(-)-Carvone Inhibits Oxytocin-induced Writhing Via Uterine Relaxation in Rodents.

(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.

Metabolomics analysis of human spermatozoa reveals impaired metabolic pathways in asthenozoospermia.

BACKGROUND: Infertility is a major health issue, affecting 15% of reproductive-age couples with male factors contributing to 50% of cases. Asthenozoospermia (AS), or low sperm motility, is a common cause of male infertility with complex aetiology, involving genetic and metabolic alterations, inflammation and oxidative stress. However, the molecular mechanisms behind low motility are unclear. In this study, we used a metabolomics approach to identify metabolic biomarkers and pathways involved in sperm motility. METHODS: We compared the metabolome and lipidome of spermatozoa of men with normozoospermia (n = 44) and AS (n = 22) using untargeted LC-MS and the metabolome of seminal fluid using 1H-NMR. Additionally, we evaluated the seminal fluid redox status to assess the oxidative stress in the ejaculate. RESULTS: We identified 112 metabolites and 209 lipids in spermatozoa and 27 metabolites in the seminal fluid of normozoospermic and asthenozoospermic men. PCA analysis of the spermatozoa's metabolomics and lipidomics data showed a clear separation between groups. Spermatozoa of asthenozoospermic men presented lower levels of several amino acids, and increased levels of energetic substrates and lysophospholipids. However, the metabolome and redox status of the seminal fluid was not altered inAS. CONCLUSIONS: Our results indicate impaired metabolic pathways associated with redox homeostasis and amino acid, energy and lipid metabolism in AS. Taken together, these findings suggest that the metabolome and lipidome of human spermatozoa are key factors influencing their motility and that oxidative stress exposure during spermatogenesis or sperm maturation may be in the aetiology of decreased motility in AS.

Enduring metabolic modulation in the cardiac tissue of elderly CD-1 mice two months post mitoxantrone treatment.

Mitoxantrone (MTX) is a therapeutic agent used in the treatment of solid tumors and multiple sclerosis, recognized for its cardiotoxicity, with underlying molecular mechanisms not fully disclosed. The cardiotoxicity is influenced by risk factors, including age. Our study intended to assess the molecular effect of MTX on the cardiac muscle of old male CD-1 mice. Mice aged 19 months received a total cumulative dose of 4.5 mg/kg of MTX (MTX group) or saline solution (CTRL group). Two months post treatment, blood was collected, animals sacrificed, and the heart removed. MTX caused structural cardiac changes, which were accompanied by extracellular matrix remodeling, as indicated by the increased ratio between matrix metallopeptidase 2 and metalloproteinase inhibitor 2. At the metabolic level, decreased glycerol levels were found, together with a trend towards increased content of the electron transfer flavoprotein dehydrogenase. In contrast, lower glycolysis, given by the decreased content of glucose transporter GLUT4 and phosphofructokinase, seemed to occur. The findings suggest higher reliance on fatty acids oxidation, despite no major remodeling occurring at the mitochondrial level. Furthermore, the levels of glutamine and other amino acids (although to a lesser extent) were decreased, which aligns with decreased content of the E3 ubiquitin-protein ligase Atrogin-1, suggesting a decrease in proteolysis. As far as we know, this was the first study made in old mice with a clinically relevant dose of MTX, evaluating its long-term cardiac effects. Even two months after MTX exposure, changes in metabolic fingerprint occurred, highlighting enduring cardiac effects that may require clinical vigilance.

Clinical Correlation of Transcription Factor SOX3 in Cancer: Unveiling Its Role in Tumorigenesis.

Members of the SOX (SRY-related HMG box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular modelsBy providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

Exposure to toxicologically relevant atrazine concentrations impair the glycolytic function of mouse Sertoli cells through the downregulation of lactate dehydrogenase.

