Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2.

COVID-19, caused by SARS-CoV-2, affects neuronal cells, causing several symptoms such as memory loss, anosmia and brain inflammation. Curcuminoids (Me08 e Me23) and curcumin (CUR) are derived from Curcuma Longa extract (EXT). Many therapeutic actions have been linked to these compounds, including antiviral action. Given the severe implications of COVID-19, especially within the central nervous system, our study aims to shed light on the therapeutic potential of curcuminoids against SARS-CoV-2 infection, particularly in neuronal cells. Here, we investigated the effects of CUR, EXT, Me08 and Me23 in human neuroblastoma SH-SY5Y. We observed that Me23 significantly decreased the expression of plasma membrane-associated transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, consequently mitigating the elevated ROS levels induced by SARS-CoV-2. Furthermore, Me23 exhibited antioxidative properties by increasing NRF2 gene expression and restoring NQO1 activity following SARS-CoV-2 infection. Both Me08 and Me23 effectively reduced SARS-CoV-2 replication in SH-SY5Y cells overexpressing ACE2 (SH-ACE2). Additionally, all of these compounds demonstrated the ability to decrease proinflammatory cytokines such as IL-6, TNF-α, and IL-17, while Me08 specifically reduced INF-γ levels. Our findings suggest that curcuminoid Me23 could serve as a potential agent for mitigating the impact of COVID-19, particularly within the context of central nervous system involvement.

Leiomyoma and the importance of genetic variation on genes related to the vasculature system - CßS, MTHFR, NOS3, CYBA, and ACE1.

OBJECTIVE: The link between the systemic vasculature system and tumor biology is here investigated by studying the contribution of CßS (844ins68), MTHFR (677C > T), NOS3 (4a/4b), CYBA (C242T), and ACE1 (I/D) genes to leiomyoma onset, uterus and leiomyoma volumes. METHODS: DNA samples from 130 women with leiomyomas and 527 from healthy women were genotyped by PCR or PCR-RFLP. Qui-square (χ2) or Fisher's exact test were used to test associations. All the mentioned tests were performed in IBM® SPSS® Statistics Version 28. Statistical significance was defined as a p-value < 0.05. RESULTS: Results revealed that CßS (in the codominant and allelic models, p = 0.044 and, p = 0.015, OR = 1.791 [1.114-2.879], respectively), MTHFR (in the codominant, allelic and dominant models, p = 0.009, p = 0.002, OR = 0.585 [0.416-0.824] and p = 0.003, OR = 0.527 [0.346-0.802], respectively) and ACE1 (dominant model, p = 0.045, OR = 0.639 [0.411-0.992]) genes are associated with leiomyoma onset. NOS3 4a4a genotype is associated with a lower uterus volume (p = 0.004). This study also uncovers intriguing epistatic interactions among some genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the CC genotype (MTHFR) and (+/+) (CßS; p = 0.003), 4b4b (NOS3; p = 0.006, OR = 2.050 [1.223-3.439]) or DD (ACE1; p < 0.001, OR = 2.362 [1.438-3.880]) were shown to be associated with the disease, while 4a presence (NOS3) in epistasis with I presence (ACE1), increased the effect protection having just the I allele presence (p = 0.029, OR = 0.446 [0.214-0.930]). CONCLUSIONS: We conclude that variation in genes related to the systemic vascular system can play a role in the onset and development of leiomyoma.

Quercetin-1,2,3-Triazole Hybrids as Multifunctional Anti-Alzheimer's Agents.

The number of patients with Alzheimer's disease (AD) continues to rise and, despite the efforts of researchers, there are still no effective treatments for this multifaceted disease. The main objective of this work was the search for multifunctional and more effective anti-Alzheimer agents. Herein, we report the evaluation of a library of quercetin-1,2,3-triazole hybrids (I-IV) in antioxidant, hydrogen peroxide-induced oxidative stress protection, and cholinesterases (AChE and BuChE) inhibitory activities. Hybrids IIf and IVa-d showed potent in vitro inhibitory activity on eqBuChE (IC50 values between 11.2 and 65.7 µM). Hybrid IIf, the best inhibitor, was stronger than galantamine, displaying an IC50 value of 11.2 µM for eqBuChE, and is also a competitive inhibitor. Moreover, toxicity evaluation for the most promising hybrids was performed using the Artemia salina toxicity assay, showing low toxicity. Hybrids IIf, IVb, and IVd did not affect viability at 12.5 µM and also displayed a protective effect against oxidative stress induced by hydrogen peroxide in cell damage in MCF-7 cells. Hybrids IIf, IVb, and IVd act as multifunctional ligands in AD pathologies.

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes.

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CßS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

A surveillance program for long-term central venous access-associated infections in outpatient chemotherapy services.

