Impact of repeated ovarian hyperstimulation on the reproductive function.

One of six couples (17.5 % of the adult population) worldwide is affected by infertility during their lifetime. This number represents a substantial increase in the prevalence of this gynecological condition over the last decade. Ovulatory dysfunction and anovulation are the main causes of female infertility. Timed intercourse, intrauterine insemination, and assisted reproductive technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the most common interventions for infertile couples. Ovulation induction protocols for IVF/ICSI routinely use supraphysiological doses of gonadotropins to stimulate many preovulatory follicles. Animal and human studies suggested that ovarian hyperstimulation, alone or repeatedly, for ART cycles can induce changes in the immune response and increase the oxidative stress (OS) in the ovarian microenvironment. The consequences of repeated ovarian hyperstimulation on the human ovary remain poorly understood, particularly in relation to the effects of ovarian stimulation on the immune system and the potential for ovarian stimulation to cause OS. Animal studies have observed that repeated cycles of ovarian hyperstimulation can accelerate ovarian aging. Changes in ovarian hormone levels, accelerated loss of ovarian reserve, disorders in ovarian ultrastructure, ovarian senescence, and decreased reproductive performance represent possible long-term effects of repeated ovarian hyperstimulation. The short and long-term impact of the combination of antioxidant agents in ovarian hyperstimulation protocols in women undergoing ART must urgently be better understood. The recent increase in the number of ART and fertility preservation cycles may accelerate ovarian aging in these women, promoting consequences beyond the reproductive function and including health deterioration.

Repeated ovarian hyperstimulation promotes depression-like behavior in female mice.

Controlled ovarian hyperstimulation (COH) is a common step for treating infertile couples undergoing assisted reproductive technologies and in female fertility preservation cycles. In some cases, undergoing multiple COHs is required for couples to conceive. Behavioral changes such as anxiety and depression can be caused by ovulation-inducing drugs. Sex steroids play a role in locomotor activity, behavioral changes, and nociception, specifically during fluctuations and sudden drops in estrogen levels. This study evaluated the effect of repeated ovarian hyperstimulation (ROH) on weight, locomotor activity, anxiety-like and depression-like behavior, and nociception in female mice. The animals were divided into two groups: control (placebo; Control) and treated (ROH; Treatment). Ovulation was induced once weekly for 10 consecutive weeks. Locomotor activity (open field test), anxiety-like behavior (elevated plus maze, hole board, and marble burying tests), depression-like behavior (splash and forced swim tests), and nociception (hot plate and Von Frey tests) were evaluated before and after ROH. Statistical analysis was conducted using two-way analysis of variance to evaluate the effects of ROH, age of mice, and their interaction. The results suggested that ROH contributed to weight gain, increased locomotor activity, and induced depression-like behavior in female mice. Furthermore, the age of the mouse contributed to weight gain, increased locomotor activity, and induced anxiety-like and depression-like behavior in female mice. ROH could change the behavior of female mice, particularly inducing depression-like behavior. Further studies are required to evaluate various COH protocols, specifically with drugs that prevent fluctuations and drastic drops in estrogen levels, such as aromatase inhibitors.

Effects on structure by spectroscopic investigations, valence state and morphology properties of FeCo-containing SnO2 catalysts for glycerol valorization to cyclic acetals.

The effects on the structure, valence state and morphological properties of FeCo-containing SnO2 nanostructured solids were investigated. The physicochemical features were tuned by distinct synthesis routes e.g., sol-gel, coprecipitation and nanocasting, to apply them as catalysts in the glycerol valorization to cyclic acetals. Based on Mössbauer and XPS spectroscopy results, all nanosized FeCoSn solids have Fe-based phases, which contain Co and Sn included in the structure, and well-dispersed Fe3+ and Fe2+ surface active sites. Raman, FTIR and EPR spectroscopies measurements of the spent solids demonstrated structural stability for the sol-gel based solid, which is indeed responsible for the highest catalytic performance, among the nanocasted and coprecipitated counterparts. Morphological and elemental analyses illustrated distinct morphologies and composition on solid surface, depending on the synthesis route. The Fe/Co and Fe/Sn surface ratios are closely related to the catalytic performance. The improved glycerol conversion and selectivities of the solid obtained by sol-gel method was ascribed to the leaching resistance and the Sn action as a structural promoter.