Atrazine (ATZ), a widely used herbicide with potent endocrine-disrupting properties, has been implicated in hormonal disturbances and fertility issues. Sertoli cells (SCs) play a crucial role in providing mechanical and nutritional support of spermatogenesis. Herein, we aimed to study the effects of environmentally relevant ATZ concentrations on the nutritional support of spermatogenesis provided by SCs. For that, mouse SCs (TM4) were exposed to increasing ATZ concentrations (in µg/L: 0.3, 3, 30, 300, or 3000). After 24 h, cellular proliferation and metabolic activity were assessed. Mitochondrial activity and endogenous reactive oxygen species (ROS) production were evaluated using JC-1 and CM-H2DCFDA probes, respectively. We also analyzed protein levels of lactate dehydrogenase (LDH) using Western Blot and live cells glycolytic function through Seahorse XF Glycolysis Stress Test Kit. ATZ exposure decreased the activity of oxidoreductases in SCs, suggesting a decreased metabolic activity. Although ATZ is reported to induce oxidative stress, we did not observe alterations in mitochondrial membrane potential and ROS production across all tested concentrations. When we evaluated the glycolytic function of SCs, we observed that ATZ significantly impaired glycolysis and the glycolytic capacity at all tested concentrations. These results were supported by the decreased expression of LDH in SCs. Overall, our findings suggest that ATZ impairs the glycolytic function of SCs through LDH downregulation. Since lactate is the preferential energetic substrate for germ cells, exposure to ATZ may detrimentally impact the nutritional support crucial for spermatogenesis, hinting for a relationship between ATZ exposure and male infertility.

Mitochondrial uncoupling proteins regulate the metabolic function of human Sertoli cells.

In brief: Mitochondrial uncoupling proteins (UCPs) regulate mitochondrial activity and reactive oxygen species production through the transport of protons and metabolites. This study identified the expression of UCPs in human Sertoli cells, which proved to be modulators of their mitochondrial activity. Abstract: Mitochondrial uncoupling proteins (UCPs) are mitochondrial channels responsible for the transport of protons and small molecular substrates across the inner mitochondrial membrane. Altered UCP expression or function is commonly associated with mitochondrial dysfunction and increased oxidative stress, which are both known causes of male infertility. However, UCP expression and function in the human testis remain to be characterized. This study aimed to assess the UCP homologs (UCP1-6) expression and function in primary cultures of human Sertoli cells (hSCs). We identified the mRNA expression of all UCP homologs (UCP1-6) and protein expression of UCP1, UCP2, and UCP3 in hSCs. UCP inhibition by genipin for 24 h decreased hSCs proliferation without causing cytotoxicity (n = 6). Surprisingly, the prolonged UCP inhibition for 24 h decreased mitochondrial membrane potential, oxygen consumption rate (OCR), and endogenous reactive oxygen species (ROS) production. The metabolism of hSCs was also affected as UCP inhibition shifted their metabolism toward an increased pyruvate consumption. Taken together, these findings demonstrate that UCPs play a role as regulators of the mitochondrial function in hSCs, emphasizing their potential as targets in the study of male (in)fertility.

Impact of Different Treatment Regimens and Timeframes in the Plasmatic Metabolic Profiling of Patients with Lung Adenocarcinoma.

In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) has suffered a variety of alterations. Chemotherapy (CTX), immunotherapy (IT) and tyrosine kinase inhibitors (TKI) have shown remarkable results. However, not all patients with NSCLC respond to these drug treatments or receive durable benefits. In this framework, metabolomics has been applied to improve the diagnosis, treatment, and prognosis of lung cancer and particularly lung adenocarcinoma (AdC). In our study, metabolomics was used to analyze plasma samples from 18 patients with AdC treated with CTX or IT via 1H-NMR spectroscopy. Relevant clinical information was gathered, and several biochemical parameters were also evaluated throughout the treatments. During the follow-up of patients undergoing CTX or IT, imaging control is recommended in order to assess the effectiveness of the therapy. This evaluation is usually performed every three treatments. Based on this procedure, all the samples were collected before the beginning of the treatment and after three and six treatments. The identified and quantified metabolites in the analyzed plasma samples were the following: isoleucine, valine, alanine, acetate, lactate, glucose, tyrosine, and formate. Multivariate/univariate statistical analyses were performed. Our data are in accordance with previous published results, suggesting that the plasma glucose levels of patients under CTX become higher throughout the course of treatment, which we hypothesize could be related to the tumor response to the therapy. It was also found that alanine levels become lower during treatment with CTX regimens, a fact that could be associated with frailty. NMR spectra of long responders' profiles also showed similar results. Based on the results of the study, metabolomics can represent a potential option for future studies, in order to facilitate patient selection and the monitoring of therapy efficacy in treated patients with AdC. Further studies are needed to improve the prospective identification of predictive markers, particularly glucose and alanine levels, as well as confer guidance to NSCLC treatment and patient stratification, thus avoiding ineffective therapeutic strategies.

