Signal mining and analysis of adverse drug event signals of darolutamide / 中国药房

OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of darolutamide and provide a reference for its clinical safe use. METHODS ADEs related to darotamide were collected based on the US FDA adverse event reporting system （FAERS） database from the third quarter of 2019 to the third quarter of 2022. Data mining and analysis were conducted by the report odds ratio （ROR） and proportional reporting ratio （PRR） methods. RESULTS A total of 565 ADE reports related to darolutamide were extracted， 356 ADE reports about darolutamide as the primary suspected drug were included， 38 ADE signals with darolutamide as the primary suspected drug were excavated， involving 15 system organ class （SOC）， mainly concentrated in patients over 65 years old. The SOC of darotamide ADE signal mainly focused on various examinations， systemic diseases and various reactions at the administration site， benign/malignant tumors or those with unknown nature （including cystic and polypoid）， kidney and urinary system diseases. A total of 13 ADE signals not mentioned in the instructions included increased prostate-specific antigen， dysphagia， cognitive impairment， erectile dysfunction， rhabdomyolysis， gynecomastia and decreased platelet count， etc. CONCLUSIONS When using darolutamide， in addition to ADE in the drug instruction， we should pay close attention to potential ADE， such as increased prostate-specific antigen， rhabdomyolysis， gynecomastia and decreased platelet count， so as to avoid drug withdrawal or organ damage caused by ADE.

The value of NLR in predicting the efficacy of preoperative nimotuzumab combined with neoadjuvant chemotherapy for local advanced oral squamous cell carcinoma / 口腔疾病防治

Objective@#To investigate the value of the peripheral blood neutrophil to lymphocyte ratio (NLR) before nimotuzumab combined with neoadjuvant chemotherapy in predicting the short-term efficacy of neoadjuvant therapy for advanced oral squamous cell carcinoma (OSCC).@*Methods@#With the approval of the Ethics Committee and the informed consent of the patients, 59 patients with stage Ⅲ and Ⅳ OSCC who were admitted to the Oral and Maxillofacial Surgery Department of the First Hospital of Shanxi Medical University from September 2020 to June 2023 were enrolled. All the patients had complete clinical data, were pathologically diagnosed with squamous cell carcinoma, and received preoperative and received preoperative nimotuzumab + TP (docetaxel + cisplatin) neoadjuvant chemotherapy. The clinical data were analyzed, and the neutrophil and lymphocyte counts in peripheral blood were collected before and after nimotuzumab combined with neoadjuvant chemotherapy. The NLR was calculated, and the threshold value was calculated using the receiver operating characteristic (ROC) curve. Patients were divided into a high NLR group and a low NLR group according to the NLR threshold before nimotuzumab combined with neoadjuvant chemotherapy with TP. The clinical efficacy after nimotuzumab combined with neoadjuvant chemotherapy with TP was evaluated according to the evaluation criteria for solid tumor efficacy, and the correlation between the NLR and recent neoadjuvant therapy efficacy was analyzed. Immunohistochemical staining was used to detect the expression of epidermal growth factor receptor (EGFR) in OSCC tissues before and after nimotuzumab combined with neoadjuvant chemotherapy with TP and to analyze whether the expression of EGFR differed among the different NLR groups.@*Results@#A total of 59 patients with advanced OSCC were included. According to the ROC curve, the NLR threshold was 2.377, and the patients were divided into a <2.377 group (low NLR group), with 24 patients, and a>2.377 group (high NLR group), with 35 patients. The short-term neoadjuvant therapy effect was significantly greater in the lower NLR group than in the higher NLR group (P<0.05); EGFR expression in both the low NLR group and the high NLR group decreased after nimotuzumab combined with neoadjuvant chemotherapy with TP, and the decrease in the low NLR group was significantly greater than that in the high NLR group (P<0.05).@*Conclusion@#A low NLR before nimotuzumab combined with neoadjuvant chemotherapy with TP is associated with better neoadjuvant therapy outcomes, and such patients are more likely to benefit from preoperative nimotuzumab combined with neoadjuvant chemotherapy.