OBJECTIVE: In this study, we described the first results of a surveillance system for infections associated with long-term central venous catheters (LT-CVC) in patients under outpatient chemotherapy. DESIGN: This was a multicentric, prospective study. SETTING: Outpatient chemotherapy services. PARTICIPANTS: The study included 8 referral cancer centers in the State of São Paulo. INTERVENTION: These services were invited to participate in a newly created surveillance program for patients under chemotherapy. Several meetings were convened to share previous experiences on LT-CVC infection surveillance and to define the surveillance method. Once the program was implemented, all bloodstream infection (LT-CVC BSIs), tunnel infection, and exit-site infections associated with LT-CVC were reported. Data from January to May 2021 were analyzed. The median monthly number of chemotherapy sessions per clinic was 925 (IQR, 270-5,855). We used Poisson regression to analyze the association of rates with the characteristics of the services. RESULTS: In total, 107 LT-CVC infections were reported, of which 95% were BSIs, mostly associated with totally implantable devices (76%). Infections occurred a median of 4 days after the last catheter manipulation and 116 after the LT-CVC insertion. Also, 102 microorganisms were isolated from LT-CVC BSIs; the most common pathogen was Staphylococcus epidermidis, at 22%. Moreover, 44 infections (44%) fulfilled the criteria for CVC-related LT-CVC BSI and 27 infections (27%) met the criteria for mucosal barrier injury. The 1-year cumulative LT-CVC BSI rate was 1.94 per 1,000 CVC days of use. The rates were higher in public hospitals (IRR, 6.00; P < .001) and in hospitals that already had in place surveillance for LT-CVC infections (IRR, 2.01; P < .01). CONCLUSION: Our study describes an applicable surveillance method for infections in cancer outpatients using LT-CVC.

Validation of low anterior resection syndrome score in Brazil with Portuguese.

PURPOSE: This study was performed to investigate the convergent validity, discriminative validity, and reliability of the Brazilian version of the low anterior resection syndrome (LARS) score in a population with low educational and socioeconomic levels. METHODS: The LARS score was translated into the Portuguese language by forward- and back-translation procedures. In total, 127 patients from a public hospital in Brazil completed the questionnaires. The convergent validity was tested by comparing the LARS score with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core Module 30 (QLQ-C30) and with patients' self-reported quality of life. For the discriminative validity, we tested the ability of the score to differentiate among subgroups of patients regarding neoadjuvant radiotherapy, type of surgery, and tumor distance from the anal verge. The test-retest reliability was investigated in a subgroup of 36 patients who responded to the survey twice in 2 weeks. RESULTS: The LARS score demonstrated a strong correlation with 5 of 6 items from the EORTC QLQ-C30 (P<0.05) and good concordance with patients' self-reported quality of life (95.3%), confirming the convergent validity. The score was able to discriminate between subgroups of patients with different clinical characteristics related to LARS (P<0.001). The agreement between the test and retest showed that 86.1% of the patients remained in the same LARS category, and there was no significant difference between the LARS score numerical values (P=0.80), indicating good reliability overall. CONCLUSION: The Brazilian version of the LARS score is a valid and reliable instrument to assess postoperative bowel function in a population with low educational and socioeconomic levels.

Rastreamento da doença renal do diabetes na atenção primária à saúde / Screening for diabetes kidney disease in primary health care

A Doença Renal do Diabetes (DRD) é assintomática nos estágios iniciais da doença, e por esse motivo, a maioria dos pacientes é diagnosticada somente quando já apresenta várias complicações. O objetivo deste estudo foi avaliar se o rastreio da DRD está sendo realizado de maneira adequada em pacientes com diabetes mellitus tipo 2 (DM2) atendidos na atenção primária à saúde (APS) do Sistema Único de Saúde. Foi realizado um estudo transversal, com duração de cinco meses, na APS dos municípios de Bernardino de Campos e Salto Grande, SP. Os critérios de inclusão foram: diagnóstico de DM2, idade > 18 anos, e ser acompanhado nas unidades participantes do estudo. Um total de 1093 atenderam aos critérios de inclusão e aceitaram participar do estudo. Foi verificado que 398 (36,4%) dos pacientes nunca realizaram os exames de albumina urinária e creatinina, e não tiveram calculados a relação albumina/creatinina em amostra de urina com o cálculo da taxa de filtração glomerular (TFG) estimada pela CKD-EPI a partir da creatinina sérica; 401 (36,7%) dos pacientes realizaram estes exames e tiveram estes índices calculados nos últimos 12 meses. Estes 401 pacientes realizaram estes exames e cálculos de rastreio da DRD uma vez a cada 12 meses nos últimos 5 anos. Os demais pacientes (294; 26,9%) realizaram somente exame de creatinina sérica nos últimos 12 meses. Os resultados demonstraram que o rastreamento da DRD não está sendo realizado de maneira adequada na maioria dos pacientes (AU).

Diabetes Kidney Disease (DRD) is asymptomatic in the early stages of the disease, and for this reason, most patients are diagnosed only when they already have several complications. The aim of this study was to assess whether DRD screening is being carried out properly in patients with type 2 diabetes mellitus (DM2) treated in primary health care (PHC) of the Unified Health System. A cross-sectional study was carried out, lasting five months, in the PHC of the municipalities of Bernardino de Campos and Salto Grande, SP. Inclusion criteria were: diagnosis of DM2, age > 18 years, and being monitored in the units participating in the study. A total of 1093 met the inclusion criteria and agreed to participate in the study. It was found that 398 (36.4%) of the patients had never performed urine albumin and creatinine tests, and they did not calculate the albumin/creatinine ratio in a urine sample, together with the calculation of the glomerular filtration rate (GFR) estimated by CKD-EPI from serum creatinine; in contrast, 401 (36.7%) of the patients underwent these exams and had these indexes calculated in the last 12 months. These 401 patients had these DRD screening tests and calculations performed once every 12 months for the last 5 years. Os demais pacientes (294; 26,9%) realizaram somente exame de creatinina sérica nos últimos 12 meses. Os resultados demonstraram que o rastreamento da DRD não está sendo realizado de maneira adequada na maioria dos pacientes (AU).

Branching patterns of the superficial fibular nerve: an anatomical study with meta-analysis.