One nodule-one punction-one slide: Optimizing thyroid fine-needle aspiration for a digital workflow.

OBJECTIVE: Interventional pathologists have expanded their expertise by acquiring proficiency in ultrasound-guided thyroid fine-needle aspiration biopsy (FNAB) and are now required to optimize punction procedures due to low resources and digital workflows. The aim of this study is to compare FNAB sample adequacy in two series with one versus two slides available for cytopathological analysis and its influence on diagnosis categorization, time taken to reach a final diagnosis, scanning time and size of the digital files produced. METHODS: Patients were retrospectively selected based on the sampling of thyroid nodules using either two glass slides (two-slide group) or one slide only (one-slide group) and cytological diagnosis was performed using the second edition of the Bethesda system. For each group, the initial 15 cases were sorted to be scanned. RESULTS: From a total of 713 procedures, 328 were sampled into two slides and 385 on one slide only. No significant differences were found regarding nodule size, location or EU-TIRADS classification between the two groups. The one-slide group did not exhibit a higher prevalence of non-diagnostic or atypia of undetermined significance (AUS) categories. As expected, the mean time taken to finalize diagnoses in cases where only one slide was prepared was 1.2 days faster. Scanning time and total file size were also significantly smaller in the one-slide group. CONCLUSIONS: Adopting the 'one nodule-one puncture-one slide' strategy for thyroid FNAB optimization enhances procedural efficiency in digital workflows, leading to cost savings without compromising diagnostic accuracy.

Replacing Harmful Flame Retardants with Biodegradable Starch-Based Materials in Polyethylene Formulations.

The addition of toxic flame retardants to commercially available polymers is often required for safety reasons due to the high flammability of these materials. In this work, the preparation and incorporation of efficient biodegradable starch-based flame retardants into a low-density polyethylene (LDPE) matrix was investigated. Thermoplastic starch was first obtained by plasticizing starch with glycerol/water or glycerol/water/choline phytate to obtain TPS-G and TPS-G-CPA, respectively. Various LDPE/TPS blends were prepared by means of melt blending using polyethylene graft maleic anhydride as a compatibilizer and by varying the content of TPS and a halogenated commercial flame retardant. By replacing 38% and 76% of the harmful commercial flame retardant with safe TPS-G-CPA and TPS-G, respectively, blends with promising fire behavior were obtained, while the limiting oxygen index (LOI ≈ 28%) remained the same. The presence of choline phytate improved both the charring ability and fire retardancy of starch and resulted in a 43% reduction in fire growth index compared to the blend with commercial flame retardant only, as confirmed by means of cone calorimetry. Standard UL 94 vertical tests showed that blends containing TPS exhibited dripping behavior (rated V2), while those with commercial flame retardant were rated V0. Overall, this work demonstrates the potential of starch as a natural flame retardant that could reduce the cost and increase the safety of polymer-based materials.

DORSALIS PEDIS NEUROVASCULAR FLAP, OUR EXPERIENCE.

