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Sara Dinis,1,2 Joana Tavares de Oliveira,3,4 Rui Pinto,1,5 Francisco Cruz,1,5 CA Tony Buffington,6 Paulo Dinis1,5 1Faculty of Medicine, University of Porto, 2Department of Obstetrics and Gynecology, Hospital de São João, Porto, 3Faculty of Veterinary Medicine, ULHT, Lisbon, 4Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, 5Department of Urology, Hospital de São João, Porto, Portugal; 6Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, OH, USA Abstract: Interstitial cystitis, presently known as bladder pain syndrome, has been recognized for over a century but is still far from being understood. Its etiology is unknown and the syndrome probably harbors different diseases. Autoimmune dysfunction, urothelial leakage, infection, central and peripheral nervous system dysfunction, genetic disease, childhood trauma/abuse, and subsequent stress response system dysregulation might be implicated. Management is slowly evolving from a solo act by the end-organ specialist to a team approach based on new typing and phenotyping of the disease. However, oral and invasive treatments are still largely aimed at the bladder and are based on currently proposed pathophysiologic mechanisms. Future research will better define the disease, permitting individualization of treatment. Keywords: bladder pain syndrome, concept, treatment

Carotid bodies (CBs) are metabolic sensors whose dysfunction is involved in the genesis of dysmetabolic states. Ageing induces significant alterations in CB function also prompting to metabolic deregulation. On the other hand, metabolic disease can accelerate ageing processes. Taking these into account, we evaluated the effect of long-term hypercaloric diet intake and CSN resection on age-induced dysmetabolism and CB function. Experiments were performed in male Wistar rats subjected to 14 or 44 weeks of high-fat high-sucrose (HFHSu) or normal chow (NC) diet and subjected to either carotid sinus nerve (CSN) resection or a sham procedure. After surgery, the animals were kept on a diet for more than 9 weeks. Metabolic parameters, basal ventilation, and hypoxic and hypercapnic ventilatory responses were evaluated. CB type I and type II cells, HIF-1α and insulin receptor (IR), and GLP-1 receptor (GLP1-R)-positive staining were analyzed by immunofluorescence. Ageing decreased by 61% insulin sensitivity in NC animals, without altering glucose tolerance. Short-term and long-term HFHSu intake decreased insulin sensitivity by 55 and 62% and glucose tolerance by 8 and 29%, respectively. CSN resection restored insulin sensitivity and glucose tolerance. Ageing decreased spontaneous ventilation, but short-term or long-term intake of HFHSu diet and CSN resection did not modify basal ventilatory parameters. HFHSu diet increased hypoxic ventilatory responses in young and adult animals, effects attenuated by CSN resection. Ageing, hypercaloric diet, and CSN resection did not change hypercapnic ventilatory responses. Adult animals showed decreased type I cells and IR and GLP-1R staining without altering the number of type II cells and HIF-1α. HFHSu diet increased the number of type I and II cells and IR in young animals without significantly changing these values in adult animals. CSN resection restored the number of type I cells in HFHSu animals and decreased IR-positive staining in all the groups of animals, without altering type II cells, HIF-1α, or GLP-1R staining. In conclusion, long-term hypercaloric diet consumption exacerbates age-induced dysmetabolism, and both short- and long-term hypercaloric diet intakes promote significant alterations in CB function. CSN resection ameliorates these effects. We suggest that modulation of CB activity is beneficial in exacerbated stages of dysmetabolism.

Hypoparathyroidism is a rare endocrine disorder and its main cause is cervical surgery such as thyroidectomy. The incidence of hypoparathyroidism after total thyroidectomy varies, and is reported to be between 0.3 and 6.3%. In terms of brain imaging, hypoparathyroidism can cause calcification mainly of the basal ganglia, with other areas rarely affected. Concerning extracerebral calcification, few studies have investigated the prevalence of visceral calcifications. We describe a case of a woman with secondary hypocalcaemia who presented with a transient ischaemic attack (TIA) and the investigation revealed an extensive calcinosis of the brain and the vascular structures responsible for the event.

Abstract In this paper, we provide secrecy metrics applicable to physical-layer coding techniques with finite blocklengths over Gaussian and fading wiretap channel models and analyze their secrecy performance over several cases of concatenated code designs. Our metrics go beyond some of the known practical secrecy measures, such as bit error rate and security gap, so as to make lower bound probabilistic guarantees on error rates over short blocklengths both preceding and following a secrecy decoder. Our techniques are especially useful in cases where application of traditional information-theoretic security measures is either impractical or simply not yet understood. The metrics can aid both practical system analysis, including cryptanalysis, and practical system design when concatenated codes are used for physical-layer security. Furthermore, these new measures fill a void in the current landscape of practical security measures for physical-layer security coding and may assist in the wide-scale adoption of physical-layer techniques for security in real-world systems. We also show how the new metrics provide techniques for reducing realistic channel models to simpler discrete memoryless wiretap channel equivalents over which existing secrecy code designs may achieve information-theoretic security.

