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The term “Transgender” is used to describe individuals whose gender identity is different from their external sexual anatomy at birth. The number of people identifying as transgender has increased in recent years, and consequently, the number of gender affirmation surgeries and the use of hormonal therapies has also increased. A wide range of hormonal therapies has emerged considering the target population, age, and final outcomes, and as such these are becoming increasingly developed and complex in order to be the most appropriate for each individual. However, the side effects of these therapies remain to be fully understood. Therefore, this review aims to assess the impact of hormone therapy, in both transgender men and women of different ages, on the lipid profile. From the studies analyzed, it is possible to conclude that there is a relationship between hormone therapy and the lipid profile, with different outcomes between transgender men and women. There is a reduction in cardiovascular risk for transgender women as opposed to transgender men, in whom cardiovascular risk seems to increase due to lipid changes. It is now necessary to understand the mechanisms involved in order to reduce the consequences of these therapies and promote positive health outcomes.

BACKGROUND: Arterio-ureteral fistula (AUF) is a rare but life-threatening cause of hematuria. Most AUFs are secondary to malignancy or extensive pelvic/ vascular surgery CASE REPORT: A case of an 84-year-old patient who developed significant hematuria 4 months after pelvic surgery due to urothelial carcinoma is presented. CONCLUSION: Active surveillance of patients with predisposing risk factors and sensitivity to other differential diagnoses of hematuria such AUF, is important to avoid mortality of these patients. Percutaneous endovascular stent graft is life-saving procedure that is effective and safe.

In this study, we explore the causes and performance outcomes of switching costs in the context of new product development (NPD) from both the supplier and customer perspectives, and discuss the role that switching costs play as moderators and mediators in the relationship between social capital and NPD performance. Based on data from 214 Chinese manufacturers, we employ the structural equation model to test our conceptual model and hypotheses. The results indicate that relationship quality and customer involvement positively and negatively affect switching costs, respectively, and that switching costs negatively affect NPD performance. Switching costs mediate and moderate the relationship between social capital and NPD performance. Furthermore, switching costs significantly and positively moderate the relationship between relationship quality and NPD performance. On the other hand, switching costs insignificantly and negatively moderate the relationship between customer involvement and NPD performance. The theoretical and managerial implications of the findings are discussed.

The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others.

Resumo O artigo científico avalia os determinantes da gestão fiscal representada pelo cumprimento dos limites da Lei de Responsabilidade Fiscal (LRF) e o cumprimento da meta do resultado primário. Para atender aos objetivos propostos, fez-se uma abordagem econométrica, na qual se utilizou a variável binária para cumprimento da meta de despesa total com pessoal e do resultado primário por parte das unidades federativas brasileiras. Para a análise dos fatores determinantes, usaram-se dados sociais e contábeis, características do gestor e uma análise de regressão múltipla para dados em painel, examinando o período de 2017 a 2022. No modelo para a despesa total com pessoal, as transferências da União para os estados e a receita tributária favorecem o não cumprimento dos limites da LRF. Por outro lado, para a meta do resultado primário, as transferências, os restos a pagar, a capacidade de pagamento, a escolaridade e a idade do gestor favorecem o cumprimento da meta.

INTRODUCTION: Partial nephrectomy is considered the gold standard treatment for many renal tumors when technically feasible. Renal artery pseudoaneurysm and arteriovenous fistulas are rare life-threatening complications that occur more frequently after laparoscopic rather than open partial nephrectomy. CASE REPORT: The authors present a case of a 67-year-old female patient with persistent hematuria due to a renal pseudoaneurysm after partial laparoscopic nephrectomy is presented. The patient underwent selective embolization of the pseudoaneurysm using CONCLUSION: Arterial lesions after partial nephrectomy may be amenable to embolization with the advantage of renal parenchyma and function preservation, by comparison with more invasive interventions such as total nephrectomy. Active surveillance of patients after laparoscopic partial nephrectomy should be performed.

BACKGROUND: Calciphylaxis is a rare disease with a poor prognosis predominantly found in end-stage renal disease patients treated with dialysis. This pathology most commonly presents with painful non-healing ulcers, predisposing to high risk of sepsis and death. The authors present a case of bilateral leg ulcers due to calciphylaxis. CASE REPORT: A 40-year-old female patient presented with painful ulcers in both lower limbs, for two months. She had a history of end-stage renal disease, morbid obesity, severe hypertension, arterial fibrillation and secondary hyperparathyroidism. Duplex examination releveled biphasic curves in the foot arteries. The ankle-brachial index was carried out with a result of 1.1, obtaining a WIFi stage of 3 (2/0/2). Venous disease was excluded. A biopsy was obtained, revealing small thick-walled vessels with dystrophic calcification of the intima and media. After surgical debridement, antibiotics directed at the superimposed infection were administered and local wound care with chemical debridement was performed. The ulcers healed completely after 8 weeks and there was no recurrence after 6 months. CONCLUSION: The diagnosis is made by clinical and histological findings. Treatment involves a multidisciplinary approach with medical treatment and wound care. Drugs such as sodium thiosulphate and cinacalcet have shown good results in the healing of ulcers. Vascular surgeons, as they often deal with patients with leg ulcers, should be aware of calciphylaxis as a differential diagnosis when vascular disease is excluded.

A comprehensive biophysical analysis of disease-associated mutations in the voltage-gated sodium channel gene, SCN2A, suggests that dynamic action potential clamp may be a better predictor than voltage clamp of how these mutations alter neuronal excitability, though other approaches are needed to predict severity.

INTRODUCTION: The Abdominal aortic aneurysm (AAA) module of the Portuguese National Vascular Registry (RNPV) is a prospective, voluntary, population-based registry, that encompasses more than 90% of portuguese vascular departments. The aim of this study was to evaluate the results of the first 1000 infra-renal AAA included in the Portuguese RNPV. METHODS: Data were collected from November 2019 to December 2022 and analyzed for demographic aspects, treatment indication, aneurysm anatomic characteristics, type of intervention (EVAR and open surgical repair - OSR), outcome at 30-days and 1-year. EVAR and OSR were compared within elective and urgent settings. RESULTS: A total of 1122 patients were included in the period of study. After applying the exclusion criteria, we analyzed the first consecutive 1000 patients with infra-renal aneurysm submitted to EVAR or OSR, in elective or urgent settings. Elective procedures were perfomed in 79.2% of cases. Patients were predominantly male (91.8%), with a mean age of 74.1 ± 10.6 years. The overall 30-day mortality was 2.7% (EVAR 1.8% and OSR 5.9%; p=0.003). Pos- operative complications were more frequent in the OSR group, with significant repercussion in hospital length, reinterventions and early mortality. Baseline AAA diameter was identified as a predictor of 30-day mortality. Intra- hospital mortality was inversely related with the caseload of the center (p=0.032), mainly due to higher mortality in OSR (p=0.04). The center caseload did not impact the intra-hospital mortality in elective standard EVAR procedures. Urgent repair was performed in 205 patients with significantly larger AAA-diameter (70.5 ± 21.5 mm versus 57.5 ± 14.3 mm, p

ABSTRACT Chlorophyll content is a widely used parameter for nutritional status diagnosis in sugarcane. This study aimed to develop a predictive model of chlorophyll content in sugarcane seedlings using spectral imagery analysis within the electromagnetic spectrum visible range. The experiment was carried out in a split-plot design, with two fertilization rates and three sugarcane cultivars. For chlorophyll analysis, 144 leaves were collected from seedlings. Chlorophyll contents were extracted and measured by SPAD-502 meter. Spectral images within the range of 480 to 710 nm were analyzed using reflectance, absorbance (white source), and fluorescence (source at 405 and 470 nm) responses. Predictive models were developed using multivariate regression methods such as Principal Component Regression and Partial Least Squares Regression. We chose the best model through absorbance response using variable selection and the PLSR method (R2P = 0.718 and RMSEP = 7.665). The wavelengths of 480, 490, 500, 600, 630, and 640 nm were identified as the best for total chlorophyll content determination. The spectral image processing-based method can provide a chlorophyll measurement equivalent to SPAD, with the advantage of having a higher spatial coverage over the entire leaf area. Besides, it can also support automation of the chlorophyll measurement in greenhouses.