Relationship Between Peripheral Blood T Lymphocyte Subsets and Prognosis of Patients with Advanced Non-small Cell Lung Cancer Treated with Camrelizumab / 肿瘤防治研究

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

Association between index finger and ring finger length ratios and polymorphism of homeobox A11 gene locus among Ningxia college students / 解剖学报

Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.

Effect of Terpenes on the enhancement of skin permeation of lipophilic drugs: A systematic review

Objectives@#The stratum corneum (SC) remains an obstacle to the passage of drugs applied topically. Several investigations have focused on enhancing the penetration of drugs through the SC by integrating permeation enhancers (PE) into the drug formulation. Terpenes are among the PE utilized in formulations and are categorized by the regulatory bodies as generally recognized as safe (GRAS). This study aimed to comparatively analyze the skin permeation enhancing effect of terpenes on lipophilic drugs. @*Methods@#The present study reviewed the effects of terpenes on the permeation of lipophilic small-molecule drugs through the skin using original research published between 2000 - 2022 retrieved from PubMed®. The search phrase used was (lipophilic drug) AND (terpene) AND (permeation enhancer). @*Results@#Terpenes increase the percutaneous permeation of lipophilic small molecule drugs by 1.06 – 256.80-fold. Linear correlation analysis of terpenes’ cLog P with enhancement ratio (ER) revealed moderate and strong positive correlations in pig skin (r = 0.21) and mouse skin (r = 0.27), and rat skin (r = 0.41) and human skin (r = 0.67), respectively. Drug cLog P is a poor (r = -0.06) predictor of permeation enhancement. Terpenes with cLog P higher than 2.40 had ER greater than 10. Higher ERs (>30) were recorded for nerolidol, carvacrol, borneol, terpineol, limonene, menthone, pulegone, and menthol among the terpene-chemical penetration enhancers. @*Conclusion@#cLog P of terpene-based chemical permeation enhancers (CPE) is strongly correlated with ER of lipophilic drugs across human skin. Non-polar groups in terpenes and hydrogen bond interactions by terpenes with SC lipid enhance cutaneous drug penetration of lipophilic drugs.

The Electroacoustic Performance of Digital Noise Reduction Systems in Commercial Hearing Aids with Malay Speech-Plus-Noise Test Signals (Prestasi Elektroakustik Sistem Pengurangan Hingar Digital dalam Alat Bantu Pendengaran Komersial dengan Isyarat Ujian Pertuturan-Dalam-Bising Bahasa Melayu) / Jurnal Sains Kesihatan Malaysia

@#One of the most frequent complaints of individuals with hearing impairment is listening comfort in noisy environments. In order to improve listening comforts in background noise, digital noise reduction (DNR) systems are incorporated into hearing aids (HAs). Each hearing aid manufacturer has its proprietary algorithm for the DNR system. The amount of attenuation (dB) provided by the DNR system can be quantified using the hearing aid analyser. However, the standard test signals in the hearing aid analyser could not quantify the attenuation of DNR for speech mixed with noise signals. Therefore, this study aimed to (i) develop speech-plus-noise test signals that incorporate Malay sentences and (ii) quantify the efficacy of DNR systems in commercial hearing aids using the newly developed test signals. Six different brands of hearing aids with identical technology but from different manufacturers were subjected to electroacoustic testing utilising newly created Malay speech-in-noise test signals with and without DNR enabled. The total root-meansquare (RMS) gain reduction for each HA was calculated. The results show that the types of noise, the signal-to-noise ratio and the gender of the speaker have a significant effect (p<0.05) on the amount of gain reduction in the HA output as a result of the DNR system in each HA . In conclusion, the newly developed Malay speech-in-noise test signals can be used to verify the efficacy of DNR system in commercial hearing aids.

Phallus eversion sexing in Phrynops geoffroanus (Testudines: Chelidae): a new non-invasive approach

Abstract The sexing of species is an important tool for population management. In tortoises and turtles, sexing is usually done according to secondary characteristics, such as plastron morphology or phallus eversion techniques. In this paper, we present the phallus eversion method and compare its efficiency to other existing techniques. This new method aims at shortening the management time and reducing the physical aftereffects on the animals, fostering the clinical and reproductive management of Geoffroys side-necked turtle (Phrynops geoffroanus) and related species. A sample of fifty individuals was taken in the central region of Piauí state, Northeastern Brazil. The proposed method consisted of moving the head from its resting position. The methods achieving a success rate higher than 80% were compared to each other as for the stimulation time required for phallus eversion. The method as here proposed achieved 100% efficiency in the sex determination of specimens with a linear carapace length between 10 and 34 cm. Also, when compared to the second most efficient method, it substantially reduced the time needed for managing the specimens (91%), avoiding possible sequelae in the individuals handled.

