Hypothalamic inflammation and the development of an obese phenotype induced by high-fat diet consumption is exacerbated in alpha7 nicotinic cholinergic receptor knockout mice.

Hypothalamic inflammation and metabolic changes resulting from the consumption of high-fat diets have been linked to low grade inflammation and obesity. Inflammation impairs the hypothalamic expression of α7 nicotinic acetylcholine receptor (α7nAChR). The α7nAChR is described as the main component of the anti-inflammatory cholinergic pathway in different inflammation models. To assess whether the reduction in α7nAChR expression exacerbates hypothalamic inflammation induced by a high-fat diet (HFD), were used male and female global α7nAChR knockout mouse line in normal or high-fat diet for 4 weeks. Body weight gain, adiposity, glucose homeostasis, hypothalamic inflammation, food intake, and energy expenditure were evaluated. Insulin sensitivity was evaluated in neuronal cell culture. Consumption of an HFD for 4 weeks resulted in body weight gain and adiposity in male Chrna7-/- mice and the hypothalamus of male Chrna7-/- mice showed neuroinflammatory markers, with increased gene expression of pro-inflammatory cytokines and dysregulation in the nuclear factor kappa B pathway. Moreover, male Chrna7-/- mice consuming an HFD showed alterations in glucose homeostasis and serum of Chrna7-/- mice that consumed an HFD impaired insulin signalling in neuronal cell culture experiments. In general, female Chrna7-/- mice that consumed an HFD did not show the phenotypic and molecular changes found in male mice, indicating that there is sexual dimorphism in the analysed parameters. Thus, receptor deletion resulted in increased susceptibility to hypothalamic inflammation and metabolic damage associated with HFD consumption in male mice.

Knockdown of regulatory associated protein of TOR (raptor) in hypothalamus-stimulated folliculogenesis and induced ovarian cysts.

CONTEXT: Mammalian target of rapamycin complex 1 (mTORC1) is an essential sensor that regulates fundamental biological processes like cell growth, proliferation and energy metabolism. The treatment of disease by sirolimus, a mTORC1 inhibitor, causes adverse effects, such as female fertility disorders. AIMS: The objective of the study was to decipher the reproductive consequences of a downregulation of mTORC1 in the hypothalamus. METHODS: The reduced expression of mTORC1 was induced after intracerebroventricular injection of lentivirus expressing a short hairpin RNA (shRNA) against regulatory associated protein of TOR (raptor) in adult female mice (ShRaptor mice). KEY RESULTS: The ShRaptor mice were fertile and exhibited a 15% increase in the litter size compared with control mice. The histological analysis showed an increase in antral, preovulatory follicles and ovarian cysts. In the hypothalamus, the GnRH mRNA and FSH levels in ShRaptor mice were significantly elevated. CONCLUSIONS: These results support the hypothesis that mTORC1 in the central nervous system participates in the regulation of female fertility and ovarian function by influencing the GnRH neuronal activity. IMPLICATIONS: These results suggest that a lower mTORC1 activity directly the central nervous system leads to a deregulation in the oestrous cycle and an induction of ovarian cyst development.

Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

AIMS: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation. METHODS AND RESULTS: Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective. CONCLUSION: Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

New-onset refractory status epilepticus (NORSE) in paediatric patients: causes, characteristics and outcomes.

Background: New-onset refractory status epilepticus (NORSE) refers to patients without a previous history of seizures who have refractory status epilepticus for at least 72 hours without an identified aetiology. Despite the severe neurological sequelae of NORSE, little is known about this condition in paediatric patients. Objective: To describe the profile of paediatric patients with NORSE, the profile of seizures, possible causes attributed to this condition, treatments offered to patients and the outcomes at discharge from the paediatric intensive care unit (PICU). Methods: This retrospective, multicentre, descriptive study (case series) was conducted in the PICUs of three tertiary hospitals. We reviewed the medical records of all patients aged 0-16 years admitted to the participating PICUs between December 2013 and December 2017 with refractory status epilepticus, without a previous history of seizures or neurological disease. Results: Fifteen patients (2.4%) had NORSE. The median age of patients was 62.3 (IQR 26.2-75.4) months. All patients experienced prodromes before progressing to refractory status epilepticus. Twelve patients (80%) had fever up to 24 hours before seizures. NORSE was classified as cryptogenic in 66% of patients. Twelve patients were treated with complementary therapies, in addition to anticonvulsants. There was no standardisation in the treatment of patients. The overall mortality rate was 20%. Conclusions: NORSE is associated with high morbidity and mortality, without an identified aetiology in most cases and with a wide range of proposed therapies.

