Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

A formação acadêmica em educação física para a atenção básica do SUS: uma revisão integrativa em teses e dissertações / Academic training in physical education for primary care in the SUS: an integrative review of theses and dissertations / La formación académica en educación física para la atención primaria en el SUS: una revisión integradora de tesis y disertaciones

Faz-se necessário abordar criticamente a promoção da saúde e os elementos que impactam o processo saúde/doença no cotidiano da formação do professor de Educação Física (EF). Portanto, este estudo tem como objetivo analisar teses e dissertações produzidas sobre a formação acadêmica em EF e sua relação com a saúde no contexto do Sistema Único de Saúde (SUS), por meio de uma revisão integrativa. O estudo encontrou seis dissertações que mostraram que apesar da percepção das universidades de que a formação acadêmica permite aos professores de EF atuar no SUS, é possível identificar a manutenção do discurso conservador e biomédico, o que afeta a compreensão, a percepção e a ação dos professores de EF em equipes multiprofissionais no contexto da Saúde Coletiva presente no SUS (AU).

It is necessary to critically approach health promotion and the elements that impact the health/disease process in the daily training of Physical Education (PE) teachers. Therefore, this study aims to analyze the theses and dissertations produced on academic training in PE and its relationship with health in the context of the Unified Health System (SUS), through an integrative review. The study found six dissertations that showed that, despite the universities' perception that academic training allows PE teachers to work in the SUS, it is possible to identify the maintenance of the conservative and biomedical discourse, which affects understanding, perception and action of PE teachers in multidis-ciplinary teams in the context of Collective Health in the present SUS (AU)

Es necesario abordar críticamente la promoción de la salud y los elementos que impactan el proceso salud/enfermedad en la formación diaria de los docentes de Educación Física (EF). Por lo tanto, este estudio tiene como objetivo analizar tesis y disertaciones producidas sobre la formación académica en EF y su relación con la salud en el contexto del Sistema Único de Salud (SUS), a través de una revisión integradora. El estudio encontró seis disertaciones que demostraron que, a pesar de la percepción de las universidades de que la formación académica permite que los profesores de EF actúen en el SUS, es posible identificar el mantenimiento del discurso conservador y biomédico, que afecta la comprensión, la percepción y la acción de los profesores de EF en equipos multidisciplinarios en el contexto de la Salud Colectiva en el SUS actual

Maternal exposure to glyphosate-based herbicide causes vascular dysfunction in offspring female rats.

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their female offspring and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of Glyphosate-based herbicide (O-GBH) and controls (O-CON) rats at six months of age. Relaxation to acetylcholine was reduced in O-GBH than in O-CON. Acute Indomethacin and Apocynin increased relaxation to acetylcholine in O-GBH. The aorta from O-GBH was hyperactive to phenylephrine; the preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GBH. TEMPOL similarly reduced phenylephrine response, and L-NAME prevented this effect. The TBARS and GSH levels were increased in O-GBH than in O-CON. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that oxidative stress parameters altered, and the current levels considered safe for exposure to Glyphosate deserve further investigation, especially in the female gender.

The potential exploitation of the Malay-red apple (Syzygium malaccense) seed as source of a phosphorylated starch.

This work presents the characterization of a novel naturally phosphorylated starch extracted from an unconventional and non-utilized source, the seeds of the stone fruit Syzygium malaccense. The morphology and chemical characteristics of the extracted starch were examined by scanning electron microscopy, FTIR, 1H/13C/31P NMR and 13C-CP/MAS-NMR, HPAEC-PAD chromatography, XRD, DSC, and RVA. The extraction yielded a highly pure starch (95.6 %) with an average granule size of 13 µm. The analysis of the starch components revealed an amylose content of 28.1 % and a predominance (65 %) of B-chains (B1-B3 65 %) in the amylopectin, as shown through HPAEC-PAD chromatography. The X-ray diffractogram was compatible with B-type starch, which was confirmed by the deconvolution of the C1 peak in the 13C-CP/MAS-NMR. X-Ray diffractogram also showed that S. malaccense has 28.5 % of crystallinity. DSC analysis showed values of 82.6 °C and -12.41 J g-1 for Tc and ΔH, respectively, which is compatible with a highly ordered starch granule structure. The values observed for peak (4678 mPa•s), trough (3055 mPa•s), and final viscosity (6526 mPa•s) indicated that S. malaccense may be used as a thickener in hot food.