Resumo A sexagem das espécies é uma ferramenta importante para o manejo populacional. Em tartarugas, cágados e jabutis, a sexagem geralmente é feita de acordo com características secundárias, como morfologia do plastrão ou técnicas de eversão do falo. Neste artigo, apresentamos o método de eversão do falo e comparamos sua eficiência com outras técnicas existentes. Este novo método visa encurtar o tempo de manejo e reduzir os efeitos colaterais físicos nos animais, promovendo o manejo clínico e reprodutivo do cágado-de-barbicha (Phrynops geoffroanus) e espécies relacionadas. Uma amostra de cinquenta indivíduos foi coletada na região central do estado do Piauí, Nordeste do Brasil. O método proposto consiste em remover a cabeça de sua posição de repouso. Os métodos que obtiveram índice de sucesso superior a 80% foram comparados entre si quanto ao tempo de estimulação necessário para a eversão do falo. O método aqui proposto alcançou 100% de eficiência na determinação do sexo de espécimes com comprimento de carapaça linear entre 10 e 34 cm. Além disso, quando comparado ao segundo método mais eficiente, reduziu substancialmente o tempo necessário para o manejo dos espécimes (91%), evitando possíveis sequelas nos indivíduos manuseados.

Association between plasma leptin/adiponectin ratio and insulin resistance indexes in prepubertal children

ABSTRACT Objective: To assess the association between leptin/adiponectin ratio (LAR) and insulin resistance surrogates in prepubertal children. Subjects and methods: Study based on data from the Growth and Obesity Chilean Cohort Study (GOCS) involving 968 Chilean prepubertal children. Plasma insulin, leptin, and adiponectin were determined by immunoassays. Several common insulin resistance surrogates were calculated, including the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride/HDL cholesterol index, triglyceride-glucose (TyG) index, and the TyG index corrected for body mass index (BMI; TyG-BMI) and waist circumference (WC; TyG-WC). Associations among variables were assessed using multiple linear and logistic regression analysis. Results: There was a significant direct association between plasma leptin and LAR with BMI z-score but no association between plasma adiponectin and adiposity. After adjustments for sex and age, LAR was significantly associated with all insulin resistance surrogates (which were categorized using the 75th percentile as the cutoff point), with the TyG-WC index emerging as the surrogate with the highest magnitude of association (odds ratio [OR] 2.44, 95% confidence interval [CI] 2.05-2.9). After additional adjustment for BMI z-score, only the association between LAR and TyG-WC remained significant (OR 1.64, 95% CI 1.27-2.12). Conclusion: Plasma leptin and LAR were strongly associated with several common insulin resistance surrogates in prepubertal children, most notably with the TyG-WC index. Associations between LAR and insulin resistance indexes were mainly driven by the effect of plasma leptin, which is also directly associated with increased adiposity.

Influência da terapia neoadjuvante na razão de linfonodos / Influence of neoadjuvant therapy on the ratio of lymph nodes

ABSTRACT Background: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. Methods: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. Results: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). Conclusion: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS.