PURPOSE: To review variations regarding the branching patterns of the superficial fibular nerve (SFN) concerning the deep fascia of leg and to the ankle joint level. METHODS: Searches were conducted in PubMed, Scopus, Lilacs, and Web of Science databases on October 14th, 2021. We followed the PRISMA guidelines to report this review. Articles with data on SFN variations prevalence were included. The data were extracted and pooled into a meta-analysis. We also dissected 60 formalin-fixed Brazilian fetuses (n = 120 lower limbs). RESULTS: Twenty-five studies (n = 1272 lower limbs) comprised this review. Concerning the SFN branching at the deep fascia, Type 1 variation (in which the SFN pierces the fascia as a single nerve trunk) had a pooled prevalence of 86.4% (95% CI 84.5-88.2), while Type 2 had a pooled prevalence of 13.6% (95% CI 11.8-15.5). At the ankle joint level, Type 2 variation (in which the SFN branches off below the joint level) was the most common anatomical pattern, with a pooled prevalence of 78.7% (95% CI 74.5-82.7). CONCLUSION: Typically, the SFN branches off between its exit from the deep fascia and the ankle joint level. The SFN variations have great importance for surgeries, such as arthroscopies and fascia release surgeries, regional anesthesia, and clinical evaluation of SFN entrapment syndrome.

Epidemiological analysis of stroke patients with emphasis on access to acute-phase therapies / Análise epidemiológica de pacientes com AVC com ênfase no acesso às terapias de fase aguda

ABSTRACT Background: Stroke is a public health problem. For patients with ischemic stroke, venous thrombolysis and mechanical thrombectomy are effective therapeutic options. However, even after the National Stroke Treatment Guidelines were published in 2012, the number of cases treated is still lower than expected. Objective: To identify the determining factors for obtaining access to acute-phase therapies in the state of Espírito Santo (ES) and investigate the profile of stroke patients treated at the Central State Hospital (HEC). Methods: Retrospective data from the medical records of 1078 patients from May 2018 to December 2019 were analyzed. Results: Among the 1,078 patients, 54.9% were men and the most prevalent age group was 60 to 79 years. Systemic arterial hypertension was the main single risk factor. Regarding treatment modality among the patients who arrived at the HEC within the therapeutic window, 47% received some type of acute-phase therapy. Waking up with the deficit was the main contraindication for venous thrombolysis in these cases. Conclusions: Application of the flowchart established by SESA-ES seemed to be effective for enabling responsiveness of care for stroke victims. Public emergency transport services had a fundamental role in this process. In addition, the care provided by the tertiary stroke center provided excellent access to acute-phase therapies. However, despite the efficiency of the service provided at the HEC, it only reached a maximum of 50% of the ES population. This service model therefore needs to be expanded throughout the state.

RESUMO Antecedentes: O acidente vascular cerebral (AVC) é um problema de saúde pública. Nos casos de AVC isquêmico, a trombólise venosa e a trombectomia mecânica são efetivas opções terapêuticas de fase aguda. Entretanto, mesmo com a Diretriz Nacional de AVC publicada desde 2012, o número de casos tratados ainda é baixo. Objetivo: Apurar os fatores determinantes para o acesso às terapias de fase aguda na realidade espírito-santense e investigar o perfil dos pacientes de AVC atendidos no Hospital Estadual Central de Vitória (HEC). Métodos: O presente estudo analisou dados retrospectivos de prontuários de 1.078 pacientes no período de maio de 2018 a dezembro de 2019. Resultados: Dos 1.078 pacientes, 54,9% eram homens e a faixa etária mais prevalente foi a de 60 a 79 anos. A hipertensão arterial sistêmica foi o principal fator de risco isolado. Quanto ao tratamento, identificou-se que entre os pacientes que chegaram ao HEC na janela terapêutica 47% receberam terapia de fase aguda e que acordar com o déficit foi a principal contraindicação para trombólise venosa nesses casos. Conclusões: As análises demonstraram que a aplicação do fluxograma estabelecido pela Secretaria de Estado da Saúde do Espírito Santo parece ser eficaz na agilidade de atendimento das vítimas de AVC e que o Serviço de Atendimento Móvel de Urgência tem um papel fundamental nesse processo. Além disso, a assistência de um centro terciário de AVC permite acesso às terapias de fase aguda com excelência. Todavia, mesmo que o modelo de serviço prestado no HEC seja eficiente, ele atinge no máximo 50% da população do ES, sendo necessária a sua ampliação.

Feasibility Study of Transanal Irrigation Using a Colostomy Irrigation System in Patients With Low Anterior Resection Syndrome.

