistance, care and solidarity in these dis/organizing times of contested spaces, identities and agencies as we are living-working-caring at home during lockdowns., (© 2020 John Wiley & Sons Ltd.)

We compared changes in academic achievement across 3years between children in elementary schools receiving the Academic Achievement and Physical Activity Across the Curriculum intervention (A+PAAC), in which classroom teachers were trained to deliver academic lessons using moderate-to-vigorous physical activity (MVPA) compared to a non-intervention control. Elementary schools in eastern Kansas (n=17) were cluster randomized to A+PAAC (N=9, target ≥100min/week) or control (N=8). Academic achievement (math, reading, spelling) was assessed using the Wechsler Individual Achievement Test-Third Edition (WIAT-III) in a sample of children (A+PAAC=316, Control=268) in grades 2 and 3 at baseline (Fall 2011) and repeated each spring across 3years. On average 55min/week of A+PACC lessons were delivered each week across the intervention. Baseline WIAT-III scores (math, reading, spelling) were significantly higher in students in A+PAAC compared with control schools and improved in both groups across 3years. However, linear mixed modeling, accounting for baseline between group differences in WIAT-III scores, ethnicity, family income, and cardiovascular fitness, found no significant impact of A+PAAC on any of the academic achievement outcomes as determined by non-significant group by time interactions. A+PAAC neither diminished or improved academic achievement across 3-years in elementary school children compared with controls. Our target of 100min/week of active lessons was not achieved; however, students attending A+PAAC schools received an additional 55min/week of MVPA which may be associated with both physical and mental health benefits, without a reduction in time devoted to academic instruction., (Copyright © 2017. Published by Elsevier Inc.)

Background: Hepatitis B virus (HBV) infection is a significant public health problem in Vietnam, yet few data exist about the extent of infection., Purpose: To determine seroprevalence of HBV and the risk factors for HBV infection using a population-based epidemiological study in Vietnam., Methods: A 400 person survey for seroprevalence of hepatitis B surface antigen (HBsAg) and HBV infection was carried out in five hamlets in the Linhson village of Thainguyen province from June to August 2006. HBV infection was defined as the presence of antibodies to hepatitis core antigen (HBcAb) and/or HBsAg, with or without HBsAg. Potential risk factors for HBV transmission were determined by a structured questionnaire., Results: Of the 383 respondents aged 18-70 years, 34 (8.8%) tested positive for HBsAg, of whom 21 (61.8%) were HBeAg-negative and hepatitis Be antibody (HBeAb) positive, and 22 (64.7%) had normal alanine aminotransferase (ALT) levels. The prevalence of HBV infection was 51.8% and increased significantly with age. Only 5.2% showed evidence of vaccination. On multivariate analysis, five predictors were found for HBV infection: male gender (OR 1.6; 95% CI 1.3-1.7), age greater than 40 (OR 2.1; 95% CI 1.4-3.3), Kinh ethnicity (OR 1.8; 95% CI 1.1-2.7), a low level of education (OR 1.7; 95% CI 1.0-2.7), and a history of surgery (OR 1.9; 95% CI 1.0-3.5)., Conclusions: The observed high prevalence of current and past infection with HBV in rural Vietnam highlights the need for close monitoring.

Background: The radial approach to cardiac catheterization is increasingly popular due to shorter procedural and recovery times and greater patient comfort., Methods: Comparative cost analysis between radial or femoral (with or without closure device) approaches were performed., Results: Radial (R), femoral (F), and femoral with a closure device (F +/- C) approaches were used in 70, 62 and 49 consecutive cases, respectively. Group R had higher access equipment cost (93.0 dollars +/- 9.5 vs. 40.5 dollars) in group F (p < 0.001), but lower catheter cost (19.7 dollars +/- 12.7 vs. 31.1 dollars +/- 9.3; p < 0.001) than Group F, and lower contrast cost (26.9 dollars +/- 17.0 vs. 42.9 dollars +/- 25.0) in Group F +/- C (p < 0.001). There was a lower postprocedure recovery cost (185.2 dollars +/- 52.7) in Group R compared to 337.5 dollars +/- 59.0 in Group F (p < 0.001) and 208 dollars +/- 70.4 in Group F +/- C (p < 0.001), with a median recovery time of 126.0 +/- 36.0 minutes in group R vs. 240.0 +/- 42.0 minutes, and 150.0 +/- 48.0 minutes in groups F and F +/- C, respectively (both p < 0.05). The total variable procedural cost, which includes approach-dependent equipment and recovery room stay, was significantly lower in the Radial group than in the Femoral group (369.5 dollars +/- 74.6 vs. 446.9 dollars +/- 60.2 and 553.4 dollars +/- 81.0; p < 0.001)., Conclusion: The radial artery approach to diagnostic cardiac catheterization is clearly more cost effective than the femoral approach, with or without the use of a femoral closure device.