RESUMO Contexto: Avaliar a relação entre a razão de linfonodos (RLA) acometidos e variáveis clínicas e anatomopatológicas em portadores de adenocarcinoma de reto submetidos ou não à quimiorradioterapia neoadjuvante. Métodos: A RLA foi determinada dividindo-se o número total de linfonodos (LFNs) dissecados no espécime cirúrgico pelo número de comprometidos. Os doentes foram divididos em dois grupos: com QRT e sem QRT. Em cada grupo foi avaliada a relação entre a RLA e as seguintes variáveis: grau de diferenciação celular, profundidade de invasão na parede retal, invasão angiolinfática/perineural, grau de regressão tumoral e ocorrência de metástases. Avaliou-se a RLA em pacientes com mais do que 12 LFNs (RLA>12) ou menos (RLA<12) na peça cirúrgica com a sobrevida global (SG) e sobrevida livre de doença (SLD). Os resultados foram expressos pela média com o respectivo desvio padrão. As variáveis qualitativas foram analisadas utilizando-se o teste exato de Fisher, enquanto as quantitativas pelos testes de Kruskal-Wallis e Mann-Whitney. O nível de significância foi de 5%. Resultados: Foram avaliados 282 pacientes com QRT e 114 sem QRT, entre 1995-2011. No Grupo QRT, RLA mostrou associação significativa com os tumores mucinosos (P=0,007) e grau de regressão tumoral (P=0,003). Nos dois grupos, a RLA associou-se com tumores pouco diferenciados (P=0,001 e P=0,02), presença de invasão angiolinfática (P<0,0001 e P=0,01), perineural (P=0,0007 e P=0,02), grau de invasão da parede retal (T3>T2; P<0,0001 e P=0,02); LFNs comprometidos (P<0,0001 e P<0,01), metástases (P<0,0001 e P<0,01). Nos pacientes com QRT, a RLA <12 associou-se com a SLD (5,889; IC95%1,935-19,687; P=0,018) e a RLA >12 com SLD e SG (17,984; IC95%5,931-54,351; P<0,001 e 10,286; IC95%2,654-39,854; P=0,007, respectivamente). Conclusão: A RLA associou-se a aspectos histológicos de mau prognóstico, independentemente do emprego de QRT. Na ocorrência de menos de 12 LFNs avaliados, a RLA associou-se apenas com a SLD.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Impact of anthro-metabolic indices and gestational weight gain on maternal and neonatal outcomes: a prospective observational study

SUMMARY OBJECTIVE: The aim of this study was to examine the relationship of anthro-metabolic indices on maternal and neonatal outcomes. METHODS: This prospective observational study was conducted on healthy mother-baby pairs between January 1, 2023 and July 1, 2023. Detailed sociodemographic information was collected through an interview with the mother. Clinical, biochemical, obstetric, fetal, and neonatal outcomes were abstracted from hospital medical records. Anthropometric measurements were obtained from the examination of mother-baby pairs. RESULTS: A total of 336 healthy mothers-children pairs were included. Mothers of newborn ≥4000 g had higher gestational age (p=0.003), body mass index (p=0.003), gestational weight gain (p=0.016), waist circumferences (p=0.002), and hip circumferences (p=0.001). gestational weight gain was associated with the mode of delivery (p=0.023). waist-to-hip ratio (p=0.005), gestational weight gain (p=0.013), and a body shape ındex (p<0.001) were associated with longer length of hospital stay. Age (p<0.001) and inter-pregnancy interval (p=0.004) were higher in pre-pregnancy underweight/obese mothers. Receiver operating characteristic analysis revealed that maternal waist circumferences (AUC: 0.708, p=0.005), maternal weight (AUC: 0.690, p=0.010), and hip circumferences (AUC: 0.680, p=0.015) were sufficient to predict macrosomia (p<0.05). CONCLUSION: The study demonstrated a significant association between gestational weight gain and cesarean delivery, prolonged hospital stay, and macrosomia. It was also found that maternal body mass index, waist circumferences, and hip circumferences during pregnancy were associated with macrosomia. On the contrary, no significant relationship was found between maternal anthro-metabolic characteristics and maternal-fetal and birth outcomes.

Postoperative Prognostic Nutritional Index and Fibrinogen Could Well Predict Poor Prognosis of Acute Type A Aortic Dissection Patients After Surgery

ABSTRACT Introduction: Inflammatory and immunological factors play pivotal roles in the prognosis of acute type A aortic dissection. We aimed to evaluate the prognostic values of immune-inflammatory parameters in acute type A aortic dissection patients after surgery. Methods: A total of 127 acute type A aortic dissection patients were included. Perioperative clinical data were collected through the hospital's information system. The outcomes studied were delayed extubation, reintubation, and 30-day mortality. Multivariate logistic regression analysis and receiver operating characteristic analysis were used to screen the risk factors of poor prognosis. Results: Of all participants, 94 were male, and mean age was 51.95±11.89 years. The postoperative prognostic nutritional indexes were lower in delayed extubation patients, reintubation patients, and patients who died within 30 days. After multivariate regression analysis, the postoperative prognostic nutritional index was a protective parameter of poor prognosis. The odds ratios (95% confidence interval) of postoperative prognostic nutritional index were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. Low postoperative fibrinogen could also well predict poor clinical outcomes. The odds ratios (95% confidence interval) of postoperative fibrinogen were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality. Conclusion: Postoperative prognostic nutritional index and postoperative fibrinogen could be two promising markers to identify poor prognosis of acute type A aortic dissection patients after surgery.

