Assessment of the Risk Impact of SARS-CoV-2 Infection Prevalence between Cats and Dogs in America and Europe: A Systematic Review and Meta-Analysis.

The COVID-19 pandemic represented a huge obstacle for public health and demonstrated weaknesses in surveillance and health promotion systems around the world. Its etiological agent, SARS-CoV-2, of zoonotic origin, has been the target of several studies related to the control and prevention of outbreaks and epidemics of COVID-19 not only for humans but also for animals. Domestic animals, such as dogs and cats, have extensive contact with humans and can acquire the infection both naturally and directly from humans. The objective of this article was to summarize the seroprevalence findings of SARS-CoV-2 in dogs and cats and correlate them with the strength of infection risk between each of them. This is a systematic review and meta-analysis following the recommendations of PRISMA 2020. The search and selection of papers was carried out using in vivo experimental works with animals using the descriptors (MeSH/DeCS) "Animal", "Public Health", "SARS-CoV-2" and "Pandemic" (together with AND) in English, Portuguese or Spanish for Science Direct, PUBMED, LILACS and SciELO databases. The ARRIVE checklist was used for methodological evaluation and the Comprehensive Meta-Analysis v2.2 software with the Difference Risk (RD) test to evaluate statistical inferences (with subgroups by continent). Cats showed greater susceptibility to SARS-CoV-2 compared to dogs both in a joint analysis of studies (RD = 0.017; 95% CI = 0.008-0.025; p < 0.0001) and in the American subgroup (RD = 0.053; 95% CI = 0.032-0.073; p < 0.0001), unlike the lack of significant difference on the European continent (RD = 0.009; 95% CI = -0.001-0.018; p = 0.066). Therefore, it was observed that cats have a greater interest in health surveillance due to the set of biological and ecological aspects of these animals, but also that there are a set of factors that can influence the spread and possible spillover events of the virus thanks to the anthropozoonotic context.

Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.

BACKGROUND: Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features. OBJECTIVE: We aimed to address these 3 challenges to inform future work in stratified analyses. METHODS: Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model. RESULTS: We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression. CONCLUSIONS: This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.

Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal.

OBJECTIVES: Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up. METHODS: This was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021. RESULTS: A total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1-3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening ( P = 0.843, Mann-Whitney U test) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects. CONCLUSION: Our study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.

DES c.1360C>T: A Rare Desmin Variant Causing Early Distal Myopathy and Cardiomyopathy.

Desmin-related myopathies are characterized by progressive, distal skeletal muscle weakness, cardiomyopathy, and cardiac conduction disease caused by mutations of Desmin. A 43-year-old man with a history of heart transplant due to heart failure associated with restrictive cardiomyopathy, presented with slowly progressive distal muscle weakness in all four extremities for five years. On examination, predominantly distal quadriparesis and atrophy were noted, worse on the upper limbs, and reduced reflexes with normal sensation. His electromyographic studies were suggestive of subacute moderate motor axonal polyneuropathy secondary to the transplant immunosuppression. The patient's father died at 33 years due to heart failure, and his 37-year-old brother, who also had a heart transplant, had noticed the development of muscle atrophy. Another electroneuromyography performed on our index patient confirmed features consistent with a distal myopathy. A genetic panel for distal myopathies with cardiac involvement identified the pathological desmin gene mutation DES (NM_001927.4) - c.1360C>T; (p.(Arg454Trp)). Desmin-related myopathies are a diagnostic challenge. The beginning of neurological symptoms several years after the cardiac symptoms and the use of immunosuppressive agents may have contributed to the early misdiagnosis.

