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Introduction: Despite treatment with hypothermia, 40% of newborns with hypoxic-ischaemic encephalopathy die or suffer moderate to severe disability. Near-infrared spectroscopy (NIRS) could be a useful, non-invasive tool to establish the prognosis. Objectives: To evaluate the prognostic value of NIRS in predicting neurodevelopmental outcomes at 18–36 months in newborns with hypoxic-ischaemic encephalopathy, and to establish the time points and cut-off values of regional cerebral oxygen saturation that exhibit the strongest correlation to these outcomes. Patients and methods: The study included all term newborns with hypoxic-ischaemic encephalopathy managed with hypothermia and NIRS between 2013 and 2016. We established 3 outcome categories: normal neurodevelopment, moderate disability and severe disability. Results: The sample comprised 28 newborns (median gestational age, 39 weeks; median birth weight, 3195 g). The median regional cerebral oxygen saturation increased from 65% to 85% at 48 h post birth. Neurodevelopmental outcomes were normal in 28.6%, while 35.7% developed moderate disability and 35.7% severe disability; 3 patients died. We found a statistically significant difference between groups at 48 h (P = .005) and after hypothermia (P = .03), with higher values in patients with disability. When we compared patients with severe disability group with the other groups, we found a statistically significant area under the ROC curve at 48 h of 0.872 (P = .001) applying a regional cerebral oxygen saturation cutoff of 83.5%. After hypothermia, regional cerebral oxygen saturation values below 66.0% (AUC, 0.794; P = .017) predicted normal development, while values above 82% (AUC, 0.881; P = .001) predicted severe disability. Conclusions: NIRS seems to be a valuable tool to predict neurodevelopmental outcomes in patients with hypoxic-ischaemic encephalopathy, even after hypothermia, with higher cerebral oxygen saturation values in patients with disability. Resumen: Introducción: A pesar del tratamiento con hipotermia, el 40% de los neonatos con encefalopatía hipóxico-isquémica fallecen o sufren discapacidad moderada-grave. La espectroscopia cercana al infrarrojo (NIRS) se propone como una herramienta útil y no invasiva para establecer el pronóstico. Objetivos: evaluar el valor pronóstico de la NIRS en el resultado del neurodesarrollo entre los 18–36 meses en neonatos con encefalopatía hipóxico-isquémica y establecer el tiempo y los puntos de corte de la saturación cerebral de oxígeno que mejor se relacionan con el pronóstico. Pacientes y métodos: Se incluyeron todos los neonatos a término con encefalopatía hipóxico-isquémica, sometidos a hipotermia y NIRS, entre 2013−2016. Con respeto al resultado, se constituyeron tres grupos: neurodesarrollo normal, discapacidad moderada y grave. Resultados: Se incluyeron 28 neonatos (edad gestacional mediana: 39 semanas; peso al nacimiento mediano: 3195 gramos). La saturación cerebral de oxígeno tendió a aumentar desde una mediana de 65% hasta 85%, a las 48 horas de vida. El resultado del neurodesarrollo fue normal en 28,6%, el 35,7% adquirió discapacidad moderada y el 35,7% discapacidad grave (tres fallecieron). Se halló una diferencia estadística entre los grupos a las 48 horas (p = 0,005) y después de la hipotermia (p = 0,03), con valores más altos en los pacientes con discapacidad. Teniendo en cuenta el grupo con discapacidad grave frente a los otros, la curva de ROC a las 48 horas resultó en un área debajo de la curva (AUC) significativa de 0,872 (p = 0,001), con un punto de corte de saturación cerebral de oxígeno de 83,5%. Después de la hipotermia, los valores de saturación cerebral de oxígeno por debajo del 66,0% (AUC 0,794; p = 0,017) predijeron el desarrollo normal mientras que valores por encima del 82% (AUC 0,881; p = 0,001) predijeron discapacidad grave. Conclusiones: El NIRS parece constituir una herramienta útil en la predicción del resultado del neurodesarrollo de pacientes con encefalopatía hipóxico-isquémica, incluso después de la hipotermia, con valores más altos de saturación cerebral de oxígeno en pacientes con discapacidad.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Centro Hospitalar Universitário Lisboa Central / Hospital Santa Marta With the gains in life expectancy of patients (P) with heart disease, population with cardiac implantable electronic devices (CIED) therapy for the treatment of heart failure and life-threatening arrhythmias has increasingly became a challenge, regarding the number of complications following an implantation. Aim: To analyze clinical outcomes of P with CIED participating in an integrated nursing approach in an outpatient clinic of a tertiary center. Methods: Systematic review of clinical follow-up data of P undergoing CIED implantation who were observed by a specialized nursing team after discharge. Data regarding complications related to the surgical wound, treatment, timings and outcomes were collected. Results: In 2020, out of 927 P treated with CIED in our center, 157 were referred to the nursing outpatient clinic due high risk features such as anticoagulation and frailty, previously identified surgical wound related complications or advanced hearth failure. The CIED observed were replaced devices (17%), cardioverter defibrillator (41%), cardiac resynchronization therapy with defibrillator (27%), pacemakers (11%), and event recorders (4%). In average, the first appointment took place 16 days after the procedure. In 73 cases, presenting with pocket complaints (hematoma - 34%, local edema or pain - 10%, wound scab - 36%, exteriorized suture or staple - 20%), the average number of days until medical discharge was 36 days, with an average of 5 appointments per patient. In this group, 42% were under oral coagulants, 38% under antiaggregant drugs and 11% under both. Treatment options included antibiotic prescription in 25% of the cases, cryotherapy in 22%, dressing of the surgical wound in 10% and absorbable suture or staple removal in 10%. Four P (0.43%) were submitted to complete system removal due to CIED infection. Conclusions: Surgical wound related complaints in CIED P are relatively common and represent a factor of morbidity and increase in public health spending. An integrated trained team may aid in the prompt identification and management of these complications.