Breastfeeding and autism spectrum disorder: case-control study / Transtorno do espectro do autismo e aleitamento materno: estudo de caso controle

Abstract Objectives: to evaluate the association between breastfeeding and Autism Spectrum Disorder (ASD) in children and adolescents. Methods: this is a case-control study carried out in the north of the state of Minas Gerais, Brazil, which included 248 children and adolescents diagnosed with ASD (case group) and 886 children and adolescents without a diagnosis of ASD (control group).Interviews were conducted with the mothers of children and adolescents and a semi-structured questionnaire was used to collect data. For data analysis, a multiple logistic regression model was adopted. The magnitude of associations was estimated by the odds ratio (OR). Three multiple models were fitted: Model 1: presence or absence of breastfeeding; Model 2: duration of breastfeeding; Model 3: duration of exclusive breastfeeding. Results: ASD was associated with the absence of breastfeeding in the three adjusted models: Model 1: OR=2.1, CI95%=1.1-4.1; Model 2: OR=2.3, CI95%=1.2-4.5; Model 3: OR=2.3, CI95%=1.2-4.5. Conclusions: individuals with ASD were more likely to have not received breastfeeding, however, due to the nature of case control studies, it cannot be stated that breastfeeding prevents ASD. Conducting a cohort study may clarify this relationship.

Resumo Objetivos: avaliar a associação entre aleitamento materno e Transtorno do Espectro do Autismo (TEA) em crianças e adolescentes. Métodos: trata-se de um estudo caso-controle realizado no norte de Minas Gerais, Brasil, que incluiu 248 crianças e adolescentes com diagnóstico de TEA (grupo caso) e 886 crianças e adolescentes sem diagnóstico de TEA (grupo controle). Foram realizadas entrevistas com as mães das crianças e adolescentes e utilizado um questionário semiestruturado para coleta dos dados. Para análise dos dados foi adotado modelo de regressão logística múltipla. A magnitude das associações foi estimada pela Odds Ratio (OR). Três modelos múltiplos foram ajustados: Modelo 1: presença ou ausência de aleitamento materno; Modelo 2: duração do aleitamento materno; Modelo 3: duração do aleitamento materno exclusivo. Resultados: o TEA foi associado à ausência de aleitamento materno nos três modelos ajustados: Modelo 1: OR=2,1, IC95%=1,1-4,1; Modelo 2: OR=2,3, IC95%=1,2-4,5; Modelo 3: OR=2,3, IC95%=1,2-4,5. Conclusões: os indivíduos com TEA tiveram maiores chances de não terem recebido aleitamento materno, no entanto, devido à natureza dos estudos de caso-controle, não se pode afirmar que o aleitamento materno previna o TEA. A realização de um estudo de coorte poderá esclarecer essa relação.

Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

BACKGROUND: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. RESULTS: Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-ß, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. CONCLUSIONS: Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.

Phallus eversion sexing in Phrynops geoffroanus (Testudines: Chelidae): a new non-invasive approach / Sexagem por eversão do falo em Phrynops geoffroanus (Testudines: Chelidae): uma nova abordagem não invasiva

Abstract The sexing of species is an important tool for population management. In tortoises and turtles, sexing is usually done according to secondary characteristics, such as plastron morphology or phallus eversion techniques. In this paper, we present the phallus eversion method and compare its efficiency to other existing techniques. This new method aims at shortening the management time and reducing the physical aftereffects on the animals, fostering the clinical and reproductive management of Geoffroy's side-necked turtle (Phrynops geoffroanus) and related species. A sample of fifty individuals was taken in the central region of Piauí state, Northeastern Brazil. The proposed method consisted of moving the head from its resting position. The methods achieving a success rate higher than 80% were compared to each other as for the stimulation time required for phallus eversion. The method as here proposed achieved 100% efficiency in the sex determination of specimens with a linear carapace length between 10 and 34 cm. Also, when compared to the second most efficient method, it substantially reduced the time needed for managing the specimens (91%), avoiding possible sequelae in the individuals handled.