Antiparasitic treatment using herbs and spices: A review of the literature of the phytotherapy.

This study sought to make a literature review of the medicinal plants Origanum majorana, Origanum vulgare L., Thymus vulgaris L., Cuminum cynimum L., and Rosmarinus officinalis L. with antiparasitic potential. Articles and theses were selected from the LILACS, PubMed, and Google Scholar databases, which comprised the period from 2000 to 2021 (22 years). In all, 49 studies were selected, and the majority were with the plant Origanum vulgare L. (oregano), followed by Thymus vulgaris L. (thyme). Twenty-five genera of parasites were detected, which were described being tested with phytotherapic. The nematode Haemonchus spp. was the most evaluated in these studies, followed by the parasite genera Leishmania, Trichostrongylus, and Toxocara. All plants showed antiparasitic effects, with more or less action, therefore with the potential to continue research in the search for biomolecules to control these parasites.

O presente trabalho faz uma revisão bibliográfica das plantas medicinais Origanum majorana, Origanum vulgare L., Thymus vulgaris L., Cuminum cynimum L. e Rosmarinus officinalis L. com potencial antiparasitário. Foram selecionados artigos e teses nos bancos de dados LILACS, PubMed e Google Acadêmico que compreendiam o período de publicação de 2000 a 2021 (22 anos). Ao todo, foram selecionados 49 estudos, sendo que na maioria constava a planta Origanum vulgare L. (orégano), seguido de Thymus vulgaris L. (tomilho). Foram detectados 25 gêneros de parasitos, os quais foram descritos sendo testados frente a algum fitoterápico. O nematoda Haemonchus spp. foi o mais avaliado nestes estudos, seguido dos gêneros dos parasitos Leishmania, Trichostrongylus e Toxocara. Todas as plantas apresentaram efeitos antiparasitários, com maior ou menos ação, portanto com potencial para dar continuidade aos estudos em buscas de biomoléculas para controle destes parasitos.

Views and practice of abortion among Queensland midwives and sexual health nurses.

BACKGROUND: A significant barrier to the access of safe abortion is the lack of trained abortion providers. Recent studies show that with appropriate education, nurses and midwives can provide abortions as safely as medical practitioners. AIMS: To examine the attitudes and practices of registered midwives (RMs) and sexual health nurses (SHNs) in Queensland toward abortion. MATERIALS AND METHODS: A cross-sectional mixed-methods questionnaire was distributed to RMs and SHNs from the Queensland Nursing and Midwifery Union. Data were described and analysed both quantitatively and qualitatively. RESULTS: There was a 20% response rate (n = 624) to the survey from the overall study population. There were 53.5% who reported they would support the provision of abortion in any situation at all; 7.4% held views based on religion or conscience that would make them completely opposed to abortion. There were 92.9% who felt that education surrounding abortion should be part of the core curriculum for midwifery and/or nursing students in Australia. The qualitative responses demonstrated a variety of views and suggestions regarding the practice of abortion. CONCLUSIONS: There was a wide variation in views toward induced abortion from RMs and SHNs in Queensland. While a proportion of respondents opposed abortion in most circumstances, a significant group was in support of abortion in any situation and felt involvement in initiating and/or performing abortion would be within the scope of RMs and SHNs.

An in-silico assessment of efficacy of two novel intra-cardiac electrode configurations versus traditional anti-tachycardia pacing therapy for terminating sustained ventricular tachycardia.

The implanted cardioverter defibrillator (ICD) is an effective direct therapy for the treatment of cardiac arrhythmias, including ventricular tachycardia (VT). Anti-tachycardia pacing (ATP) is often applied by the ICD as the first mode of therapy, but is often found to be ineffective, particularly for fast VTs. In such cases, strong, painful and damaging backup defibrillation shocks are applied by the device. Here, we propose two novel electrode configurations: "bipolar" and "transmural" which both combine the concept of targeted shock delivery with the advantage of reduced energy required for VT termination. We perform an in silico study to evaluate the efficacy of VT termination by applying one single (low-energy) monophasic shock from each novel configuration, comparing with conventional ATP therapy. Both bipolar and transmural configurations are able to achieve a higher efficacy (93% and 85%) than ATP (45%), with energy delivered similar to and two orders of magnitudes smaller than conventional ICD defibrillation shocks, respectively. Specifically, the transmural configuration (which applies the shock vector directly across the scar substrate sustaining the VT) is most efficient, requiring typically less than 1 J shock energy to achieve a high efficacy. The efficacy of both bipolar and transmural configurations are higher when applied to slow VTs (100% and 97%) compared to fast VTs (57% and 29%). Both novel electrode configurations introduced are able to improve electrotherapy efficacy while reducing the overall number of required therapies and need for strong backup shocks.

