Effect of duration of estradiol exposure on embryo survival and endometrial gene expression in anestrous embryo recipient mares.

Previous studies indicate a positive correlation between the duration of estrus prior to ovulation and likelihood of pregnancy in embryo recipient mares. However, the mechanisms by which the duration of estrus before may affect fertility remains unclear. This study aimed to determine the effect of different durations of estradiol exposure, prior to progesterone administration, on embryo viability in anestrous recipient mares, and endometrial expression of genes thought to influence embryo survival. Three groups of anestrous recipient mares treated with different duration of estradiol were used: long (LE), short (SE) and no treatment (NE). Day 8 embryos were transferred into recipient mares four days after long-acting progesterone administration and recovered 48h later to examine embryo growth and viability. The endometrial gene expression profile of selected genes was also investigated. The likelihood of recovering an embryo 48h after transfer was 46.1% (6/13), 62.5% (5/8) and 85.7% (6/7) for recipient mares from the NE, SE and LE groups, respectively (P = .09). Embryos recovered from the different groups of recipients did not, however, differ in size, morphology or the proportion of nuclei undergoing mitosis (P > .05). Abundance of mRNA for uterocalin (P19) and insulin-like growth factor 1 (IGF1) were increased in the LE compared to the NE group, while fibroblast growth factor 2 (FGF2), progesterone receptor (PGR) and insulin-like growth factor 1 receptor (IGF1R) transcript abundances were increased (P < 0.05) in the NE group compared to both SE and LE groups. In conclusion, a longer exposure of the endometrium to estradiol before progesterone tended to improve embryo survival within 48h of transfer. However, the grade, growth rate, and proportion of mitotic cells in surviving embryos did not differ among groups. If embryos are destined to fail in a suboptimal endometrial environment, they die and disappear quickly. Moreover, a more adequately estradiol-primed uterus, before the progesterone rise, seems to create a uterine environment, in terms of P19, IGF1, FGF2 and PGR gene expression, more conducive to embryo survival and further development.

The Ketone Bridge Between the Heart and the Bladder: How Fast Should We Go?

Metabolic syndrome (MS) is associated with both cardiovascular and bladder dysfunction. Insulin resistance (IR) and central obesity, in particular, are the main risk factors. In these patients, vicious pathological cycles exacerbate abnormal carbohydrate metabolism and sustain an inflammatory state, with serious implications for both the heart and bladder. Ketone bodies serve as an alternative energy source in this context. They are considered a "super-fuel" because they generate adenosine triphosphate with less oxygen consumption per molecule, thus enhancing metabolic efficiency. Ketone bodies have a positive impact on all components of MS. They aid in weight loss and glycemic control, lower blood pressure, improve lipid profiles, and enhance endothelial function. Additionally, they possess direct anti-inflammatory, antioxidant, and vasodilatory properties. A shared key player in dysfunction of both the heart and bladder dysfunction is the formation of the NLRP3 inflammasome, which ketone bodies inhibit. Interventions that elevate ketone body levels-such as fasting, a ketogenic diet, ketone supplements, and sodium-glucose cotransporter 2 inhibitors-have been shown to directly affect cardiovascular outcomes and improve lower urinary tract symptoms derived from MS. This review explores the pathophysiological basis of the benefits of ketone bodies in cardiac and bladder dysfunction.

Control of CCR5 Cell-Surface Targeting by the PRAF2 Gatekeeper.

The cell-surface targeting of neo-synthesized G protein-coupled receptors (GPCRs) involves the recruitment of receptors into COPII vesicles budding at endoplasmic reticulum exit sites (ERESs). This process is regulated for some GPCRs by escort proteins, which facilitate their export, or by gatekeepers that retain the receptors in the ER. PRAF2, an ER-resident four trans- membrane domain protein with cytoplasmic extremities, operates as a gatekeeper for the GB1 protomer of the heterodimeric GABAB receptor, interacting with a tandem di-leucine/RXR retention motif in the carboxyterminal tail of GB1. PRAF2 was also reported to interact in a two-hybrid screen with a peptide corresponding to the carboxyterminal tail of the chemokine receptor CCR5 despite the absence of RXR motifs in its sequence. Using a bioluminescence resonance energy transfer (BRET)-based subcellular localization system, we found that PRAF2 inhibits, in a concentration-dependent manner, the plasma membrane export of CCR5. BRET-based proximity assays and Co-IP experiments demonstrated that PRAF2/CCR5 interaction does not require the presence of a receptor carboxyterminal tail and involves instead the transmembrane domains of both proteins. The mutation of the potential di-leucine/RXR motif contained in the third intracellular loop of CCR5 does not affect PRAF2-mediated retention. It instead impairs the cell-surface export of CCR5 by inhibiting CCR5's interaction with its private escort protein, CD4. PRAF2 and CD4 thus display opposite roles on the cell-surface export of CCR5, with PRAF2 inhibiting and CD4 promoting this process, likely operating at the level of CCR5 recruitment into COPII vesicles, which leave the ER.