Resumo A sexagem das espécies é uma ferramenta importante para o manejo populacional. Em tartarugas, cágados e jabutis, a sexagem geralmente é feita de acordo com características secundárias, como morfologia do plastrão ou técnicas de eversão do falo. Neste artigo, apresentamos o método de eversão do falo e comparamos sua eficiência com outras técnicas existentes. Este novo método visa encurtar o tempo de manejo e reduzir os efeitos colaterais físicos nos animais, promovendo o manejo clínico e reprodutivo do cágado-de-barbicha (Phrynops geoffroanus) e espécies relacionadas. Uma amostra de cinquenta indivíduos foi coletada na região central do estado do Piauí, Nordeste do Brasil. O método proposto consiste em remover a cabeça de sua posição de repouso. Os métodos que obtiveram índice de sucesso superior a 80% foram comparados entre si quanto ao tempo de estimulação necessário para a eversão do falo. O método aqui proposto alcançou 100% de eficiência na determinação do sexo de espécimes com comprimento de carapaça linear entre 10 e 34 cm. Além disso, quando comparado ao segundo método mais eficiente, reduziu substancialmente o tempo necessário para o manejo dos espécimes (91%), evitando possíveis sequelas nos indivíduos manuseados.

Índice neutrófilo-linfocito e índice plaquetas-linfocito: herramientas pronósticas del cáncer de pulmón

El cáncer de pulmón es la neoplasia maligna que causa mayor mortalidad en el mundo. Dentro de los factores pronósticos de esta entidad, se encuentran el índice neutrófilo-linfocito y el índice plaquetas-linfocito, parámetros hematológicos que se utilizan para evaluar la inflamación y la respuesta inmunitaria en el cuerpo humano. Se realizó una revisión bibliográfica con el objetivo de exponer el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón, teniendo en cuenta la evidencia científica publicada hasta el momento. Se estudiaron 46 artículos, 28 de los cuales resultaron seleccionados para la elaboración de la investigación. Se emplearon como criterios de selección la calidad de los estudios, el nivel de actualización sobre el tema en cuestión, así como la fiabilidad de la fuente. Se usaron los recursos disponibles en la red Infomed para la selección de la información, entre ellos: PubMed, SciELO, EBSCO, Cumed, LILACS y Scopus, además de Medline, Academic Search Premier y MedicLatina. Se expuso el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón de células no pequeñas, en todos los estadios y con modalidades terapéuticas diferentes.

Lung cancer is the malignant neoplasm that causes higher mortality in the world. Among the prognostic factors of this entity are the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, hematological parameters that are used to assess inflammation and the immune response in the human body. A bibliographic review was carried out with the objective of exposing the value of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool for lung cancer, taking into account the scientific evidence published to date. A total of 46 articles were studied, of which 28 were selected for the development of the research. The quality of the studies, the level of updating on the subject in question, as well as the reliability of the source was used as selection criteria. The resources available in the Infomed network were used to select the information, including PubMed, SciELO and EBSCO, Cumed, LILACS and Scopus, as well as Medline, Academic Search Premier and MedicLatina databases. The value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool in non-small cell lung cancer at all stages and with different therapeutic modalities was exposed.

Comparing follow-up of patients with vitamin K antagonists in a health center: pre- and post-COVID-19 pandemic / Comparação do seguimento de doentes hipocoagulados com antagonistas da vitamina K numa unidade de saúde: pré e pós pandemia COVID-19