Treatment challenges in adult female acne and future directions.

Introduction: Acne is a chronic, inflammatory, and immune-mediated disease of the pilosebaceous unit, highly prevalent in adolescents. However, an increasing number of adults over 25 years old with facial acne, particularly women, have been observed. It is considered a different disease when compared to acne vulgaris. Face is the mainly involved area with inflammatory lesions and more sensitive skin, pointing out the need of a holistic approach.Areas covered: We performed a comprehensive literature search on PubMed database, up to January 2021, regarding adult female acne. We synthesized data about pathogenesis; differences compared to acne vulgaris; and treatment, with focus in the management challenges and perspectives.Expert opinion: It is essential to value the negative impact on quality of life of adult female acne, independently of severity. The disease has prolonged evolution, and patient might be resilient once the improvement, regardless of the treatment option, will just be noticeable after 3 months. Aggravating factors should be clearly discussed, such as the need of changing many habits, especially lesions manipulation. The therapeutic regimen includes make-up and tailored skin care (considering proneness to sensitivity), while anti-acne drugs should be chosen in accordance with desire to be pregnant, presence of pregnancy or breastfeeding.

Acute Normovolemic Hemodilution in Spinal Deformity Surgery / Hemodiluição normovolêmica aguda em cirurgias de deformidade da coluna

Abstract Objective To prospectively compare the clinical and laboratorial aspects of patients undergoing spine deformity surgery, using the acute normovolemic hemodilution technique with tranexamic acid, versus a control group with tranexamic acid alone, and to evaluate the influence of hemodilution in intraoperative bleeding and the need for homologous transfusion. Materials and Methods Comparative prospective study with patients aged between 12 and 65 years undergoing spine deformity surgery with the acute normovolemic hemodilution technique associated with tranexamic acid versus a control group to which only tranexamic acid (15 mg/kg) was administered. Laboratorial exams were performed and analyzed in three different moments. Results A total of 30 patients were included in the present study: 17 in the hemodilution group, and 13 in the control group. The mean duration of the surgery in the hemodilution group was longer. The number of levels submitted to surgery ranged from 7 to 16 in the hemodilution group, and from 4 to 13 in the control group. Osteotomy, predominantly of the posterior kind, was performed in 20 patients. There was more intraoperative bleeding in the control group. All patients were stable during the procedures. Only 6 participants needed homologous blood transfusion, mostly from the control group (p > 0.05). Conclusion There was no significant difference between the two groups regarding the need for blood transfusion and intraoperative bleeding. The severity of the deformity was the main determinant for homologous blood transfusion.

Resumo Objetivo Comparar de modo prospectivo os parâmetros clínicos e laboratoriais dos pacientes submetidos a hemodiluição normovolêmica aguda associada ao ácido tranexâmico com um grupo de controle que recebeu apenas ácido tranexâmico, durante cirurgia de correção de deformidades da coluna, e avaliar a influência da técnica de hemodiluição no sangramento perioperatório e a necessidade de transfusão de sangue homólogo. Materiais e Métodos Estudo prospectivo comparativo, com pacientes entre 12 e 65 anos submetidos a cirurgia para correção de deformidades da coluna vertebral, com a técnica de hemodiluição normovolêmica aguda associada ao ácido tranexâmico, versus grupo de controle com ácido tranexâmico isolado na dose de 15 mg/kg. Exames laboratoriais foram feitos e analisados em três momentos de avaliação diferentes. Resultados Participaram deste estudo 30 pacientes: 17 no grupo de hemodiluição e 13 no grupo de controle. O tempo médio de cirurgia foi maior para o grupo de hemodiluição. O número de níveis operados variou entre 7 e 16 no grupo de hemodiluição, e entre 4 e 13 no grupo de controle. Fez-se osteotomia, predominantemente posterior, em 20 pacientes. O valor médio de sangramento intraoperatório foi maior no grupo de controle. Os parâmetros clínicos se mantiveram estáveis durante todos os procedimentos. Apenas 6 pacientes necessitaram de transfusão sanguínea homóloga, a maioria dos quais pertencia ao grupo de controle (p > 0,05). Conclusão Não houve diferença significativa entre os dois grupos quanto à necessidade de transfusão e sangramento intraoperatório. A gravidade da deformidade foi o principal fator determinante da transfusão.