Summary Objectives This review aims to analyze the available data, mainly the most recent, regarding L-carnitine supplementation and exercise performance, in order to understand if L-carnitine can still be considered an ergogenic supplement. Moreover, it also aims to briefly analyze other potential uses, more specifically the effects on weight loss, recovery after exercise and aging. News A literature search, using the online scientific databases PubMed and Scopus, was conducted to identify studies related to L-carnitine supplementation and athletic performance. The discovery that skeletal muscle carnitine content can be increased through oral supplementation in humans represented a significant progress in this area. More recently, due to this discovery, new research has been done to investigate whether L-carnitine supplementation could have an impact on fuel metabolism. However, the inconsistency of results led to a change in the focus of research, shifting towards the investigation of the impact L-carnitine could have on the process of recovery after exercise and on aging. Prospects and projects In future research, this new area needs to be more explored. Nevertheless, the study of the L-carnitine supplementation impact on fuel selection during exercise should continue and it is crucial to use athletes. Conclusion Despite some performance benefits have been demonstrated, more research needs to be done. Presently, the available data is still not enough to widely recommend the use of L-carnitine supplements with the aim of improving exercise performance.

Highlights • SARS-CoV-2 can infect multiple organs leading to their dysfunction, so a pleiotropic therapy would be advantageous. • MSC: MSC can simultaneously address injuries in multiple organs and promote their repair. • MSC, immunomodulators by excellence, may counteract infection and cytokine storm in COVID-19 patients. • MSC therapy is being tested in clinical trials for COVID-19 patients and proved to be safe and effective so far. • More clinical studies, addressing MSC use for COVID-19, with bigger cohorts and suitable controls are welcome., The devastating global impact of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has prompted scientists to develop novel strategies to fight Coronavirus Disease of 2019 (COVID-19), including the examination of pre-existing treatments for other viral infections in COVID-19 patients. This review provides a reasoned discussion of the possible use of Mesenchymal Stromal Cells (MSC) or their products as a treatment in SARS-CoV-2-infected patients. The main benefits and concerns of using this cellular therapy, guided by preclinical and clinical data obtained from similar pathologies will be reviewed. MSC represent a highly immunomodulatory cell population and their use may be safe according to clinical studies developed in other pathologies. Notably, four clinical trials and four case reports that have already been performed in COVID-19 patients obtained promising results. The clinical application of MSC in COVID-19 is very preliminary and further investigational studies are required to determine the efficacy of the MSC therapy. Nevertheless, these preliminary studies were important to understand the therapeutic potential of MSC in COVID-19. Based on these encouraging results, the United States Food and Drug Administration (FDA) authorized the compassionate use of MSC, but only in patients with Acute Respiratory Distress Syndrome (ARDS) and a poor prognosis. In fact, patients with severe SARS-CoV-2 can present infection and tissue damage in different organs, such as lung, heart, liver, kidney, gut and brain, affecting their function. MSC may have pleiotropic activities in COVID-19, with the capacity to fight inflammation and repair lesions in several organs.