Introduction and objectives: During the COVID-19 pandemic, the follow-up of patients treated with vitamin K antagonists (VKAs) may have been affected. This study aims to compare how these patients were monitored pre- and post-COVID-19 pandemic and understand the impact of non-face-to-face appointments on their follow-up. Methods: We conducted a retrospective cohort study in a Portuguese Health Center. The study included patients treated with VKAs and followed at the Health Center for international normalized ratio (INR) monitoring between March 2019 and March 2021. Data collected: sex, age, type of VKA; INR; date of INR assessment, type of appointment (face-to-face or phone/e-mail). Rosendaal's method was used to calculate pre-COVID-19 and post-COVID-19 time in therapeutic range (TTR). Good TTR control was defined if values ≥ 70%. Results: 44 patients were included. The mean TTR in the pre-COVID-19 period was 64.55% (95% CI: 58.10 - 71.00%). The post-COVID-19 mean was slightly higher (+ 2.26%), 66.81% (95% CI: 59.66 - 73.97%), but the difference was not statistically significant (p = 0.576). The use of non-face-to-face appointments did not contribute to worsening post-pandemic TTR, show-ing no lower follow-up than during pre-pandemic period in which all contacts were face-to-face [CI (95%) -0.397 - 0.196 for a reference range -0.489 - 0.693]. Conclusions: The TTR value in both periods was similar and lower than the value defined for effective hypocoagulation. The use of non-face-to-face consultation in the post-COVID-19 period does not seem to have influenced the quality of hypocoagulation (AU).

Introdução e objetivos: Durante a pandemia COVID-19 o acompanhamento de doentes medicados com antagonistas da vitamina K (AVKs) pode ter sido afetado. Este estudo pretende comparar a forma como estes doentes foram monitorizados antes e depois da pandemia COVID-19 e compreender o impacto da consulta não presencial no seu seguimento. Métodos: Estudo de coorte retrospetivo num Centro de Saúde em Portugal. O estudo incluiu doentes tratados com AVKs e seguidos no Centro de Saúde para monitorização do International Normalized Ratio(INR) entre março de 2019 e março de 2021. Dados recolhidos: sexo, idade, tipo de AVK; INR; data da avaliação do INR, tipo de consulta (presencial ou por telefone/e-mail). Foi utilizado o método de interpolação linear de Rosendaal para calcular o tempo em intervalo terapêutico (TTR) pré- e pós-COVID-19. Foi definido um bom controle se valores de TTR ≥ 70%. Resultados: Foram incluídos 44 doentes. A média de TTR no período pré-COVID-19 foi de 64,55% (95% IC: 58,10 - 71,00%). A média pós-COVID-19 foi ligeiramente superior (+ 2,26%), 66,81% (95% IC: 59,66 - 73,97%), mas a diferença não foi estatisticamente significativa (p = 0,576). A utilização da consulta não presencial não contribuiu para o agravamento do TTR no período pós-pandemia, não mostrando um seguimento inferior ao do período pré-pandemia em que todos os contatos foram presenciais [IC (95%) -0,397 - 0,196 para um intervalo de referência -0,489 - 0,693]. Conclusões: O valor de TTR em ambos os períodos foi semelhante e inferior ao valor definido para hipocoagulação eficaz. A utilização da consulta não presencial no período pós-COVID-19 não parece ter influenciado a qualidade da hipocoagulação (AU).

Valores del perímetro abdominal e índice cintura-cadera en pacientes con hipertensión arterial / Values of abdominal perimeter and waist-hip ratio in patients with hypertension i: en

Introducción: La hipertensión arterial constituye un problema de salud pública en casi todo el mundo. Entre los factores de riesgo vinculados a ella se destaca la acumulación de grasa, que puede, a su vez, establecer los riesgos, las comorbilidades y la mortalidad asociados a esta entidad nosológica. Objetivo: Determinar las variaciones de los valores del perímetro abdominal y el índice cintura-cadera en pacientes con hipertensión arterial, según variables epidemiológicas y clínicas seleccionadas. Métodos: Se realizó un estudio descriptivo, prospectivo y transversal de 221 pacientes con hipertensión arterial, pertenecientes al Consultorio 19 del Policlínico Docente Josué País García del municipio de Santiago de Cuba, desde junio del 2019 hasta diciembre del 2020. Resultados: Predominó el sexo femenino y el grupo etario de 65-74 años (28,5 %). Los indicadores antropométricos perímetro abdominal e índice cintura-cadera tuvieron valores que superaron los parámetros normales establecidos para ambos sexos. El cálculo del perímetro abdominal reveló un predominio de la obesidad en el sexo femenino, en tanto se clasificó como aumentado en el sexo masculino. Conclusiones: Los valores del índice cintura-cadera y del perímetro abdominal en ambos sexos estuvieron por encima de los clasificados por la Organización Mundial de la Salud como de alto riesgo de presentar la enfermedad.