Evaluation of a real-time magnetic resonance imaging-guided electrophysiology system for structural and electrophysiological ventricular tachycardia substrate assessment.

AIMS: Potential advantages of real-time magnetic resonance imaging (MRI)-guided electrophysiology (MR-EP) include contemporaneous three-dimensional substrate assessment at the time of intervention, improved procedural guidance, and ablation lesion assessment. We evaluated a novel real-time MR-EP system to perform endocardial voltage mapping and assessment of delayed conduction in a porcine ischaemia-reperfusion model. METHODS AND RESULTS: Sites of low voltage and slow conduction identified using the system were registered and compared to regions of late gadolinium enhancement (LGE) on MRI. The Sorensen-Dice similarity coefficient (DSC) between LGE scar maps and voltage maps was computed on a nodal basis. A total of 445 electrograms were recorded in sinus rhythm (range: 30-186) using the MR-EP system including 138 electrograms from LGE regions. Pacing captured at 103 sites; 47 (45.6%) sites had a stimulus-to-QRS (S-QRS) delay of ≥40 ms. Using conventional (0.5-1.5 mV) bipolar voltage thresholds, the sensitivity and specificity of voltage mapping using the MR-EP system to identify MR-derived LGE was 57% and 96%, respectively. Voltage mapping had a better predictive ability in detecting LGE compared to S-QRS measurements using this system (area under curve: 0.907 vs. 0.840). Using an electrical threshold of 1.5 mV to define abnormal myocardium, the total DSC, scar DSC, and normal myocardium DSC between voltage maps and LGE scar maps was 79.0 ± 6.0%, 35.0 ± 10.1%, and 90.4 ± 8.6%, respectively. CONCLUSION: Low-voltage zones and regions of delayed conduction determined using a real-time MR-EP system are moderately associated with LGE areas identified on MRI.

Medical students and midwives - How do they view each other?

Medical students from James Cook University who had completed their rotation in obstetrics, and midwives working in Cairns Hospital who had undertaken supervision of medical students in the birth suite, were invited to complete anonymous questionnaires on their views of their respective roles in the birth suite. Several issues were identified including increased medical and midwifery student numbers, and lack of communication between midwives and medical students. Increased cooperation and communication between medical and midwifery education providers is urgently needed to improve both student groups' learning experiences.

Non-Clinical Studies for Evaluation of 8-C-Rhamnosyl Apigenin Purified from Peperomia obtusifolia against Acute Edema.

Compound 8-C-rhamnosyl apigenin (8CR) induced a moderate reduction in the enzymatic activity of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus and cytosolic phospholipase A2 (cPLA2), but the compound also significantly inhibited the enzymatic activity of the enzyme cyclooxygenase. In vitro assays showed that the compound induced a slight change in the secondary structure of sPLA2 from Crotalus durissus terrificus snake venom. In vivo assays were divided into two steps. In the first step, the 8CR compound was administered by intraperitoneal injections 30 min prior to administration of sPLA2. In this condition, 8CR inhibited edema and myonecrosis induced by the sPLA2 activity of Crotalus durissus terrificus in a dose-dependent manner by decreasing interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and lipid peroxidation. This has been demonstrated by monitoring the levels of malondialdehyde (MDA) in rat paws after the course of edema induced by sPLA2. These results, for the first time, show that sPLA2 of Crotalus durissus terrificus venom induces massive muscle damage, as well as significant edema by mobilization of cyclooxygenase enzymes. Additionally, its pharmacological activity involves increased lipid peroxidation as well as TNF-α and IL-1ß production. Previous administration by the peritoneal route has shown that dose-dependent 8CR significantly decreases the enzymatic activity of cyclooxygenase enzymes. This resulted in a decrease of the amount of bioactive lipids involved in inflammation; it also promoted a significant cellular protection against lipid peroxidation. In vivo experiments performed with 8CR at a concentration adjusted to 200 µg (8 mg/kg) of intraperitoneal injection 15 min after sPLA2 injection significantly reduced sPLA2 edema and the myotoxic effect induced by sPLA2 through the decrease in the enzymatic activity of cPLA2, cyclooxygenase, and a massive reduction of lipid peroxidation. These results clearly show that 8CR is a potent anti-inflammatory that inhibits cyclooxygenase-2 (COX-2), and it may modulate the enzymatic activity of sPLA2 and cPLA2. In addition, it was shown that Crotalus durissus terrificus sPLA2 increases cell oxidative stress during edema and myonecrosis, and the antioxidant properties of the polyphenolic compound may be significant in mitigating the pharmacological effect induced by sPLA2 and other snake venom toxins.

Evaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2.

Rhamnetin (Rhm), 3-O-methylquercetin (3MQ), and Rhamnazin (Rhz) are methylated derivatives of quercetin commonly found in fruits and vegetables that possess antioxidant and anti-inflammatory properties. Phospholipase A2 (PLA2) displays several important roles during acute inflammation; therefore, this study aimed at investigating new compounds able to inhibit this enzyme, besides evaluating creatine kinase (CK) levels and citotoxicity. Methylated quercetins were compared with quercetin (Q) and were incubated with secretory PLA2 (sPLA2) from Bothrops jararacussu to determine their inhibitory activity. Cytotoxic studies were performed by using the J774 cell lineage incubated with quercertins. In vivo tests were performed with Swiss female mice to evaluate decreasing paw edema potential and compounds' CK levels. Structural modifications on sPLA2 were made with circular dichroism (CD). Despite Q and Rhz showing greater enzymatic inhibitory potential, high CK was observed. Rhm exhibited sPLA2 inhibitory potential, no toxicity and, remarkably, it decreased CK levels. The presence of 3OH on the C-ring of Rhm may contribute to both its anti-inflammatory and enzymatic inhibition of sPLA2, and the methylation of ring A may provide the increase in cell viability and low CK level induced by sPLA2. These results showed that Rhm can be a candidate as a natural compound for the development of new anti-inflammatory drugs.

Plantas medicinais: percepção, utilização e indicações terapêuticas de usuários da estratégia saúde da família do município de Criciúma- SC vinculados ao PET- Saúde / Medicinal plants: perception, utilization and therapeutic indications of users of the family health strategy of the city of Criciúma-SC linked to PET- Saúde

Introdução - Apesar dos avanços da medicina, a utilizaçãode plantas medicinais (PM) se mantém no cotidianodas pessoas e a incorporação da fitoterapia no âmbito daSaúde Pública é uma recomendação da OMS. Objetivo- Reconhecer a utilização da fitoterapia pelos usuáriosda Estratégia Saúde da Família (ESF). Metodologia -Trata-se de um estudo exploratório transversal de caráterdescritivo utilizando como técnica de coleta de dadosa entrevista estruturada, realizado com 672 usuários deESF do município de Criciúma/SC que são vinculadasao PET-Saúde. Resultados - Dos entrevistados, 69% afirmaramo uso de PM, principalmente, para afecções nossistemas digestório, nervoso e respiratório, sendo as PMmais citadas o boldo, hortelã e camomila. Por ser consideradonatural, 51% dos usuários não acreditam que ouso de PM pode fazer mal a saúde. E 90% têm interesseem receber informações sobre PM por profissionais desaúde. Conclusão - Fica evidenciado neste estudo, a necessidadede ampliação de informações para a utilizaçãoracional das PM. Considerando que, existe interesse dosusuários a utilização de tal opção terapêutica sugere-secapacitação dos profissionais de saúde, além de um planejamentode ações com intuito de implantar a fitoterapiano município, de forma articulada com a ESF.

Introduction - Despite advances of the medicine, theutilization of medicinal plants (MP) remains in people?sdaily life, being that incorporation of the phytotherapy inthe ambit Public Health is a OMS recommendation andofficial in our country in 2006 by the National Policyof Medicinal Plants and phytotherapics. Objective -To identify the use of phytotherapy by the users of theFamily Health Strategy (FHS). Methods - This is an exploratorystudy transverse of descriptive character usingtechnical data collection the structured interview, realizedwith 672 users of four FHS of the city of Criciúma/ SC that are linked to PET-Saúde. Results - Of the interviewed,69% affirmed the use of MP, mainly, forafections in digestive system, nervous and respiratory,being the MP the most cited bilberry, mint and chamomile.Being considered natural, 51% of users do not believethat the use of MP can harm health. And 90% areinterested in receiving information about MP by healthprofessionals. Conclusions - It?s evident the need for expansion of informations for the rational use of MP andconsidering that, there are user interest in the use of MPit is suggested that capacitation of health professionals,beyond as action planning with the intention to implantthe phytotherapy in the city, in articulated with the FHS.