Application of multiple validated algorithms for identifying incident breast cancer among individuals with atopic dermatitis.

PURPOSE: Validated algorithms (VAs) in insurance claims databases are often used to estimate the prevalence and incidence of comorbidities and evaluate safety signals. However, although they are then used in different data sources or subpopulations from those in which they were developed the replicability of these VAs are rarely tested, making their application and performance in these settings potentially unknown. This paper describes testing multiple VAs used to identify incident breast cancer cases in a general population and in an indication-specific population, patients with atopic dermatitis (AD). METHODS: Two algorithms were tested in multiple insurance claims databases and four cohorts were created. Modifications were made to account for the US insurance setting. The resulting incidence rates (IRs) were then compared across algorithms and against surveillance, epidemiology, and end results (SEER) estimates to assess reliability. RESULTS: Algorithm 1 produced low IRs compared to Algorithm 2. Algorithm 2 provided similar estimates to those of SEER. Individuals in the AD cohorts experienced lower incident breast cancer cases than those in the general population cohorts. CONCLUSION: Regardless of an algorithm's reported accuracy, the original study setting and targeted population for the VAs may matter when attempting to replicate the algorithm in an indication-specific subpopulation or varying data sources. Investigators should use caution and conduct sensitivity analyses or use multiple algorithms when attempting to calculate incidence or prevalence estimates using VAs.

Potential of the Blue Calm® food supplement in the treatment of alcohol withdrawal-induced anxiety in adult zebrafish (Danio rerio).

Alcohol use disorder (AUD) is characterized by a set of behavioral, cognitive, nutritional, and physiological phenomena derived from the uncontrolled use of alcoholic beverages. There are cases in which AUD is associated with anxiety disorder, and when untreated, it requires careful pharmacotherapy. Blue Calm® (BC) is a food supplement indicated to aid restorative sleep, which has traces of medicinal plant extracts, as well as myo-inositol, magnesium bisglycinate, taurine, and L-tryptophan as its main chemical constituents. In this context, this study aimed to evaluate the potential of the BC in the treatment alcohol withdrawal-induced anxiety in adult zebrafish (aZF). Initially, BC was submitted to antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl radical. Subsequently, the aZF (n = 6/group) were treated with BC (0.1 or 1 or 10 mg/mL; 20 µL; p.o.), and the sedative effect and acute toxicity (96 h) were evaluated. Then, the anxiolytic-like effect and the possible GABAergic mechanism were analyzed through the Light & Dark Test. Finally, BC action was evaluated for treating alcohol withdrawal-induced anxiety in aZF. Molecular docking was performed to evaluate the interaction of the major chemical constituents of BC with the GABAA receptor. BC showed antioxidant potential, a sedative effect, was not toxic, and all doses of BC had an anxiolytic-like effect and showed potential for the treatment of alcohol withdrawal-induced anxiety in aZF. In addition to the anxiolytic action, the main chemical constituents of BC were confirmed in the molecular docking, thus suggesting that BC is an anxiolytic that modulates the GABAergic system and has pharmacological potential for the treatment of alcohol withdrawal-induced anxiety.

Control, elimination, and eradication efforts for neglected tropical diseases in the World Health Organization African region over the last 30 years: A scoping review.

OBJECTIVES: NTDs historically receive less attention than other diseases in the same regions. Recent gap analyses revealed notable shortcomings despite NTD elimination progress. This systematic scoping review was conducted to understand NTD control, elimination, and eradication efforts in the WHO African region over the last 30 years. METHODS: Peer-reviewed publications from PubMed, Web of Science, and Cochrane databases related to NTD control, elimination, and eradication in the WHO African Region from 1990 to 2022 were reviewed. Included articles were categorized based on NTD; study location, type, and period; and topic areas. Technical and guidance documents from WHO, UN, partner, and academic/research institutions were reviewed. Country-specific multi-year NTD master plans were documented. RESULTS: Four hundred eighty peer-reviewed articles, six Cochrane reviews, and 134 technical reports were included. MDA and non-interventional/survey-related studies were common topics. Lymphatic filariasis, trachoma, schistosomiasis, and onchocerciasis were the most frequently studied NTDs. Tanzania, Ethiopia, and Nigeria were the most represented countries; multi-country studies were limited. CONCLUSION: The review highlights progress made in NTD control, elimination, and eradication efforts in the WHO African Region and can inform national/regional strategies. Disease and geographical disparities were evident, warranting focus and research in certain countries. A standardized approach to NTD control programs is needed for sustained progress. FUNDING: There was no funding source for this study.