Malignant lung PEComa (clear cell tumor): rare case report and literature review.

Clear cell tumors of the lung (CCTL), or "sugar tumors" of lung, are very uncommon lesions and are mostly benign perivascular epithelioid cell (PEC) tumors with no specific morphologic features. Fewer than 100 cases have been reported; the aggressive nature demonstrated in sporadic reports has rarely been described in the literature. Although the course is generally described as benign, eight reported cases showed malignant behavior. We report a case of a PEC with a malignant presentation in a young man, correlating the main characteristics of the tumor with other cases reported in the literature to better elucidate this rare presentation. We also performed a literature review of reports on benign and malignant CCTL cases, with a focus on clinical, imaging, and immunohistochemical differentiation. CCTLs are rare tumors that require histopathological and immunohistochemical confirmation; to date, criteria that can predict malignant evolution are lacking.

Maternal exposure to glyphosate-based herbicide causes changes in the vascular function of offspring adult rats.

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their offspring, focusing on the influence of age and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of glyphosate herbicide-based (O-GHB) and controls (O-CON) rats at 3, 6, and 12 months of age. O-GHB groups showed no changes in arterial blood pressure or aorta histological analysis. Relaxation to acetylcholine was reduced in O-GHB than O-CON. Acute TEMPOL increased relaxation to acetylcholine in O-GHB at 6 and 12 months of age. The aorta from O-GHB was hyperactive to phenylephrine only at 6 months of age. Preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GHB. TEMPOL similarly reduced phenylephrine response. This effect was prevented by L-NAME. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that although no changes in cardiac or histological parameters have been demonstrated, the current levels considered safe for exposure to glyphosate deserve further investigation, especially during pregnancy.

Scleral communication between Glaucoma drainage device capsule and the suprachoroidal space simulating amelanotic choroidal melanoma / Comunicação escleral entre a cápsula de dispositivo de drenagem para glaucoma e o espaço supracoroidal simulando melanoma de coroide amelanótico

ABSTRACT This is a case report involving a 56-year-old male patient with a history of pars plana vitrectomy due to a rhegmatogenous retinal detachment in the right eye that resulted in the implantation of a drainage device after the patient developed secondary glaucoma. Two years after the device's implantation, the patient was referred to our care as his visual acuity had decreased to 20/200 (1.00 LogMAR). At the fundus evaluation, a choroidal amelanotic elevation was observed at the upper temporal equator, and a potential diagnosis was made of amelanotic choroidal melanoma. The ultrasound exam visualized the patient's implanted superotemporal justabulbar drainage device, which revealed a transscleral communication from the plate fibrocapsular's draining space to the suprachoroidal space (fistula). The ultrasound also revealed a focal pocket of choroidal detachment in the patient's superotemporal region, simulating an amelanotic choroidal melanoma. A new pars plana vitrectomy was performed to remove the internal limiting membrane without repercussions at the fistula site. The patient's recovery progressed well, and he regained a visual acuity of 20/70 (0.55 LogMAR). To the best of our knowledge, this is the first case report of this condition.

RESUMO Relato de caso de paciente 56 anos, sexo masculino, com histórico de vitrectomia via pars plana por descolamento de retina em olho direito e posterior implante de dispositivo de drenagem por glaucoma secundário. Dois anos após o procedimento foi encaminhado ao serviço por baixa de acuidade visual (AV) de 20/200 (1.00 LogMAR). À fundoscopia, observou-se uma elevação amelanótica temporal no equador com hipótese diagnóstica de melanoma de coroide amelanótico. O exame de ultrassom mostrou implante de dispositivo de drenagem justabulbar temporal superior com comunicação transescleral para espaço subcoroidal (fístula), sugerindo bolsão focal de descolamento de coroide em equador temporal superior simulando melanoma de coroide amelanótico. O paciente foi abordado cirurgicamente devido membrana epirretiniana com nova vitrectomia via pars plana para peeling de membrana limitante interna, sem repercussões no local da fístula, evoluindo bem com acuidade visual de 20/70 (0.55 LogMAR). Ao nosso conhecimento, este é o primeiro caso relatado nessa condição.