Objectives: Analyze the donor site morbidity of the dorsalis pedis neurovascular flap in traumatic injuries with hand tissue loss. Material and Methods: The study involved dorsalis pedis neurovascular flaps that were used to reconstruct the hands of eight male patients, between 1983 and 2003, aged between 21 and 53 years (mean 34.6, SD ± 10.5 years). The size of the lesions ranged from 35 to 78 cm2 (mean 53, SD ± 14.4 cm2). Surgical procedures were performed two to 21 days after the injuries had occurred. The patients were followed up for an average of 10.3 years (ranging 8-14, SD ± 2.1 years). Results: Regarding the donor site, in one case there was hematoma formation, which was drained; in another case, the skin graft needed to be reassessed. All patients experienced delayed healing, with complete healing from 2 to 12 months after the surgery (mean 4.3, SD ± 3.2 months). Conclusion: Despite the advantages of the dorsalis pedis neurovascular flap, we consider that the sequelae in the donor site is cosmetically unacceptable. Nowadays, this procedure is only indicated and justified when associated with the second toe transfer. Level of Evidence IV; Case series .

Objetivos: Analisar a morbidade da área doadora do retalho neurovascular do dorso do pé em lesões traumáticas com perda de tecido da mão. Material e métodos: O estudo envolveu retalhos neurovasculares do dorso do pé usados para reconstruir as mãos de oito pacientes do sexo masculino, entre 1983 e 2003, com idades entre 21 e53 anos (média de 34,6, DP ± 10,5 anos). O tamanho das lesões variou de 35 a 78 cm2 (média de 53, DP ± 14,4 cm2). Os procedimentos cirúrgicos foram realizados entre dois a 21 dias após a ocorrência das lesões. Os pacientes foram acompanhados por uma média de10,3 anos (variando de 8 a 14, DP ± 2,1 anos). Resultados: Quanto ao local doador, em um caso houve formação de hematoma, que foi drenado; em outro caso, o enxerto de pele precisou ser reavaliado. Todos os pacientes apresentaram retardo na cicatrização, com cicatrização completa de 2 a 12 meses após a cirurgia (média de 4,3, DP ± 3,2 meses). Conclusão: Apesar das vantagens do retalho neurovascular do dorso do pé, consideramos que as sequelas no local doador são cosmeticamente inaceitáveis. Atualmente, esse procedimento só é indicado e justificado quando associado à transferência do segundo dedo do pé. Nível de evidência IV; Série de casos .

The Influence of Adipocyte Secretome on Selected Metabolic Fingerprints of Breast Cancer Cell Lines Representing the Four Major Breast Cancer Subtypes.

Molecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.

The progression from mild to severe hyperglycemia coupled with insulin resistance causes mitochondrial dysfunction and alters the metabolic secretome of epithelial kidney cells.

Diabetic nephropathy (DN) and insulin resistance (IR) in kidney cells are considered main causes for end-stage renal failure. However, it is unclear how IR affects early stages of the disease. Here, we investigate the impact of mild (11 mM) and severe (22 mM) hyperglycemia, with and without induced IR, on cellular metabolism and mitochondrial bioenergetics in a human kidney cell line (HK-2). IR in HK-2 cells was induced with palmitic acid and cellular cytotoxicity was studied. We evaluated the impact of mild and severe hyperglycemia with and without IR on the metabolic secretome of the cells, their live-cell mitochondria function, mitochondrial membrane potential, and mitochondrial complex activities. Furthermore, we measured fatty acid oxidation and lipid accumulation. Cells cultured under mild hyperglycemic conditions exhibited increased mitochondrial bioenergetic parameters, such as basal respiration, ATP-linked production, maximal respiration capacity, and spare respiration capacity. However, these parameters decreased when cells were cultured under higher glucose concentrations when IR was induced. Our data suggests that progression from mild to severe hyperglycemia induces a metabolic shift, where gluconeogenic amino acids play a crucial role in supplying the energy requirements of HK-2. To our knowledge, this is the first study to evaluate the progression from mild to severe hyperglycemia allied to IR in human kidney cells. This work highlights that this progression leads to mitochondrial dysfunction and alters the metabolic profile of kidney cells. These results identify possible targets for early intervention in DN.