BACKGROUND: Low anterior resection syndrome has a negative impact on quality of life. Intestinal irrigation is a method of lavage consisting of a scheduled evacuation. OBJECTIVE: This study aims to evaluate functional and quality-of-life outcomes in patients with low anterior resection syndrome after transanal irrigation using a colostomy irrigation system. DESIGN: This was a prospective case series. SETTINGS: This study presents a single-center experience at a tertiary oncological center in an upper-middle-income country. PATIENTS: Patients classified as having minor or major low anterior resection syndrome 12 months after their operation were selected. INTERVENTIONS: Transanal irrigation was performed using an ostomy irrigation kit. Questionnaires assessing patients' bowel function (low anterior resection syndrome and Wexner score) and quality of life (Short Form-36 questionnaire) were applied before and after treatment. MAIN OUTCOME MEASURES: The primary outcomes were low anterior resection syndrome score and quality-of-life improvement after a 12-month treatment. RESULTS: Of the 22 patients included, 20 had major and 2 had minor low anterior resection syndrome, with a median score of 39, especially high rates of incontinence for liquid stool (21; 95.5%), clustering (21; 95.5%), and urgency (17; 77.3%). All patients successfully completed the 3-day training, and there were no complications during the treatment. After the 12-month period, the median score was 8, with 90% of the patients classified as having "no syndrome" and great improvement in all domains of this score. The most improved quality-of-life sections were patient vitality (p = 0.025) and physical (p = 0.002), social (p = 0.001), and emotional aspects (p = 0.001). LIMITATIONS: The study was limited by its small sample size and the limited follow-up period. CONCLUSIONS: This study presents a safe implementation protocol of an ostomy irrigation device for transanal irrigation. It also adds to the literature that transanal irrigation is a safe, effective, and easily implemented procedure for patients with low anterior resection syndrome with a significant improvement in quality of life. See Video Abstract at http://links.lww.com/DCR/B563.ESTUDIO DE FACTIBILIDAD DE LA IRRIGACIÓN TRANSANAL UTILIZANDO EL SISTEMA DE IRRIGACIÓN PARA COLOSTOMÍA EN PACIENTES CON SÍNDROME DE RESECCIÓN ANTERIOR BAJAANTECEDENTES:El síndrome de resección anterior baja tiene un impacto negativo en la calidad de vida de los pacientes. La irrigación intestinal es un método de lavado que consiste en evacuaciones programadas.OBJETIVOS:Evaluar los resultados de la funcionalidad e impacto en la calidad de vida de los pacientes con síndrome de resección anterior y baja posterior a la irrigación transanal utilizando un sistema de irrigación de colostomía.DISEÑO:Es estudio prospectivo de una serie de casos.ESCENARIO:En este estudio se muestra la experiencia de un centro oncológico de tercer nivel en un país en vías de desarrollo.PACIENTES:Aquellos clasificados como síndrome con afección en menor o mayor grado doce meses después de la cirugía.METODO:Se efectuó irrigación transanal utilizando un equipo de irrigación de estomas. Se aplicaron cuestionarios para valorar la función intestinal de los pacientes (síndrome de resección anterior baja y la escala de Wexner) y para calidad de vida (Cuestionario Corto-36) antes y después del tratamiento.EVALUACION DE LOS RESULTADOS PRINCIPALES:Los principales resultados se obtuvieron de la escala del síndrome de resección baja y la mejoría en la calidad vida doce meses después de tratamiento.RESULTADOS:De los veintidós pacientes incluidos, veinte presentaron manifestaciones mayores del síndrome de resección baja y dos, manifestaciones menores. Con una media de treinta y nueve, se encontraron, especialmente, altos índices de incontinencia a líquidos (21; 95'5%) hiperdefecación "clustering" (21; 95'5%) y urgencia (17; 77'3%). Todos los pacientes completaron en forma satisfactoria el entrenamiento de tres días sin presentarse complicaciones durante el tratamiento. Al término del mes doce la media fue de ocho, con el 90% de los pacientes clasificados como "sin síndrome" y se observó una mejoría substancial en todos los puntos de la evaluación. Las secciones de calidad de vida que mostraron una mejoría significativa fueron: la vitalidad del paciente (p = 0'025), física (p = 0'002), social (p = 0'001) y emocional (p = 0'001).LIMITACIONES:El tamaño de la muestra es pequeño y el tiempo de seguimiento corto.CONCLUSIONES:Este estudio muestra la implementación de un protocolo seguro para la irrigación de estomas mediante un dispositivo transanal. Además contribuye con el concepto en la literatura de que la seguridad de la irrigación transanal es seguro, efectivo y facilmente reproducible para pacientes con síndrome de resección anterior baja con una mejoría significativa en la calidad de vida. Consulte Video Resumen en http://links.lww.com/DCR/B563. (Traducción-Dr. Miguel Esquivel-Herrera).

Venlafaxine-induced adrenergic signaling stimulates Leydig cells steroidogenesis via Nur77 overexpression: A possible role of EGF.

Venlafaxine, a norepinephrine and serotonin reuptake inhibitor, impairs rat sperm parameters, spermatogenesis and causes high intratesticular estrogen and testosterone levels, indicating that Leydig cells (LCs) may be a venlafaxine target. We evaluated the effect of venlafaxine treatment on rat LCs, focusing on adrenergic signaling, EGF immunoexpression and steroidogenesis. Germ cells mitotic/meiotic activity and UCHL1 levels were also evaluated in the seminiferous epithelium. Eighteen adult male rats received 30 mg/kg of venlafaxine (n = 9) or distilled water (n = 9). The seminiferous tubules, epithelium and LCs nuclear areas were measured, and the immunoexpression of Ki-67, UCHL1, StAR, EGF, c-Kit and 17ß-HSD was evaluated. UCHL1, StAR and EGF protein levels and Adra1a, Nur77 and Ndrg2 expression were analyzed. Malondialdehyde (MDA) and nitrite testicular levels, and serum estrogen and testosterone levels were measured. Venlafaxine induced LCs hypertrophy and Ndrg2 upregulation in parallel to increased number of Ki-67, c-Kit- and 17ß-HSD-positive interstitial cells, indicating that this antidepressant stimulates LCs lineage proliferation and differentiation. Upregulation of Adra1a and Nur77 could explain the high levels of StAR and testosterone levels, as well as aromatization. Enhanced EGF immunoexpression in LCs suggests that this growth fact is involved in adrenergically-induced steroidogenesis, likely via upregulation of Nur77. Slight tubular atrophy and weak Ki-67 immunoexpression in germ cells, in association with high UCHL1 levels, indicate that spermatogenesis is likely impaired by this enzyme under supraphysiological estrogen levels. These data corroborate the unchanged MDA and nitrite levels. Therefore, venlafaxine stimulates LCs steroidogenesis via adrenergic signaling, and EGF may be involved in this process.