Fatores relacionados à funcionalidade da comunicação social em crianças com transtorno do espectro do autismo: estudo preliminar / Factors related to social communication functionality in children with autism spectrum disorder: a preliminary study

RESUMO Objetivo analisar a associação entre funcionalidade da comunicação social de crianças com transtorno do espectro do autismo (TEA) segundo aspectos sociodemográficos, atos comunicativos, gravidade do TEA e percepção da família. Métodos trata-se da etapa piloto de um estudo observacional analítico de recorte transversal. Crianças com TEA foram avaliadas e seus cuidadores foram entrevistados. As variáveis analisadas foram: gravidade do TEA, aspectos socioeconômicos, atos comunicativos, dificuldades comunicativas e a classificação de funcionalidade da comunicação social. Para as análises de associação foram utilizados os testes Qui-quadrado de Pearson e Kruskal-Wallis. Resultados foram avaliadas 16 crianças com idade entre 3 e 10 anos. Os participantes incluídos no estudo apresentaram níveis medianos de funcionalidade da comunicação social. As crianças com mais dificuldades na comunicação social foram as que os cuidadores afirmaram ter a impressão de que as pessoas zombavam delas. Não houve associação em relação à funcionalidade da comunicação e aspectos socioeconômicos, gravidade do TEA e atos comunicativos por minuto. Conclusão este estudo faz a triangulação entre a funcionalidade da comunicação de crianças com TEA com fatores ambientais e sociais. Crianças com TEA em atendimento ambulatorial em serviço especializado apresentaram níveis intermediários em comunicação social. As dificuldades na aceitação e inclusão social são mais observadas em crianças com TEA com maiores déficits de comunicação.

ABSTRACT Purpose to analyze the association between social communication functionality in children with Autism spectrum disorder (ASD) according to sociodemographic aspects, communicative acts, severity of ASD and family perception. Methods this is the pilot stage of a cross-sectional analytical observational study. Children with ASD were evaluated and their caregivers were interviewed. The variables analyzed were ASD severity, socioeconomic aspects, communicative acts, communicative difficulties and the classification of functionality of social communication. For association analyses, the Pearson and Kruskal-Wallis chi-square tests were used. Results Sixteen children aged between 3 and 10 years were evaluated. The participants included in the study presented median levels of social communication functionality. The children with the greatest social communication difficulties were the ones caregivers had the impression other people made fun of . There was no association regarding communication functionality and socioeconomic aspects, ASD severity and communicative acts per minute. Conclusion This study triangulates the communication functionality of children with ASD with environmental and social factors. Children with ASD in outpatient care at a specialized service showed intermediate levels of social communication. Difficulties in acceptance and social inclusion are more commonly observed in children with ASD with greater communication deficits.

Cerebral venous thrombosis in a young asymptomatic COVID-19 patient.

We report an unusual case of cerebral venous thrombosis (CVT temporally associated with an otherwise asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While coronavirus disease 2019 (COVID-19) has been associated with thrombotic events at different sites, most published cases report on symptomatic SARS-CoV-2 infection. We are confident this was an otherwise asymptomatic infection as the patient reported no symptoms and molecular and serological testing was consistent with infection more than 3weeks in the past. We believe this is an important report as it adds to the existing literature on thrombotic events in patients with COVID. It may even inform discussion of COVID vaccines and CVT since our patient, as those reported in association with vaccines, also had thrombocytopenia on admission.

Curaua-Aramid Hybrid Laminated Composites for Impact Applications: Flexural, Charpy Impact and Elastic Properties.

Curaua, as a leaf-based natural fiber, appears to be a promising component with aramid fabric reinforcement of hybrid composites. This work deals with the investigation of flexural, impact and elastic properties of non-woven curaua-aramid fabric hybrid epoxy composites. Five configurations of hybrid composites in a curaua non-woven mat with an increasing quantity of layers, up to four layers, were laminated through the conventional hand lay-up method. The proposed configurations were idealized with at least 60 wt% reinforcement in the non-alternating configuration. As a result, it was observed that the flexural strength decreased by 33% and the flexural modulus by 56%. In addition, the energy absorbed in the Charpy impact also decreased in the same proportion as the replaced amount of aramid. Through the impulse excitation technique, it was possible observe that the replacement of the aramid layers with the curaua layers resulted in decreased elastic properties. However, reduction maps revealed proportional advantages in hybridizing the curaua with the aramid fiber. Moreover, the hybrid composite produced an almost continuous and homogeneous material, reducing the possibility of delamination and transverse deformation, which revealed an impact-resistant performance.