Oxidative Stress as a Therapeutic Target of Cardiac Remodeling.

Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that clinically manifest as changes in the heart's size, mass, geometry, and function after different stimuli. It is important to emphasize that remodeling plays a pathophysiological role in the onset and progression of ventricular dysfunction and subsequent heart failure. Therefore, strategies to mitigate this process are critical. Different factors, including neurohormonal activation, can regulate the remodeling process and increase cell death, alterations in contractile and regulatory proteins, alterations in energy metabolism, changes in genomics, inflammation, changes in calcium transit, metalloproteases activation, fibrosis, alterations in matricellular proteins, and changes in left ventricular geometry, among other mechanisms. More recently, the role of reactive oxygen species and oxidative stress as modulators of remodeling has been gaining attention. Therefore, this review assesses the role of oxidative stress as a therapeutic target of cardiac remodeling.

Role of Nutrients and Foods in Attenuation of Cardiac Remodeling through Oxidative Stress Pathways.

Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that manifest clinically as changes in the heart's size, mass, geometry, and function after different injuries. Importantly, remodeling is associated with increased risk of ventricular dysfunction and heart failure. Therefore, strategies to attenuate this process are critical. Reactive oxygen species and oxidative stress play critical roles in remodeling. Importantly, antioxidative dietary compounds potentially have protective properties against remodeling. Therefore, this review evaluates the role of nutrients and food as modulators of cardiac remodeling.

Scleral communication between Glaucoma drainage device capsule and the suprachoroidal space simulating amelanotic choroidal melanoma.

This is a case report involving a 56-year-old male patient with a history of pars plana vitrectomy due to a rhegmatogenous retinal detachment in the right eye that resulted in the implantation of a drainage device after the patient developed secondary glaucoma. Two years after the device's implantation, the patient was referred to our care as his visual acuity had decreased to 20/200 (1.00 LogMAR). At the fundus evaluation, a choroidal amelanotic elevation was observed at the upper temporal equator, and a potential diagnosis was made of amelanotic choroidal melanoma. The ultrasound exam visualized the patient's implanted superotemporal justabulbar drainage device, which revealed a transscleral communication from the plate fibrocapsular's draining space to the suprachoroidal space (fistula). The ultrasound also revealed a focal pocket of choroidal detachment in the patient's superotemporal region, simulating an amelanotic choroidal melanoma. A new pars plana vitrectomy was performed to remove the internal limiting membrane without repercussions at the fistula site. The patient's recovery progressed well, and he regained a visual acuity of 20/70 (0.55 LogMAR). To the best of our knowledge, this is the first case report of this condition.

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion. The initial approach is similar in most cases, but a definitive treatment depends on etiology, that is why etiological investigation is mandatory in all cases. The majority of patients are asymptomatic and diagnosed during routine exams; only a small percentage of patients present with severe manifestations which can affect neurological, muscular, gastrointestinal, renal, and cardiovascular systems. Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms. Critically ill patients should receive treatment as soon as diagnosis is made. Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption such as bisphosphonates and, more recently, denosumab, in refractory cases; also, corticosteroids and calcitonin can be used in specific cases. This review aims to provide a clinical update on current concepts of the pathophysiology of calcium homeostasis, epidemiology, screening, clinical presentation, diagnosis, and management of hypercalcemia.

Post-Cardiac Arrest: Mechanisms, Management, and Future Perspectives.

Cardiac arrest is an important public health issue, with a survival rate of approximately 15 to 22%. A great proportion of these deaths occur after resuscitation due to post-cardiac arrest syndrome, which is characterized by the ischemia-reperfusion injury that affects the role body. Understanding physiopathology is mandatory to discover new treatment strategies and obtain better results. Besides improvements in cardiopulmonary resuscitation maneuvers, the great increase in survival rates observed in recent decades is due to new approaches to post-cardiac arrest care. In this review, we will discuss physiopathology, etiologies, and post-resuscitation care, emphasizing targeted temperature management, early coronary angiography, and rehabilitation.

Heart failure as an adverse effect of infliximab for Crohn's disease: A case report and review of the literature.