Review on the current long-term, limited lead electroencephalograms.

In the last century, 10-20 lead EEG recordings became the gold standard of surface EEG recordings, and the 10-20 system provided comparability between international studies. With the emergence of advanced EEG sensors, that may be able to record and process signals in much more compact units, this additional sensor technology now opens up opportunities to revisit current ambulatory EEG recording practices and specific patient populations, and even electrodes that are embedded into the head surface. Here, we aim to provide an overview of current limited sensor long-term EEG systems. We performed a literature review using Pubmed as a database and included the relevant articles. The review identified several systems for recording long-term ambulatory EEGs. In general, EEGs recorded with these modalities can be acquired in ambulatory and home settings, achieve good sensitivity with low false detection rates, are used for automatic seizure detection as well as seizure forecasting, and are well tolerated by patients, but each of them has advantages and disadvantages. Subcutaneous, subgaleal, and subscalp electrodes are minimally invasive and provide stable signals that can record ultra--long-term EEG and are in general less noisy than scalp EEG, but they have limited spatial coverage and require anesthesia, a surgical procedure and a trained surgeon to be placed. Behind and in the ear electrodes are discrete, unobtrusive with a good sensitivity mainly for temporal seizures but might miss extratemporal seizures, recordings could be obscured by muscle artifacts and bilateral ictal patterns might be difficult to register. Finally, recording systems using electrodes in a headband can be easily and quickly placed by the patient or caregiver, but have less spatial coverage and are more prone to movement because electrodes are not attached. Overall, limited EEG recording systems offer a promising opportunity to potentially record targeted EEG with focused indications for prolonged periods, but further validation work is needed.

Randomized clinical trial comparing the efficacy and safety of ketamine and fentanyl for analgesia in pediatric orthopedic procedures / Ensaio clínico randomizado comparando a eficácia e a segurança da cetamina e do fentanil para analgesia em procedimentos ortopédicos pediátricos

ABSTRACT BACKGROUND AND OBJECTIVES: Bone fractures constitute a frequent cause of emergency care in the pediatric population. Opioid drugs are routinely used for analgesia during the hospitalization of children victims of trauma. Few studies have evaluated the importance of a multimodal approach to analgesia in this context. The aim of this study was to compare the analgesic effect and possible side effects of fentanyl compared to those of ketamine. METHODS: The study analyzed 50 children and adolescents, aged between 24 and 192 months, submitted to surgical treatment of upper limb fractures in a tertiary trauma care hospital. The participants were randomized into two groups: one that received Ketamine and the other Fentanyl. In the post-anesthetic recovery room (PARR), pain intensity and the occurrence of delirium were measured for a period of 30 minutes. The incidence of respiratory depression, nausea, vomiting and other side effects during the surgical procedure were assessed. RESULTS: The sample consisted mostly of male individuals (76.0%). The mean age of the participants was 90.1 months. The use of a low-flow oxygen cannula was necessary in 30.0% of the participants. The incidence of vomiting and laryngospasm was 2.0% among the participants, and 6.0% presented increased salivary secretion. The occurrence of pain, delirium and respiratory depression was not different between the two assessed groups, as well as the occurrence of nausea and laryngospasm. CONCLUSION: Ketamine is not an effective and safe option to opioids for analgesia in children undergoing surgical procedures to treat upper limb fractures.