Aß1-42 peptides blunt the adenosine A2A receptor-mediated control of the interplay between P2X7 and P2Y1 receptors mediated calcium responses in astrocytes.

The contribution of astrocytes to Alzheimer's disease (AD) is still ill defined. AD involves an abnormal accumulation of amyloid-ß peptides (Aß) and increased production of danger signals such as ATP. ATP can direct or indirectly, through its metabolism into adenosine, trigger adaptive astrocytic responses resulting from intracellular Ca2+ oscillations. AD also triggers an upregulation of astrocytic adenosine A2A receptors (A2AR), which blockade prevents memory dysfunction in AD. We now investigated how Aß peptides affect ATP-mediated Ca2+ responses in astrocytes measured by fluorescence live-cell imaging and whether A2AR control astrocytic Ca2+ responses mediated by ATP receptors, mainly P2X7R and P2Y1R. In primary cultures of rat astrocytes exposed to Aß1-42, ATP-evoked Ca2+ responses had a lower amplitude but a longer duration than in control astrocytes and involved P2X7R and P2Y1R, the former potentiating the later. Moreover, Aß1-42 exposure increased protein levels of P2Y1R in astrocytes. A2AR antagonism with SCH58261 controlled in a protein kinase A-dependent manner both P2X7R- and P2Y1R-mediated Ca2+ responses in astrocytes. The interplay between these purinoceptors in astrocytes was blunted upon exposure to Aß1-42. These findings uncover the ability of A2AR to regulate the inter-twinned P2X7R- and P2Y1R-mediated Ca2+ dynamics in astrocytes, which is disrupted in conditions of early AD.

Isolated distal pisiform dislocation: Case Report.

Isolated pisiform dislocation is a rare lesion with few cases described in the literature. This type of lesion is typically observed in young males and can be easily overlooked at first assessment. Isolated proximal dislocation is more common due to the action of the flexor carpi ulnaris (FCU) muscle. We present the case of a 19-year-old male patient with isolated distal pisiform dislocation after wrist trauma. He underwent open reduction and internal fixation with Kirschner wires with excellent functional outcomes. Although there is no consensual therapeutic method, closed reduction is a first-line treatment for acute presentations. Pisiform open reduction or excision may be performed alternatively or after a failed closed reduction.

EFAS Score - Validation of Portuguese Version by the Score Committee of the European Foot and Ankle Society (EFAS).

BACKGROUND: The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in ten languages (English, German, French, Italian, Polish, Dutch, Swedish, Finnish, Turkish, Portuguese). From other languages under validation, the Portuguese version completed data acquisition and underwent further validation. METHODS: The Portuguese version of the EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during initial validation study), 2) item reduction and scale exploration (completed during initial validation study), 3) confirmatory analyses and responsiveness of Portuguese version (completed during initial validation study in nine other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory. RESULTS: The internal consistency was confirmed in the Portuguese version (Cronbach's Alpha 0.84). The Standard Error of Measurement (SEM) was 0.27 and is similar to other language versions. Between baseline and follow-up, 69.4% of patients showed an improvement on their EFAS score, with adequate responsiveness (effect size 0.64). CONCLUSIONS: The Portuguese EFAS Score version was successfully validated in patients with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.net.

Isolated distal pisiform dislocation: Case Report / Luxação distal isolada do pisiforme: Relato de caso

Abstract Isolated pisiform dislocation is a rare lesion with few cases described in the literature. This type of lesion is typically observed in young males and can be easily overlooked at first assessment. Isolated proximal dislocation is more common due to the action of the flexor carpi ulnaris (FCU) muscle. We present the case of a 19-year-old male patient with isolated distal pisiform dislocation after wrist trauma. He underwent open reduction and internal fixation with Kirschner wires with excellent functional outcomes. Although there is no consensual therapeutic method, closed reduction is a first-line treatment for acute presentations. Pisiform open reduction or excision may be performed alternatively or after a failed closed reduction.