BACKGROUND: Anti-tumor necrosis factor agents were the first biologic therapy approved for the management of Crohn's disease (CD). Heart failure (HF) is a rare but potential adverse effect of these medications. The objective of this report is to describe a patient with CD who developed HF after the use of infliximab. CASE SUMMARY: A 50-year-old woman with a history of hypertension and diabetes presented with abdominal pain, diarrhea, and weight loss. Colonoscopy and enterotomography showed ulcerations, areas of stenosis and dilation in the terminal ileum, and thickening of the intestinal wall. The patient underwent ileocolectomy and the surgical specimen confirmed the diagnosis of stenosing CD. The patient started infliximab and azathioprine treatment to prevent post-surgical recurrence. At 6 mo after initiating infliximab therapy, the patient complained of dyspnea, orthopnea, and paroxysmal nocturnal dyspnea that gradually worsened. Echocardiography revealed biventricular dysfunction, moderate cardiac insufficiency, an ejection fraction of 36%, and moderate pericardial effusion, consistent with HF. The cardiac disease was considered an infliximab adverse effect and the drug was discontinued. The patient received treatment with diuretics for HF and showed improvement of symptoms and cardiac function. Currently, the patient is using anti-interleukin for CD and is asymptomatic. CONCLUSION: This reported case supports the need to investigate risk factors for HF in inflammatory bowel disease patients and to consider the risk-benefit of introducing infliximab therapy in such patients presenting with HF risk factors.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3­0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59­1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61­8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.

Oxidative stress induced by prenatal LPS leads to endothelial dysfunction and renal haemodynamic changes through angiotensin II/NADPH oxidase pathway: Prevention by early treatment with α-tocopherol.

We investigated whether hypertension induced by maternal lipopolysaccharide (LPS) administration during gestation is linked to peripheral vascular and renal hemodynamic regulation, through angiotensin II → NADPH-oxidase signalling, and whether these changes are directly linked to intrauterine oxidative stress. Female Wistar rats were submitted to LPS, in the absence or presence of α-tocopherol during pregnancy. Malondialdehyde in placenta and in livers from dams and foetuses was enhanced by LPS. Tail-cuff systolic blood pressure (tcSBP) was elevated in the 16-week-old LPS offspring. Renal malondialdeyde and protein expression of NADPH oxidase isoform 2 were elevated in these animals at 20 weeks of age. Maternal α-tocopherol treatment prevented the elevation in malondialdehyde induced by LPS on placenta and livers from dams and foetuses, as well as prevented the elevation in tcSBP and the elevation in renal malondialdehyde in adult life. LPS offspring presented impairment of endothelium-dependent relaxation in aorta and mesenteric rings, which was blunted by angiotensin type 1 receptor (AT1R) blockade and NADPH oxidase inhibition. At age of 32 weeks, renal hemodynamic parameters were unchanged in anaesthetised LPS offspring, but angiotensin II infusion led to an increased glomerular filtration rate paralleled by filtration fraction elevation. The renal haemodynamic changes provoked by angiotensin II was prevented by early treatment with α-tocopherol and by late treatment with NADPH oxidase inhibitor. These results point to oxidative stress as a mediator of offspring hypertension programmed by maternal inflammation and to the angiotensin II → NADPH oxidase signalling pathway as accountable for vascular and renal dysfunctions that starts and maintains hypertension.

Pain and musculoskeletal discomfort in military police officers of the Ostensive Motorcycle Patrol Group / Dor e desconforto musculoesquelético em policiais militares do Grupamento de Rondas Ostensivas com Apoio de Motocicletas