Introduction: Energy drinks are youth-targeted beverages that contain high amounts of caffeine and other stimulants. A number of deleterious health effects associated with consumption of these drinks have already been reported. Despite the health concerns, energy drinks research has been sparse, especially at younger ages. The main purpose of this study was to determine the prevalence of energy drinks consumption and patterns of use among adolescents. Materials and Methods: Cross-sectional study of students aged between 11 – 17 years-old attending four public schools in Braga, cluster sampled. A self-administrated questionnaire was used to access sociodemographic data, self-reported academic performance as well as energy drinks consumption patterns, attitudes, awareness and associated symptoms. Results: In a total of 1414 adolescents studied (mean age 15.1 ± 1.5 years; 53.9% were females), 56.7% reported to have used energy drinks at least once (62.5% in males; 52.1% in females). Of those, 34% described a regular consumption (at least once a month) and 14.1% a weekly consumption. The most common reasons for energy drinks consumption were the pleasant taste (49%), desire to increase global energy (35%) or sports performance (33%). On average, energy drinks users were older compared with non-users. Energy drinks consumption was associated with male gender and with self-reported worse academic performance. Approximately onethird experienced at least one symptom after consumption. In addition, 39.9% of energy drinks consumers reported mixing those with alcohol. Discussion: Consumption of energy drinks has been increasing. The prevalence found for its consumption in this study is similar to that reported in the literature. Knowledge about motivation, general awareness of the risks or other variables related to consumption of these drinks might allow a better characterization of this behavior. Conclusion: This study showed a high prevalence of energy drinks consumption among adolescents from a city in Northern Portugal, with self-reported symptoms after consumption and common concomitant use of alcohol.

Digitalization in education sphere is the new paradigm of high technologies development. The article proves that digital technologies are relevant and widely used in various areas of society: management, economic relations, science and education. However, digitalization of the educational process is of particular importance, because the several factors such an advance of the quality and relevant experience in this sphere. Today, important transformation processes are taking place in the field of education: electronic textbooks, Internet portals, databases of information needs are spreading, systems of online courses and distance learning are actively developing.

Objectives: We aimed to identify clinical and serological predictors of myositis in mixed connective tissue disease (MCTD)., Methods: We performed a nationwide, retrospective, multicentre study including adult-onset MCTD patients fulfilling at least one of the following diagnostic criteria: Sharp's, Kasukawa, Alarcón-Segovia, or Kahn's. Univariate analysis was performed using Chi-square, Fisher exact, Student's t or Mann-Whitney U tests, as appropriate. Multivariate analysis was performed using binary logistic regression., Results: Ninety-eight patients were included. Myositis was observed in 43.9% of patients, of whom 60.5% had myositis at disease onset. Proximal muscle weakness was described in 30 patients with muscle involvement (70%). Gastrointestinal involvement was identified in 28% and respiratory involvement in 29% of myositis patients. In the same subgroup of patients, 41.7% had a myopathic pattern on electromyography, and 47.1% had histological myositis features in the muscle biopsy. Fever (OR=6.96, p=0.022) was an independent predictor of myositis, regardless of sex, age at diagnosis, ancestry, and respiratory involvement. African ancestry (OR=8.39, p=0.019), leukopenia at the disease onset (OR 6.24, p=0.021), and younger age at diagnosis (OR=1.07/year, p=0.035) were identified as independent predictors of myositis at disease onset, regardless of sex and scleroderma pattern in capillaroscopy., Conclusions: Myositis is a common manifestation of MCTD, even at the disease onset. African ancestry, leukopenia at the disease onset, younger age at diagnosis, and fever should prompt a thorough evaluation for myositis.