BackgroundSeveral studies have investigated the acoustic effects of diagnosed anxiety and depression. Anxiety and depression are not characteristics of the typical aging process, but minimal or mild symptoms can appear and evolve with age. However, the knowledge about the association between speech and anxiety or depression is scarce for minimal/mild symptoms, typical of healthy aging. As longevity and aging are still a new phenomenon worldwide, posing also several clinical challenges, it is important to improve our understanding of non-severe mood symptoms’ impact on acoustic features across lifetime. The purpose of this study was to determine if variations in acoustic measures of voice are associated with non-severe anxiety or depression symptoms in adult population across lifetime.MethodsTwo different speech tasks (reading vowels in disyllabic words and describing a picture) were produced by 112 individuals aged 35-97. To assess anxiety and depression symptoms, the Hospital Anxiety Depression Scale (HADS) was used. The association between the segmental and suprasegmental acoustic parameters and HADS scores were analyzed using the linear multiple regression technique.ResultsThe number of participants with presence of anxiety or depression symptoms is low (>7: 26.8% and 10.7%, respectively) and non-severe (HADS-A: 5.4 ± 2.9 and HADS-D: 4.2 ± 2.7, respectively). Adults with higher anxiety symptoms did not present significant relationships associated with the acoustic parameters studied. Adults with increased depressive symptoms presented higher vowel duration, longer total pause duration and short total speech duration. Finally, age presented a positive and significant effect only for depressive symptoms, showing that older participants tend to have more depressive symptoms.ConclusionsNon-severe depression symptoms can be related to some acoustic parameters and age. Depression symptoms can be explained by acoustic parameters even among individuals without severe symptom levels.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. \ud \ud \ud METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. \ud \ud \ud FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. \ud \ud \ud INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. \ud \ud \ud FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Objective To identify the outcomes of physical function, physical fitness, training, and cuff parameters, used in BFRT in ACL rehabilitation. Methods This scoping review was initiated on April 25th, 2020, according to the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Relevant literature was identified searching three main concepts: BFRT, rehabilitation and ACL injury on MEDLINE (PubMed), CENTRAL of Cochrane Library, Web of Science and PEDro. Studies looking at adults with a primary ACL injury undergoing conservative or pre/post-surgery rehabilitation with BFR or BFRT, with physical fitness and physical function as outcomes or other physical outcomes were included. Results Sixty-eight articles were identified and six were included. One article was added through backward tracking. All studies used BFRT in the ACL injury surgical rehabilitation. Most studies evaluated physical fitness (muscular strength and volume) however, physical function was not considered a primary outcome. Training and cuff parameters were heterogeneously prescribed. Conclusion The existing evidence is not enough to draw definitive conclusions due to the heterogenous reported outcomes and parameters. Future investigation with standardized outcome measures and specific protocols are needed to draw conclusions on patients’ physical function, so BFRT can be used more effectively in clinical rehabilitation practice.

Introduction Chest pain is a very frequent reason for seeking medical care. When there is no obvious cause, patients are sometimes subjected to tests and treatments that may be unnecessary and potentially harmful. Mondor's disease is a rare but usually benign and self-limited entity characterized by thrombophlebitis in a specific region. Case report We report the clinical case of a 51-year-old man admitted to the emergency department with a 24-hour history of left chest pain with no other symptoms. Physical examination revealed a palpable subcutaneous cord-like structure that ultrasound confirmed to be thrombophlebitis of a superficial vein in the mammary region. Secondary causes were ruled out, and the condition resolved with ibuprofen and the application of local ice. Discussion Mondor's disease can be associated with neoplasms, trauma or hyperviscosity states, but it is mostly idiopathic. Usually, it resolves completely in 4-8 weeks without specific treatment. Because this infrequent diagnosis mainly relies on clinical findings, it is important that clinicians can recognize the syndrome. Learning points Mondor's disease is a rare but benign disease, with no proof that specific treatment, such as anticoagulation, is beneficial.It may be secondary to underlying disease as malignancy, vasculitis, trauma or hyperviscosity states, which should be excluded.Treatment in the majority of the cases is symptomatic, but if it is secondary Mondor's disease, the underlying problem should be investigated. Physicians should be aware of this condition in order to address patient concerns and avoid unnecessary treatments or investigations.

BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19, in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

The first clinical description of cannabinoid hyperemesis syndrome comes from an article by Allen et al. published in 2004. Since then, several publications have focused on its conceptualization and clinical approach, although it remains largely unknown among the medical community. This syndrome is characterized by the triad of chronic cannabinoid consumption, cyclic hyperemesis, and compulsive hot baths or showers for symptom relief. Abdominal pain and other symptoms may also occur. Its true prevalence is unknown, despite growing evidence that it is more frequent than previously thought. There are several hypotheses that aim to explain its pathogenesis, namely related to the cannabinoid and vanilloid receptors, the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Regarding its therapeutic approach, support measures could be justified in the acute phase (e.g. hydration), and there is evidence for the utilization of benzodiazepines (especially lorazepam), haloperidol and topical capsaicin for symptomatic relief. The only intervention that leads to the definite remission of symptoms is abstinence of cannabinoid use, with psychoeducation and adequate therapeutic guidance of the patient. Our knowledge about cannabinoid hyperemesis syndrome is still growing. The lack of awareness of the disease can lead to invasive and expensive diagnostic tests, multiple visits to the emergency department, and persistence of symptoms. This article aims to systematize the lines of clinical intervention of the disease and to promote a greater awareness of this entity among health professionals, allowing for a better identification and therapeutic approach of the condition.