Seasonal absence of supplementary corpora lutea in pregnant mares and the relationship with pregnancy loss.

Two experiments were conducted in the Northern (UK) and Southern (Brazil) hemispheres to determine the effect of season (month of conception) on the development of supplementary CL (SCL) and the relationship with pregnancy loss. In experiment 1, 199 pregnancies were followed between Day 14 and term, to determine the number of SCL and pregnancy viability (Northern Hemisphere). From the 199 pregnancies, 178 were obtained from inseminations during the breeding season (March-September), while the rest, 21 pregnancies resulted from conceptions in the non-breeding season (October to February). Pregnancies conceived in the breeding season were more likely (P < 0.01) to have at least 1 SCL (75.8 %, 135/178) than pregnancies from the non-breeding season (33 %, 7/21). However, the pregnancy loss between Days 35 and 120 of pregnancy in mares with no SCL was similar (3.5 %, 2/57; P >0.1) than from mares with SCL (1.4 %, 2/142). In Experiment 2 (Southern Hemisphere), three groups of recipients were used based on their ovarian activity at the time of embryo transfer: Anestrus (n = 8), transitional (n = 7) and cyclic (n = 7) recipient mares. While all transitional and cyclic mares developed at least 1 SCL, only 50 % of anestrous recipients (4/8) developed SCL by 120 of gestation. In conclusion, the development of SCL in pregnant mares is influenced by the time of season of conception, therefore it appears to be regulated by the photoperiod and the endogenous seasonal variation in gonadotropin concentrations. Mares with no SCL were not at increased risk of pregnancy loss.

Plasma Estradiol Profile After Administration of Different Types of Estradiol Esters in Acyclic Mares.

Although the use of different estradiol esters has been extensively studied in hormonal protocols in cows, such information is lacking in mares. The present study aimed to assess the effects of treatment with the same doses and administration frequency of estradiol cypionate, estradiol benzoate and 17ß estradiol on plasma estradiol (E2) concentrations of acyclic mares and correlate the E2 profile to the endometrial edema score. Sixteen treatments were performed in 14 mares randomly divided into three groups: EB (n = 5), EC (n = 5), and 17ß (n = 6), receiving 10 mg on day 0 (D0), 6 mg on D1, and 4 mg on D2 of estradiol benzoate, estradiol cypionate, and estradiol 17ß, respectively. Blood samples, rectal palpations, and ultrasound evaluations were performed once daily, starting before the first estradiol treatment (D0) until edema disappearance or D8. Moderate to high edema was observed in all groups 24 hours after the first estradiol administration. Edema persisted above score 2 until D7, D5, and D4 in groups EC, EB, and 17ß, respectively. Higher edema was found on D2 in EB group compared to 17ß, on D6 and D7 in EC compared to 17ß, and on D8 in EC compared to EB (p ≤ .05). Maximum E2 concentrations were detected on D1 in groups: EB, showing a sharp decrease from D2 to D3 (p < .0001); and 17ß, where no differences were observed between treatment days (p ≥ .05). In the EC group, maximum concentrations were observed on D2, which remained high from D2 to D4 compared to the other days (p < .0001). Plasma concentration of E2 was higher in EB than the other groups on D0 and D1, and EB>EC>17ß on D2. Plasma E2 concentrations and edema score were positively correlated, being moderate in groups EB and EC and weak in the 17ß group. In conclusion, the most pronounced plasma E2 concentration was observed in EB group 24 hours after the administration of the first dose. Estradiol concentrations peaked 48 hours after EC administration, while a distinct peak was not observed in a 24h interval evaluation in the 17ß group. Moreover, high edema does not necessarily reflect on high E2 concentrations in acyclic mares.

A scoring tool to predict mortality and dependency after cerebral venous thrombosis.