Análise da assistência prestada na atenção primária e fatores associados na perspectiva de idosos diabéticos / Analysis of the assistance provided in primary care and associated factors from the perspective of elderly patients with diabetes / Análisis de la asistencia proporcionada en atención primaria y factores asociados desde la perspectiva del anciano con diabetes

A atenção primária à saúde é fundamental para validar a atenção à saúde de idosos diabéticos, sendo importante sua qualificação por meio de abordagens que evidenciem as perspectivas dos usuários. Neste trabalho, objetivou-se analisar os aspectos associados à satisfação com a assistência prestada no âmbito da atenção primária na perspectiva de idosos com diabetes. Trata-se de um estudo quantitativo, de corte transversal, realizado com 37 idosos diabéticos cadastrados na Estratégia Saúde da Família de um município do estado do Paraná. Aplicou-se um instrumento adaptado que continha questões sobre a caracterização sociodemográfica e clínica, a assistência prestada ao usuário e a satisfação com o atendimento recebido. Os dados foram submetidos à análise descritiva utilizando frequências absolutas e relativas. A avaliação positiva/intermediária da assistência prevaleceu em 70,3% dos entrevistados. Os fatores que apresentaram relação foram: aferição da pressão arterial (100%) e da glicemia capilar (80,77%); ausculta cardíaca (76,92%); oferecimento de antidiabéticos orais/insulina (84,62%) e de orientações sobre seu uso (69,23%), sobre a doença e formas de tratamento (69,23%), sobre complicações (65,38%), sobre a importância da prática de atividade física (61,54%) e de uma alimentação adequada (61,54%); questionamento sobre a saúde e o diabetes (76,92%); percepção do interesse profissional em perguntar sobre o tratamento medicamentoso (92,31%) e sua frequência (84,62%), em compreender, acolher e esclarecer preocupações, dúvidas ou problemas com o diabetes (84,62%) e em dar tempo suficiente para o paciente se expressar (84,62%). Os resultados reforçam a importância da promoção da saúde permeada pelo acolhimento e pelo diálogo sobre boas práticas em saúde, além de uma avaliação clínica de qualidade e oferta de subsídios necessários ao tratamento da doença.

The primary health care is fundamental to validate the health care of elderly diabetics, and it is important to qualify it with approaches that show the perspectives of users. In this work, the objective was to analyze aspects associated with satisfaction with the care provided in the context of primary care from the perspective of elderly people with diabetes. This is a quantitative, cross-sectional study conducted with 37 elderly diabetics registered in the Family Health Strategy in a municipality in the state of Paraná. An adapted instrument was applied, including questions about the sociodemographic and clinical characterization, the assistance provided to the user, and the satisfaction with the care received. Data were submitted to descriptive analysis using absolute and relative frequencies. The positive/intermediate assessment of care prevailed in 70.3% of respondents. The factors that were related were: blood pressure measurement (100%) and capillary blood glucose (80.77%), cardiac auscultation (76.92%); offer of oral antidiabetics/insulin (84.62%), and guidance on their use (69.23%), on the disease and forms of treatment (69.23%), complications (65.38%), importance of physical activity (61.54%), and proper nutrition (61.54%); questioning about health and diabetes (76.92%); perception of professional interest in questioning drug treatment (92.31%), and its frequency (84.62%), in understanding, welcoming, and clarifying concerns, doubts, or problems with diabetes (84.62%), and giving enough time for the patients to express themselves (84.62%). The results reinforce the importance of health promotion permeated by acceptance and dialogue about good health practices, in addition to a clinical quality assessment and the provision of subsidies relevant to the treatment of the disease.