Introduction: Hypertension constitutes a problem of public health in almost all over the world. Among the risk factors associated with it, the accumulation of fat is notable, which can, in turn, establish risks and determine comorbidities and mortality associated with this nosological entity. Objective: To determine the variations in the values of the abdominal perimeter and waist-hip ratio in patients with hypertension, according to selected epidemiological and clinical variables. Methods: A descriptive, prospective and cross-sectional study was carried out on 221 patients with hypertension, belonging to doctor's office 19 of Josué País García Teaching Polyclinic in Santiago de Cuba municipality, from June, 2019 to December, 2020. Results: There was a prevalence of the female sex and the 65-74 age group (28.5%). The anthropometric indicators, abdominal perimeter and waist-hip ratio, had values that exceeded the established normal parameters for both sexes. The calculation of the abdominal perimeter revealed a predominance of obesity in the female sex, while it was classified as increased in the male sex. Conclusions: The values of the waist-hip ratio and abdominal perimeter exceeded those classified by the World Health Organization as high risk of presenting the disease in both sexes.

Profile of Ankle Isokinetic Strength and Proprioception in Elite Female Handball Players / Perfil de Fuerza Isokinética del Tobillo y Propiocepción en Jugadoras de Balonmano de Élite

SUMMARY: The evaluation of the invertor and evertor muscle strength and proprioception are important in terms of determining the risk of injury in handball players. The aim of this study was to determine the isokinetic strength and proprioception profile of the ankle invertor and evertor muscles of elite female handball players. Fifteen elite female handball players were included. Ankle invertor and evertor muscle strength and proprioception were evaluated using the isokinetic system. The isokinetic strength test was performed in concentric mode at 30°/s (5 repetitions) and 120°/s (10 repetitions). Proprioception sense was evaluated as active joint position sense. There was no statistically significant difference between the dominant and nondominant sides in terms of invertor and evertor muscle strength, evertor/invertor (Ever/Inver) ratio, and active joint position sense at both angular speeds (p>0.05). The Ever/Inver ratio on both sides was lower than normal values. It was concluded that the female handball players showed bilateral symmetry in the invertor and evertor muscles. However, the fact that the Ever/Inver strength ratio was lower than normal values on both sides suggested that caution should be exercised in terms of risks such as ankle sprain or chronic ankle instability. Pre-season evaluations should be made and it would be beneficial to add strengthening exercises to related muscle groups in training programs to normalize the unilateral ratios in these athletes.

La evaluación de la fuerza muscular inversora y eversora y la propiocepción son importantes para determinar el riesgo de lesión en los jugadores de balonmano. El objetivo de este estudio fue determinar la fuerza isocinética y el perfil de propiocepción de los músculos inversores y eversores del tobillo de jugadoras de balonmano de élite. Se incluyeron 15 jugadoras de élite de balonmano. La fuerza muscular inversora y eversora del tobillo y la propiocepción se evaluaron mediante el sistema isocinético. El test de fuerza isocinética se realizó en modo concéntrico a 30º/s (5 repeticiones) y 120º/s (10 repeticiones). El sentido de propiocepción se evaluó como sentido activo de posición articular. No hubo diferencias estadísticamente significativas entre los lados dominante y no dominante en términos de fuerza muscular inversora y eversora, relación eversor/inversor (Ever/ Inver) y sentido activo de la posición de la articulación en ambas velocidades angulares (p>0.05). La relación Ever/Inver en ambos lados fue inferior a los valores normales. Se concluyó que las jugadoras de balonmano presentaron simetría bilateral en los músculos inversores y eversores. Sin embargo, el hecho de que la relación de fuerza Ever/Inver fuera inferior a los valores normales en ambos lados sugirió que se debe tener precaución en términos de riesgos como el esguince de tobillo o la inestabilidad crónica de tobillo. Se deben realizar evaluaciones de pretemporada y sería beneficioso agregar ejercicios de fortalecimiento a los grupos musculares relacionados en los programas de entrenamiento para normalizar las proporciones unilaterales en estas atletas.