BACKGROUND AND PURPOSE: A prognostic score was developed to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials. METHODS: Data from the International CVT Consortium were used. Patients with pre-existent functional dependency were excluded. Logistic regression was used to predict poor outcome (modified Rankin Scale score 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunk using ridge regression to adjust for optimism in internal validation. RESULTS: Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, the SI2 NCAL2 C score was derived utilizing the following components: absence of female-sex-specific risk factor, intracerebral hemorrhage, infection of the central nervous system, neurological focal deficits, coma, age, lower level of hemoglobin (g/l), higher level of glucose (mmol/l) at admission, and cancer. C-statistics were 0.80 (95% confidence interval [CI] 0.75-0.84), 0.84 (95% CI 0.80-0.88) and 0.84 (95% CI 0.80-0.88) for the poor outcome, 30-day and 1-year mortality model, respectively. Calibration plots indicated a good model fit between predicted and observed values. The SI2 NCAL2 C score calculator is freely available at www.cerebralvenousthrombosis.com. CONCLUSIONS: The SI2 NCAL2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted.

Migraine: from pathophysiology to treatment.

Migraine is an extremely disabling, common neurological disorder characterized by a complex neurobiology, involving a series of central and peripheral nervous system areas and networks. A growing increase in the understanding of migraine pathophysiology in recent years has facilitated translation of that knowledge into novel treatments, which are currently becoming available to patients in many parts of the world and are substantially changing the clinical approach to the disease. In the first part of this review, we will provide an up to date overview of migraine pathophysiology by analyzing the anatomy and function of the main regions involved in the disease, focusing on how these give rise to the plethora of symptoms characterizing the attacks and overall disease. The second part of the paper will discuss the novel therapeutic agents that have emerged for the treatment of migraine, including molecules targeting calcitonin gene-related peptide (gepants and monoclonal antibodies), serotonin 5-HT1F receptor agonists (ditans) and non-invasive neuromodulation, as well as providing a brief overview of new evidence for classic migraine treatments.

Evaluating migraine with typical aura with neuroimaging.

Objective: To provide an up-to-date narrative literature review of imaging in migraine with typical aura, as a means to understand better migraine subtypes and aura biology. Background: Characterizing subtypes of migraine with typical aura and appreciating possible biological differences between migraine with and without aura, are important to understanding the neurobiology of aura and trying to advance personalized therapeutics in this area through imaging biomarkers. One means of doing this over recent years has been the use of increasingly advanced neuroimaging techniques. Methods: We conducted a literature review of neuroimaging studies in migraine with aura, using a PubMed search for terms 'imaging migraine', 'aura imaging', 'migraine with aura imaging', 'migraine functional imaging' and 'migraine structural imaging'. We collated the findings of the main studies, excluding small case reports and series with n < 6, and have summarized these and their implications for better understanding of aura mechanisms. Results: Aura is likely mediated by widespread brain dysfunction in areas involving, but not limited to, visual cortex, somatosensory and insular cortex, and thalamus. Higher brain excitability in response to sensory stimulation and altered resting-state functional connectivity in migraine sufferers with aura could have a genetic component. Pure visual aura compared to visual aura with other sensory or speech symptoms as well, may involve different functional reorganization of brain networks and additional mitochondrial dysfunction mediating more aura symptoms. Conclusion: There is a suggestion of at least some distinct neurobiological differences between migraine with and without aura, despite the shared phenotypic similarity in headache and other migraine-associated symptoms. It is clear from the vast majority of aura phenotypes being visual that there is a particular predisposition of the occipital cortex to aura mechanisms. Why this is the case, along with the relationships between cortical spreading depression and headache, and the reasons why aura does not consistently present in affected individuals, are all important research questions for the future.

Intervenção educativa multiprofissional para conservação de energia em paciente idosa com insuficiência cardíaca: relato de experência / Multidisciplinary educational intervention for energy conservation in elderly patients with heart failure: experience report