An Evaluation of Human Induced Pluripotent Stem Cells to Test for Cardiac Developmental Toxicity.

To prevent congenital defects arising from maternal exposure, safety regulations require pre-market developmental toxicity screens for industrial chemicals and pharmaceuticals. Traditional embryotoxicity approaches depend heavily on the use of low-throughput animal models which may not adequately predict human risk. The validated embryonic stem cell test (EST) developed in murine embryonic stem cells addressed the former problem over 15 years ago. Here, we present a proof-of-concept study to address the latter challenge by updating all three endpoints of the classic mouse EST with endpoints derived from human induced pluripotent stem cells (hiPSCs) and human fibroblasts. Exposure of hiPSCs to selected test chemicals inhibited differentiation at lower concentrations than observed in the mouse EST. The hiPSC-EST also discerned adverse developmental outcomes driven by novel environmental toxicants. Evaluation of the early cardiac gene TBX5 yielded similar toxicity patterns as the full-length hiPSC-EST. Together, these findings support the further development of hiPSCs and early molecular endpoints as a biologically relevant embryotoxicity screening approach for individual chemicals and mixtures.

Venlafaxine-induced damage to seminiferous epithelium, spermiation, and sperm parameters in rats: A correlation with high estrogen levels.

BACKGROUND: Venlafaxine (selective serotonin and norepinephrine reuptake inhibitor) use has increased worldwide. However, the impact of venlafaxine on testes and sperm parameters has not been investigated. OBJECTIVES: We evaluated venlafaxine impact on testicular and sperm parameters and verified whether the changes are reversible. METHODS: Animals from venlafaxine-35 days and venlafaxine-65 days groups received 30 mg/kg of venlafaxine for 35 days. Control-35 days and control-65 days received distilled water. In control-65 days and venlafaxine-65 days, the treatment was interrupted for 30 days. Sperm concentration, morphology, motility, and mitochondrial activity were analyzed. Number of step 19 spermatids (NLS), frequency of tubules with spermiation failure, Sertoli cells number, and TUNEL-positive germ cells were quantified. Testicular aromatase, connexin 43 (Cx43) immunoexpression, Cx43 protein levels, and Cx43 expression were evaluated. Either intratesticular testosterone or estrogen levels were measured. RESULTS: Venlafaxine impaired sperm morphology, reduced sperm concentration, mitochondrial activity, and sperm motility. The frequency of tubules with spermiation failure and NLS increased in parallel to increased Cx43 immunoexpression; mRNA and protein levels; and aromatase, testosterone, and estrogen levels. An increase in germ cell death and decreased Sertoli cells number were observed. In venlafaxine-65 days, except for sperm motility, mitochondrial activity, Sertoli cells number, and germ cell death, all other parameters were partially or totally recovered. CONCLUSION: Venlafaxine increases testosterone aromatization and Cx43. This drug, via high estrogen levels, disturbs Sertoli cells, induces germ cell death, and impairs spermiation and sperm parameters. The restoration of spermiation associated with the decreased Cx43 and hormonal levels in venlafaxine-65 days reinforces that high estrogen levels are related to venlafaxine-induced changes. The presence of damaged Sertoli cells, germ cell death, and low sperm motility in venlafaxine-65 days indicates that interruption of treatment for 30 days was insufficient for testicular recovery and points to a long-term estrogen impact on the seminiferous epithelium.

Relationship between food consumption of pregnant women and birth weight of newborns / Relación entre el consumo de alimentos de gestantes y el peso al nacer de los recién nacidos

The aim of this study was to investigate the relationship between food consumption of 99 pregnant women aged 16-44 years who gave birth at a maternity hospital in Rio de Janeiro and newborn birth weight. Maternal consumption of unprocessed or minimally processed and ultra-processed foods was evaluated through the Food Consumption Markers Form. For ultra-processed foods, most pregnant women regularly consumed sweets (73.7%), soft drinks (71.7%), sausages (65.7%), salted crackers (63.6%) and fried foods (55.6%). Among unprocessed or minimally processed foods, most pregnant women consumed beans (85.9%) and milk or yogurt (60.6%), while less than half consumed fruits (44.4%), raw vegetables (28.3%) and cooked vegetables (27.3%) regularly. Among newborns, 13.5% presented low birth weight. There was a significant relationship between consumption of sausages (p= 0.02) and sweets (p= 0.04) by pregnant women and low birth weight of newborns. Maternal consumption of sausages increased the odds of newborn low birth weight (OR 1.46, 95% CI 1.02-2.10).

El objetivo fue investigar la relación entre el consumo de alimentos de 99 gestantes de 16 a 44 años, atendidas en una maternidad de Río de Janeiro, y el peso al nacer de los recién nacidos. El consumo materno de alimentos no procesados o mínimamente procesados y ultraprocesados se evaluó a través del Formulario de Marcadores de Consumo de Alimentos. Se observó que entre los recién nacidos, 13,5% tenían bajo peso al nacer. La evaluación del consumo de alimentos maternos mostró que, entre los alimentos ultraprocesados, la mayoría de las gestantes consumieron regularmente dulces (73,7%), gaseosas (71,7%), embutidos (65,7%), galletas saladas (63,6%) y frituras (55,6%). Entre los alimentos no procesados o mínimamente procesados, la mayoría de las gestantes consumieron frijoles (85,9%) y leche o yogur (60,6%), mientras que menos de la mitad utilizaba frutas (44,4%), verduras crudas (28,3%) y verduras cocidas (27,3%) regularmente. Se observó una relación significativa entre el consumo de embutidos (p= 0,02) y dulces (p= 0,04) en gestantes con el bajo peso al nacer. El consumo materno de embutidos aumenta la probabilidad de que los recién nacidos presenten bajo peso al nacer, a medida que aumenta su consumo (OR 1,46, IC 95% 1,02-2,10).