Background: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. Methods: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 10 10 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT 50]; a microneutralisation assay [MNA 50, MNA 80, and MNA 90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Findings: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p80 and in 35 (100%) participants when measured in PRNT 50. After a booster dose, all participants had neutralising activity (nine of nine in MNA 80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R 2=0·67 by Marburg VN; p

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3, the most common dominant spinocerebellar ataxia (SCA) worldwide, is caused by over-repetition of a CAG repeat in the ATXN3/MJD1 gene, which translates into a polyglutamine tract within the ataxin-3 protein. There is no treatment for this fatal disorder. Despite evidence of the safety and efficacy of mesenchymal stromal cells (MSCs) in delaying SCA disease progression in exploratory clinical trials, unanticipated regression of patients to the status prior to treatment makes the investigation of causes and solutions urgent and imperative. In the present study, we compared the efficacy of a single intracranial injection with repeated systemic MSC administration in alleviating the MJD phenotype of two strongly severe genetic rodent models. We found that a single MSC transplantation only produces transient effects, whereas periodic administration promotes sustained motor behavior and neuropathology alleviation, suggesting that MSC therapies should be re-designed to get sustained beneficial results in clinical practice. Furthermore, MSC promoted neuroprotection, increased the levels of GABA and glutamate, and decreased the levels of Myo-inositol, which correlated with motor improvements, indicating that these metabolites may serve as valid neurospectroscopic biomarkers of disease and treatment. This study makes important contributions to the design of new clinical approaches for MJD and other SCAs/polyglutamine disorders.

Tumor thrombosis of the internal jugular vein (IJV) represents an uncommon event, usually in the setting of underlying thyroid neoplasms. Extraosseous plasmacytoma (EMP) with tumor thrombosis of the IJV has not yet been reported in the literature. We present a unique case of a plasmacytoma in the left parapharyngeal space with direct extension to the left IJV, documented with contrast enhanced computed tomography and US Doppler. Presence of avid thrombus enhancement allowed differentiation between tumoral extension and thrombothic changes. Keywords: Plasmacytoma, Jugular vein, Tumoral thrombus

Production of polyhydroxyalkanoates (PHAs) by open mixed microbial cultures (MMCs) has been attracting increasing interest as an alternative technology to PHA production by pure cultures, due to the potential for lower costs associated with the use of open systems (eliminating the requirement for sterile conditions) and the utilisation of cheap feedstock (industrial and agricultural wastes). Such technology relies on the efficient selection of an MMC enriched in PHA-accumulating organisms. Fermented cheese whey, a protein-rich complex feedstock, has been used previously to produce PHA using the feast and famine regime for selection of PHA accumulating cultures. While this selection strategy was found efficient when operated at relatively low organic loading rate (OLR, 2g-CODL-1d-1), great instability and low selection efficiency of PHA accumulating organisms were observed when higher OLR (ca. 6g-CODL-1d-1) was applied. High organic loading is desirable as a means to enhance PHA productivity. In the present study, a new selection strategy was tested with the aim of improving selection for high OLR. It was based on uncoupling carbon and nitrogen supply and was implemented and compared with the conventional feast and famine strategy. For this, two selection reactors were fed with fermented cheese whey applying an OLR of ca. 8.5g-CODL-1 (with 3.8g-CODL-1 resulting from organic acids and ethanol), and operated in parallel under similar conditions, except for the timing of nitrogen supplementation. Whereas in the conventional strategy nitrogen and carbon substrates were added simultaneously at the beginning of the cycle, in the uncoupled substrates strategy, nitrogen addition was delayed to the end of the feast phase (i.e. after exogenous carbon was exhausted). The two different strategies selected different PHA-storing microbial communities, dominated by Corynebacterium and a Xantomonadaceae, respectively with the conventional and the new approaches. The new strategy originated a more efficient PHA-production process than the conventional one (global PHA productivity of 6.09g-PHAL-1d-1 and storage yield of 0.96 versus 2.55g-PHAL-1d-1 and 0.86, respectively). Dissociation between the feast to famine length ratio (F/F) and storage efficiency was shown to be possible with the new strategy, allowing selection of an efficient PHA-storing culture with complex feedstock under high organic loading rates.