Resumo Na sequência da integração europeia, os fluxos migratórios portugueses foram diminuindo, de tal forma que, na viragem do século, acreditou-se que Portugal tinha passado de “país de emigrantes” para “país de imigrantes”. Com efeito, nas últimas décadas do século XX, Portugal atraiu inclusive cidadãos do país que, tradicionalmente, recebeu as mais significativas levas de expatriados portugueses (o Brasil) e, no contexto global, passou a integrar o conjunto de países atrativos para os migrantes económicos. Não obstante, a recente crise económica que pautou os primeiros anos do século XXI veio pôr a descoberto que essa realidade não estava solidificada, pelo menos não tanto como alguns cientistas sociais defenderam. Isto porque novos fluxos migratórios emergiram no território nacional, particularmente visíveis em áreas de baixa densidade, como é o caso da maior parte do distrito da Guarda. Neste trabalho, tendo como pano de fundo a região da Guarda, procuram-se equacionar “as molas impulsionadoras” que estão, novamente, a impelir estes portugueses a procurarem melhores condições de vida longe do país, na tentativa de perceber até que ponto estes novos fluxos migratórios têm uma génese comum aos que os precederam ou se, pelo contrário, têm configurações particulares que os individualizam no panorama migratório português.

Introdução: Os registos clínicos são ferramentas fundamentais para a conhecer a realidade e poder auditar o tratamento de aneurismas da aorta abdominal (AAA). A Sociedade Portuguesa de Angiologia e Cirurgia Vascular, promotora do Registo Nacional de Procedimentos Vasculares (RNPV), desenvolveu um módulo para esta patologia que iniciou o seu funcionamento em Dezembro de 2019. O objetivo deste artigo é apresentar dados referentes ao primeiro ano de funcionamento do módulo de AAA. Métodos: O módulo de AAA do RNPV abriu a possibilidade (voluntária) de registo em Dezembro de 2019. Após formação específica aos investigadores, os centros participantes deram início aos registos, de forma progressiva, ao longo do ano de 2020. O registo é realizado numa ferramenta informática especialmente desenvolvida para o efeito. São registados todos os casos de AAA (incluindo justa- ou supra-renais), com ou sem envolvimento das artérias ilíacas, de etiologia degenerativa. São excluídos aneurismas toraco-abdominais e ilíacos isolados. São registados dados demográficos, anatómicos, co-morbilidades, modo de admissão, detalhes sobre o tratamento e seguimento até aos 30-dias/intra- -hospitalar. O seguimento aos 1 ano e 5 anos é opcional. Para a finalidade deste relatório, foram apenas analisados dados referentes ao modo de admissão e tipo de tratamento, assim como a mortalidade aos 30-dias/intra-hospitalar. Resultados: Entre Dezembro de 2019 e Dezembro de 2020, foram registados 350 doentes na plataforma do módulo de AAA do RNPV. A idade média dos doentes registados é de 74.3 ± 13.7 anos, e 92.0% são do sexo masculino. O modo de admissão foi eletivo em 76,9% dos casos. O diâmetro máximo do aneurisma aórtico foi em média 63.9mm ± 19.9mm. A maioria dos doentes apresentava AAA infra-renal, numa percentagem semelhante em casos eletivos e em urgência (79% vs 76%), p=0.16. A indicação para tratamento foi o diâmetro aórtico em 59.4% dos casos. O tratamento endovascular (EVAR) foi utilizado em 68.9% dos casos. Em cirurgia eletiva, a percentagem de EVAR foi 75.7% e em urgência 45.7%, p < 0.01. Em cirurgia eletiva, a mortalidade aos 30 dias ou intra-hospitalar foi de 3.3% (8 doentes). Para doentes tratados por EVAR foi de 2.8% e para cirurgia aberta 5.2%, p

O linfangioma cístico é uma malformação benigna e rara do sistema linfático, cuja localização retroperitoneal corresponde a cerca de 1% de todos os linfangiomas. A sua apresentação clínica é frequentemente inespecífica. Os autores relatam o caso de uma mulher de 38 anos de idade com dor abdominal persistente e refratária à terapêutica médica, que por esse motivo realizou exames de imagem (ecografia abdominal e tomografia computadorizada toraco-abdomino- pélvica) que revelou uma imagem retroperitoneal de natureza cística, sugestiva de linfangioma. Foi proposta laparotomia para excisão completa da lesão. O exame histopatológico da peça operatória confirmou o diagnóstico de linfangioma cístico. A excisão cirúrgica completa é considerada a terapêutica de eleição, para além de permitir o diagnóstico definitivo.

Introduction: EVAR represents the preferred modality for Abdominal Aortic Aneurysms (AAA) repair. However, a comprehension regarding its limits is paramount to avoid future complications. AAA sac diameter has been described as a relevant risk factor for late complications. The purpose of this study is to summarize relevant findings regarding the association between AAA diameter and AAA-related complications. Methods: MEDLINE databases were searched to identify data addressing specific information on the relation between AAA sac diameter and incidence of AAA-related complications. Only articles in English language between 2003 and 2019 was included. Primary endpoint was freedom from aneurysm-related complications. Results: Five studies were included in our report, including 8443 patients. In two of the included studies patients with larger AAA sacs were at increased risk for aneurysm-related complications after EVAR (HR 1.02 per mm increase CI95% 1.01–1.04 and HR 1.8 95% CI, 1.20–2.72; P = .005). Two studies reported a higher risk of post implant ruptures (HR: 7.7 CI95% 3.1–18.7;) and late conversions (HR 1.6 CI 95% 1.1–2.3) in patients with AAA diameters over 6 and 6.5 cm, respectively. Finally, one study reported a higher rate of neck-related events in patients with AAA diameter > 65mm [HR: 6.4 (2.3–17.7)]. Conclusion: AAA diameter is a relevant risk factor for late complications. However, research is needed to clarify is these are attributable to the challenging associated anatomy or to the space free of thrombus within the sac. Judicious technique choice along with tailored follow-up strategies are advised in this subgroup of patients.

Cardiovascular diseases are important causes of mortality and morbidity worldwide. Vascular smooth muscle cells (SMCs) are major components of blood vessels and are involved in physiologic and pathophysiologic conditions. In healthy vessels, vascular SMCs contribute to vasotone and regulate blood flow by cyclic nucleotide intracellular pathways. However, vascular SMCs lose their contractile phenotype under pathological conditions and alter contractility or signalling mechanisms, including cyclic nucleotide compartmentation. In the present review, we focus on compartmentalized signaling of cyclic nucleotides in vascular smooth muscle. A deeper understanding of these mechanisms clarifies the most relevant axes for the regulation of vascular tone. Furthermore, this allows the detection of possible changes associated with pathological processes, which may be of help for the discovery of novel drugs.