RESUMO JUSTIFICATIVA E OBJETIVOS: As fraturas ósseas constituem causa frequente de atendimento de emergência na população pediátrica. Fármacos opioides são rotineiramente utilizados para analgesia durante a hospitalização de crianças vítimas de trauma. Poucos estudos avaliaram a importância de uma abordagem multimodal para analgesia nesse contexto. O objetivo deste estudo foi comparar o efeito analgésico e possíveis efeitos adversos do fentanil em relação aos da cetamina. MÉTODOS: Foram analisados 50 crianças e adolescentes, com idade entre 24 e 192 meses, submetidos ao tratamento cirúrgico das fraturas de membros superiores em um hospital terciário de atendimento ao trauma. Os participantes foram aleatorizados em dois grupos: um recebeu cetamina e outro fentanil. Na sala de recuperação pós-anestésica (SRPA), a intensidade da dor e a ocorrência de delirium foram mensuradas por um período de 30 minutos. A incidência de depressão respiratória, náuseas, vômitos e outros efeitos adversos durante o procedimento cirúrgico foram avaliados. RESULTADOS: A amostra foi composta, em sua maioria, por indivíduos do sexo masculino (76,0%). A média de idade dos participantes foi de 90,1 meses. O uso de cânula de oxigênio de baixo fluxo foi necessário em 30,0% dos participantes. A incidência de vômitos e laringoespasmo foi de 2,0% entre os participantes, sendo que 6,0% apresentaram aumento da secreção salivar. A ocorrência de dor, delirium e depressão respiratória não foi diferente entre os dois grupos avaliados, assim como a ocorrência de náuseas e laringoespasmo. CONCLUSAO: Acetamina não se mostrou uma opção eficaz e segura aos opioides para analgesia em crianças submetidas a procedimentos cirúrgicos para tratamento de fraturas de membros superiores.

Bromelain regulates TRP channels to induce orofacial nociception relief in adult zebrafish.

Bromelain, the main protease enzyme found in the pineapple plant (Ananas comosus), has had its antinociceptive effect previously demonstrated. This investigation aimed to appraise the role of TRP (Transient Receptor Potential) channels in the nociception-relieving effects of bromelain in the orofacial region of adult zebrafish. The animals were pretreated with bromelain (3.0, 10.0 or 30.0 mg/mL; gavage) and submitted to open field and acute orofacial (capsaicin - TRPV1 agonist, cinnamaldehyde - TRPA1 agonist or menthol - TRPM8 agonist) nociception tests. The investigation also explored the contribution of central afferent C-fibers. Naive groups were included for comparison. Bromelain did not independently affect the zebrafish movement patterns. However, bromelain decreased the nociceptive responses elicited by all three TRP channel activators. Capsazepine (TRPV1 inhibitor) and AMTB (TRPM8 inhibitor), but not HC-030031 (TRPA1 inhibitor), prevented the antinociceptive effect of bromelain. Moreover, capsaicin-induced desensitization effectively nullified the antinociceptive effect of bromelain. Collectively, these findings corroborate the therapeutic relevance of bromelain as a suppressor of orofacial nociception, which seems to be intricately connected to the modulation of TRP channels.

The prevalence and risk factors of PTSD symptoms among nurses during the COVID-19 pandemic-A systematic review and meta-analysis.

Since the first reported outbreak in China, the Coronavirus disease 2019 (COVID-19) has raised serious concerns globally. The COVID-19 pandemic has caused a severe psychological impact on healthcare workers (HCWs), and especially nurses, who are the most numerous and exposed frontline group. This systematic review and meta-analysis aims to summarise extant literature on the effects of the COVID-19 pandemic on the psychological health of nurses, particularly concerning the prevalence and risk factors for post-traumatic stress disorder (PTSD). A systematic search was conducted on PubMed, Embase and PsycInfo from March 2020 to July 2023. Articles were included/excluded on predetermined eligibility criteria. A random-effect meta-analysis was performed using proportions to determine the pooled prevalence for PTSD among nurses. Subgroup analyses were also performed, and heterogeneity across studies was analysed using meta-regression. Relatively high prevalence rates of PTSD were reported among nurse populations during the COVID-19 pandemic in twenty-six different countries, globally. Risk factors associated with PTSD include having prior mental health co-morbidities, being a female, having high exposure/contact with COVID-19 patients, having insufficient protective conditions and having intensive workloads. The overall pooled prevalence was 29.1% (95% C.I. = 23.5%, 35.5%) using a random-effects model in 55 studies. The regression test of funnel plot asymmetry indicated a significant level of publication bias among studies. The COVID-19 pandemic is associated with significant levels of PTSD among frontline nurses globally. A high level of heterogeneity was observed across studies. Psychological, social and administrative interventions should be implemented to mitigate heavy psychological distress in nurses.