Over the last decade many organizations began to recognize that the implementation of Project Management (PM) practices was a necessity rather than an option. In order to improve the success of projects, organizations have been adopting specialized structures (normally called PM Offices or PMOs) that carry out the management of projects in a coordinated and centralized way. In recent years, several PMO models and functions have been proposed by many authors. The major challenge for most organizations is to decide which specific functions in a particular context should be implemented. In fact, PMOs roles and functions, though standardized and clearly defined in literature, vary in practice. The main goal of this research was to propose a set of functions for a supportive PMO in an engineering and construction company. For example, develop and implement a PM methodology, provide a set of tools to support PM, and develop PM competences.

Temporomandibular disorders (TMD) are a set of disorders related to the masticatory muscles, a temporomandibular joint and adjacent structures (articular pathology) [1, 2, 3, 4].

The identification process in cases of natural disasters and crimes is a necessity in every investigation process. With the technology evolving, new techniques have been developed in order to facilitate identification in an easier and efficient way. In edentulous individuals, dentures are one of the most valuable tools due to the incorporation of elements that can allow identification. In the last years, QR code have been studied for this purpose, since it presents more advantages than other methods. In order to minimize the size of a QR code, titanium and cobalt-chrome pieces were milled in different sizes. Two different ways of reading the QR codes were used. Despite not being capable to read the three different sizes, two of them were perfectly readable. The QR code use in dentures can play an important role, since the information included in it can save lives or help to identify human beings. However, more studies must be done in order to make this a common procedure.

Radiotherapy planning is a crucial task in cancer patients’ management. This task is, however, very time consuming and prone to a high intra and inter subject variance and human errors.

A 29-year-old HIV-infected man, on antiretroviral treatment with negative viral load and a low CD4+ T-cell count (344/mm3), presented with right eyelid ptosis and diplopia. On examination, right pupil was dilated, without reaction to light or accommodation. Extraocular movements were impaired in all directions, except abduction.

Polyglutamine (polyQ) diseases are a family of neurodegenerative disorders with very heterogeneous clinical presentations, although with common features such as progressive neuronal death. Thus, at the time of diagnosis patients might present an extensive and irreversible neuronal death demanding cell replacement or support provided by cell-based therapies. For this purpose stem cells, which include diverse populations ranging from embryonic stem cells (ESCs), to fetal stem cells, mesenchymal stromal cells (MSCs) or induced pluripotent stem cells (iPSCs) have remarkable potential to promote extensive brain regeneration and recovery in neurodegenerative disorders. This regenerative potential has been demonstrated in exciting pre and clinical assays. However, despite these promising results, several drawbacks are hampering their successful clinical implementation. Problems related to ethical issues, quality control of the cells used and the lack of reliable models for the efficacy assessment of human stem cells. In this chapter the main advantages and disadvantages of the available sources of stem cells as well as their efficacy and potential to improve disease outcomes are discussed.

Although the real actual incidence of metallosis is unknown, it is described as a rare diagnosis with a 5% estimated incidence in the hip prosthetic replacements. The adoption of non-metallic articular prosthetic devices, made of polyethylene and ceramic, is the main reason to the diminishing number of reported cases. We present a case of metallosis with a clinical systemic presentation in a patient with a non-metallic hip prosthesis, which occurred due to a fracture of the acetabular liner component, leading to abnormal metal–metal contact. The metallic debris leads to a massive local and systemic release of cytokines. Revision is necessary whenever osteolysis and loosening of the prosthesis occur. Imaging evaluation, especially CT, has a central role in diagnosis and planning the surgical treatment.

Introduction: Influenza can be associated with large numbers of hospitalizations and have a substantial health impact. Aims: To identify clinical characteristics and outcomes associated with Influenza hospitalized patients in the 2016/17 season. Methods: Patients admitted in a tertiary hospital with laboratory confirmed Influenza between October 1st 2016 and March 31st 2017. Demographic and clinical data were collected by chart review. Statistical analysis was performed using Microsoft Excel and SPSS Software. Results: 82 hospital admissions corresponding to 81 patients (53,1% male; mean age 77,7±12,4 years); 93,9% occurred in December and January and mean length of hospital stay was 10±8,8 days. The main comorbidities found were COPD (33%), chronic heart failure (29,6%), diabetes (27,1%) and chronic kidney disease (18,5%); 51,9% had smoking history and 40,2% were vaccinated for seasonal influenza. Dyspnoea and fever were the most frequent manifestations (85,4 and 36,6%, respectively) and the mean length of symptoms before admission was 5,6 days; 19 pneumonias and 2 viral myocarditis were observed. Intermediate/intensive care admission was needed in 22 – 91% of which required ventilatory support. Antiviral treatment was given in 25,6%. Twelve patients died (75% male; mean age 82,5±9 years) – there was a three fold odds of mortality for men (OR 3,0, 95% CI) and a statistically significant relation between PaO2 levels on admission and risk of death. Although with no statistical significance, age and RCP means were higher in deceased patients when compared to the general group. Conclusions: Identification of characteristics associated with hospitalization can help in early diagnosis and mortality reduction.