Introduction: Endovascular aneurysm repair (EVAR) has expanded into progressively more challenging anatomies. Proximal neck-morphology represents the major determinant of EVAR durability. Neck-diameter constitutes one of the most important anatomical neck features and influence proximal sealing over time. The purpose of this study is to investigate the influence of wide proximal necks on outcome after standard EVAR. Methods: MEDLINE databases were searched to identify publications addressing the relation between aortic neck diameter and incidence of AAA-related complications. Results: Six studies were included in our review, addressing 6602 patients: 1616 with large necks and 4986 with small necks. Five studies, including 6446 patients, reported higher rates of type 1A endoleak in patients with large necks with hazard/ odds ratios ranging between 2.3–4.1. One study found a higher risk of post-implant rupture in patients with necks>30mm (HR: 5.1; 95% CI, 1.4–19.2). Four studies reported on the influence of wide necks on AAA-related mortality without finding any association. Reduced overall survival was seen in patients with large necks in 4 studies (long term survival ranged between 61.6 and 68% for wide neck patients and 75–90 % for small neck patients), mostly attributable to cardiovascular causes. Conclusions: Patients with wide proximal necks are at greater risk for type 1A endoleak, post-implant rupture and overall-mor- tality. This subgroup of patients may be considered for more complex proximal seal strategies with fenestrated/branched devices or open repair, although there is no evidence of superiority of alternative strategies to standard EVAR in large necks. This subgroup should be offered more stringent imaging follow-up and aggressive treatment of medical comorbidities.

Potassium (K+) channels are usually predominant in the membranes of vascular smooth muscle cells (SMCs). These channels play an important role in regulating the membrane potential and vessel contractility—a role that depends on the vascular bed. Thus, the activity of K+ channels represents one of the main mechanisms regulating the vascular tone in physiological and pathophysiological conditions. Briefly, the activation of K+ channels in SMC leads to hyperpolarization and vasorelaxation, while its inhibition induces depolarization and consequent vascular contraction. Currently, there are four different types of K+ channels described in SMCs: voltage-dependent K+ (KV) channels, calcium-activated K+ (KCa) channels, inward rectifier K+ (Kir) channels, and 2-pore domain K+ (K2P) channels. Due to the fundamental role of K+ channels in excitable cells, these channels are promising therapeutic targets in clinical practice. Therefore, this review discusses the basic properties of the various types of K+ channels, including structure, cellular mechanisms that regulate their activity, and new advances in the development of activators and blockers of these channels. The vascular functions of these channels will be discussed with a focus on vascular SMCs of the human umbilical artery. Then, the clinical importance of K+ channels in the treatment and prevention of cardiovascular diseases during pregnancy, such as gestational hypertension and preeclampsia, will be explored.

Na conjuntura global, em que vivemos, a imagem é determinante para o sucesso dos territórios, pois as imagens apelativas atraem investidores e visitantes ao passo que as imagens pouco atrativas os repelem. São várias as narrativas que concorrem para a formação da imagem holística dos territórios ou regiões. Tradicionalmente a maior parcela dessa função coube aos média impressos, mas o cinema tem vindo a jogar um papel cada vez mais importante em todo esse complexo processo. Isto porque o advento do cinema desencadeou um novo hábito cultural que modificou as modalidades de lazer e rapidamente introduziu profundas alterações nos costumes de milhões de pessoas um pouco por todo o mundo. De facto, diversas pesquisas têm demonstrado que o cinema e a publicidade, em conjunto ou separados, são responsáveis, se não pela criação, pelo menos pela difusão, em grande escala, da maior parte da iconografia da sociedade de consumo. Também para o turismo a imagem joga um papel determinante, por essa razão neste trabalho procurou-se refletir sobre o papel do cinema no complexo processo de formação de imagens turísticas apelativas, tomando como objeto de estudo a região da Serra da Estrela.

Introdução: A oclusão da artéria hipogástrica pode ser necessária na reparação endovascular de aneurismas da aorta abdominal (EVAR). A oclusão intencional da hipogástrica pode ter complicações isquémicas. As endopróteses de bifurcação ilíaca (IBD) surgiram como alternativa endovascular à oclusão da hipogástrica em doentes com elevado risco para isquemia pélvica. Os autores descrevem um caso de oclusão precoce do ramo hipogástrico de IBD com graves consequências clínicas. Caso clínico: Sexo masculino, de 74 anos, com aneurisma da aorta abdominal (diâmetro máximo de 55mm) com envolvimento de ambas as bifurcações ilíacas e segmentos proximais das hipogástricas (diâmetro máximo de 31 e 32 mm), submetido a EVAR com revascularizac¸ão hipogástrica esquerda via IBD (Cook Zenith®) e coiling + overstenting da artéria hipogástrica contralateral. O procedimento decorreu sem complicações e a angiografia final mostrava permeabilidade da hipogástrica revascularizada e escassa colateralidade pélvica. O pós-operatório imediato complicou-se de dor lombar e glútea bilateral associada a manifestações cutâneas isquémicas e monoparesia do membro inferior esquerdo. Por agravamento progressivo nas primeiras 24 h e angioTC com oclusão do stent da hipogástrica esquerda, procedeu-se novamente a revascularização da hipogástrica, com bom resultado na angiografia final. Apesar da revascularização bem-sucedida, houve agravamento progressivo do estado geral, com isquemia pélvica irreversível e rabdomiólise. Óbito ao 5.◦ dia pós-operatório. Conclusão: A isquemia pélvica aguda é uma complicação grave e frequentemente fatal que pode advir da oclusão bilateral das artérias hipogástricas. A falência da revascularização por IBD pode ser fatal, pelo que os autores aconselham um cuidado redobrado no controlo angiográfico final e um baixo limiar para investigação na suspeita de complicações pós-operatórias. Se maior risco de falência técnica, embolização ou escassa colateralidade pélvica, a preservação bilateral de fluxo nas artérias hipogástricas pode estar recomendada.