INTRODUÇÃO: A insuficiência cardíaca (IC) é a via final das cardiopatias, causando nos acometidos congestão pulmonar, dispneia, ortopneia, fadiga e edema, comprometendo a qualidade de vida dos portadores de IC. OBJETIVO: Relatar a experiência de desenvolvimento e implementação de um plano terapêutico individualizado destinado à atenção a paciente com IC hospitalizada. METODOLOGIA: Trata-se de um relato de caso que traz menção à intervenção educativa realizada durante um cenário de atuação Multiprofissional do Programa de Residência Multiprofissional em Saúde Cardiovascular em instituição pública da cidade de São Paulo especializada em cardiologia. O grupo realizou a coleta de dados e reunião com familiares e pessoas de referência envolvidas no cuidado de uma paciente com IC internada em uma enfermaria, afim de esclarecimento de dados que direcionassem a conduta profissional. Foram estabelecidas as necessidades por meio de uma coleta de dados com uso de escalas e questionários validados e foi estabelecido como diagnóstico de enfermagem prioritário tolerância à atividade diminuída, de acordo com a Taxonomia NANDA-I. Todo o processo foi pautado na Teoria Holística de Myra Levine para compreender e embasar os processos adaptativos incluídos no processo saúde-doença, além de planejar os cuidados transicionais. RESULTADOS: Paciente idosa, portadora de IC de etiologia valvar, Classe Funcional NYHA III e verbalizava sua insatisfação com a sua situação clínica. A partir das necessidades levantadas, traçou-se uma intervenção educativa com o objetivo de favorecer o autocuidado frente às novas situações vivenciadas a partir do adoecimento, respeitando os desejos e o sentido atribuído à vida da paciente e de auxiliá-la com orientações baseadas em evidências científicas sobre métodos para conservação de energia, a fim de melhorar os sintomas apresentados. Sendo assim, optou-se pela construção de um livro contendo um breve resumo da história do sujeito, orientações sobre os cuidados necessários, sobretudo sobre medidas de conservação de energia, e um espaço para que este possa se expressar. Com isso, o vínculo entre paciente- -profissional foi aprimorado e, ainda na internação, apresentou melhora importante dos sintomas, evoluindo para Classe Funcional NYHA II. CONCLUSÃO: Durante a intervenção da equipe multiprofissional pautada em modelos teóricos, foi possível o estabelecimento de vínculo entre paciente, rede de apoio e equipe. Ademais, houve melhora dos sintomas apresentados, caracterizando um avanço no processo de adaptação da paciente frente à sua nova realidade.

[Evaluation of the Knowledge of Women of Childbearing Age with Epilepsy about the Impact of Their Disease in Contraception, Pregnancy and Breastfeeding: A Multicenter Cross-Sectional Study]. / Avaliação do Conhecimento das Mulheres com Epilepsia em Idade Fértil sobre o Impacto da sua Doença na Contraceção, Gravidez e Amamentação: Um Estudo Transversal Multicêntrico.

INTRODUCTION: The interaction of antiseizure medication with contraceptives, its potential teratogenicity and implications in pregnancy and breastfeeding are aspects to consider in the neurological care of women with epilepsy of childbearing age. To ensure the commitment in therapeutic decisions and the appropriate planning of maternity, it is essential that women are informed about the implications of their disease in these domains. The main aim of this study was to assess the knowledge of women of childbearing age with epilepsy concerning the impact of epilepsy in contraception, pregnancy and breastfeeding. As secondary aims we defined (1) the demographic, clinical and therapeutic characterization of this group of patients, (2) the identification of variables that correlated with the level of knowledge of women with epilepsy, and (3) the identification of preferential methods to acquire new knowledge about epilepsy. MATERIAL AND METHODS: The study was observational, cross-sectional and multicentric, and was carried out in five hospitals of the Lisbon metropolitan area. After identifying all women of childbearing age with epilepsy followed in the epilepsy clinic of each center, we applied an electronic questionnaire based on a non-systematic review of the literature. RESULTS: One hundred and fourteen participants were validated, with a median age of 33 years. Half of the participants were on monotherapy, and the majority had no seizures in the last six months. We identified important gaps in the participants' knowledge. Sections about complications and administration of antiseizure medication during pregnancy were the ones with the worst results. None of the clinical and demographic variables correlated with the final questionnaire score. Having had a previous pregnancy and the desire to breastfeed in a future pregnancy were positively correlated with the performance in breastfeeding section. Face-to-face discussion during medical outpatient visits was selected as the preferential method to learn about epilepsy, and the internet and social media were the least preferred ones. CONCLUSION: The knowledge of women of childbearing age with epilepsy in the Lisbon metropolitan area concerning the impact of epilepsy in contraception, pregnancy and breastfeeding seems to have significant gaps. Medical teams should consider engaging in patient education particularly during outpatient clinics.