Freshwater fishes of the Bahia State, Northeastern Brazil / Peixes de água doce do Estado da Bahia, Nordeste do Brasil

Abstract: This work was carried out from the assessment of the conservation status of the freshwater ichthyofauna from Bahia State. The inventory data and species distribution were obtained from the specialized scientific literature and representative ichthyological collections. A total of 281 native species was recorded in Bahia State, distributed in the Northeastern Mata Atlantica (NMA) and São Francisco (SFR) freshwater ecoregions. There was a larger number of species in the NMA (187 spp.), composed by several coastal basins, than in the SFR (134 spp.), composed by São Francisco river basin. Among the 30 families recorded, Characidae and Rivulidae were the most representative, with 53 and 48 species, respectively. The conservation status of 214 species was assessed and 33 of them (15%) were included in the IUCN threat categories. Of these, 11 species were classified as vulnerable (VU), 12 as endangered (EN), and 10 as critically endangered (CR). Most threatened species (n = 14) belongs to the family Rivulidae. The larger number of threatened species in the NMA: (n = 23) is mainly related to the high endemism of restricted-range species associated with the human occupation impacts along the coastal regions. In the SFR, most of threatened species are annual killifishes, which are locally disappearing due to increasing degradation of their temporary habitats.

Resumo: Este trabalho foi realizado a partir da avaliação do estado de conservação da ictiofauna de água doce do Estado da Bahia. Os dados de inventário e distribuição das espécies foram obtidos a partir da literatura científica especializada e de coleções ictiológicas representativas. Um total de 281 espécies nativas foi registrado no Estado da Bahia, distribuídas nas ecorregiões de água doce Mata Atlântica Nordeste (NMA) e São Francisco (SFR). A riqueza de espécies foi maior na NMA (187 spp.), composta por diversas bacias costeiras, do que na SFR (134 spp.), composta pela bacia do rio São Francisco. Das 30 famílias registradas, as mais representativas foram Characidae e Rivulidae, com 53 e 48 espécies, respectivamente. O estado de conservação de 214 espécies foi avaliado e 33 (15%) destas foram classificadas em alguma categoria de ameaça da IUCN. Destas, 11 foram classificadas como vulneráveis (VU), 12 em perigo (EN) e 10 criticamente em perigo (CR). A maioria das espécies ameaçadas (n = 14) pertence à família Rivulidae. O elevado número de espécies ameaçadas na NMA: (n = 23) está associado ao alto endemismo das espécies com distribuição restrita e aos impactos da ocupação humana ao longo da região costeira. Na SFR, a maioria das espécies ameaçadas é de peixes anuais, que estão localmente desaparecendo devido à degradação crescente de seus habitats temporários.

Preliminary assessment of anti-α-Gal IgG and IgM levels in patients with patent Plasmodium vivax infection

Anti-α-Gal responses may exert a protective effect in falciparum malaria. However, the biological role of such antibodies is still unknown during Plasmodium vivax infections. We investigated IgG and IgM responses to α-Gal in individuals with vivax malaria. Anti-α-Gal IgG and IgM levels were higher in these patients than in controls, but no significant correlation was found between parasitaemia and anti-α-Gal response, nor between this response and ABO blood group status. This is the first study to investigate anti-α-Gal antibodies in P. vivax-infected patients; a larger survey is necessary to achieve a better understanding of host immune response during vivax malaria.

Standardization of the technique to perform the transanal therapeutic irrigation / Padronização da técnica para realização da irrigação transanal terapêutica

ABSTRACT Purpose: This article aims to present a standardization of the technique of transanal therapeutic irrigation, which is an old technique that has passed through history and is now used as a medical procedure to assist in the treatment of defecation disorders. Methods: This protocol was developed in patients with myelomeningocele submitted to the standard transanal therapeutic irrigation technique, in accordance with the protocol established at the Clinic of defecation disorders at a public university hospital in Brazil. The presented standard technique highlights the following topics: preparation of the patient before the treatment; interdisciplinary approach; training of the patient or the family member responsible for the patient and the step-by-step technique itself. The research ethics committee at the university approved this study. Discussion: Transanal therapeutic irrigation is indicated in neurogenic bowel dysfunctions and functional disorders of defecation. Training the patient or a family member responsible for irrigation is performed on three consecutive days, all of them supervised by the nurse. This technique aims to re-establish control over defecation and bowel function, and consists in an infusion of warm tap water through the anus, which allows the patient to evacuate daily the stool and keep the colon empty for longer periods. This avoids fecal incontinence and increases the quality of life of patients with defecation disorders. Conclusion: Transanal therapeutic irrigation is an effective, well-tolerated and safe procedure, which is better compared to the standard clinical care.