Resumo A luxação isolada do pisiforme é uma lesão rara com poucos casos descritos na literatura. Esse tipo de lesão é observado tipicamente em adultos jovens do sexo masculino e pode ser facilmente negligenciada numa primeira avaliação. A luxação proximal isolada é mais comum devido à ação do flexor ulnar do carpo (FUC). Apresentamos o caso de um paciente do sexo masculino, com 19 anos de idade, com luxação distal isolada do pisiforme após traumatismo do punho. O paciente foi submetido a uma redução aberta e fixação interna com fios de Kirschner com excelente resultado funcional. Apesar de não existir um método de tratamento consensual, a redução fechada perfila-se como tratamento de primeira linha na apresentação aguda. Em caso de insucesso ou como método alternativo pode-se optar pela redução aberta ou a excisão do pisiforme.

Plant height and spatial context influence individual connectivity and specialization on seed dispersers in a tree population.

While network analyses have stimulated a renewed interest in understanding patterns and drivers of specialization within communities, few studies have explored specialization within populations. Thus, in plant populations, causes and consequences of individual variation in their interactions with mutualistic animals remain poorly understood. Studying a Brazilian pepper (Schinus terebinthifolia) population, we measured the extent of individual variation in interactions with seed dispersers and tested whether connectivity (number of seed dispersers) and specialization (exclusiveness of partners) are associated with phenotypic and phenological traits of individuals and their spatial context. We found that: (i) individuals varied broadly in their connectivity and specialization on seed dispersers; (ii) phenotypic traits and spatial context matter more than fruiting duration in determining how many and how exclusive are seed dispersers of an individual; (iii) the individual-based network was nested and indicated that the less connected individuals were shorter, occurred in neighborhoods with fewer fruits, and tended to interact with a subset of the partners of more generalist individuals which, in turn, were taller and inserted in higher fruit density neighborhoods; (iv) modularity indicated the existence of subsets of individuals that interacted disproportionately with distinct groups of partners, which may occur due to differences in bird habitat use across the landscape. Our study underlines a remarkable interindividual variation that is overlooked when interactions are compiled to describe species-level interactions. Traits and spatial contexts that define variation among individuals may have important implications not only for fitness but also for sampling and description of interactions at species level.

Delirium severity in critical patients with COVID-19 from an Infectious Disease Intensive Care Unit.

BACKGROUND: COVID-19 is mainly characterized by respiratory manifestations. Nevertheless, neurologic complications have been described, including delirium, which appears to be frequent, prolonged, and severe. METHODS: We conducted a retrospective analysis of demographic, clinical, and laboratory data of two cohorts: patients with COVID-19 admitted to the infectious disease intensive care unit (ID-ICU) and patients admitted to the ID-ICU with other respiratory infections in 2018-2019. Outcomes were defined as the presence, duration, and severity of delirium. Doses of antipsychotics used to control delirium were converted to equivalents and used as delirium severity. Logistics regression models were used to correlate COVID-19 with the outcomes. RESULTS: Ninety-nine patients with COVID-19 and 40 patients without COVID-19 were included. The mean age of the COVID-19 cohort was 63 years, with a male predominance. Delirium developed in 42%, with a median duration of 3 days and an equivalent dose of olanzapine use of 10 mg/day. In univariate analysis, COVID-19 was not associated with the development or different duration of delirium when compared with patients without COVID-19. There was an association between COVID-19 and severity of delirium in a binary logistic regression model controlled to confounding variables. CONCLUSION: COVID-19 is not associated with a higher prevalence or duration of delirium than in cohorts without COVID-19. However, it is associated with more severe forms of delirium.

Cognitive screening in HTLV-1-infected people using a self-perceived memory score and auditory P300.