Interstitial lung disease (ILD) frequently complicates mixed connective tissue disease (MCTD) and contributes to increased mortality. We aimed to identify predictors of ILD in MCTD patients. This is a nationwide, multicentre, retrospective study including patients with an adult-onset MCTD clinical diagnosis who met Sharp's, Kasukawa, Alarcón-Segovia, or Kahn's diagnostic criteria and had available chest high-resolution computed tomography (HRCT) data. Univariate and multivariate analyses were conducted. We included 57 MCTD patients, with 27 (47.4%) having ILD. Among ILD patients, 48.1% were asymptomatic, 80.0% exhibited a restrictive pattern on pulmonary function tests, and 81.5% had nonspecific interstitial pneumonia on chest HRCT. Gastroesophageal involvement (40.7% vs. 16.7%, p = 0.043) and lymphadenopathy at disease onset (22.2% vs. 3.3%, p = 0.045) were associated with ILD. Binary logistic regression identified lymphadenopathy at disease onset (OR 19.65, 95% CI: 1.91-201.75, p = 0.012) and older age at diagnosis (OR 1.06/year, 95% CI: 1.00-1.12, p = 0.046) as independent ILD predictors, regardless of gender and gastroesophageal involvement. This study is the first to assess a Portuguese MCTD cohort. As previously reported, it confirmed the link between gastroesophageal involvement and ILD in MCTD patients. Additionally, it established that lymphadenopathy at disease onset and older age at diagnosis independently predict ILD in MCTD patients.

Introduction/objectives: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis., Method: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed., Results: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015)., Conclusions: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Aims: To characterise the idiopathic inflammatory myopathies (IIM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/myositis) and the patients in its cohort., Methods: Reuma.pt is a web-based system with standardised patient files gathered in a registry. This was a multicentre open cohort study, including patients registered in Reuma.pt/myositis up to January 2022., Results: Reuma.pt/myositis was designed to record all relevant data in clinical practice and includes disease-specific diagnosis and classification criteria, clinical manifestations, immunological data, and disease activity scores. Two hundred eighty patients were included, 71.4% female, 89.4% Caucasian, with a median age at diagnosis and disease duration of 48.9 (33.6-59.3) and 5.3 (3.0-9.8) years. Patients were classified as having definite (N=57/118, 48.3%), likely (N=23/118, 19.5%), or possible (N=2/118, 1.7%) IIM by 2017 EULAR/ACR criteria. The most common disease subtypes were dermatomyositis (DM, N=122/280, 43.6%), polymyositis (N=59/280, 21.1%), and myositis in overlap syndromes (N=41/280, 14.6%). The most common symptoms were proximal muscle weakness (N=180/215, 83.7%) and arthralgia (N=127/249, 52.9%), and the most common clinical signs were Gottron's sign (N=75/184, 40.8%) and heliotrope rash (N=101/252, 40.1%). Organ involvement included lung (N=78/230, 33.9%) and heart (N=11/229, 4.8%) involvements. Most patients expressed myositis-specific (MSA, N=158/242, 65.3%) or myositis-associated (MAA, 112/242, 46.3%) antibodies. The most frequent were anti-SSA/SSB (N=70/231, 30.3%), anti-Jo1 (N=56/236, 23.7%), and anti-Mi2 (N=31/212, 14.6%). Most patients had a myopathic pattern on electromyogram (N=101/138, 73.2%), muscle oedema in magnetic resonance (N=33/62, 53.2%), and high CK (N=154/200, 55.0%) and aldolase levels (N=74/135, 54.8%). Cancer was found in 11/127 patients (8.7%), most commonly breast cancer (N=3/11, 27.3%). Most patients with cancer-associated myositis had DM (N=8/11, 72.7%) and expressed MSA (N=6/11) and/or MAA (N=3/11). The most used drugs were glucocorticoids (N=201/280, 71.8%), methotrexate (N=117/280, 41.8%), hydroxychloroquine (N=87/280, 31.1%), azathioprine (N=85/280, 30.4%), and mycophenolate mofetil (N=56/280, 20.0%). At the last follow-up, there was a median MMT8 of 150 (142-150), modified DAS skin of 0 (0-1), global VAS of 10 (0-50) mm, and HAQ of 0.125 (0.000-1.125)., Conclusions: Reuma.pt/myositis adequately captures the main features of inflammatory myopathies' patients, depicting, in this first report, a heterogeneous population with frequent muscle, joint, skin, and lung involvements.