Actinomycosis remains characteristically uncommon, but is still an important cause of morbidity. Its clinical presentation is usually indolent and chronic as slow growing masses that can evolve into fistulae, and for that reason are frequently underdiagnosed. Actinomyces spp is often disregarded clinically and is classified as a colonizing microorganism. In this review of literature, we concomitantly present 11 cases of actinomycosis with different localizations, diagnosed at a tertiary hospital between 2009 and 2016. We outline the findings of at least one factor of immunosuppression in > 90% of the reported cases.

Nanotechnology offers substantial prospects for the development of innovative products and it is expected that the number of nanotechnology-based products will increase in the future. A number of promising applications are emerging, such as, smart packaging, nanosensors for pathogen detection, agrochemical nanoformulations, and nanoencapsulation of food ingredients for chemical preservation and shelf life extension. In this chapter, a special attention is given on how nanotechnology can mitigate the chemical changes of bioactive compounds, mainly those with nutritional value, occurring in food industry chain. Within this framework, an overview of the main external (oxygen, temperature, and light) factors that cause chemical degradation of some bioactive compounds present in food and affect food quality, and consequently contribute to food spoilage, and safety is also presented.

Krabbe's disease (KD) is a demyelinating disorder caused by the deficiency of lysosomal galactocerebrosi-dase (GALC), affecting both the central (CNS) and the peripheral nervous system (PNS). A current therapy, hematopoietic stem cell transplantation (HSCT), is ineffective at correcting the PNS pathology. We have previously shown that systemic delivery of immortalized bone marrow-derived murine mesenchymal stromal cells (BM-MSCs) diminishes the neuropathology of transplanted Twitcher mice, a murine model of KD. In this study, to move one step closer to clinical application, the effectiveness of a systematic delivery of primary BM-MSCs to promote recovery of the Twitcher PNS was assessed. Primary BM-MSCsgrafted to the Twitcher sciatic nerve led to increased GALC activity that was not correlated to decreased psychosine (the toxic GALC substrate) accumulation. Nevertheless, BM-MSC transplantation rescued the axonal phenotype of Twitcher mice in the sciatic nerve, with an increased density of both myelinated and unmyelinated axons in transplanted animals. Whereas no increase in myelination was observed, upon transplantation an increased proliferation of Schwann cell precursors occurred. Supporting these findings, in vitro, BM-MSCs promoted neurite outgrowth of Twitcher sensory neurons and proliferation of Twitcher Schwann cells. Moreover, BM-MSCs expressed nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and promoted increased BDNF synthesis by neighboring Schwann cells. Besides their action in neurons and glia, BM-MSCs led to macrophage activation in Twitcher sciatic nerves. In summary, primary BM-MSCs diminish the neuropathology of Twitcher sciatic nerves by coordinately affecting neurons, glia, and macrophages.

In the era of Multislice Computed Tomography (MSCT), few studies have been dedicated to the evaluation of coronary anomalies and variants. We aim to present, describe and assess the prevalence of congenital coronary variants and anomalies (CVA) in the MSCT coronary angiographic studies performed in our department. All the MSCT coronary angiographies performed in our department, between April 1, 2007 and May 31, 2012 were reviewed. Coronary anomalies and variants were characterized and grouped according to their type: origin, course (including myocardial bridging) and distal ending. A total of 663 patients underwent a MSCT coronary evaluation during this period. A total of 84 anomalies and variants were identified in 80 individuals: 12.1% of the population (80/663). The most frequent variant was the myocardial bridging of the anterior descending artery. Four (4.7%) of the anomalies were considered malignant, corresponding to a prevalence of 0.6% (4/663) in the population. Congenital coronary anomalies and variants are relatively common. In our study, the prevalence was 12.1%, myocardial bridging being the most common. This fact may explain the higher prevalence compared to some series based on the cardiac catheterization studies. Few of these anomalies were considered malignant, with prevalence rates similar to those found in the cardiac catheterization studies.