The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the most common neurological manifestation associated with human T-cell lymphotropic virus type-1 (HTLV-1) infection. Although cognitive impairment has been highlighted in the spectrum of HTLV-1 neurological manifestations, it may go unnoticed in those who do not spontaneously report it. We aimed at evaluating the applicability of a self-perceived memory score (SMS) and the cognitive event-related potential (P300) for early detection of cognitive impairment in HTLV-1-infected people. The SMS was measured by a 0-10 point numeric scale combined with a sad-happy face rating scale. The higher the number, the better was the SMS. The P300 was obtained through an oddball paradigm with a mental counting task. The participants were 15 (21.4%) individuals with HAM/TSP, 20 (28.6%) HTLV-1 asymptomatic carriers, and 35 (50%) seronegative controls. We found that SMS (p < 0.001) and P300 latency (p < 0.001) got progressively worse from the seronegative controls to the asymptomatic carriers and then to the HAM/TSP. The results that indicated cognitive impairment were SMS < 7.2 points and P300 latency > 369.0 ms. The HAM/TSP group showed the highest prevalence of altered P300 (80%) and SMS (87%). Interestingly, the asymptomatic group also presented significantly higher prevalence of altered SMS (60%) and P300 (35%) when compared to controls (< 10%). The frequency of cognitive impairment was 16 times higher in the HTLV-1 asymptomatic group and 69 times higher in the HAM/TSP group when compared to controls. The use of SMS in the medical consultation was a useful and easy-to-apply method to screen HTLV-1-infected subjects for everyday memory complaints.

Acute Myocardial Infarction after Intravenous Thrombolysis for Acute Ischemic Stroke: Case Series and Systematic Review.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IV-rtPA) has been suggested as a potential cause of myocardial infarction (MI) after acute ischemic stroke (AIS), with randomized clinical trials showing a higher number of cardiac events within the thrombolysis group. We assessed the prevalence and MI mechanisms after IV-rtPA for AIS. METHODS: Retrospective review of consecutive AIS patients admitted to six stroke units and systematic literature review searching for AIS patients who suffered a MI less than 24 h after IV-rtPA. In those with available coronary angiography, MI etiology was defined as atherosclerotic or embolic. Patients' characteristics were compared between groups. RESULTS: Fifty-two patients were included. Thirty-two patients (61.5%) derived from hospital cases, after reviewing 6958 patients treated with IV-rtPA [0.5% (95% CI 0.38-0.54) of total hospital cases]. After coronary angiography (n = 25, 48.1%), 14 (54%) patients were considered to have an atherosclerotic MI, and 11 (46%) due to coronary embolism. Patients with an embolic MI more frequently had a cardioembolic AIS (72.7% vs 28.6%; p-value = 0.047) and an intracardiac thrombus (27.3% vs 0.0%; p-value = 0.044). Although not statistically significant, patients with an embolic MI had apparent lower time intervals between starting IV-rtPA infusion and MI occurrence [2 h (0.2-3.0) vs 3 h (1.0-15.0); p-value = 0.134]. CONCLUSIONS: MI within the first 24 h after IV-rtPA for AIS is an infrequent event, and more frequently non-embolic. However, the prevalence of embolic MI was superior to what is found in the general population with MI. There was an association between the pathophysiology of AIS and MI. The low number of events and publication bias may have limited our conclusions.

Clinical Evaluation of the Reconstruction of the Biceps Brachii using Triceps Graft.

Objective Clinical and functional evaluation of the surgical treatment for chronic injury of the distal biceps brachii applying a surgical technique with grafting of the distal triceps brachii tendon. Methods A study based on a review of the medical records and clinical evaluation of the patients submitted to surgical treatment for chronic injury to the distal insertion of the biceps brachii between February 2015 and February 2017. In a 12-month-minimum postoperative follow-up, 7 patients were evaluated regarding the range of motion of the operated and non-operated elbows, flexion, upper-limb extension and supination with a digital dynamometer, the hook test, the satisfaction index, and the Disabilities of the Arm, Shoulder and Hand (DASH) and Mayo Elbow Performance Score (MEPS) intruments. Results During the postoperative functional evaluation, no patient reported dissatisfaction with the esthetic outcome of the incisions, and all of them were satisfied/very satisfied with the range of motion and strength of the operated limb. No neurovascular complications, surgical site infection or tendon rupture were observed. On the MEPS and DASH scales, all patients scored 100 and 0 respectively. The mean flexion was of 133.5° on the operated side, versus 139.2° on the non-operated side. The mean extension was of 5° on the operated side versus 0° on the non-operated side. The supination was of 86.5° versus 90°, and the pronation, 80° versus 80°, when comparing the operated and non-operated sides respectively. The mean flexion, extension and supination corresponded respectively to 92.5%, 96.4% and 86.8% of those of the non-operated limb. Conclusion Recosntruction of the distal biceps brachii with triceps grafting seems to be an effective and safe option for the treatment of chronic distal biceps injuries.