OBJETIVO: Descrever a prevalência dos fatores de risco gestacionais e sua associação com desfechos materno-fetais desfavoráveis. MÉTODOS: Estudo longitudinal, descritivo e analítico, levando em conta 204 gestantes atendidas no ambulatório de pré-natal de maternidade pública entre maio de 2007 e dezembro de 2008. Os fatores de risco incluíram aspectos sociodemográficos, antecedentes pessoais, obstétricos e familiares, índice de massa corpórea (IMC) pré-gestacional elevado, excesso de ganho de peso gestacional e anemia. Desfechos adversos incluíram pré-eclâmpsia (PE), diabetes mellitus gestacional (DMG), parto cesariano, prematuridade e recém-nascido (RN) com peso alterado. RESULTADOS: A média de idade foi 26±6,4 anos, predominando as pardas (59,8%), com segundo grau completo e superior incompleto de escolaridade (51,8%), união estável (67,2%) e ocupação remunerada (51,0%). A maioria foi admitida no segundo trimestre (63,7%) e 16,7% no primeiro; 42,6% eram primíparas. Hipertensão arterial crônica (2,9%), pré-eclâmpsia (9,8%), excessivo ganho de peso na gestação (15,2%) e diabetes mellitus gestacional (1,0%) foram relatados em gestações anteriores. Na atual gestação foi encontrado IMC pré-gestacional elevado em 34,6% e ganho excessivo de peso em 45,5%, bem como anemia em 25,3% e dislipidemia em 47,3%. O rastreamento para diabetes mellitus gestacional indicado em 17,5% foi confirmado em 3,4% das mulheres. A proteína urinária elevada em amostra única ocorreu em 16,4%. Resultados materno-fetais adversos incluíram PE (4,5%), DMG (3,4%), prematuridade (4,4%) e partos cesarianos (40,1%). RNs grandes para a idade gestacional (GIG) somaram 9,8% e pequenos para a idade gestacional (PIG), 13,8%. A análise de regressão de Poisson multivariada identificou IMC pré-gestacional elevado (>25 kg/m²) como preditor independente para PE (risco relativo (RR) de 17,2 e intervalo de confiança (IC) 95% 2,1-137,5) e parto cesariano (RR=1,8; IC95% 1,1-2,8). A cesárea prévia mostrou-se preditora para novo parto cirúrgico (RR=2,3; IC95% 1,3-3,9). Ganho de peso gestacional excessivo e anemia foram preditores de risco para RN com peso aumentado (RR=4,7; IC95% 1,6-14,0 e RR=3,4; IC95% 1,4-8,1, respectivamente). CONCLUSÃO: O sobrepeso e a obesidade pré-gestacionais, o ganho excessivo de peso na gestação e a anemia foram fatores de risco para pré-eclâmpsia, parto cesariano e alteração de peso do RN.PURPOSE: To assess the prevalence of obstetric risk factors and their association with unfavorable outcomes for the mother and fetus. METHODS: A longitudinal, descriptive and analytical study was conducted on 204 pregnant women between May 2007 and December 2008. Clinical and laboratory assessments followed routine protocols. Risk factors included socio-demographic aspects; family, personal and obstetric history; high pre-gestational body mass index (BMI); excessive gestational weight gain and anemia. Adverse outcomes included pre-eclampsia (4.5%), gestational diabetes mellitus (3.4%), premature birth (4.4%), caesarian birth (40.1%), high birth weight (9.8%) and low birth weight (13.8%). RESULTS: The average age was 26±6.4 years; the mothers were predominantly non-white (84.8%), 51.8% had incomplete or complete secondary level schooling, 67.2% were in a stable marital relationship and 51.0% had a regular paid job; 63.7% were admitted to the prenatal clinic during the second trimester and 16.7% during the first, with 42.6% being primiparous. A past history of chronic hypertension was reported by 2.9%, pre-eclampsia by 9.8%, excessive gestational weight gain by 15.2% and former gestational diabetes mellitus by 1.0%. In the current pregnancy, elevated pre-gestational BMI was found in 34.6%; 45.5% presented with excessive gestational weight gain, 25.3% with anemia and 47.3% with dyslipidemia. Of the 17.5% of cases with altered blood glucose, gestational diabetes mellitus was confirmed in 3.4% and proteinuria occurred in 16.4% of all cases. Adverse maternal fetal outcomes included pre-eclampsia (4.5%), gestational diabetes mellitus (3.4%), premature birth (4.4%), caesarean birth (40.1%) and high and low birth weight (9.8% and 13.8%, respectively). Independent predictors of adverse maternal fetal outcomes were identified by Poisson multivariate regression analysis: pre-gestational BMI>25 kg/m² was a predictor for pre-eclampsia (RR=17.17; 95%CI 2.14-137.46) and caesarian operation (RR=1.79; 95%CI 1.13-2.85), previous caesarean was a predictor for present caesarean operation (RR=2.28; 95%CI 1.32-3.92) and anemia and high gestational weight gain were predictors for high birth weight (RR=3.38; 95%CI 1.41-8.14 and RR=4.68; 95%CI 1.56-14.01, respectively). CONCLUSION: Pre-gestational overweight/obesity, previous caesarean, excessive weight gain and anemia were major risk factors for pre-eclampsia, caesarean operations and high birth weight.

Introdução: Os Falsos Aneurismas (FA) são uma das complicações mais frequentemente associadas à punção femoral diagnóstica e de intervenção cardíaca. A sua abordagem terapêutica tem evoluído no sentido da preponderância das técnicas não invasivas sendo a Cirurgia Convencional cada vez menos frequentemente praticada. Objectivos: Os autores propõem a propósito de um caso clínico, e através de uma revisão da literatura discutir a abordagem terapêutica dos FA e as indicações da Cirurgia Convencional. Caso clínico: Doente de sessenta e um anos, sexo masculino, com antecedentes de hipertensão arterial, doença coronária com enfarte agudo do miocárdio prévio, miocardiopatia dilatada, fibrilhação auricular paroxística sendo portador de cardiodesfibrilhador. Foi submetido a cateterismo cardíaco por via femoral direita para ablação do Feixe de His, tendo sido referenciado ao Serviço de Angiologia e Cirurgia Vascular por desenvolvimento progressivo de massa pulsátil dolorosa acompanhada de hipostesia da face anterior da coxa. A Angiodinografia confirmou a presença de falso aneurisma da artéria femoral profunda direita com 3cm de maior diâmetro e a presença de uma fístula entre a artéria e a veia femorais superficiais direitas. Por abordagem cirúrgica aberta, foi realizada a exclusão do falso aneurisma e rafia da artéria e veia femorais superficiais. Conclusão: A abordagem de primeira linha dos falsos aneurismas iatrogénicos pós cateterismo cardíaco é não invasiva mas a Cirurgia Convencional detém ainda um lugar primordial para um grupo restrito de doentes.Introduction: Pseudoaneurysms (PAN) are one of the most common complications of cardiac catheterization. Treatment has evolved towards a less invasive approach, reducing the number of Open repairs. Objectives: The authors propose to discuss the contemporary management of PAN and the remaining indications for Conventional Surgical Repair based upon a case report. Case Report: Sixty-one year old Caucasian male, with personal history of Hypertension, previous myocardial infarct, dilated myocardiopathy, paroxistic auricular fibrillation, with an implanted cardiodefibrillator, was submitted to His Bundle ablation by right femoral catheterization. He was referred because of the presence of a painful pulsating mass at the catheterization site. A color-Doppler confirmed the diagnosis of Pseudoaneurysm of the right Deep Femoral Artery with 3cm of diameter and the presence of an Arteriovenous Fistula between the superficial femoral vessels. The patient was treated in a Classic fashion, with exclusion of the pseudoaneurysm and repair of the superficial artery and vein. Conclusion: First-line treatment for PAN remains non-invasive but Open Surgical repair is still an important alternative in the management of a restrict group of patients.