Introdução: A interação dos fármacos anticrise epilética com os métodos contracetivos, a sua potencial teratogenicidade e as implicações na gravidez e amamentação são aspetos a considerar no acompanhamento de mulheres com epilepsia em idade fértil. Para o seu desejado envolvimento nas decisões terapêuticas e o adequado planeamento da maternidade, é essencial que as mulheres estejam corretamente informadas acerca das implicações da sua doença. O objetivo principal do presente estudo foi avaliar o conhecimento das mulheres com epilepsia em idade fértil sobre o impacto da epilepsia na contraceção, gravidez e amamentação. Como objetivos secundários definiram-se (1) a caracterização demográfica, clínica e terapêutica deste grupo de doentes, (2) a identificação de variáveis correlacionadas com o nível de conhecimento das mulheres com epilepsia, e (3) a identificação de meios e suportes preferenciais para aquisição de novos conhecimentos sobre epilepsia. Material e Métodos: O estudo foi observacional, transversal e multicêntrico, tendo decorrido em cinco centros hospitalares da região metropolitana de Lisboa. Após identificação das mulheres com epilepsia em idade fértil seguidas na Consulta de Epilepsia de cada centro, aplicou-se um questionário eletrónico construído após revisão não sistemática da literatura. Resultados: Foram validadas 114 participantes, com uma idade mediana de 33 anos. Metade das participantes apresentavam-se sob monoterapia, tendo a maioria a epilepsia controlada há pelo menos seis meses. Identificaram-se importantes lacunas no conhecimento das participantes. Conceitos sobre complicações dos fármacos anticrise epilética e a sua administração durante a gravidez motivaram piores resultados. Não houve correlação entre variáveis clinico-demográficas e o resultado no questionário. A ocorrência de gravidez prévia e o desejo de amamentar numa gravidez futura correlacionaram-se com o desempenho na secção sobre amamentação. A discussão oral na consulta foi a forma preferencial para aquisição de novos conhecimentos sobre epilepsia, tendo a internet e as redes sociais sido os meios menos escolhidos. Conclusão: O conhecimento das mulheres com epilepsia em idade fértil na área metropolitana de Lisboa sobre o impacto da sua doença na contraceção, gravidez e amamentação parece apresentar lacunas importantes. A educação para a saúde deste grupo deverá constituir uma preocupação por parte das equipas médicas, devendo privilegiar-se a consulta como local de ensino.

The Effect of Treatment with Oestradiol Benzoate on Oestrus Expression and Endometrial Oedema in Anovulatory and Cyclic Mares.

Oestrogens treatment is often used to induce oestrus behaviour in anoestrous mares to aid in the collection of stallion semen and as recipient mares to receive embryos when combined with progesterone. However, there are no studies to describe the effect of dose and individual mare on the intensity and duration of the response, in both anoestrous and cyclic mares. In Experiment 1, 13 anoestrous mares were treated with one of five doses of oestradiol benzoate (OB) (1, 1.5, 2, 3 and 4 mg) per mare in five consecutive treatment periods (n = 65), to determine the response in terms of endometrial oedema and oestrous behaviour. Experiment 2 and 3 used 3 mg of OB in cyclic mares to confirm or deny the presence of an active corpus luteum (CL). There was a dose rate of OB and individual mare effect (p < 0.05) on the intensity and persistence of endometrial oedema and oestrous behaviour. A total of 2 mg OB was enough to induce endometrial oedema and oestrous behaviour within 48 h in most mares. Mares with an active CL did not show endometrial oedema following treatment of 3 mg OB.

Visual snow syndrome and migraine: a review.

Visual snow syndrome is a neurological condition characterized by ongoing prominent phenomena described consistently as tiny dots moving across the entire visual field, often associated with complex visual symptoms. These can take the form of afterimages, entoptic phenomena, nyctalopia and light sensitivity. Although some of these symptoms can be benign, they can nonetheless become significantly impactful for many who experience them, particularly in cases that have a sudden and abrupt start. As visual snow syndrome becomes increasingly recognized in clinical practice we begin to learn about its typical presentation and underlying pathophysiology. Treatment of visual snow, however, still proves quite challenging, and efforts need to be focused on unravelling the biological mechanisms of the syndrome. This endeavour has characterized the most recent research on visual snow, mostly involving neuroimaging, neurophysiological and neurobehavioral studies aimed at understanding its underlying neural signature. Another important aspect of the syndrome, which will likely prove critical in deepening our understanding of visual snow, is represented by the intricate biological and historical connexion with migraine. This narrative review focused on visual snow syndrome will explore its clinical, pathophysiological and treatment aspects in detail.