RESUMO Objetivo: Este artigo tem como objetivo apresentar uma padronização da técnica de irrigação transanal terapêutica, uma técnica antiga que passou pela história e tem sido utilizada como procedimento médico para auxiliar no tratamento de distúrbios de defecação. Métodos: Este protocolo foi desenvolvido em pacientes com mielomeningocele submetidos à técnica de irrigação terapêutica transanal padrão, de acordo com o protocolo estabelecido na Clínica de Distúrbios da Defecação de um hospital universitário público no Brasil. A técnica padrão apresentada destaca os seguintes tópicos: preparação do paciente antes do tratamento; Abordagem interdisciplinar; treinamento do paciente ou do membro da família responsável pelo paciente e a técnica passo a passo em si. O comitê de ética em pesquisa da universidade aprovou este estudo. Discussão: A irrigação transanal terapêutica está indicada nas disfunções intestinais neurogênicas e nos distúrbios funcionais da defecação. O treinamento do paciente ou de um familiar responsável pela irrigação é realizado em três dias consecutivos, todos supervisionados por uma enfermeira. Esta técnica visa restabelecer o controle sobre a evacuação e a função intestinal, e consiste em uma infusão de água da torneira quente através do ânus, que permite ao paciente evacuar diariamente as fezes e manter o cólon vazio por períodos mais longos. Isso evita a incontinência fecal e aumenta a qualidade de vida dos pacientes com distúrbios de defecação. Conclusão: A irrigação terapêutica transanal é um procedimento efetivo, bem tolerado e seguro, o qual é melhor quando comparado ao tratamento clínico padrão.

Technique and results of the first six cases of anal sphincteroplasty with Deoti's flap for complex anatomical deformity of the perineum / Técnica e resultados dos primeiros seis casos de esfincteroplastia anal com retalho Deoti para deformidade anatômica complexa do períneo

ABSTRACT Objectives: Anal sphincteroplasty with Deoti's flap is a recently published procedure for the treatment of fecal incontinence with severe perineal deformity. The aim of this study is to report six cases of patients, analyzing their results in fecal incontinence questionnaires and proposing a new scale to better assess our technique's main objective, the reconstruction of the perianal anatomy. Methods: Six patients were submitted to anal sphincteroplasty with Deoti's flap and follow-up was performed every six months. Functional results and Quality of Life were measured by Wexner Score and Fecal Incontinence Quality of Life Scale, respectively. Results: All operations were carried out without failure to perform Deoti's flap rotation. The sample presented medians of 18.5 and 3.5 on Wexner Score, before and after surgery, respectively. In the Fecal Incontinence Quality of Life Scale, the medians before and after surgery are, respectively, 1.75 and 3.35 (Scale 1), 1.54 and 2.60 (Scale 2), 2.35 and 3.28 (Scale 3), 1.49 and 3.33 (Scale 4). The p-values were 0.0173 for Wexner Score and 0.0260, 0.0411, 0.0368 and 0.0952 for Scales 1, 2, 3 and 4 of Fecal Incontinence Quality of Life Scale, respectively. All patients presented sustained improvement in Wexner Score and in quality of life questionnaire (in all scales of Fecal Incontinence Quality of Life Scale). Conclusions: Deoti's surgical flap with sphincteroplasty successfully reconstructs complex anatomical deformities of the perineum. Current questionnaires to assess fecal incontinence may not evaluate properly the anatomical result of the technique, thus we propose a visual scale. In addition, sphincteroplasty with Deoti's flap may have longer-term outcomes in functional results than sphincteroplasty alone.

RESUMO Objetivos: A esfincteroplastia anal com retalho Deoti é um procedimento publicado recentemente para o tratamento de deformidade perineal grave. O objetivo deste estudo é relatar seis pacientes, analisando seus resultados em questionários de incontinência fecal e propondo uma nova escala para avaliar melhor o objetivo principal da nossa técnica, a reconstrução da anatomia perianal. Métodos: Seis pacientes foram submetidos à esfincteroplastia anal com retalho de Deoti e o acompanhamento foi realizado a cada seis meses. Os resultados funcionais e a qualidade de vida foram medidos pelas Escalas Wexner Score e FIQL, respectivamente. Resultados: Não houve falhas na rotação do retalho Deoti. A amostra apresentou medianas de 18,5 e 3,5 na Wexner Score, antes e depois da cirurgia, respectivamente. Na Escala FIQL, as medianas antes e depois da cirurgia são, respectivamente, 1,75 e 3,35 (Escala 1); 1,54 e 2,60 (Escala 2); 2,35 e 3,28 (Escala 3); 1,49 e 3,33 (Escala 4). Os valores de p foram 0,0173 para Wexner Score e 0,0260; 0,0411; 0,0368 e 0,0952 para Escalas 1; 2; 3 e 4 de FIQL, respectivamente. Todos os pacientes apresentaram melhora sustentada na pontuação de Wexner e no questionário de qualidade de vida (em todas as escalas do FIQL). Conclusões: O retalho de Deoti com esfincteroplastia reconstrói com sucesso as deformidades anatômicas complexas do períneo. Os questionários atuais para avaliar a incontinência fecal podem não avaliar adequadamente o resultado anatômico da técnica, por isso propomos uma escala visual. Além disso, a esfincteroplastia com retalho de Deoti pode apresentar resultados funcionais mais duradouros do que a esfincteroplastia isolada.