FUNDAMENTO: Fatores relacionados ao nível sócio-econômico, à qualidade e à gestão assistencial podem influenciar na letalidade e morbidade por infarto agudo do miocárdio (IAM). OBJETIVO: Comparar letalidade e morbidade por IAM entre hospital público e privado. MÉTODOS: Estudo observacional, com grupos de comparação. Avaliação clínica na admissão e registro de dados diagnósticos, terapêuticos e evolutivos até a alta ou o óbito. Comparação das características clínicas por análise univariada seguida de análise bivariada, avaliando a associação de preditores com óbito e morbidade (Killip >I), SPSS, versão 13,0. RESULTADOS: Avaliados 150 pacientes, 63 (42,0%) privados e 87 (58,0%) públicos, com 63,1% e 62,1% de homens e idades de 61,1±13,8 e 60,0±11,6 anos, respectivamente. A letalidade por IAM foi de 19,5% nos públicos vs 4,8% nos privados (p=0,001) e a morbidade (Killip classe >1) de 34,3% nos públicos vs 15,0% nos privados (p=0,012). Houve diferença significativa nos públicos devido à menor renda familiar e escolaridade (70,1% com um a dois salários vs 19,0%, p1 hora: 76,9% vs 48,6%; p=0,003) e maior tempo para ser medicado (THM>15 minutos: 47,1% vs 8,0%, pFUNDAMENTO: Factores relacionados al nivel socioeconómico, a la calidad y a la gestión asistencial pueden influir en la letalidad y la morbilidad por infarto agudo de miocardio (IAM). OBJETIVO: Comparar letalidad y morbilidad por IAM entre hospital público y privado. MÉTODOS: Estudio observacional, con grupos de comparación. Evaluación clínica al ingreso y registro de datos diagnósticos, terapéuticos y evolutivos hasta el alta u óbito. Comparación de las características clínicas por análisis univariado, seguida de análisis bivariado, evaluando la asociación de predictores con óbito y morbilidad (Killip >I), SPSS, versión 13,0. RESULTADOS: Se evaluaron a 150 pacientes, 63 pacientes privados (42,0%) y 87 públicos (58,0%), con un 63,1% y un 62,1% de varones y edades variando de 61,1±13,8 a 60,0±11,6 años, respectivamente. La letalidad por IAM fue de un 19,5% en los pacientes públicos vs. un 4,8% en los privados (P=0,001), y la morbilidad (Killip classe >1) de un 34,3% en los públicos vs. el 15% en los pacientes privados (P=0,012). Hubo diferencia significativa en los pacientes públicos por culpa de la menor renta familiar y de la baja escolaridad (un 70,1% con uno a dos salarios vs. el 19%, P1 hora: un 76,9% vs. un 48,6%; P=0,003) y un mayor tiempo transcurrido hasta la administración de los medicamentos (THM>15 minutos: 47,1% vs. 8,0%, PBACKGROUND: Factors related to socioeconomic status and health care quality and management may influence mortality and morbidity rates due to acute myocardial infarction (AMI). OBJECTIVE: To compare mortality and morbidity in patients with AMI hospitalized in public and private hospitals. METHODS: An observational study, with comparison groups. Clinical evaluation on admission, and recording of diagnostic, therapeutic and evolution data until discharge or death. Comparison of clinical characteristics by univariate analysis followed by bivariate analysis, evaluating the combination of predictors with death and morbidity (Killip> I), SPSS, version 13.0. RESULTS: 150 patients were evaluated, 63 (42.0%) of private hospitals and 87 (58.0%) of public hospitals, with 63.1% and 62.1% of males, aged 61.1 ± 13.8 and 60.0 ± 11.6 years, respectively. The mortality from AMI was 19.5% in public hospitals vs 4.8% in private hospitals (p = 0.001), and morbidity (Killip class> I) was 34.3% in public hospitals vs 15.0% in private hospitals (p = 0.012). There was a significant difference between public and private patients, due to lower family income and education (70.1% with one to two salaries vs 19.0%, p 1 hour: 76.9% vs 48.6%, p = 0.003); and a longer period of time before being medicated (AMT > 15 minutes: 47.1% vs 8.0%; p

This paper is an attempt to explain the process and outcomes of customer services levels and how they shape customer perceptions (of their relationship with services providers) and reactions. As an entirely conceptual work, this paper proposes a model for understanding the pathway and the end of good and bad customer service. Implications of the study on theory and practice are discussed.

The main objective of this article is to analyze the insertion of environmental management in theorganizational structure of 9 Brazilian companies, in search of a better relationship with the environment.Further, we intend to show an agenda with research opportunities for future research in this area ofknowledge. A theoretical review of the relationship between environmental management and organizationalstructure was done. This theoretical review was the big picture to development of 9 case studies withISO14001 certified companies located in São Paulo State. The results show that: (a) for all the cases,environmental management is under quality management area; (b) only two companies adopt moreadvanced environmental management practices and these two companies have more complex organizationalstructure; (c) only two companies have the environmental management structure named “matrix”, while theother companies have the type named “limited environmental management insertion”; (d) it is possible todevelop a framework designed to understanding the process of greening organization to the 9 cases in study.Further these results, we designed a research agenda as a guide to future research initiatives.O objetivo deste artigo é analisar a incorporação da gestão ambiental na estrutura organizacional de nove empresas brasileiras, engajadas na busca pela melhoria do seu relacionamento com o meio ambiente.Adicionalmente, persegue-se o objetivo de delinear uma agenda de pesquisas futuras para o tema. Para aconsecução desses objetivos, realizou-se uma fundamentação teórica sobre estrutura organizacional e suarelação com a gestão ambiental organizacional. Essa construção teórica serviu de pano de fundo para arealização de nove estudos de caso, em empresas com certificação ISO 14001, localizadas no Estado de SãoPaulo. Os resultados indicam que: (a) a área de gestão ambiental tende a ser subordinada à área de qualidade;(b) dentre as nove organizações, duas tendem a adotar práticas mais avançadas e complexas de gestãoambiental, que as leva a ter uma estrutura organizacional também mais complexa; (c) apenas duasorganizações incorporaram a gestão ambiental do tipo “matricial”, enquanto sete organizações podem serclassificadas no tipo “integração pontual da gestão ambiental”; (d) é possível propor um framework paracompreender o processo de incorporação das questões ambientais nos nove casos analisados. Além dessesresultados, apresenta-se uma agenda temática para pesquisas vindouras.

Introduction. Primary venous tumours are a rare cause of deep vein thrombosis. The authors present a case where the definitive diagnosis was delayed by inconclusive complementary imaging. Clinical Case. A thirty-seven-year-old female presented with an iliofemoral venous thrombosis of the right lower limb. The patient had presented with an episode of femoral-popliteal vein thrombosis five months before and was currently under anticoagulation. Phlegmasia alba dolens installed progressively, as thrombus rapidly extended to the inferior vena cava despite systemic thrombolysis and anticoagulation. Diagnostic imaging failed to identify the underlying aetiology of the deep vein thrombosis. The definitive diagnosis of primary venous leiomyosarcoma was reached by a subcutaneous abdominal wall nodule biopsy. Conclusion. Primary venous leiomyosarcoma of the iliac vein is a rare cause of deep vein thrombosis, which must be considered in young patients with recurrent or refractory to treatment deep vein thrombosis.

Normas de concretude para 909 palavras foram coletadas utilizando-se uma escala de julgamento com sete pontos, onde cada extremo representava os níveis altamente abstrato ou concreto, respectivamente. Os resultados evidenciaram uma distribuição bi-modal sugerindo que as palavras podem ser classificadas nas categorias concreta ou abstrata. A confiabilidade média das normas foi r=0,97. Não foram detectadas influências do sexo, idade, freqüência de ocorrência das palavras em materiais escritos ou tamanho da categoria nos julgamentos de concretude. Os resultados sugerem que a concretude pode ser considerada como um atributo independente das palavras.