Machine learning for brain age prediction: Introduction to methods and clinical applications.

The rise of machine learning has unlocked new ways of analysing structural neuroimaging data, including brain age prediction. In this state-of-the-art review, we provide an introduction to the methods and potential clinical applications of brain age prediction. Studies on brain age typically involve the creation of a regression machine learning model of age-related neuroanatomical changes in healthy people. This model is then applied to new subjects to predict their brain age. The difference between predicted brain age and chronological age in a given individual is known as 'brain-age gap'. This value is thought to reflect neuroanatomical abnormalities and may be a marker of overall brain health. It may aid early detection of brain-based disorders and support differential diagnosis, prognosis, and treatment choices. These applications could lead to more timely and more targeted interventions in age-related disorders.

Acute Inflammation in Cerebrovascular Disease: A Critical Reappraisal with Focus on Human Studies.

Recent attention has been focused on the field of inflammatory biomarkers associated with vascular disorders, regarding diagnosis, prognosis, and possible therapeutical targets. In this study, we aimed to perform a comprehensive review of the literature regarding the use of inflammatory biomarkers in stroke patients. We searched studies that evaluated inflammation biomarkers associated with Cerebrovascular Disease (CVD), namely, ischemic Stroke (IS), Intracerebral Hemorrhage (ICH) and Cerebral Venous Thrombosis (CVT). As of today, neutrophil-lymphocyte ratio (NLR) seems the be the most widely studied and accepted biomarker for cerebrovascular disease due to its easy access and availability. Although demonstrated as a prognostic risk factor, in IS, ICH and CVT, its diagnostic role is still under investigation. Several other prognostic factors could be used or even combined together into a diagnostic or prognostic index. Multiple inflammatory biomarkers appear to be involved in IS, ICH, and CVT. Blood inflammatory cells, easily measured and accessible at admission may provide information regarding accurate diagnosis and prognosis. Although not yet a reality, increasing evidence exists to suggest that these may become potential therapeutic targets, likely influencing or mitigating complications of CVD and improving prognosis. Nevertheless, further larger, well-designed randomized clinical trials are still needed to follow up this hypothesis.

Using normative modelling to detect disease progression in mild cognitive impairment and Alzheimer's disease in a cross-sectional multi-cohort study.

Normative modelling is an emerging method for quantifying how individuals deviate from the healthy populational pattern. Several machine learning models have been implemented to develop normative models to investigate brain disorders, including regression, support vector machines and Gaussian process models. With the advance of deep learning technology, the use of deep neural networks has also been proposed. In this study, we assessed normative models based on deep autoencoders using structural neuroimaging data from patients with Alzheimer's disease (n = 206) and mild cognitive impairment (n = 354). We first trained the autoencoder on an independent dataset (UK Biobank dataset) with 11,034 healthy controls. Then, we estimated how each patient deviated from this norm and established which brain regions were associated to this deviation. Finally, we compared the performance of our normative model against traditional classifiers. As expected, we found that patients exhibited deviations according to the severity of their clinical condition. The model identified medial temporal regions, including the hippocampus, and the ventricular system as critical regions for the calculation of the deviation score. Overall, the normative model had comparable cross-cohort generalizability to traditional classifiers. To promote open science, we are making all scripts and the trained models available to the wider research community.