Characterization of trigeminal C-fiber reactivity through capsaicin-induced release of calcitonin gene-related peptide.

OBJECTIVE: We hypothesized that the response of trigeminal dermal blood flow (DBF) in the trigeminal system and consecutive expansion of flare response to capsaicin would differ from the somatosensory system (arm). We also investigated whether there are differences between patients with migraine and healthy controls (HC). BACKGROUND: Functional differences between the trigeminal and extracephalic somatosensory systems may partly explain the susceptibility for headaches in patients with migraine. Capsaicin-induced activation of nociceptive C-fibers in the skin is mainly mediated by calcitonin gene-related peptide (CGRP) and induces cutaneous vessel dilatation and flare response. METHODS: Female patients with migraine (n = 38) and age-matched HC (n = 35) underwent DBF measurement at baseline and after topical capsaicin administration using laser speckle imaging. DBF before and after capsaicin stimulation was analyzed over ophthalmic nerve/maxillary nerve/mandibular nerve (V1/V2/V3) dermatomes and the forearm as an extracephalic control. RESULTS: Capsaicin-induced DBF increased more in the trigeminal dermatomes than on the forearm. The V1 dermatome showed a smaller increase of DBF in patients with migraine compared to HC. CONCLUSION: Our results suggest that the trigeminovascular system reacts differently from extracephalic areas, which may explain the trigeminal susceptibility to CGRP-mediated pain attacks. By demonstrating a different reactivity of the V1 dermatome in patients with migraine, our finding suggests that the first trigeminal branch is functionally different from the second and third branches; however, only in patients with migraine.

Differential Diagnosis of Visual Phenomena Associated with Migraine: Spotlight on Aura and Visual Snow Syndrome.

Migraine is a severe and common primary headache disorder, characterized by pain as well as a plethora of non-painful symptoms. Among these, visual phenomena have long been known to be associated with migraine, to the point where they can constitute a hallmark of the disease itself. In this review we focus on two key visual disorders that are directly or indirectly connected to migraine: visual aura and visual snow syndrome (VSS). Visual aura is characterized by the transient presence of positive and negative visual symptoms, before, during or outside of a migraine attack. VSS is a novel stand-alone phenomenon which has been shown to be comorbid with migraine. We discuss key clinical features of the two disorders, including pathophysiological mechanisms, their differential diagnoses and best treatment practices. Our aim is to provide an aid for clinicians and researchers in recognizing these common visual phenomena, which can even appear simultaneously in patients with an underlying migraine biology.

Galcanezumab modulates Capsaicin-induced C-fiber reactivity.

BACKGROUND: The vasodilatory calcitonin-gene related peptide (CGRP) is understood as pivotal mediator in migraine pathophysiology. Blocking CGRP with small molecules or monoclonal antibodies (CGRP-mAb) reduces migraine frequency. However, prescription of CGRP-mAbs is still regulated and possible predictive measures of therapeutic success would be useful. METHODS: Using standardized capsaicin-induced dermal blood flow model, 29 migraine patients underwent a laser speckle imaging measurement before and after administration of galcanezumab. At both sessions dermal blood flow before and after capsaicin stimulation as well as flare size were analyzed over all three trigeminal branches and the volar forearm for extracranial control. Long-term measures were repeated in 14 patients after continuous treatment ranging from 6 to 12 months. RESULTS: Resting dermal blood flow remained unchanged after administration of galcanezumab. Capsaicin-induced dermal blood flow decreased significantly after CGRP-mAb in all tested areas compared to baseline and this was consistent even after 12 months of treatment. However, following galcanezumab administration, the flare size decreased only in the three trigeminal dermatomes, not the arm and was therefore specific for the trigemino-vascular system. None of these two markers distinguished between responders and non-responders. CONCLUSION: CGRP-mAb changed blood flow response to capsaicin stimulation profoundly and this effect did not change over a 12-month application. Neither capsaicin-induced flare nor dermal blood flow can be used as a predictor for treatment efficacy. These data suggest that the mechanism of headache development in migraine is not entirely CGRP-mediated.

The effect of priming and duration of oestradiol benzoate treatment before progesterone administration on embryo development and survival in anestrous recipient mares.