La atención primaria de salud es fundamental para validar la atención a la salud de los ancianos diabéticos, y es importante calificarla mediante enfoques que muestren las perspectivas de los usuarios. El objetivo de este trabajo fue analizar los aspectos asociados a la satisfacción con la atención prestada en el contexto de la atención primaria en la perspectiva de los ancianos con diabetes. Se trata de un estudio cuantitativo, transversal, realizado con 37 ancianos diabéticos afiliados a la Estrategia de Salud Familiar, que actúa en un municipio del estado de Paraná (Brasil). Se aplicó un instrumento adaptado que contenía preguntas sobre la caracterización sociodemográfica y clínica, la asistencia prestada al usuario y la satisfacción con la atención recibida. Los datos se sometieron a análisis descriptivo utilizando frecuencias absolutas y relativas. La valoración positiva/intermedia del cuidado predominó en el 70,3% de los encuestados. Los factores que se relacionaron fueron: Medición de la presión arterial (100%) y glucemia capilar (80,77%); auscultación cardiaca (76,92%); recibir antidiabéticos orales/insulina (84,62%) y orientación sobre su uso (69,23%), sobre enfermedad y formas de tratamiento (69,23%), sobre complicaciones (65,38%), sobre la importancia de la actividad física (61,54%) y de nutrición adecuada (61,54%); cuestionamiento sobre salud y diabetes (76,92%); percepción del interés profesional en cuestionar el tratamiento farmacológico (92,31%) y su frecuencia (84,62%) en comprender, acoger y aclarar inquietudes, dudas o problemas con la diabetes (84,62%) y darse tiempo suficiente para expresarse (84,62%). Los resultados demuestran la importancia de la promoción de la salud permeada por la aceptación y el diálogo sobre buenas prácticas de salud, además de una evaluación de la calidad clínica y la provisión de subsidios pertinentes al tratamiento de la enfermedad.

Isolated Area Postrema Syndrome Preceding the Diagnosis of Giant Cell Arteritis: A Case Report.

OBJECTIVE: We report a case of biopsy-proven giant cell arteritis after an initial presentation of area postrema syndrome. METHODS: A 65-year-old man was evaluated using MRI, temporal artery biopsy, and ultrasound. RESULTS: The patient presented with refractory nausea, vomiting, and hiccups that caused weight loss without any other neurologic or clinical symptoms. His MRI scan 15 days later revealed a hyperintense sign on the area postrema with no abnormal diffusion or contrast enhancement, compatible with isolated area postrema syndrome. An extensive workup for inflammation and other etiologies including neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disorder, and multiple sclerosis (MS) showed negative results. The patient responded to treatment with methylprednisolone. Two months after the initial clinical manifestation, the patient developed fatigue, headache, and scalp tenderness. He was diagnosed with giant cell arteritis after ultrasonography and biopsy were performed. He responded well to oral glucocorticoids and had only 1 relapse during tapering. He has not had arteritic ischemic optic neuropathy or any new episodes of area postrema syndrome. DISCUSSION: This case demonstrates the importance of expanding the differential diagnosis in patients with area postrema syndrome and no other signs of NMOSD.

Inhibition of Mitochondrial Uncoupling Proteins Arrests Human Spermatozoa Motility without Compromising Viability.

Mitochondrial uncoupling proteins (UCPs) are central in the regulation of mitochondrial activity and reactive oxygen species (ROS) production. High oxidative stress is a major cause of male infertility; however, UCPs expression and function in human spermatozoa are still unknown. Herein, we aimed to assess the expression and function of the different homologs (UCP1-6) in human spermatozoa. For this purpose, we screened for the mRNA expression of all UCP homologs. Protein expression and immunolocalization of UCP1, UCP2, and UCP3 were also assessed. Highly motile spermatozoa were isolated from human normozoospermic seminal samples (n = 16) and incubated with genipin, an inhibitor of UCPs (0, 0.5, 5, and 50 µM) for 3 h at 37 °C. Viability and total motility were assessed. Mitochondrial membrane potential and ROS production were evaluated. Media were collected and the metabolic profile and antioxidant potential were analyzed by 1H-NMR and FRAP, respectively. The expression of all UCP homologs (UCP1-6) mRNA by human spermatozoa is herein reported for the first time. UCP1-3 are predominant at the head equatorial segment, whereas UCP1 and UCP2 are also expressed at the spermatozoa midpiece, where mitochondria are located. The inhibition of UCPs by 50 µM genipin, resulting in the UCP3 inhibition, did not compromise sperm cell viability but resulted in irreversible total motility loss that persisted despite washing or incubation with theophylline, a cAMP activator. These effects were associated with decreased mitochondrial membrane potential and lactate production. No differences concerning UCP3 expression, however, were observed in spermatozoa from normozoospermic versus asthenozoospermic men (n = 6). The inhibition of UCPs did not increase ROS production, possibly due to the decreased mitochondrial activity and genipin antioxidant properties. In sum, UCPs are major regulators of human spermatozoa motility and metabolism. The discovery and characterization of UCPs' role in human spermatozoa can shed new light on spermatozoa ROS-related pathways and bioenergetics physiology.

