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Doentes com passado de tuberculose que apresentam sequelas do parênquima pulmonar e deformidade da parede torácica têm um risco acrescido para insuficiência respiratória com hipoxemia e hipercápnia. Justifica-se nestes casos a terapêutica combinada com oxigénio e ventilação mecânica não invasiva. Este estudo teve como objectivo avaliar a opção terapêutica com melhor taxa de sobrevida em doentes com deformidade da parede torácica pós-tuberculose e insuficiência respiratória. Foram incluídos 188 doentes entre 1996 e 2004, seguidos prospectivamente até Outubro 2006, sendo a mortalidade a principal variável. Destes, 103 iniciaram apenas oxigenoterapia de longa duração e a 85 foi prescrito ventilação, dos quais 15 casos receberam também terapêutica com O2. A vasta maioria fez ventilação não invasiva e apenas 2 casos receberam ventilação pela traqueostomia.. A análise dos resultados mostrou uma melhoria estatisticamente significativa (p

Resumo: Doentes com passado de tuberculose que apresentam sequelas do parênquima pulmonar e deformidade da parede torácica têm um risco acrescido para insuficiência respiratória com hipoxemia e hipercápnia. Justifica-se nestes casos a terapêutica combinada com oxigénio e ventilação mecânica não invasiva.Este estudo teve como objectivo avaliar a opção terapêutica com melhor taxa de sobrevida em doentes com deformidade da parede torácica pós-tuberculose e insuficiência respiratória.Foram incluídos 188 doentes entre 1996 e 2004, seguidos prospectivamente até Outubro 2006, sendo a mortalidade a principal variável. Destes, 103 iniciaram apenas oxigenoterapia de longa duração e a 85 foi prescrito ventilação, dos quais 15 casos receberam também terapêutica com O2. A vasta maioria fez ventilação não invasiva e apenas 2 casos receberam ventilação pela traqueostomia.A análise dos resultados mostrou uma melhoria estatisticamente significativa (p

Introduction: Our retrospective study evaluates the impact of time from diagnosis to treatment (TDT) on outcomes of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated within the Veterans Health Administration (VHA)., Methods: VHA patients diagnosed with DLBCL between 2011 and 2019 were included, while those with primary central nervous system lymphoma were excluded. The median overall survival and progression-free survival were estimated with the Kaplan-Meier method. Univariate, bivariate, and multivariable analyses were performed using the Cox proportional hazards model. The odds ratio for refractory outcomes was calculated using logistic regression., Results: A total of 2448 patients were included. The median time from diagnosis to treatment of the cohort was 19 days. When comparing median progression-free survival, median overall survival, and the 2-year overall survival between the group that started treatment within 1 week and each of the other groups individually, there was a significant difference favoring improved survival in all groups with a TDT longer than 1 week (P < .0001). These patients also had a lower odds ratio for refractory outcomes. On multivariable analysis, TDT remained an independent prognostic factor., Conclusion: Our study shows that a TDT equal to or less than 1 week is associated with adverse clinical factors, worse outcomes, and response in DLBCL, even after adjusting for multiple known poor prognostic factors. This was the first time that response to first-line therapy was correlated to time to treatment. Our findings support ongoing efforts to improve currently standardized prognostic tools and the incorporation of TDT into clinical trials to avoid selection bias., Competing Interests: Disclosure Zohra Nooruddin: Research support from AstraZeneca. Consulting fees from Gilead Sciences Inc; Supreet Kaur: Speaker support from Eli Lilly. The other authors report that there are no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Previous studies on the association between abdominal and general obesity and respiratory disease have provided conflicting results., Aims and Objectives: We aimed to explore the associations of abdominal obesity with respiratory symptoms, asthma, and chronic obstructive pulmonary disease independently from general obesity in women and men., Methods: This cross-sectional study was based on the Respiratory Health in Northern Europe (RHINE) III questionnaire (n = 12 290) conducted in 2010-2012. Abdominal obesity was self-measured waist circumference using a sex-specific standard cut-off point: ≥102 cm in males and ≥88 cm in females. General obesity was defined as self-reported BMI ≥30.0 kg/m 2 ., Results: There were 4261 subjects (63% women) with abdominal obesity and 1837 subjects (50% women) with general obesity. Both abdominal and general obesity was independent of each other and associated with respiratory symptoms (odds ratio (OR) from 1.25 to 2.00)). Asthma was significantly associated with abdominal and general obesity in women, OR (95% CI) 1.56 (1.30-1.87) and 1.95 (1.56-2.43), respectively, but not in men, OR 1.22 (0.97-3.17) and 1.28 (0.97-1.68) respectively. A similar sex difference was found for self-reported chronic obstructive pulmonary disease., Conclusions: General and abdominal obesity were independent factors associated with respiratory symptoms in adults. Asthma and chronic