A female second twin infant was born to a 39-year-old primigravida via elective caesarean section at 28 weeks of gestation due to intrauterine growth restriction of the second fetus. A full course of antenatal corticosteroid therapy was administered. The birth weight was 645 g, and the Apgar score

The efficacy, cellular uptake and specific transport of dietary antioxidants to target organs, tissues and cells remains the most important setback for their application in the treatment of oxidative-stress related disorders and in particular in neurodegenerative diseases, as brain targeting remains a still unsolved challenge. Nanotechnology based delivery systems can be a solution for the above mentioned problems, specifically in the case of targeting dietary antioxidants with neuroprotective activity. Nanotechnology-based delivery systems can protect antioxidants from degradation, improve their physicochemical drug-like properties and in turn their bioavailability. The impact of nanomedicine in the improvement of the performance of dietary antioxidants, as protective agents in oxidative- stress events, specifically through the use of drug delivery systems, is highlighted in this review as well as the type of nanomaterials regularly used for drug delivery purposes. From the data one can conclude that the research combining (dietary) antioxidants and nanotechnology, namely as a therapeutic solution for neurodegenerative diseases, is still in a very early stage. So, a huge research area remains to be explored that hopefully will yield new and effective neuroprotective therapeutic agents in a foreseeable future., This project was supported by the Foundation for Science and Technology (FCT), Portugal (PEst-C/QUI/UI0081/2013 and QREN (FCUP-CIQ-UP-NORTE-07-0124-FEDER- 000065). FCT grants of Carlos Fernandes (SFRH/BD/98519/2013), Catarina Oliveira (SFRH/BD/88773/2012) and Sofia Benfeito (SFRH/BD/99189/2013) are also acknowledged.

Lateral consonants are complex and variable sounds. Static MRI provides relevant information regarding /l/ geometry, but does not address dynamic properties. Real-time MRI is a well suited technique for dealing with temporal aspects. However, large amounts of data have to be processed to harness its full potential. The main goal of this paper is to extend a recently proposed quantitative framework to the analysis of real-time MRI data for European Portuguese /l/. Several vocal tract configurations of the alveolar consonant, acquired in different syllable positions and vocalic contexts, were compared. The quantitative framework revealed itself capable of dealing with the data for the /l/, allowing a systematic analysis of the multiple realisations. The results regarding syllable position effects and coarticulation of /l/ with adjacent vowels are in line with previous findings.

The world’s population is getting older with the percentage of people over 60 increasing more rapidly than any other age group. Telerehabilitation may help minimise the pressure this puts on the traditional healthcare system, but recent studies showed ease of use, usability, and accessibility as unsolved problems, especially for older people who may have little experience or confidence in using technology. Current migration towards multimodal interaction has benefits for seniors, allowing hearing and vision problems to be addressed by exploring redundancy and complementarity of modalities. This chapter presents and contextualizes work in progress in a new telerehabilitation service targeting the combined needs of the elderly to have professionally monitored exercises without leaving their homes with their need regarding interaction, directly related to age-related effects on, for example, vision, hearing, and cognitive capabilities. After a brief general overview of the service, additional information on its two supporting applications are presented, including information on user interfaces. First results from a preliminary evaluation are also included.

Leukodystrophies are a group of disorders characterized by myelin dysfunction, either at the level of myelin formation or maintenance, that affect the central nervous system (CNS) and also in some cases, to a lesser extent, the peripheral nervous system (PNS). Although these genetic-based disorders are generally rare, all together they have a significant impact in the society, with an estimated overall incidence of 1 in 7,663 live births. Currently, there is no cure for leukodystrophies, and the development of effective treatments remains challenging. Not only leukodystrophies generally progress very fast, but also most are multifocal needing the simultaneous targeting at multiple sites. Moreover, as the CNS is affected, the blood–brain barrier (BBB) limits the efficacy of treatment. Recently, interest on cell therapy has increased, and the leukodystrophies for which metabolic correction is needed have become first-choice candidates for cell-based clinical trials. In this review, we present and discuss the available cell transplantation therapies in metabolic leukodystrophies including fucosidosis, X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Canavan disease, and Krabbe's disease. We will discuss the latest advances of cell therapy and its pitfalls in this group of disorders, taking into account, among others, the limitations imposed by reduced cell migration in multifocal conditions, the need to achieve corrective enzyme threshold levels, and the growing awareness that not only myelin but also the associated axonopathy needs to be targeted in some leukodystrophies.