If the Patient Does Not Take the Medication, It Will Not Work.

COGNITIVE AND BEHAVIORAL COMORBIDITIES: AN UNWANTED EFFECT OF ANTIEPILEPTIC DRUGS IN CHILDREN: Adriana Ulate-Campos, Iván Sánchez Fernández Seminars in Pediatric Neurology Volume 24, Issue 4, November 2017, Pages 320-330 Epilepsy is one of the most common neurological disorders and, despite optimally chosen and dosed antiepileptic drugs (AEDs), approximately 20%-30% of patients will continue to have seizures. Behavior and cognition are negatively impacted by seizures, but AEDs are also a major contributor to behavioral and cognitive deficits. However, the cognitive and behavioral effect of AEDs in children is insufficiently emphasized in the literature. This review summarizes the cognitive and behavioral effects of AEDs in the pediatric population with the objective of helping pediatricians and pediatric neurologists to select the AEDs with the best profile for their individual patient's needs.

Three-year survival and distribution of lymph node metastases in gastric cancer following neoadjuvant chemotherapy: results from a European randomized clinical trial.

BACKGROUND: Adequate lymphadenectomy is an important step in gastrectomy for cancer, with a modified D2 lymphadenectomy being recommended for advanced gastric cancers. When assessing a novel technique for the treatment of gastric cancer, lymphadenectomy should be non-inferior. The aim of this study was to assess completeness of lymphadenectomy and distribution patterns between open total gastrectomy (OTG) and minimally invasive total gastrectomy (MITG) in the era of peri-operative chemotherapy. METHODS: This is a retrospective analysis of the STOMACH trial, a randomized clinical trial in thirteen hospitals in Europe. Patients were randomized between OTG and MITG for advanced gastric cancer after neoadjuvant chemotherapy. Three-year survival, number of resected lymph nodes, completeness of lymphadenectomy, and distribution patterns were examined. RESULTS: A total of 96 patients were included in this trial and randomized between OTG (49 patients) and MITG (47 patients). No difference in 3-year survival was observed, this was 57.1% in OTG group versus 46.8% in MITG group (P = 0.186). The mean number of examined lymph nodes per patient was 44.3 ± 16.7 in the OTG group and 40.7 ± 16.3 in the MITG group (P = 0.209). D2 lymphadenectomy of 71.4% in the OTG group and 74.5% in the MITG group was performed according to the surgeons; according to the pathologist compliance to D2 lymphadenectomy was 30% in the OTG group and 36% in the MITG group. Tier 2 lymph node metastases (stations 7-12) were observed in 19.6% in the OTG group versus 43.5% in the MITG group (P = 0.024). CONCLUSION: No difference in 3-year survival was observed between open and minimally invasive gastrectomy. No differences were observed for lymph node yield and type of lymphadenectomy. Adherence to D2 lymphadenectomy reported by the pathologist was markedly low.

Bean Leaves Ameliorate Lipotoxicity in Fatty Liver Disease.

Bioactive compounds in plant-based food have protective effects against metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Bean leaves are widely cultivated in the world and are a source of dietary fiber and polyphenols. High fat/high fructose diet animal models promote deleterious effects in adipose and non-adipose tissues (lipotoxicity), leading to obesity and its comorbidities. Short-term supplementation of bean leaves exhibited anti-diabetic, anti-hyperlipidemic, and anti-obesity effects in high-fat/high-fructose diet animal models. This study aimed to evaluate the effect of bean leaves supplementation in the prevention of lipotoxicity in NAFLD and contribute to elucidating the possible mechanism involved for a longer period of time. During thirteen weeks, male Wistar rats (n = 9/group) were fed with: (1) S: Rodent Laboratory Chow 5001® (RLC); (2) SBL: 90% RLC+ 10% dry bean leaves; (3) H: high-fat/high-fructose diet; (4) HBL: H+ 10% of dry bean leaves. Overall, a HBL diet enhanced impaired glucose tolerance and ameliorated obesity, risk factors in NAFLD development. Additionally, bean leaves exerted antioxidant (↑serum GSH) and anti-inflammatory (↓mRNA TNFα in the liver) effects, prevented hepatic fat accumulation by enhanced ↑mRNA PPARα (ß oxidation), and enhanced lipid peroxidation (↓liver MDA). These findings suggest that bean leaves ameliorated hepatic lipotoxicity derived from the consumption of a deleterious diet.