obstructive pulmonary disease were independently linked to abdominal and general obesity in women but not men., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Sipuleucel-T is an autologous cellular immunotherapy indicated for patients with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer (mCRPC). Since radiation therapy (RT) can suppress bone marrow function and immune responses, previous studies evaluating sipuleucel-T excluded patients who received RT less than or equal to 28 days prior to sipuleucel-T therapy. Recent evidence suggests that RT may act synergistically with immunotherapy to enhance and broaden antitumor immune response., Methods: Patients who met standard criteria for sipuleucel-T were randomized to receive sipuleucel-T alone (Arm A) or sipuleucel-T initiated 1 week after completing sensitizing RT to single metastatic site (Arm B). RT was delivered at 300cGy/day to 3000 cGy total. The primary endpoint was the ability to safely combine sipuleucel-T preceded by RT and generate sipuleucel-T with adequate product immune activation parameters. Secondary endpoints included the measurement of systemic immune responses to prostatic acid phosphatase (PAP), a target for sipuleucel-T immune therapy and PA20204 (recombinant fusion protein utilized in the generation of sipuleucel-T)., Results: 51 pts were enrolled, 2 did not receive any sipuleucel-T because of vascular access problems and were excluded. 24 were treated on Arm A, 25 on Arm B. 47/49 patients received all 3 sipuleucel-T infusions. Median age was 66 yrs (range 45-90). Sipuleucel-T product parameters including: total nucleated cell (TNC) count, antigen presenting cell (APC) count were similar in both groups. Cumulative APC upregulation was higher in Arm A. 1 patient in Arm A demonstrated PSA response. Median progression free survival (PFS) was 2.46 months on Arm A and 3.65 months on Arm B (p = 0.06). Both arms showed similar increases in humoral responses to PA2024 and PAP. IFN-ƴ ELISPOT T-cell activation responses to PA20204 were observed in both arms, but were more robust in the Arm A (p = 0.028). Both arms were well-tolerated, with fatigue as the most common grade 2 adverse event (1 patient in Arm A and 3 patients in Arm B)., Conclusions: Sensitizing RT completed 1 week before generation of sipuleucel-T did not affect the majority of product parameters and the ability to deliver sipuleucel-T therapy. RT did not enhance the humoral and cellular responses associated with sipuleucel-T therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea., Methods: Twenty-two patients undergoing palatal surgery due to snoring and sleep apnea were investigated for a swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring subjects were included as control subjects. Tissue samples from the soft palate at the base of the uvula were obtained in all patients and control subjects. Nerves and muscle were analyzed with immunohistochemical and morphologic methods, and the findings were correlated with swallowing function and degree of sleep apnea., Results: In the soft palate of patients, nerve fascicles exhibited a significantly lower density of axons (5.4 vs 17.9 × 10 -3 axons/μm 2 ; P = .02), a smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and a larger number of circular shaped Schwann cells lacking central axons (43.0% vs 12.7%; P < 0.001) compared with control subjects. The low density of axons was significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed in patients compared with control subjects (11.3 ± 4.2% vs 4.8 ± 2.4%; P = .02)., Conclusions: Axon degeneration in preterminal nerves of the soft palate is associated with pharyngeal dysfunction in snorers and patients with sleep apnea. The most likely cause for the nerve injuries is traumatic snoring vibrations and tissue stretch, leading to swallowing dysfunction and increased risk for upper airway obstruction during sleep., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Between 12 July and 29 September 2013, 29 individuals in five Canadian provinces became ill following infection with the same strain of Escherichia coli O157:H7 as defined by molecular typing results. Five case patients were hospitalized, and one died. Twenty-six case patients (90%) reported eating Gouda cheese originating from a dairy plant in British Columbia. All of the 22 case patients with sufficient product details available reported consuming Gouda cheese made with raw milk; this cheese had been produced between March and July 2013 and was aged for a minimum of 60 days. The outbreak strain was isolated from the implicated Gouda cheese, including one core sample obtained from an intact cheese wheel 83 days after production. The findings indicate that raw milk was the primary source of the E. coli O157:H7, which persisted through production and the minimum 60-day aging period. This outbreak is the third caused by E. coli O157:H7 traced to Gouda cheese made with raw milk in North America. These findings provide further evidence that a 60-day ripening period cannot ensure die-off of pathogens that might be present in raw milk Gouda cheese after production and have triggered an evaluation of processing conditions, physicochemical parameters, and options to mitigate the risk of E. coli O157:H7 infection associated with raw milk Gouda cheese produced in Canada.