The effect of three different hormonal protocols to prepare anestrous recipient mares on embryo survival was evaluated. The first group consisted of only progesterone administration (NE) 4 days before embryo transfer, while the recipients from the other two groups received a single administration of 2.5 mg of oestradiol benzoate (SE) 2 days earlier or 8 mg of oestradiol split in increasing doses for 5 consecutive days (LE) ending 3 days before progesterone treatment. The likelihood of recovering an embryo 2 days after transfer was 46.1% (6/13), 62.5% (5/8) and 85.7% (6/7) for recipient mares from the no oestrus, short and long oestrous groups respectively (p = .09). In conclusion, the presence and duration of oestradiol treatment before progesterone administration tended to influence the embryo survival in anestrous recipients 2 days after transfer. The surviving embryos recovered from the three different groups of recipients did not show any difference in size and morphology.

Negative impacts of the administration of hydroxycloroquine and anticoagulant in patients with SARS-COV-2 infection: a randomized clinical trial / Impactos negativos da administração de hidroxicloroquina e anticoagulante em pacientes com infecção por SARS-COV-2: um ensaio clínico randomizado

Purpose: To evaluate antimalarial with or without anticoagulant treatment, in patients with recent SARS-COV-2 infection. Methods: Clinical study carried out at Samuel Libânio Clinic Hospital, University of Vale do Sapucaí, Pouso Alegre-MG. Approved by the Ethics Committee (4.034.077) and registered in the Clinical Trials (NCT04788355). Suspected patients for COVID-19 were included in the emergency room. The groups were: C (control) with 6 patients, A (anticoagulant apixaban) with 9 patients, H (hydroxychloroquine) with 5 patients and HA (hydroxychloroquine and anticoagulant apixaban) with 8 patients. Results: there were no significant differences between groups. The HA group, in which there was an intervention with two drugs, presented a greater number of days with symptoms (p = 0.037) and worse results, when compared to the control: most relevant symptoms, were: cough (p = 0.001), and anosmia / ageusia (p = 0.011) headache (p = 0.001). Conclusion: The present study began when there were doubts about the use of drugs such as Hydroxychloroquine (HCQ) and apixaban (APX). The reduced "n" was defined through bureaucratic and polemic issues independent of the authors' actions. No clinical benefit was associated with HCQ and APX. There was an increase in the number of symptomatic days when HCQ and APX were administered. Despite the limitations, there was no therapeutic indication of the evaluated drugs. [au]

Objetivo: Avaliar antimalárico com ou sem tratamento anticoagulante, em pacientes com infecção recente por SARS-COV-2. Métodos: Estudo clínico realizado no Hospital das Clínicas Samuel Libânio da Universidade do Vale do Sapucaí, Pouso Alegre-MG. Aprovado pelo Comitê de Ética (4.034.077) e registrado nos Ensaios Clínicos (NCT04788355). Pacientes suspeitos de COVID-19 foram incluídos na sala de emergência. Os grupos foram: C (controle) com 6 pacientes, A (anticoagulante apixabana) com 9 pacientes, H (hidroxicloroquina) com 5 pacientes e HA (hidroxicloroquina e anticoagulante apixabana) com 8 pacientes. Resultados: não houve diferenças significativas entre os grupos. O grupo HA, no qual houve intervenção com dois medicamentos, apresentou maior número de dias com sintomas (p = 0,037) e piores resultados, quando comparado ao controle: os sintomas mais relevantes foram: tosse (p = 0,001), e anosmia/ageusia (p = 0,011) cefaléia (p = 0,001). Conclusão: O presente estudo teve início quando havia dúvidas sobre o uso de medicamentos como hidroxicloroquina (HCQ) e apixabana (APX). O "n" reduzido foi definido por meio de questões burocráticas e polêmicas independentes das ações dos autores. Nenhum benefício clínico foi associado com HCQ e APX. Houve um aumento no número de dias sintomáticos quando HCQ e APX foram administrados. Apesar das limitações, não houve indicação terapêutica dos medicamentos avaliados. [au]

Terapia Ocupacional e telessaúde: relato de experiência de atendimento a criança com transtornos do desenvolvimento / Occupational therapy in telehealth: experience report of care for children with development disorders / Terapia ocupacional y telesalud: informe de experiencia de servicio a niños con transtornos del desarrollo