Aim: The aim of the present study was to define whether cardiac myosin contributes to energy conservation in the heart of hibernating mammals., Methods: Thin cardiac strips were isolated from the left ventricles of active and hibernating grizzly bears; and subjected to loaded Mant-ATP chase assays, X-ray diffraction and proteomics., Main Findings: Hibernating grizzly bears displayed an unusually high proportion of ATP-conserving super-relaxed cardiac myosin molecules that are likely due to altered levels of phosphorylation and rod region stability., Conclusions: Cardiac myosin depresses the heart's energetic demand during hibernation by modulating its function., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julien Ochala reports financial support was provided by Carlsberg Foundation. Henk Granzier reports financial support was provided by National Institutes of Health. Weikang Ma reports financial support was provided by National Institutes of Health. Weikang Ma reports a relationship with Edgewise Therapeutics, Inc. that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: Some studies in humans show that the concurrent use of clopidogrel and omeprazole decreases plasma clopidogrel active metabolite (CAM) concentrations and clopidogrel antiplatelet effects. Whether this drug interaction occurs in cats is unknown., Hypothesis: We hypothesized that administration of clopidogrel with omeprazole would decrease plasma CAM concentrations and decrease clopidogrel antiplatelet effects in healthy cats., Animals: Ten domestic cats., Methods: In this 2-sequence, 2-period, 2-treatment randomized crossover study, healthy cats were randomly assigned to receive clopidogrel only (18.75 mg PO q24h) or clopidogrel with omeprazole (1 mg/kg PO q12h) for 10 days, followed by a 2-week washout period, and then the opposite treatment for another 10 days. Blood was collected by jugular venipuncture on days 0, 5, and 10. Plasma CAM concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. Platelet function was evaluated using Plateletworks, Multiplate Analyzer, and Platelet Function Analyzer-100 (PFA-100)., Results: Multiplate Analyzer and PFA-100 detected no difference in platelet function between days or treatment groups. Plateletworks detected a significant difference (P < .001) in platelet function from day 0 to 5 and day 0 to 10 in both treatment groups but no difference between treatment groups. Plasma CAM concentrations were significantly lower on day 10 (P < .02) in cats receiving both medications versus clopidogrel only., Conclusions and Clinical Importance: Concurrent omeprazole and clopidogrel administration was associated with altered pharmacokinetics on day 10, but no difference in pharmacodynamics between the 2 treatment groups. The short-term use of clopidogrel and omeprazole does not seem to alter platelet function significantly., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Epidemiological and observational studies suggest that vitamin D has potential for the chemoprevention of ovarian cancer. The anticancer effect of vitamin D in the fallopian tube epithelium (FTE), which is now thought to harbor the precursor cells for high grade ovarian cancer, is not known. The purpose of this study was to investigate whether vitamin D can inhibit carcinogenesis in the mogp-TAg fallopian tube (FT) ovarian cancer mouse model and examine underlying mechanisms. To test this hypothesis, 3 groups of 40 5-week-old female mogp-TAg mice were divided equally into two cohorts of 20 mice, treated with either vehicle (vitamin D solvent) or the active 1,25(OH)2D3 analogue EB1089, delivered via mini-pump or IP injection or cholecalciferol delivered in the feed. The FTs were characterized histologically and pathologically after 3 and 7 weeks of treatment. The effect of vitamin D on cultured human FTE cells was also examined. After 3 weeks, vitamin D, delivered as either cholecalciferol or EB1089 significantly inhibited FT carcinogenesis. After 7 weeks, cholecalciferol significantly reduced p53 signatures, serous tubal epithelial carcinoma, FT cancer, and plasma CA125 while increasing apoptosis in the FTE. EB1089 had no significant effect on FT carcinogenesis at 7 weeks. Cholecalciferol significantly reduced proliferation and increased apoptosis in vitro in p53-altered FTE cells. In conclusion, vitamin D inhibited FT carcinogenesis by clearing cells with p53 alterations. These data suggest that vitamin D has merit for the chemoprevention of fallopian tube/ovarian cancer. The optimal chemopreventive effect may be dependent on the route of vitamin D administration.

Objective: Recent evidence suggests that the fimbriated end of the fallopian tube harbors the precursor cells for many high-grade ovarian cancers, opening the door for development of better screening methods that directly assess the fallopian tube in women at risk for malignancy. Previously we have shown that the karyometric signature is abnormal in the fallopian tube epithelium in women at hereditary risk of ovarian cancer. In this study, we sought to determine whether the karyometric signature in serous tubal intraepithelial carcinoma (STIC) is significantly different from normal, and whether an abnormal karyometric signature can be detected in histologically normal tubal epithelial cells adjacent to STIC lesions., Methods: The karyometric signature was measured in epithelial cells from the proximal and fimbriated portion of the fallopian tube in fallopian tube specimens removed from women at: 1) average risk for ovarian cancer undergoing surgery for benign gynecologic indications (n = 37), 2) hereditary risk of ovarian cancer (germline BRCA alterations) undergoing risk-reducing surgery (n = 44), and 3) diagnosed with fimbrial STICs (n = 17)., Results: The karyometric signature in tubes with fimbrial STICs differed from that of tubes with benign histology. The degree of karyometric alteration increased with increasing proximity to fimbrial STICs, ranging from moderate in the proximal portion of the tube, to greatest in both normal appearing fimbrial cells near STICs as well as in fimbrial STIC lesions., Conclusion: These data demonstrate an abnormal karyometric signature in STICs that may extend beyond the STIC, potentially providing an opportunity for early detection of fallopian tube neoplasia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Trazodone is a serotonin antagonist/reuptake inhibitor medication commonly used for anxiety in dogs. Therapy with selective serotonin reuptake inhibitors in humans is associated with bleeding disorders and increased arrhythmogenesis., Hypothesis/objectives: To evaluate markers of primary hemostasis and corrected QT (cQT) interval in dogs before and after oral administration of standard dosages of trazodone or placebo., Animals: Fifteen apparently healthy, client-owned dogs., Methods: A single-blinded, randomized placebo-controlled crossover study was performed. Dogs were administered trazodone (5 to 7.5 mg/kg PO Q12h) or placebo. [Correction added after first online publication on 14 October 2023. In the abstract (methods) section (57.5 mg/kg PO Q12h) changed as (5 to 7.5 mg/kg PO Q12h).] Buccal mucosal bleeding time (BMBT), platelet count, platelet aggregation via Plateletworks, PFA-100 closure time and cQT interval were measured. A Shapiro-Wilk test was performed followed by either a paired t test or a Wilcoxon signed-rank test., Results: No significant difference was detected in the BMBT, PFA-100 closure times, platelet counts, and cQT interval between trazodone or placebo. However, using Plateletworks, there was a significant decrease in platelet aggregation after administration of trazodone (95%; 81-97 vs 62%; 39-89, P = .002) and not placebo (95%; 81-97 vs 91%; 81-96, P = .21)., Conclusions: It is unknown if this represents a clinically relevant change or if dogs with preexisting impairment in primary hemostasis or receiving higher dosages or longer durations of trazodone could have a more substantial change in hemostatic variables., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Recent studies suggest that the fallopian tube epithelium (FTE) harbors the precursor for high-grade ovarian cancer, creating opportunities for targeting the FTE for ovarian cancer prevention. Preclinical evidence supports progestins as ovarian cancer preventives, but the effect of progestins on the FTE is not well characterized. The murine oviduct-specific glycoprotein promotor-driven simian virus 40 large T-Antigen (mogp-TAg) transgenic mouse model develops neoplastic lesions in the fallopian tube in a manner similar to that described in human fallopian tube and ovarian cancers. In this study, we investigated the inhibitory effects of the progestin depo-medroxyprogesterone acetate (DMPA) on fallopian tube carcinogenesis following treatment for 3 and 7 weeks in 5-week-old mogp-TAg mice. Overall, compared with vehicle-treated mice, the fallopian tube of DMPA-treated mice was significantly smaller ( P < 0.0005), accumulated fewer p53-positive cells, had normal distribution of ciliated cells, less nuclear pleomorphism and epithelial tufting, and had a significantly lower proliferative index ( P = 0.001). Accumulation of p53 signatures and serous tubal intraepithelial carcinomas (STIC) in the fallopian tube was significantly reduced in the DMPA ( P < 0.0005) treatment group. Moreover, the fallopian tube of the DMPA-treated mice developed significantly less adenocarcinoma compared with vehicle ( P < 0.005) at both treatment time points. DMPA treatment significantly induced cleaved caspase-3 ( P < 0.0005) in the FTE compared with vehicle suggesting that apoptosis is involved in DMPA-related clearance of abnormal cells from the fallopian tube. These data demonstrate that DMPA targets early events in fallopian tube carcinogenesis by clearing genetically damaged cells, leading to marked reduction in adenocarcinoma, supporting progestins as chemopreventive agents for fallopian tube and ovarian cancers. PREVENTION RELEVANCE: The fallopian tube is thought to harbor the cell of origin for most ovarian cancers. We show in a mouse model of fallopian tube cancer that progestin eradicates the earliest known precancerous lesions and markedly inhibits fallopian tube carcinogenesis, adding to growing preclinical evidence supporting progestins as potent ovarian cancer chemopreventive agents., (©2021 American Association for Cancer Research.)