Understanding consumers' food safety practices and knowledge supports food safety education for the prevention of foodborne illness. The objective of this study was to describe Canadian consumer food safety practices and knowledge. This study identifies demographic groups for targeted food safety education messaging and establishes a baseline measurement to assess the effectiveness of food safety interventions over time. Questions regarding consumer food safety practices and knowledge were included in a population-based telephone survey, Foodbook, conducted from November 2014 to March 2015. The results were analyzed nationally by age group and by gender. The results showed that approximately 90% of Canadians reported taking the recommended cleaning and separating precautions when handling raw meat to prevent foodborne illness. Only 29% of respondents reported using a food thermometer when cooking any meat, and even fewer (12%) reported using a food thermometer for small cuts of meat such as chicken pieces. The majority (>80%) of Canadians were aware of the foodborne illness risks related to chicken and hamburger, but fewer (<40%) were aware of the risks related to frozen chicken nuggets, alfalfa sprouts, soft unpasteurized cheese, and unpasteurized juices. Generally, men were less likely to follow cooking instructions on packaging and took fewer steps to prevent cross-contamination than women. The youngest (18 to 29 years) age group was less likely to take steps to avoid cross-contamination and was less aware of the risks associated with eating an undercooked hamburger. The oldest (60+ years) respondents were less likely to be aware of the risks associated with raw eggs, alfalfa sprouts, and unpasteurized juice than the middle (30 to 59 years) age group. As a priority, food safety education in Canada should focus on increasing people's awareness of high-risk foods, specifically foods for which the awareness of risk found in this study was low; targeting messaging to demographic groups as appropriate; and promoting the use of food thermometers when cooking meat and poultry.

Background: Despite the well-known association between asthma and rhinitis, in Swedish adults the prevalence of rhinitis rose from 22% to 31% between 1990 and 2008 while asthma prevalence was unchanged. We tested whether the association of rhinitis with asthma was stable over time using the same population-based databases., Methods: Two surveys of adults (20-44 years) living in three regions of Sweden, carried out in 1990 (n = 8982) and 2008 (n = 9156) were compared. Identical questions regarding respiratory symptoms, asthma and rhinitis were used. Asthmatic wheeze: Wheeze with breathlessness apart from colds. Current asthma: Asthma attacks and/or asthma medication use., Results: Subjects with rhinitis had level time trends in asthmatic wheeze, current asthma and most nocturnal respiratory symptoms between 1990 and 2008, adjusted for age, sex, area and smoking. Any wheeze however decreased slightly. In never-smokers asthma symptoms were similarly associated with rhinitis in 1990 and 2008: any wheeze OR 4.0 vs. 4.4 (p = 0.339); asthmatic wheeze OR 6.0 vs. 5.9 (p = 0.937); and current asthma OR 9.6 vs. 7.7 (p = 0.213). In the whole population there were decreases in the asthma symptoms most closely associated to smoking, which decreased by half 1990-2008. Conversely current asthma, which was strongly associated with rhinitis and not with smoking, increased (p < 0.001)., Conclusions: The association of rhinitis with asthma was stable between 1990 and 2008. The pattern in the time trends of asthma outcomes strongly suggests that decreased smoking counterbalanced the driving effect of increased rhinitis on asthma prevalence. The findings illustrate the public health benefits of decreased smoking., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Psychological factors such as anxiety and depression are prevalent in patients with asthma. The purpose of this study was to investigate the relationship between respiratory symptoms and psychological status and to estimate the importance of psychological status in comparison with other factors that are known to be associated with respiratory symptoms. This study included 2270 subjects aged 20-44 (52% female) from Sweden, Iceland, and Norway. Each participant underwent a clinical interview including questions on respiratory symptoms. Spirometry and methacholine challenge were performed. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Eighty-two percent of the subjects reported no anxiety or depression whatsoever, 11% reported anxiety, 2.5% depression and 4% reported both anxiety and depression. All respiratory symptoms, such as wheezing, breathlessness and nightly symptoms, were more common, at a statistically significant level, in participants who had depression and anxiety, even after adjusting for confounders (ORs 1.33-1.94). The HADS score was the most important determinant for nightly symptoms and attacks of breathlessness when at rest whereas bronchial responsiveness was the most important determinant for wheezing, and breathlessness when wheezing. The probability of respiratory symptoms related to HADS score increased with increasing HADS score for all respiratory symptoms. In conclusion, there is a strong association between respiratory symptoms and psychological status. There is therefore a need for interventional studies designed to improve depression and anxiety in patients with respiratory symptoms., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We have used solid-phase chemistry to synthesize proteins equivalent to a human ubiquitin precursor (ubiquitin-52-amino-acid ribosomal protein fusion; UBICEP52) and representative of isopeptide-linked ubiquitin-protein conjugates [ubiquitin-(epsilonN)-lysine]; these proteins were precisely cleaved by a purified recombinant Drosophila deubiquitinating enzyme (DUB), UCH-D. Along with the previously synthesized ubiquitin-(alphaN)-valine, these synthetic proteins were used as substrates to assess the catalytic capacities of a number of diverse DUBs expressed in Escherichia coli: human HAUSP; mouse Unp; and yeast Ubps 1p, 2p, 3p, 6p, 11p, and 15p and Yuh1p. Distinct specificities of these enzymes were detected; notably, in addition to UCH-D, isopeptidase activity [ubiquitin-(epsilonN)-lysine cleavage] was only associated with Yuh1p, Unp, Ubp1p, and Ubp2p. Additionally, human placental 26S proteasomes were only able to cleave UBICEP52 and ubiquitin-(epsilonN)-lysine, suggesting that 26S proteasome-associated DUBs are class II-like. This work demonstrates that the synthetic approach offers an alternative to recombinant methods for the production of small proteins in vitro., (Copyright 1999 Academic Press.)

Ubiquitin is expressed in eukaryotic cells as precursors, fused via its carboxyl terminus either to other ubiquitin sequences in linear polyubiquitin arrays or to specific ribosomal proteins. In some of the polyubiquitin fusions a single amino acid (e.g., valine in humans) is attached to the carboxyl terminus. These gene products are rapidly (probably cotranslationally) cleaved by ubiquitin carboxyl-terminal hydrolase (UCH) enzymes; therefore, although ubiquitin precursors are suitable substrates for assays of UCH activity, they are difficult to isolate from nucleated cells. While the recombinant approach allows the production of ubiquitin precursors in prokaryotic cells (which do not contain the ubiquitin system), proteins produced in this manner require purification and may also be susceptible to modification by bacterial enzymes, e.g., adventitious proteolysis. As an alternative we have chemically synthesized human ubiquitin-valine. In the assay described here the cleavage of ubiquitin-valine to ubiquitin (77 and 76 residue proteins, respectively) by a purified recombinant Drosophila UCH was monitored by capillary electrophoresis. Mass spectrometry verified the precise cleavage of ubiquitin-valine, confirming that this synthetic protein is a UCH substrate. Synthetic ubiquitin-valine may serve as a generic substrate for UCHs allowing the purification and identification of new members of this enzyme family.

The efficacy of a 10-day course of bovine colostrum with high antibody titre against the four known human rotavirus serotypes in protecting children against rotavirus infection was examined in patients admitted to hospital. Children aged 3 to 15 months were blocked in pairs according to ward accommodation (ie, isolation or open area). Each block contained 1 treated and 1 control child. The allocation to treatment or control (an artificial infant formula) was randomised. 9 of 65 control children but none of 55 treated children acquired rotavirus infection during the treatment period (p less than 0.001). The importance of protecting against rotavirus infection was highlighted by the fact that parents of symptomatic rotavirus-positive children sought medical attention seven times more often than did parents of symptomatic rotavirus-negative children (p less than 0.05).