Contextualização: Relato de experiência do estágio obrigatório do Curso de Graduação em Terapia Ocupacional e da Especialização em Transtorno do Espectro do Autismo (TEA) da Universidade Federal de Minas Gerais. Processo de Intervenção: Participaram 8 estagiários de graduação, 1 terapeuta ocupacional pós-graduanda em TEA e uma docente terapeuta ocupacional, prestando atendimentos remotos a 14 crianças de 1 a 9 anos de idade e suas famílias. As intervenções ocorreram de maneira síncrona, assíncrona ou ambas. Análise crítica da prática: foram observados resultados positivos no desenvolvimento de habilidades das crianças, bem como em seu desempenho e satisfação, avaliados pela Medida Canadense de Desempenho Ocupacional. Síntese de considerações: O estágio no formato telessaúde possibilitou a continuidade das intervenções das crianças previamente atendidas, capacitar pais e cuidadores, além de averiguar possibilidades de atuação em terapia ocupacional pediátrica nesta modalidade, no contexto da COVID-19.(AU) Palavras-chave: telessaúde; terapia ocupacional; transtornos do desenvolvimento

Contextualization: Experience report of the mandatory internship of the Undergraduate Course in Occupational Therapy and of the Specialization in Autism Spectrum Disorder (ASD) of Universidade Federal de Minas Gerais Intervention Process: 8 undergraduate interns participated, 1 occupational therapist specializing in ASD and a teaching occupational therapist, providing remote assistance to 14 children aged 1 and 9 years and their families. The interventions took place in a synchronous, asynchronous or both ways. Critical analysis of the practice: positive results were observed in the development of children's skills, as well as in their performance and satisfaction, assessed by the Canadian Occupational Performance Measure. Summary of considerations: The internship in the telehealth format made it possible to continue the interventions of children previously attended, to train parents and caregivers, in addition to investigating possibilities of work in pediatric occupational therapy in this modality, in the context of COVID-19.(AU) Keywords: telehealth; occupational therapy; developmental disorder

Contextualización: Antecedentes: Informe de experiencia de la pasantía obligatoria del Curso de Grado en Terapia Ocupacional y de la Especialización en Trastorno del Espectro Autista (TEA) da Universidade Federal de Minas Gerais. Proceso de intervención: participaron 8 pasantes de pregrado, 1 terapeuta ocupacional especialista en TEA y un terapeuta ocupacional docente, brindando asistencia remota a 14 niños de 1 y 9 años y sus familias. Las intervenciones se produjeron de forma sincrónica, asincrónica o en ambos sentidos. Análisis crítico de la práctica: se observaron resultados positivos en el desarrollo de las habilidades de los niños, así como en su desempeño y satisfacción, evaluados por la Canadian Occupational Performance Measure. Resumen de consideraciones: La pasantía en el formato de telesalud permitió continuar las intervenciones de los niños previamente atendidos, capacitar a los padres y cuidadores, además de investigar posibilidades de trabajo en terapia ocupacional pediátrica en esta modalidad, en el contexto de COVID- 19.(AU) Palabras clave: telesalud; terapia ocupacional; trastornos del desarrollo

Function, strength, and muscle activation of the shoulder complex in Crossfit practitioners with and without pain: a cross-sectional observational study.

BACKGROUND: The shoulder joint is the most commonly injured joint in CrossFit practitioners, because of the high intensity and loads associated with this sport. Despite the large number of clinical cases, there is a shortage of studies that investigate influence of biomechanical aspects of upper limbs' injuries on CrossFit practitioners. This study hypothesized that there would be a difference in function, strength, and muscle activation between Crossfit practitioners with and without shoulder pain. METHODS: We divided 79 Crossfit practitioners into two groups according to whether they reported pain (n = 29) or no pain (n = 50) in the shoulder during Crossfit training. Muscle function, strength, and activation were assessed using the Disability Arm, Shoulder and Hand function questionnaire, Upper Quarter Y Balance Test and Closed Kinetic Chain Upper Extremity Stability Test shoulder tests, isometric muscle strength assessment by manual dynamometry and muscle activation by surface electromyography and pain report. RESULTS: The function based on questionnaire was associated with pain (p = 0.004). We observed a statistically significant difference between the two groups only in the surface electromyography activity of the lower trapezius, and in the variables of shoulder pain and function (p = 0.038). CONCLUSION: Crossfit practitioners with shoulder pain occurring during training showed good function and stability of the shoulder joint, but there was a reduction in the activation of stabilizing muscles, especially the lower trapezius. Trial registration Registro Brasileiro de Ensaios Clinico (Brasilian National Registry) with the ID: RBR-2gycyv.