Hair cortisol concentration (HCC) is being used increasingly to evaluate long-term stress in many mammalian species. Most of the cortisol is assumed to passively diffuse from circulating blood into hair follicles and gradually accumulate in growing hair. However, our research with free-ranging grizzly bears (Ursus arctos) suggests HCC increases significantly within several hours following capture, a time too brief to be explained by this mechanism alone. In this study with captive grizzly bears, we sought to determine if a brief spike in blood cortisol concentration, thus mimicking a single stressful event, would cause an increase in HCC over a 7-day period. To do this, we administered a single intravenous dose (5 μg/kg) of cosyntropin to three captive unanaesthetised adult female grizzly bears on two occasions, during April when hair growth was arrested and during August when hair was growing. In both trials, the cosyntropin caused a two-fold or greater increase in serum cortisol levels within 1 hr but did not appear to influence HCC at 1, 48, and 168 hr following cosyntropin administration. We conclude the cosyntropin-induced cortisol spike was likely insignificant when compared to the adrenocortical response that occurs in free-ranging bears when captured. We suggest further study with a larger sample of captive bears to evaluate the combined effects of anaesthesia and multiple doses of cosyntropin administered over several hours would better simulate the adrenocortical response of free-ranging grizzly bears during capture., (© 2021 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Significance: Most cases of high-grade serous ovarian carcinoma originate as serous tubal intraepithelial carcinoma (STIC) lesions in the fallopian tube epithelium (FTE), enabling early endoscopic detection., Aim: The cell-acquiring fallopian endoscope (CAFE) was built to meet requirements for locating potentially pathological tissue indicated by an alteration in autofluorescence or presence of a targeted fluorophore. A channel was included for directed scrape biopsy of cells from regions of interest., Approach: Imaging resolution and fluorescence sensitivity were measured using a standard resolution target and fluorescence standards, respectively. A prototype was tested in ex vivo tissue, and collected cells were counted and processed., Results: Measured imaging resolution was 88  μm at a 5-mm distance, and full field of view was ∼45  deg in air. Reflectance and fluorescence images in ex vivo porcine reproductive tracts were captured, and fit through human tracts was verified. Hemocytometry counts showed that on the order of 105  cells per scrape biopsy could be collected from ex vivo porcine tissue., Conclusions: All requirements for viewing STIC in the FTE were met, and collected cell counts exceeded input requirements for relevant analyses. Our benchtop findings suggest the potential utility of the CAFE device for in vivo imaging and cell collection in future clinical trials.

The purpose of this study was to investigate changes in expression of known cellular regulators of metabolism during hyperphagia (Sept) and hibernation (Jan) in skeletal muscle and adipose tissue of brown bears and determine whether signaling molecules and transcription factors known to respond to changes in cellular energy state are involved in the regulation of these metabolic adaptations. During hibernation, serum levels of cortisol, glycerol, and triglycerides were elevated, and protein expression and activation of AMPK in skeletal muscle and adipose tissue were reduced. mRNA expression of the co-activator PGC-1α was reduced in all tissues in hibernation whereas mRNA expression of the transcription factor PPAR-α was reduced in the vastus lateralis muscle and adipose tissue only. During hibernation, gene expression of ATGL and CD36 was not altered; however, HSL gene expression was reduced in adipose tissue. During hibernation gene expression of the lipogenic enzyme DGAT in all tissues and the expression of the FA oxidative enzyme LCAD in the vastus lateralis muscle were reduced. Gene and protein expression of the glucose transporter GLUT4 was decreased in adipose tissue in hibernation. Our data suggest that high cortisol levels are a key adaptation during hibernation and link cortisol to a reduced activation of the AMPK/PGC-1α/PPAR-α axis in the regulation of metabolism in skeletal muscle and adipose tissue. Moreover, our results indicate that during this phase of hibernation at a time when metabolic rate is significantly reduced metabolic adaptations in peripheral tissues seek to limit the detrimental effects of unduly large energy dissipation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Revealing the mechanisms underlying the reversible physiology of hibernation could have applications to both human and animal health as hibernation is often associated with disease-like states. The present study uses RNA-sequencing to reveal the tissue and seasonal transcriptional changes occurring in grizzly bears ( Ursus arctos horribilis ). Comparing hibernation to other seasons, bear adipose has a greater number of differentially expressed genes than liver and skeletal muscle. During hyperphagia, adipose has more than 900 differentially expressed genes compared to active season. Hibernation is characterized by reduced expression of genes associated with insulin signaling, muscle protein degradation, and urea production, and increased expression within muscle protein anabolic pathways. Across all three tissues we find a subset of shared differentially expressed genes, some of which are uncharacterized, that together may reflect a common regulatory mechanism. The identified gene families could be useful for developing novel therapeutics to treat human and animal diseases., Competing Interests: Competing interestsThe authors declare no competing interests.

Background: Across China and Southeast Asia, an estimated 17,000 bears are currently farmed for bile, primarily for traditional medicines. Depending on country, bile is extracted daily via transabdominal gallbladder fistulas, indwelling catheters, or needle aspiration. Despite claims that bears do not develop adverse effects from bile extraction, health issues identified in bears removed from bile farms include bile-extraction site infections, abdominal hernias, peritonitis, cholecystitis, hepatic neoplasia, cardiac disease, skeletal abnormalities, and abnormal behaviors. We present a comprehensive assessment of the effects of bile farming by comparing serum biochemical and hematological values of bears from farms that were bile-extracted (BE) and bears from farms not bile-extracted (FNE) with bears from non-farm captive (ZOO) and free-range (FR) environments. We hypothesized BE bears would have significant laboratory abnormalities compared to all non-extracted bear groups. We also hypothesized BE bears would have reduced long-term survival compared to FNE bears despite removal from farms., Results: BE bears exhibited the highest values and greatest variation (on a population level) in laboratory parameters compared to all non-extracted bear groups particularly for alanine transaminase, gamma glutamyltransferase (GGT), total bilirubin (TBIL), alkaline phosphatase (ALKP), blood urea nitrogen, creatinine (CREA), and total white blood cell count. Significant differences were detected between bear groups when accounting for season, sex, and/or age. BE bears exhibited greater mean serum GGT compared to all non-extracted bear groups, and the odds of having elevated TBIL were 7.3 times greater for BE bears, consistent with hepatobiliary disease. Biochemical parameter elevations in BE bears persisted up to 14 years post-rescue, consistent with long-term effects of bile-extraction. BE bears that arrived with elevated CREA and ALKP had median survival times of 1 and 4 years respectively, and regardless of laboratory abnormalities, BE bears had significantly shorter survival times compared to FNE bears., Conclusions: Our results provide strong evidence that bile extraction practices not only represent a temporary constraint for bears' welfare, but confer distinct long-term adverse health consequences. Routine laboratory panels may be insensitive to detect the extent of underlying illness in BE bears as these bears have significantly reduced survival regardless of biochemical assessment compared to FNE bears.