Background: This study assessed the effectiveness of the NEVERMIND e-health system, consisting of a smart shirt and a mobile application with lifestyle behavioural advice, mindfulness-based therapy, and cognitive behavioural therapy, in reducing depressive symptoms among patients diagnosed with severe somatic conditions. Our hypothesis was that the system would significantly decrease the level of depressive symptoms in the intervention group compared to the control group., Methods: This pragmatic, randomised controlled trial included 425 patients diagnosed with myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants were recruited from hospitals in Turin and Pisa (Italy), and Lisbon (Portugal), and were randomly assigned to either the NEVERMIND intervention or to the control group. Clinical interviews and structured questionnaires were administered at baseline, 12 weeks, and 24 weeks. The primary outcome was depressive symptoms at 12 weeks measured by the Beck Depression Inventory II (BDI-II). Intention-to-treat analyses included 425 participants, while the per-protocol analyses included 333 participants. This trial is registered in the German Clinical Trials Register, DRKS00013391., Findings: Patients were recruited between Dec 4, 2017, and Dec 31, 2019, with 213 assigned to the intervention and 212 to the control group. The sample had a mean age of 59·41 years (SD=10·70), with 44·24% women. Those who used the NEVERMIND system had statistically significant lower depressive symptoms at the 12-week follow-up (mean difference=-3·03, p <0·001; 95% CI -4·45 to -1·62) compared with controls, with a clinically relevant effect size (Cohen's d =0·39)., Interpretation: The results of this study show that the NEVERMIND system is superior to standard care in reducing and preventing depressive symptoms among patients with the studied somatic conditions., Funding: The NEVERMIND project received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 689691., Competing Interests: BM declares that he is employed by Gaia AG, the developer and owner of Deprexis, an internet-based intervention for depression, which is offered selectively to patients within the context of the NEVERMIND system. Other authors declare that they have no competing interests., (© 2022 The Authors.)

Objectives: To understand the influence of the white coat on patient satisfaction, opinions about medical clothing, perception about confidence, empathy and medical knowledge and the satisfaction and comfort level of physicians in consultation., Setting: An interventional study was conducted with a representative sample of the population attending primary care in central Portugal., Participants: The sample was composed by 286 patients divided into two groups exposed or not to a doctor wearing a white coat. The first and last patients in consultation every day for 10 consecutive days were included., Interventions: Every other day the volunteer physicians consulted with or without the use of a white coat. At the end of the consultation, a questionnaire was distributed to the patient with simple questions with a Likert scale response, the Portuguese version of the 'Trust in physician' scale and the Jefferson Scale of Patient Perceptions of Physician Empathy - Portuguese Version (JSPPPE-VP scale). A questionnaire was also distributed to the physician., Outcomes: Planned and measured primary outcomes were patient satisfaction, trust and perception about empathy and secondary outcomes were opinion about medical clothing, satisfaction and comfort level of physicians in consultation., Results: The sample was homogeneous in terms of sociodemographic variables. There were no statistically significant differences between the groups in terms of satisfaction, trust, empathy and knowledge perceived by the patients. There were differences in the opinion of the patients about the white coat, and when the physician was wearing the white coat this group of patients tended to think that this was the only acceptable attire for the physician (p<0.001). But when the family physician was in consultation without the white coat, this group of patients tended to agree that communication was easier (p=0.001)., Conclusions: There was no significant impact of the white coat in patient satisfaction, empathy and confidence in the family physician., Trial Registration Number: ClinicalTrials.gov ID number: NCT03965416., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Depressive symptoms are common in individuals suffering from severe somatic conditions. There is a lack of interventions and evidence-based interventions aiming to reduce depressive symptoms in patients with severe somatic conditions. The aim of the NEVERMIND project is to address these issues and provide evidence by testing the NEVERMIND system, designed to reduce and prevent depressive symptoms in comparison to treatment as usual., Methods: The NEVERMIND study is a parallel-groups, pragmatic randomised controlled trial to assess the effectiveness of the NEVERMIND system in reducing depressive symptoms among individuals with severe somatic conditions. The NEVERMIND system comprises a smart shirt and a user interface, in the form of a mobile application. The system is a real-time decision support system, aiming to predict the severity and onset of depressive symptoms by modelling the well-being condition of patients based on physiological data, body movement, and the recurrence of social interactions. The study includes 330 patients who have a diagnosis of myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants are randomised in blocks of ten to either the NEVERMIND intervention or treatment as usual as the control group. Clinical interviews and structured questionnaires are administered at baseline, at 12 weeks, and 24 weeks to assess whether the NEVERMIND system is superior to treatment as usual. The endpoint of primary interest is Beck Depression Inventory II (BDI-II) at 12 weeks defined as (i) the severity of depressive symptoms as measured by the BDI-II. Secondary outcomes include prevention of the onset of depressive symptoms, changes in quality of life, perceived stigma, and self-efficacy., Discussion: There is a lack of evidence-based interventions aiming to reduce and prevent depressive symptoms in patients with severe somatic conditions. If the NEVERMIND system is effective, it will provide healthcare systems with a novel and innovative method to attend to depressive symptoms in patients with severe somatic conditions., Trial Registration: DRKS00013391. Registered 23 November 2017.