Antitumor effect of selenium-rich Brazil nuts and selenomethionine dietary supplementation on pre-existing 4T1 mammary tumor growth in mice.

Selenium (Se) is an essential micronutrient known to play an important role in the antioxidant system that can potentially influence tumor growth. We aimed to investigate the effects of dietary Se supplementation after detection of 4T1 mammary tumor growth in BALB/c mice. Thirty female mice received subcutaneous inoculation of 4T1 cells. After five days, all animals presenting palpable tumors were randomly assigned to three groups: a control group (Se-control) receiving a diet with adequate Se (0.15 mg/kg) and two other groups that received Se-supplemented diets (1.4 mg/kg of total Se) with either Brazilian nuts (Se-Nuts) or selenomethionine (SeMet). Data were assessed by either One or Two-way ANOVA followed by Tukey's HSD or Bonferroni's post hoc tests, respectively. Both Se-supplemented diets reduced tumor volume from the thirteenth day of feeding compared with the Se-adequate (control) diet (p < 0.05). The SeMet group presented a higher Se blood concentration (p < 0.05) than the Se-control group, with the Se-Nuts group presenting intermediate values. Selenoprotein P gene expression in the liver was higher in the Se-Nuts group than in the Se-control group (p < 0.05), while the SeMet group presented intermediate expression. Dietary Se supplementation, starting after detection of 4T1 palpable lesions, reduced tumor volume in mice.

Knowledge and Risk Behaviors Regarding Human Immunodeficiency Virus Transmission among Portuguese Healthcare Students.

BACKGROUND: Human immunodeficiency virus (HIV), the agent responsible for acquired immunodeficiency syndrome, remains a worldwide public health problem. Therefore, this study aimed to assess Portuguese healthcare students' knowledge of HIV, identify risk behaviors for HIV transmission, and assess the frequency of HIV testing and its dissemination by general practitioners. METHODS: A cross-sectional observational study was conducted using an anonymous questionnaire published online. The questionnaire was administered to Portuguese healthcare students who voluntarily agreed to participate in the study after clarifying its objectives and procedures. RESULTS: Most students were aware of the three main HIV transmission routes; however, 66.3% were unaware of the level A recommendation for HIV screening in adolescents and adults. In addition, 59.6% of the students were never informed by their general practitioner about HIV screening tests or risk behaviors for HIV transmission. Of the sample, 78.9% had never been tested for HIV infection. Of the 74.6% of sexually active students, 82.0% had or had already had unprotected sex (without a condom). Men showed riskier sexual behaviors than women. None of the inquiries reported intravenous drug use, and most students (69.9%) never shared personal objects. CONCLUSION: General practitioners and awareness campaigns need to alert and disseminate HIV screening tests. Sexual health and risk behaviors should be addressed more frequently in schools to educate this population because prevention is the best strategy against HIV transmission/contraction.

Health risk assessment and differential distribution of Arsenic and metals in organs of Urophycis brasiliensis a commercial fish from Southwestern Atlantic coast.

The concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, and Zn were analyzed in muscle, gills, and liver of Urophycis brasiliensis from two Southwestern Atlantic catch areas (Brazil and Argentina). Additionally, the health risk of general and fishermen populations through fish consumption was estimated. The gills showed the highest concentrations of most of the elements, followed by the liver. With the exception of As, the muscle was the organ with the lowest concentrations of most elements. Levels of arsenic in muscle of U. brasiliensis were exceeded the maximum permissible levels for human consumption recommended by local and international guidelines. The target hazard quotients (THQs) and the carcinogenic risk (CR) showed no risk for individual and all elements. These results highlight the importance of arsenic speciation in U. brasiliensis muscle in order to generate more reliable risk estimates.

Metabolomics Integration in Assisted Reproductive Technologies for Enhanced Embryo Selection beyond Morphokinetic Analysis.