Evaluation of konjac noodle as a microsurgery training model: learning curve analysis.

BACKGROUND: classical models of microsurgical anastomosis training are expensive and have ethical implications. Some alternatives join low cost and easiness to store. However, the translation of knowledge acquired by training in these methods into the traditional ones is not clear. This project aims to assess the feasibility of konjac noodles as a reliable microsurgery-training model. METHODS: 10 neurosurgery residents performed an end-to-end anastomosis in a 2-3mm placenta artery. The anastomoses were evaluated quantitatively, recording time; and qualitatively, applying a validated score (Anastomosis Lapse Index - ALI) by three experienced neurosurgeons and verifying the presence of gross leakage through the infusion of fluorescein. Subsequently, they performed 10 non-consecutive sessions of anastomosis training in the konjac noodle. Eventually, a final anastomosis in the placenta model was performed and the same parameters were scored. RESULTS: we observed a 17min reduction in the mean time to perform the anastomosis in the placenta model after the training in the konjac (p<0.05). There was a non-significant 20% reduction in gross leakage, but the training sessions were not able to consistently improve the ALI score. CONCLUSIONS: we demonstrate a reduction in anastomosis performing time in placental arteries after training sessions in the konjac noodle model, which can be regarded as a feasible low-cost method, particularly useful in centers with surgical microscopes only in the operation room.

Acute and chronic postoperative pain: knowledge of anesthesiologists and surgeons in Northeastern Brazil about its definition and prevention / Dor aguda e crônica pós-operatória: conhecimento de anestesiologistas e cirurgiões do Nordeste do Brasil sobre sua definição e prevenção