The objective of this study was to examine and attempt to confirm our previous findings of an increased frequency of the C4B null allele (C4BQ0) in subjects with autism. Newly identified subjects from Utah and Oregon were studied. Families evaluated included 85 who had a child with autism and 69 control families. Of the subjects with autism studied, 42.4% carried at least one C4BQ0, compared with 14.5% of the control subjects (p = 0.00013), with a relative risk of 4.33. Over half of the C4B null alleles in the subjects with autism involved C4A duplications. A marked increase in the ancestral haplotype 44.1 that lacks a C4B gene and has 2 C4A genes was also observed. The results of this study suggest that the human leukocyte antigen class III C4BQ0 significantly increases the risk for autism.

Tertiary trisomy, or double trisomy, is a rare occurrence. We present two individuals with a previously unreported tertiary trisomy for chromosomes 5p and 21q in an eight-generation pedigree. Their phenotypes are compared with other partial trisomies of either 5p or 21q from the literature. The propositus was diagnosed with trisomy 21 at 2 years of age after a karyotype study for short stature and developmental delay. His phenotype was described as atypical for Down syndrome. He presented at 9 years of age because of pervasive behavioral problems and obesity. He was brachycephalic with a flattened nasal bridge, but he lacked other characteristics of trisomy 21. Because of lack of phenotypic evidence of Down syndrome, a repeat karyotype was obtained and showed 47,XY, +der(21)t(5;21)(p15.1; q22.1), incorporating partial trisomies of both chromosomes 5 and 21. Mother had a balanced translocation, 46, XX,t(5;21)(p15.1; q22.1); 8 other relatives were examined. The translocation originated from the maternal great-grandmother, but only the propositus and his mentally retarded aunt had a similar phenotye and the derivative chromosome. Fluorescence in situ hybridization showed absence of band 21q22.2 in the derivative chromosome of the propositus and his aunt, indicating that neither had trisomy for the Down syndrome critical region. These cases represent a unique double partial trisomy of chromosome arms 5p and 21q that occurred because of 3:1 malsegregation of a reciprocal translocation. These cases further demonstrate that phenotypic discordance with cytogenetic results dictate further investigation using advanced cytogenetic hybridization., (Copyright 2000 Wiley-Liss, Inc.)

Alprostadil (prostaglandin E1) administration to liver transplant recipients has been shown to result in a significant reduction in the duration of hospital admission for transplantation, and in the need for re-operations (other than re-transplants) and renal support. To study the economic impact of this finding, we examined data from a controlled trial for all single-transplant surviving patients (42 alprostadil, 49 controls) for whom complete billing records were available for transplant days -2 to +150. All costs were measured in 1992 US dollars. Patients given alprostadil had lower total charges [mean +/- standard deviation (SD) $US175 297 +/- $US70 652] than patients given placebo (mean +/- SD $US225 672 +/- $US187 208) [p = 0.043]. The data suggest that the use of alprostadil may have a significant favourable impact on the cost of liver transplantation.

This brief review summarizes the physiology and pharmacology of eicosanoids and describes how they have been tested for possible application in liver disease and transplantation. The objective is to trace the stepwise application from the laboratory to the bedside. Although many questions remain to be answered, the observations summarized in this article have opened up new and potentially rewarding prospects in application to liver disease.

Significant technical innovations and improvements in immunosuppression have been introduced into our liver transplant program since its inception in 1985. The indications for transplantation have been extended to younger and older patients, and simultaneously more patients with comorbidities have been accepted for transplant. The net impact of these changes has been a continuing trend toward improved survival. Overall, patients with hepatitis B or malignancy have had poor survival rates. The introduction of prophylactic anti-hepatitis B immunoglobulin and lamivudine, and better selection of patients with malignancy may improve results for these patients in the future. As in other programs, our most vexing problem is the continuing scarcity of donor organs which has led to an ever-expanding waiting list, more deaths while awaiting transplant, and more suffering before transplantation. The introduction of living donor hepatic transplantation will be of some help in alleviating this shortage. We are confident that the evolution of our program into a joint multidisciplinary structure will provide more efficient, convenient and cost-effective care to our patients.