Embryo quality evaluation during in vitro development is a crucial factor for the success of assisted reproductive technologies (ARTs). However, the subjectivity inherent in the morphological evaluation by embryologists can introduce inconsistencies that impact the optimal embryo choice for transfer. To provide a more comprehensive evaluation of embryo quality, we undertook the integration of embryo metabolomics alongside standardized morphokinetic classification. The culture medium of 55 embryos (derived from 21 couples undergoing ICSI) was collected at two timepoints (days 3 and 5). Samples were split into Good (n = 29), Lagging (n = 19), and Bad (n = 10) according to embryo morphokinetic evaluation. Embryo metabolic performance was assessed by monitoring the variation in specific metabolites (pyruvate, lactate, alanine, glutamine, acetate, formate) using 1H-NMR. Adjusted metabolite differentials were observed during the first 3 days of culture and found to be discriminative of embryo quality at the end of day 5. Pyruvate, alanine, glutamine, and acetate were major contributors to this discrimination. Good and Lagging embryos were found to export and accumulate pyruvate and glutamine in the first 3 days of culture, while Bad embryos consumed them. This suggests that Bad embryos have less active metabolic activity than Good and Lagging embryos, and these two metabolites are putative biomarkers for embryo quality. This study provides a more comprehensive evaluation of embryo quality and can lead to improvements in ARTs by enabling the selection of the best embryos. By combining morphological assessment and metabolomics, the selection of high-quality embryos with the potential to result in successful pregnancies may become more accurate and consistent.

Dorsalis pedis neurovascular flap, our experience / Retalho neurovascular dorsal do pé, nossa experiência

ABSTRACT Objectives: Analyze the donor site morbidity of the dorsalis pedis neurovascular flap in traumatic injuries with hand tissue loss. Material and Methods: The study involved dorsalis pedis neurovascular flaps that were used to reconstruct the hands of eight male patients, between 1983 and 2003, aged between 21 and 53 years (mean 34.6, SD ± 10.5 years). The size of the lesions ranged from 35 to 78 cm2 (mean 53, SD ± 14.4 cm2). Surgical procedures were performed two to 21 days after the injuries had occurred. The patients were followed up for an average of 10.3 years (ranging 8-14, SD ± 2.1 years). Results: Regarding the donor site, in one case there was hematoma formation, which was drained; in another case, the skin graft needed to be reassessed. All patients experienced delayed healing, with complete healing from 2 to 12 months after the surgery (mean 4.3, SD ± 3.2 months). Conclusion: Despite the advantages of the dorsalis pedis neurovascular flap, we consider that the sequelae in the donor site is cosmetically unacceptable. Nowadays, this procedure is only indicated and justified when associated with the second toe transfer. Level of Evidence IV; Case series .

RESUMO Objetivos: Analisar a morbidade da área doadora do retalho neurovascular do dorso do pé em lesões traumáticas com perda de tecido da mão. Material e métodos: O estudo envolveu retalhos neurovasculares do dorso do pé usados para reconstruir as mãos de oito pacientes do sexo masculino, entre 1983 e 2003, com idades entre 21 e53 anos (média de 34,6, DP ± 10,5 anos). O tamanho das lesões variou de 35 a 78 cm2 (média de 53, DP ± 14,4 cm2). Os procedimentos cirúrgicos foram realizados entre dois a 21 dias após a ocorrência das lesões. Os pacientes foram acompanhados por uma média de10,3 anos (variando de 8 a 14, DP ± 2,1 anos). Resultados: Quanto ao local doador, em um caso houve formação de hematoma, que foi drenado; em outro caso, o enxerto de pele precisou ser reavaliado. Todos os pacientes apresentaram retardo na cicatrização, com cicatrização completa de 2 a 12 meses após a cirurgia (média de 4,3, DP ± 3,2 meses). Conclusão: Apesar das vantagens do retalho neurovascular do dorso do pé, consideramos que as sequelas no local doador são cosmeticamente inaceitáveis. Atualmente, esse procedimento só é indicado e justificado quando associado à transferência do segundo dedo do pé. Nível de evidência IV; Série de casos .