ABSTRACT BACKGROUND AND OBJECTIVES: Chronic postoperative pain (CPP) can be defined as pain that continues for two or more months after surgery, after ruling out other causes. In Brazil, there is a lack of reliable data regarding the incidence of acute and chronic postoperative pain, as well as its impact on patients. The aim of this study was to evaluate the knowledge of anesthesiologists and surgeons regarding the management of CPP. METHODS: This cross-sectional observational study was conducted using an online questionnaire distributed to a non-probabilistic convenience sample of anesthesiologists and surgeons. The questionnaire, administered through Google Forms™, consisted of 22 questions covering sociodemographic information, self-assessment of knowledge, therapeutic management of postoperative pain, and the perceived need for further training. Chi-square test or Fisher's Exact test was used to analyze the data. RESULTS: The main sociodemographic findings indicate a gender difference (p=0.03) among surgeons. Of 109 participants, most did not have expertise or specialization in pain management (p=0.02) and obtained knowledge about pain and analgesia only after undergraduate courses (p=0.013). Surgeons provided more incorrect answers about the definition of acute pain (p<0.001) and chronic pain (p=0.003) than anesthesiologists. Most participants claim to remember at least two risk factors for the development of chronic pain in surgical patients (p=0.001). Participants did not recommend the use of antidepressants (p=0.024) or antiepileptics (p=0.013) for the treatment of acute pain. Anesthesiologists considered strong opioids adequate to control acute pain (p<0.001). In relation to chronic pain, 70.7% of surgeons and 89.7% of anesthesiologists believed that antiepileptic drugs could be effective in managing this type of pain (p=0.018). Longer training time was related to less study of pain during undergraduate education (p=0.041). CONCLUSION: Surgeons and anesthesiologists showed substantial deficits in knowledge about postoperative pain. It is necessary to reassess the inclusion of the pain subject in medical curricula, and a more practical approach to the topic could greatly benefit future professionals working in this field.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor pós-operatória crônica (DPC) pode ser definida como uma dor que persiste por dois ou mais meses após a cirurgia, após a exclusão de outras causas. No Brasil, faltam dados confiáveis sobre a incidência de dor pós-operatória aguda e crônica, bem como seu impacto nos pacientes. O objetivo deste estudo foi avaliar o conhecimento de anestesiologistas e cirurgiões sobre o manejo da DPC. MÉTODOS: Este estudo observacional transversal foi realizado por meio de um questionário online distribuído a uma amostra não probabilística de conveniência de anestesiologistas e cirurgiões. O questionário, administrado por meio do Google Forms™, consistia em 22 questões abrangendo informações sociodemográficas, autoavaliação do conhecimento, manejo terapêutico da dor pós-operatória e percepção da necessidade de treinamento adicional. O teste Qui-quadrado ou o Exato de Fisher foi utilizado para analisar os dados. RESULTADOS: Os principais achados sociodemográficos indicaram diferença de sexo (p=0,03) entre os cirurgiões. Dos 109 participantes, a maioria não possuía expertise ou especialização no manejo da dor (p=0,02) e obtiveram conhecimento sobre dor e analgesia somente após a graduação (p=0,013). Os cirurgiões forneceram mais respostas incorretas sobre a definição de dor aguda (p<0,001) e dor crônica (p=0,003) do que os anestesiologistas. A maioria dos participantes afirmou se lembrar de ao menos dois fatores de risco para o desenvolvimento de dor crônica em pacientes cirúrgicos (p=0,001). Os participantes não recomendaram o uso de antidepressivos (p=0,024) ou antiepilépticos (p=0,013) para o tratamento da dor aguda. Os anestesiologistas consideraram os opioides fortes adequados para o controle da dor aguda (p<0,001). Em relação à dor crônica, 70,7% dos cirurgiões e 89,7% dos anestesiologistas acreditam que os fármacos antiepilépticos podem ser eficazes no controle desse tipo de dor (p=0,018). O maior tempo de formação foi relacionado a um menor estudo da dor durante a graduação (p=0,041). CONCLUSÃO: Cirurgiões e anestesiologistas mostraram déficits substanciais no conhecimento sobre dor pós-operatória. É preciso reavaliar a inclusão do tema da dor nos currículos médicos, e uma abordagem mais prática do tema pode beneficiar muito os futuros profissionais que atuam nessa área.

Melatonin promotes orofacial antinociception in adult zebrafish by modulating TRP channels.

Melatonin is an endogenous hormone, known as the sleep hormone, which has already demonstrated its antinociceptive effect. This study aimed to evaluate the participation of TRP's channels in the orofacial antinociceptive effect of melatonin (MT) in adult zebrafish. Initially, the open field test was performed to evaluate the effect of MT on the locomotor activity of adult zebrafish. Then, the animals were pre-treated with MT (0.1, 0.3 or 1 mg/mL; gavage) and acute orofacial nociception was induced by the application of capsaicin (TRPV1 agonist), cinnamaldehyde (TRPA1 agonist) or menthol (TRPM8 agonist) applied into the animal's lip. Naive groups were included. MT, per se, did not alter the locomotor activity of the animals. MT reduced the nociceptive behavior induced by the three agonists; however, the most significant effect was obtained with the lowest concentration tested (0.1 mg/mL) in the capsaicin test. The orofacial antinociceptive effect of melatonin was prevented by capsazepine (TRPV1 antagonist), but not by HC-030031 (TRPA1 antagonist). The molecular docking study indicated interaction between MT and the TRPV1, TRPA1 and TRPM8 channels and, in line with the in vivo results, there was greater affinity between MT and the TRPV1 channel. The results confirm the pharmacological relevance of melatonin as an inhibitor of orofacial nociception and this effect seems to be related to the modulation of TRP's channels.

Association between the Processed Dietary Pattern and Tumor Staging in Patients Newly Diagnosed with Head and Neck Squamous Cell Carcinoma.