Acute cellular rejection of the allograft is a potentially serious complication after liver transplantation, yet its true incidence is unknown. We therefore investigated the frequency of acute cellular rejection reported by transplant centers and its impact on morbidity and mortality. Morbidity was defined as duration of hospitalization. Of 200 articles screened, 18 were selected for inclusion in the study database, in which there was a total of 1,437 patients who received transplants. All contained more than 20 patients and invariably used histopathology for diagnosis of acute cellular rejection. These reports included all transplant patients within a fixed period and sufficient data to determine the incidence of acute cellular rejection. Morbidity data were obtained from our previous series. The mean incidence of acute cellular rejection in all centers was 49.8% (range between centers, 24% to 80%). Two immunosuppressive cohorts were identified: high-dose cyclosporine induction (> or = 5 mg/kg/d) and low-dose cyclosporine induction (< or = 4 mg/kg/d). Acute cellular rejection was reported in 27.0% of the high-dose group and 63.6% of the low-dose group, P = .0001. Strict adherence to Snover's histological criteria for acute cellular rejection did not alter the reported mean incidence. Frequency of acute cellular rejection was 45.2% (range between centers, 24% to 80%) in 8 studies that used Snover's criteria, and 51.6% (range between centers, 37% to 80%) in 10 studies that did not. There was no correlation between mortality and incidence of acute cellular rejection in the 9 studies that reported survival (R2 = .105). Morbidity data showed that the average length of initial hospitalization after transplantation for patients with acute cellular rejection was 52.4 +/- 8.3 (range, 14 to 124) days, in contrast to 28.3 +/- 2.3 (range, 9 to 87) days for patients with no rejection. P = .0008. The total number of hospital days in the first 6 months for patients with acute cellular rejection was 55.6 +/- 8.6 (range, 14 to 124) days and with no rejection, was 37.7 +/- 3.1 (range, 9 to 99) days. P = .0232. The incidence of acute cellular rejection varies widely among transplant centers, regardless of the use of Snover's criteria. Acute cellular rejection appeared to be less frequent in programs using high-dose cyclosporine induction regimens. The presence of acute cellular rejection seemed to have no correlation with mortality but significantly increased morbidity and therefore the cost of transplantation.

The influence upon LH secretion of doses of nalmefene, an orally effective congener of naloxone, and a placebo was compared in nine oligo-amenorrheic athletes with that in five regularly menstruating non-athletic women as a test for periodic elevations in hypothalamic opioid tone. After a 360-min control period, LH levels were followed for an additional 360 min following ingestion of the medications in random order approximately six weeks apart, 10-min blood sampling being employed throughout. The mean amplitude post-nalmefene in the athletes was significantly greater than pre (p < 0.05), although there were no differences in the frequency of LH pulses after placebo or nalmefene ingestion. Subjects were labelled as "responders" if their peak AUC after treatment exceeded their pretreatment AUC for LH by more than 1.96 SD (p < 0.05). There were no placebo responders, but 5/9 of the athletes and 1/5 of the menstruating controls were classified as nalmefene responders (p < 0.05). In addition, a variable proportion of the athletes (but none of the controls) experienced symptoms suggestive of narcotic withdrawal 1-4 h after ingesting nalmefene and again 12-18 h later. It appears that demonstrable increases in opioid tone occur at least transiently in a proportion of oligo-amenorrheic athletes.

Background: Despite the increasing success of liver transplantation, there is lack of objective data defining appropriate candidate suitability. This study was undertaken to determine preoperative risk factors that independently or in combination affected outcome after orthotopic liver transplantation., Methods: We reviewed data on 229 consecutive adult liver transplant recipients. Thirty-one preoperative risk factors recorded at the time of listing and immediately before transplantation were analyzed. Outcome variables included hospital mortality rates, bacterial or fungal sepsis, and the need for renal support., Results: The overall hospital mortality rate was 15.7%. Patients who were in the intensive care unit immediately before transplantation had the highest hospital mortality rate (32.6%; p = 0.006), incidence of bacterial sepsis (51%; p = 0.001), fungal infection rate (27.6%; p = 0.001), and need for renal support (38.7%; p = 0.001). Preoperative renal dysfunction was significantly associated with sepsis and was reflected in higher hospital mortality rates (29.5%; p = 0.011). Child-Pugh class C was associated with higher mortality rates (23.9%; p = 0.017), an increased incidence of bacterial (37.2%; p = 0.020) and fungal infection (20.3%; p = 0.049), and a 30.4% requirement for postoperative renal support (p = 0.004)., Conclusions: These results emphasize the need for earlier referral and transplantation in patients with advanced liver disease. Further studies are needed to refine identified risk profiles and devise strategies to decrease morbidity and mortality rates.

It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)