Mitochondria have long been known as the powerhouse of the cell. However, these organelles are also pivotal players in neuronal cell death. Mitochondrial dysfunction is a prominent feature of chronic brain disorders, including Alzheimer's and Parkinson's diseases, and cerebral ischemic stroke. Data derived from morphologic, biochemical and molecular genetic studies indicate that mitochondria constitute a convergence point for neurodegeneration. Conversely, mitochondria have also been implicated in the neuroprotective signaling processes of preconditioning. Despite the precise molecular mechanisms underlying preconditioning-induced brain tolerance are still unclear, mitochondrial reactive oxygen species generation and mitochondrial ATP-sensitive potassium channels activation have been shown to be involved in the preconditioning phenomenon. This review intends to discuss how mitochondrial malfunction contributes to the onset and progression of cerebral ischemic stroke and Alzheimer’s and Parkinson’s diseases, two major neurodegenerative disorders. The role of mitochondrial mechanisms involved in the preconditioning-mediated neuroprotective events will be also discussed. Mitochondrial targeted preconditioning may represent a promising therapeutic weapon to fight neurodegeneration.

Parkinson’s disease (PD) is the most common progressive neurodegenerative movement disorder, characterized by the selective loss of nigrostriatal dopaminergic neurons, and the presence of intracellular insoluble proteinaceous inclusions, known as Lewy Bodies. Although PD etiopathogenesis remains elusive, the leading hypothesis for the death of specific groups of neurons establishes that mitochondrial dysfunction, alterations in the ubiquitin-proteasomal system (UPS), and oxidative stress are major events that act synergistically causing this devastating disease. In this review we will focus on mitochondrial impairment and its implications on proteasomal function and alpha-synuclein aggregation. We will address the role of mitochondria and proteasome cross-talk in the neuronal loss that leads to PD and discuss how this knowledge might further improve patient therapy.

The use of collaborative filtering (CF) recommenders on the Web is typically done in environments where data is constantly flowing. In this paper we propose an incremental version of item-based CF for implicit binary ratings, and compare it with a non-incremental one, as well as with an incremental user-based approach. We also study the usage of sparse matrices in these algorithms. We observe that recall and precision tend to improve when we continuously add information to the recommender model, and that the time spent for recommendation does not degrade. Time for updating the similarity matrix is relatively low and motivates the use of the item-based incremental approach.

In this paper we present recent work on the development of Linguistic Models, resulting in a first "complete" articulatory-based TTS system for Portuguese. The system, based on TADA system, integrates our past work in automatic syllabification and grapheme-phone conversion plus a first gestural specification of European Portuguese sounds. The system was integrated with SAPWindows, an articulatory synthesizer for Portuguese. A demonstration of the system capabilities and a first perceptual evaluation are presented.

In this study evaluation of two self-learning methods (MBL and TBL) on European Portuguese grapheme-to-phone conversion is presented. Combinations (parallel and cascade) of the two systems were also tested. The usefulness of syllable information is also investigated. Systems with good performance were obtained both using a single self-learning method and combinations. Best performance was obtained with MBL and the parallel combination. The use of syllable information contributes to a better performance in all systems tested.

Blood-brain barrier (BBB) disruption is a common feature in neurodegenerative diseases. However, BBB integrity has not been assessed in spinocerebellar ataxias (SCAs) such as Machado-Joseph disease/SCA type 3 (MJD/SCA3), a genetic disorder, triggered by polyglutamine-expanded ataxin-3. To investigate that, BBB integrity was evaluated in a transgenic mouse model of MJD and in human post-mortem brain tissues.Firstly, we investigated the BBB permeability in MJD mice by: i) assessing the extravasation of the Evans blue (EB) dye and blood-borne proteins (e.g fibrinogen) in the cerebellum by immunofluorescence, and ii) in vivo Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI). The presence of ataxin-3 aggregates in brain blood vessels and the levels of tight junction (TJ)-associated proteins were also explored by immunofluorescence and western blotting. Human brain samples were used to confirm BBB permeability by evaluating fibrinogen extravasation, co-localization of ataxin-3 aggregates with brain blood vessels and neuroinflammation.In the cerebellum of the mouse model of MJD, there was a 5-fold increase in EB accumulation when compared to age-matched controls. Moreover, vascular permeability displayed a 13-fold increase demonstrated by DCE-MRI. These results were validated by the 2-fold increase in fibrinogen extravasation in transgenic animals comparing to controls. Interestingly, mutant ataxin-3 aggregates were detected in cerebellar blood vessels of transgenic mice, accompanied by alterations of TJ-associated proteins in cerebellar endothelial cells, namely a 29% decrease in claudin-5 oligomers and a 10-fold increase in an occludin cleavage fragment. These results were validated in post-mortem brain samples from MJD patients as we detected fibrinogen extravasation across BBB, the presence of ataxin-3 aggregates in blood vessels and associated microgliosis.Altogether, our results prove BBB impairment in MJD/SCA3. These findings contribute for a better understanding of the disease mechanisms and opens the opportunity to treat MJD with medicinal products that in normal conditions would not cross the BBB.