PURPOSE: This study aimed to assess the association between dietary patterns and tumor staging and the degree of cell differentiation in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: This cross-sectional study included 136 individuals newly diagnosed with different stages of HNSCC, aged 20- to 80 years-old. Dietary patterns were determined by principal component analysis (PCA), using data collected from a food frequency questionnaire (FFQ). Anthropometric, lifestyle, and clinicopathological data were collected from patients' medical records. Disease staging was categorized as initial stage (stages I and II), intermediary (stage III), and advanced (stage IV). Cell differentiation was categorized as poor, moderate, or well-differentiated. The association of dietary patterns with tumor staging and cell differentiation was evaluated using multinomial logistic regression models and adjusted for potential confounders. RESULTS: Three dietary patterns, "healthy," "processed," and "mixed," were identified. The "processed" dietary pattern was associated with intermediary (odds ratio (OR) 2.47; 95% confidence interval (CI) 1.43-4.26; p = 0.001) and advanced (OR 1.78; 95% CI 1.12-2.84; p = 0.015) staging. No association was found between dietary patterns and cell differentiation. CONCLUSION: A high adherence to dietary patterns based on processed foods is associated with advanced tumor staging in patients newly diagnosed with HNSCC.

Ovarian aging in humans: potential strategies for extending reproductive lifespan.

Ovarian reserve is a term used to estimate the total number of immature follicles present in the ovaries. Between birth and menopause, there is a progressive decrease in the number of ovarian follicles. Ovarian aging is a continuous physiological phenomenon, with menopause being the clinical mark of the end of ovarian function. Genetics, measured as family history for age at the onset of menopause, is the main determinant. However, physical activity, diet, and lifestyle are important factors that can influence the age of menopause. The low estrogen levels after natural or premature menopause increased the risk for several diseases, resulting in increased mortality risk. Besides that, the decreasing ovarian reserve is associated to reduced fertility. In women with infertility undergoing in vitro fertilization, reduced markers of ovarian reserve, including antral follicular count and anti-Mullerian hormone, are the main indicators of reduced chances of becoming pregnant. Therefore, it becomes clear that the ovarian reserve has a central role in women's life, affecting fertility early in life and overall health later in life. Based on this, the ideal strategy for delaying ovarian aging should have the following characteristics: (1) be initiated in the presence of good ovarian reserve; (2) maintained for a long period; (3) have an action on the dynamics of primordial follicles, controlling the rate of activation and atresia; and (4) safe use in pre-conception, pregnancy, and lactation. In this review, we therefore discuss some of these strategies and its feasibility for preventing a decline in the ovarian reserve.

Pharmacological Potential of cis-jasmone in Adult Zebrafish (Danio rerio).

This study evaluates the pharmacological potential of cis-jasmone (CJ) in adult zebrafish (Danio rerio; aZF). Initially, aZF (n = 6/group) were pretreated (20 µL; p. o.) with CJ (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.5% Tween 80). The animals were submitted to acute toxicity and locomotion tests, pentylenetetrazole-induced seizure, carrageenan-induced abdominal edema, and cinnamaldehyde-, capsaicin-, menthol-, glutamate-, and acid saline-induced orofacial nociception. The possible mechanisms of anticonvulsant, anxiolytic, and antinociceptive action were evaluated. The involvement of central afferent fibers sensitive to cinnamaldehyde and capsaicin and the effect of CJ on the relative gene expression of TRPA1 and TRPV1 in the brain of aZF were also analyzed, in addition to the study of molecular docking between CJ and TRPA1, TRPV1 channels, and GABAA receptors. CJ did not alter the locomotor behavior and showed pharmacological potential in all tested models with no toxicity. The anticonvulsant effect of CJ was prevented by flumazenil (GABAergic antagonist). The anxiolytic-like effect of CJ was prevented by flumazenil and serotonergic antagonists. The antinociceptive effect was prevented by TRPA1 and TRPV1 antagonists. Chemical ablation with capsaicin and cinnamaldehyde prevented the orofacial antinociceptive effect of CJ. Molecular docking studies indicate that CJ interacted with TRPA1, TRPV1, and GABAA receptors. CJ inhibited the relative gene expression of TRPA1 and TRPV1. CJ has pharmacological potential for the treatment of seizures, anxiety, inflammation, and acute orofacial nociception. These effects are obtained by modulating the GABAergic and serotonergic systems, as well as the TRPs and ASIC channels.