Background: Post-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes in breast cancer patients; however, some patients develop cancer or treatment-related pain that negatively impacts quality of life. This study examined an inflammatory biomarker, C-reactive protein (CRP), in RT-related pain in breast cancer., Methods: During 2008 and 2014, breast cancer patients who underwent RT were prospectively evaluated for pre- and post-RT pain. Pre- and post-RT plasma CRP levels were measured using a highly sensitive CRP ELISA kit. Pain score was assessed as the mean of four pain severity items (i.e., pain at its worst, least, average, and now) from the Brief Pain Inventory. Pain scores of 4-10 were classified as clinically relevant pain. Multivariable logistic regression analyses were applied to ascertain the associations between CRP and RT-related pain., Results: In 366 breast cancer patients (235 Hispanic whites, 73 black/African Americans, and 58 non-Hispanic whites), 17% and 30% of patients reported pre- and post-RT pain, while 23% of patients had RT-related pain. Both pre- and post-RT pain scores differed significantly by race/ethnicity. In multivariable logistic regression analysis, RT-related pain was significantly associated with elevated pre-RT CRP (≥ 10 mg/L) alone (odds ratio (OR) = 2.44; 95% confidence interval (CI) = 1.02, 5.85); or combined with obesity (OR = 4.73; 95% CI = 1.41, 15.81) after adjustment for age and race/ethnicity., Conclusions: This is the first pilot study of CRP in RT-related pain, particularly in obese breast cancer patients. Future larger studies are warranted to validate our findings and help guide RT decision-making processes and targeted interventions.

Across China and Southeast Asia, over 17,000 bears are currently farmed for bile, predominantly for traditional Chinese medicines. Bears on farms in China are cage confined and undergo repeated daily bile extraction facilitated by surgically implanted catheters or gallbladder fistulas. Numerous health problems have been reported in bile-farmed bears including peritonitis, abdominal hernias, and extraction site abscessation. Between 2009 and 2014, five Asiatic black bears ( Ursus thibetanus) and one Asiatic black/Eurasian brown bear ( Ursus arctos arctos) hybrid, rescued from the bear bile industry in China, died from ruptured and/or dissecting aortic aneurysm. Medical records were reviewed and two bears exhibited no clinical signs prior to death. In four bears, clinical findings varied and included increased stereotypic behavior prior to death, epistaxis, retinal lesions, dysphagia, weight loss, and acute onset of hyporexia. On postmortem examination, hemopericardium with dissection and/or rupture of the ascending aorta and left ventricular wall hypertrophy were present in all cases. No evidence of infectious disease, connective tissue disorders, or congenital cardiac disease was identified. Based on these observations screening thoracic radiography was performed on all bears at the rescue center and aortic dilation was identified in 73 of 134 (54.5%) bile-extracted bears. To the authors' knowledge, aortic aneurysm, rupture, and/or dissection have not been previously reported in any bear species and the high prevalence in this population of bears suggests an association with bile-farming practices. Future studies are needed to investigate the etiopathogenesis of this condition to aid in early diagnosis and improved management of bears being rescued from bile farms across Asia.

The fukutin-related protein P448L mutant mouse replicates many pathologies common to limb girdle muscular dystrophy 2i (LGMD2i) and is a potentially strong candidate for relevant drug screening studies. Because striated muscle function remains relatively uncharacterized in this mouse, we sought to identify metabolic, functional and histological metrics of exercise and cardiac performance. This was accomplished by quantifying voluntary exercise on running wheels, forced exercise on respiratory treadmills and cardiac output with echocardiography and isoproterenol stress tests. Voluntary exercise revealed few differences between wild-type and P448L mice. By contrast, peak oxygen consumption (VO 2 peak) was either lower in P448L mice or reduced with repeated low intensity treadmill exercise while it increased in wild-type mice. P448L mice fatigued quicker and ran shorter distances while expending 2-fold more calories/meter. They also received over 6-fold more motivational shocks with repeated exercise. Differences in VO 2 peak and resting metabolic rate were consistent with left ventricle dysfunction, which often develops in human LGMD2i patients and was more evident in female P448L mice, as indicated by lower fractional shortening and ejection fraction values and higher left ventricle systolic volumes. Several traditional markers of dystrophinopathies were expressed in P448L mice and were exacerbated by exercise, some in a muscle-dependent manner. These include elevated serum creatine kinase and muscle central nucleation, smaller muscle fiber cross-sectional area and more striated muscle fibrosis. These studies together identified several markers of disease pathology that are shared between P448L mice and human subjects with LGMD2i. They also identified novel metrics of exercise and cardiac performance that could prove invaluable in preclinical drug trials. NEW & NOTEWORTHY Limb-girdle muscular dystrophy 2i is a rare dystroglycanopathy that until recently lacked an appropriate animal model. Studies with the FKRP P448L mutant mouse began assessing muscle structure and function as well as running gait. Our studies further characterize systemic muscle function using exercise and cardiac performance. They identified many markers of respiratory, cardiac and skeletal muscle function that could prove invaluable to better understanding the disease and more importantly, to preclinical drug trials., (Copyright © 2017 the American Physiological Society.)

Adiponectin is the most abundant plasma adipokine, and is well known for its role in energy homeostasis and cardiac protection. In humans with dilated cardiomyopathy, myocardial adiponectin protein expression is reduced compared to normal hearts and has been implicated in the pathology of cardiomyopathy. Serum adiponectin levels are often conflicting, with higher levels associated with poor survival in humans with congestive heart failure (CHF). We evaluated adiponectin serum concentrations and myocardial protein expression in dogs with naturally occurring myxomatous mitral valve disease and CHF. We compared the findings to active and hibernating brown bears as bears are adapted to endure an extreme period of low cardiac output during their annual hibernation. Bears exhibited largely the active high-molecular weight (HMW) versus the low-molecular weight isoforms of myocardial adiponectin (HMW:LMW = 6.3) during both the active period and hibernation, while healthy dogs exhibited a more balanced mix of isoforms. Dogs with CHF expressed predominately HMW isoforms of adiponectin (HMW:LMW = 12.5), appearing more similar to bears. In contrast to humans, serum adiponectin was significantly lower in dogs with CHF and lowest levels in the severest CHF class. In both dogs and bears, myocardial adiponectin was expressed independent of circulating adiponectin concentrations, suggesting a local regulatory mechanism within the heart., Competing Interests: There are no known conflicts of interest to declare.