ABSTRACT BACKGROUND AND OBJECTIVES: Work-related musculoskeletal disorders have shown a high prevalence among workers, among these, law enforcement officers have been greatly affected. The aim of this study was to analyze the occurrence of musculoskeletal disorders symptoms in the Ostensive Motorcycle Patrol Group of the Military Police of Pernambuco, PE. METHODS: This was a cross-sectional study developed from February to June 2016. The subjects were 28 police officers from the Ostensive Motorcycle Patrol Group, of the 5th Battalion of the Military Police. Data was collected through a self-administered questionnaire with sociodemographic variables and professional characteristics. The Nordic Musculoskeletal Questionnaire and the visual analog scale were used. RESULTS: In the study sample, most of the individuals were male with an average of 62±8 working hours per week. Regarding the presence of musculoskeletal symptoms, the most affected anatomical region was the back, followed by the knees and then the chest. As for the pain perception of the subjects, the spine and lower limbs showed higher pain intensity when compared to other regions. Most of the sample believe that musculoskeletal symptoms are related to work. CONCLUSION: The findings in this study demonstrate the presence of musculoskeletal symptoms in the studied population. The analysis of the musculoskeletal disorders of these police officers will serve as an input for the planning of intervention actions to improve the general conditions of the service provided by the Ostensive Motorcycle Patrol Group.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os distúrbios osteomusculares relacionados ao trabalho têm apresentado alta prevalência nos trabalhadores, dentre esses, a classe de policiais tem sido bastante acometida. O objetivo deste estudo foi analisar a ocorrência de sintomas de distúrbios osteomusculares em policiais do Grupamento de Rondas Ostensivas Com Apoio de Motocicletas da Polícia Militar de Pernambuco, PE. MÉTODOS: Trata-se de um estudo do tipo transversal, desenvolvido entre os meses de fevereiro a junho de 2016, com 28 indivíduos da Rondas Ostensivas Com Apoio de Motocicletas da Polícia Militar do 5° Batalhão de Polícia Militar. Os dados foram obtidos por meio de um questionário autoaplicável com variáveis sociodemográficas, características profissionais, Questionário Nórdico de Sintomas Osteomusculares e escala analógica visual. RESULTADOS: Dentre a amostra estudada, a maioria dos indivíduos era do sexo masculino, sendo observada uma média de 62±8 horas trabalhadas por semana. Em relação à presença de sintomas osteomusculares, a região anatômica mais acometida foi a lombar, seguida pelos joelhos e região torácica. Quanto à percepção de dor dos policiais, a coluna vertebral e os membros inferiores apresentaram maior intensidade de dor quando comparados às outras regiões avaliadas. A maioria dos indivíduos da amostra relatou que os sintomas osteomusculares estavam relacionados ao trabalho. CONCLUSÃO: Os resultados deste estudo demonstram a presença de sintomas osteomusculares na população estudada de forma unânime. A análise dos distúrbios osteomusculares desses policiais servirá como subsídio para o planejamento de ações de intervenção voltados para a melhoria das condições gerais de prestação de serviços da Rondas Ostensivas Com Apoio de Motocicletas.

Losartan reverses COX-2-dependent vascular dysfunction in offspring of hyperglycaemic rats.

AIMS: This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. MATERIALS AND METHODS: Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day-1) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements. COX-2 expression was analyzed by Western blot; TxA2, PGE2 and PGF2α release was measured using commercial kits. KEY FINDINGS: O-DR showed increased blood pressure, impaired acetylcholine-induced vasodilation and increased noradrenaline-induced vasoconstriction than O-CR. All these parameters were normalized by losartan in O-DR. Pre-incubation of MRA with indomethacin (COX-1/2 inhibitor), NS-398 (COX-2 inhibitor) or tempol (superoxide dismutase mimetic) increased relaxation to acetylcholine and reduced contraction to noradrenaline only in O-DR. COX-2 expression, TxA2, PGE2 and PGF2α release were increased in O-DR. In losartan-treated O-DR, NS-398, indomethacin or tempol failed to produce any effect on acetylcholine or noradrenaline responses. Losartan treatment reduced COX-2 expression, TxA2, PGE2 and PGF2α release in O-DR. SIGNIFICANCE: The present results reveal that chronic losartan administration in O-DR normalizes endothelial function in MRA by correcting the existing COX-2 overexpression and the imbalance between endothelium-derived relaxing and contracting factors. These findings not only support the beneficial effects of AT1 receptor antagonist in O-DR, but also suggest the implication of angiotensin II as a putative mediator of hyperglycemia-programmed vascular dysfunction in rats.

Hyperglycaemia in pregnant rats causes sex-related vascular dysfunction in adult offspring: role of cyclooxygenase-2.