Acute appendicitis mimicking acute scrotum: a rare complication of a common abdominal inflammatory disease / Apendicite aguda mimetizando escroto agudo: uma complicação rara de uma doença inflamatória abdominal comum

ABSTRACT Introduction: Acute appendicitis is the most common surgical disease of the abdomen in clinical practice, affecting mainly young adults. It has a wide variety of clinical presentations, due to the anatomical variation of the cecal appendix. Its presentation as acute scrotum and scrotal abscess is quite rare and atypical, occurring mainly in young male patients with patent processus vaginalis. Case presentation: An 18-years-old male patient attended the emergency unit complaining of diffuse abdominal pain, fever and hyporexia for four days followed by inflammatory signs in the scrotum. He was taken to the operation room after diagnosis of scrotal and abdominal sepsis. During scrotum exploration, pus was found inside the right hemiscrotum coming down from the groin and communicating with the abdominal cavity. The laparotomy found perforated appendicitis and peritonitis leading to the scrotal abscess. The abscess was drained, appendectomy was performed and the scrotal and abdominal cavity were washed with saline solution. Despite postoperative complications such as pneumonia and intra-abdominal abscess, the reported patient recovered and was discharged in the 44th postoperative day. Conclusion: Acute appendicitis can mimic acute scrotum and surgeons must have a high index of suspicion of this complication for diagnosing. This unusual clinical presentation may be challenging and can delay the diagnosis leading to perforated peritonitis.

RESUMO Introdução: A apendicite aguda é a doença cirúrgica mais comum do abdome na prática clínica, afetando principalmente adultos jovens. Tem uma grande variedade de apresentações clínicas, devido à variação anatômica do apêndice cecal. Sua apresentação como escroto agudo e abscesso escrotal é bastante rara e atípica, ocorrendo principalmente em pacientes jovens do sexo masculino com túnica vaginalis patente. Apresentação do caso: um paciente do sexo masculino de 18 anos de idade compareceu à unidade de emergência queixando dor abdominal difusa, febre e hiporexia por quatro dias que se seguiram de sinais inflamatórios no escroto. Ele foi levado para centro cirúrgico após o diagnóstico de sepse de origem escrotal e abdominal. Durante a exploração da bolsa escrotal, secreção purulenta foi encontrada do lado direito oriunda do canal inguinal e comunicando-se com a cavidade abdominal. Durante a laparotomia observou-se sinais de apendicite aguda perfurada e peritonite levando ao abscesso escrotal. O abscesso foi drenado, a apendicectomia foi realizada e as cavidades escrotal e abdominal foram lavadas com solução salina. Apesar de complicações pós-operatórias como pneumonia e abscesso intra-abdominal, o paciente recuperou-se bem, recebendo alta hospitalar no 44° dia pós-operatório. Conclusão: A apendicite aguda pode simular o escroto agudo e os cirurgiões devem ter um alto grau de suspeição dessa complicação para o diagnóstico. Esta apresentação clínica incomum pode ser desafiadora e retardar o diagnóstico levando à peritonite por perfuração.

Fecal incontinence and quality of life assessment through questionnaires / Avaliação da incontinência fecal e impacto na qualidade de vida por questionários

ABSTRACT Background: Fecal incontinence causes a big impact on patient's quality of life. Our study analyzed the main questionnaires about fecal incontinence available internationally, aiming to delineate vantages and limitations of these instruments and their application, to mention the cultural aspects involved in the process of development and validation, as well as to suggest a reflection about the complexity of this matter. Results: Four of the instruments (Pescatori score, FISI, MSKCC bowel function instrument, and LARS score) do not include quality of life, working only as diagnostic tools. Two others, 'Jorge and Wexner Fecal Incontinence score', and 'St Marks' Fecal incontinence grading system' can diagnose and grade fecal incontinence, however they are very subtle in assessing quality of life. The 'EORTC Colorectal Cancer-specific', on the other hand, focuses exclusively on quality of life. Although the 'FIQL' questionnaire assesses quality of life related to fecal incontinence, it does not measure leakage. Lastly, the 'RAFIS' assesses both aspects but too superficially. Conclusion: None of the questionnaires analyzed were able to simultaneously assess both fecal incontinence and quality of life successfully. Furthermore, the concepts related to fecal incontinence have different meanings depending on the cultural and psychosocial context. These differences are even greater when individuals of developed countries like the ones where these questionnaires were developed are compared to the ones of developing countries, such as Brazil, which makes its very hard for these instruments to be used universally.

RESUMO Contexto: A incontinência anal acarreta grande impacto na qualidade de vida (QV) dos pacientes. Nosso estudo analisou os principais questionários sobre o tema disponíveis na literatura internacional, visando delinear vantagens e limitações desses instrumentos e de sua correta aplicação, bem como citar os aspectos culturais envolvidos no processo de sua criação e validação, e sugerir uma reflexão sobre a complexidade do tema. Métodos: Nessa revisão assistemática, utilizamos três bases de dados eletrônicas (MEDLINE, LILACS, e DeCS) para encontrar os 9 questionários mais utilizados no mundo, e palavras-chave relacionadas. Resultados: Quatro dos instrumentos estudados (Pescatori score, FISI, MSKCC bowel function instrument, e o LARS score) não abordam QV, funcionando apenas para diagnóstico. Outros dois, o 'Jorge and Wexner FI score', e o 'St Marks' FI grading system' diagnosticam e graduam bem a incontinência, porém apenas avaliam brevemente a QV. O 'EORTC Colorectal Cancer-specific', por sua vez, foca exclusivamente na QV. O questionário 'FIQL' apesar de conseguir avaliar a QV relacionada à função intestinal, não avalia vazamentos. Por fim, o 'RAFIS' avalia de forma muito simplificada esses aspectos. Conclusão: Nenhum dos questionários analisados se mostrou eficiente na avaliação simultânea da incontinência e da QV. Além disso, os conceitos que envolvem incontinência anal apresentam significados diferentes dependendo do contexto cultural e psicossocial. Essas diferenças são ainda maiores quando se comparam indivíduos dos países desenvolvidos onde esses questionários foram desenvolvidos, com os de países subdesenvolvidos como o Brasil, dificultando sua aplicação de forma universal.