NEW FINDINGS: What is the central question of this study? Hyperglycaemia during pregnancy induces vascular dysfunction and hypertension in male offspring. Given that female offspring from other fetal programming models are protected from the effects of fetal insult, the present study investigated whether there are sex differences in blood pressure and vascular function in hyperglycaemia-programmed offspring. What is the main finding and its importance? We demonstrated that hyperglycaemia in pregnant rats induced vascular dysfunction and hypertension only in male offspring. We found sex differences in oxidative stress and cyclooxygenase-2-derived prostanoid production that might underlie the vascular dysfunction. These differences, particularly in resistance arteries, may in part explain the absence of hypertension in female offspring born to hyperglycaemic dams. Exposure to maternal hyperglycaemia induces hypertension and vascular dysfunction in adult male offspring. Given that female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analysed possible differences relative to sex in blood pressure and vascular function in hyperglycaemia-programmed offspring. Hyperglycaemia was induced on day 7 of gestation (streptozotocin, 50 mg kg-1 ). Blood pressure, acetylcholine and phenylephrine or noradrenaline responses were analysed in the aorta and mesenteric resistance arteries of 3-, 6- and 12-month-old male and female offspring. Thromboxane A2 release was analysed with commercial kits and superoxide anion (O2- ) production by dihydroethidium-emitted fluorescence. Male but not female offspring of hyperglycaemic dams (O-DR) had higher blood pressure than control animals (O-CR). Contraction in response to phenylephrine increased and relaxation in response to acetylcholine decreased only in the aorta from 12-month-old male O-DR and not in age-matched O-CR. Contractile and vasodilator responses were preserved in both the aorta and mesenteric resistance arteries from female O-DR of all ages. Pre-incubation with tempol, superoxide dismutase, indomethacin, NS-398, furegrelate or SQ29548 decreased contraction in response to phenylephrine and potentiated relaxation in response to acetylcholine in 12-month-old male O-DR aorta. In this artery, thromboxane A2 release and O2- generation were greater in O-DR than O-CR groups. In conclusion, exposure to hyperglycaemia in utero results in sex-specific and age-dependent hypertension. The fact that vascular function is preserved in female O-DR may in part explain the absence of hypertension in this group. In contrast, the peripheral artery dysfunction associated with increased cyclooxygenase-2-derived production of vasoconstrictor prostanoids could underlie the increased blood pressure in male O-DR.

Increased cyclooxygenase-2-derived prostanoids contributes to the hyperreactivity to noradrenaline in mesenteric resistance arteries from offspring of diabetic rats.

This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring, focusing on the role of cyclooxygenase (COX)-derived prostanoids. Diabetes in the maternal rat was induced by a single injection of streptozotocin (50 mg/kg body weight) on day 7 of pregnancy. Contraction to noradrenaline was analyzed in isolated MRA from offspring of diabetic (O-DR) and non-diabetic (O-CR) rats at 3, 6 and 12 months of age. Release of thromboxane A(2) (TxA(2)) and prostaglandins E(2) (PGE(2)) and F(2α) (PGF(2α)), was measured by specific enzyme immunoassay kits. O-DR developed hypertension from 6 months of age compared with O-CR. Arteries from O-DR were hyperactive to noradrenaline only at 6 and 12 months of age. Endothelial removal abolished this hyperreactivity to noradrenaline between O-CR and O-DR. Preincubation with either the COX-1/2 (indomethacin) or COX-2 inhibitor (NS-398) decreased noradrenaline contraction only in 6- and 12-month-old O-DR, while it remained unmodified by COX-1 inhibitor SC-560. In vessels from 6-month-old O-DR, a similar reduction in the contraction to noradrenaline produced by NS-398 was observed when TP and EP receptors were blocked (SQ29548+AH6809). In 12-month-old O-DR, this effect was only achieved when TP, EP and FP were blocked (SQ29548+AH6809+AL8810). Noradrenaline-stimulated TxB(2) and PGE(2) release was higher in 6- and 12-month-old O-DR, whereas PGF(2α) was increased only in 12-month-old O-DR. Our results demonstrated that in utero exposure to maternal hyperglycaemia in rats increases the participation of COX-2-derived prostanoids on contraction to noradrenaline, which might help to explain the greater response to this agonist in MRA from 6- and 12-month-old offspring. As increased contractile response in resistance vessels may contribute to hypertension, our results suggest a role for these COX-2-derived prostanoids in elevating vascular resistance and blood pressure in offspring of diabetic rats.