Early-life trauma, impulsivity and suicide attempt: a systematic review and meta-analysis.

INTRODUCTION: Suicide is a worldwide health concern and up to date there is no good predictor of it except a previous suicide attempt. Therefore, there are increasing efforts in the understanding of which factors, genetic or environmental, are associated with suicide behaviour. OBJECTIVE: To review evidence of the effect of childhood trauma and impulsivity on suicidal behavior through a systematic review and meta-analysis. METHODS: Searches were conducted on the 12th of June 2021 in the PubMed, Scopus, and Web of Science databases. Two reviewers evaluated each record for eligibility and discussed upon disagreement, when no consensus was reached, a third reviewer was involved to make a decision. RESULTS: A total of 11,530 records were identified through the searches. After duplicates were removed, 6,595 records remained to be screened. The full text was sought for 1,561 records. Our qualitative synthesis included 22 studies, from which 9 were included in the meta-analyses. We found a significant effect of sexual abuse, physical abuse, emotional abuse and physical neglect on suicide attempts in the prisoners, and Substance Use Diorder (SUD) subgroups. Moreover, there was a significant effect of Childhood Trauma Questionnaire (CTQ) total score and emotional neglect dimension for all the subgroups. CONCLUSION: The present study has provided an overview of the state-of-the-art research on childhood trauma and impulsivity and their association with suicidal behavior and quantified their effects on suicide attempts. Hopefully this evidence will be considered in future research and harnessed for clinical gain in detection and treatment of suicide behaviour.

Diagnosis of bipolar and major depressive disorders: The appropriateness of MINI compared to the clinical interview in a sample of patients with mood disorders in tertiary mental health care.

OBJECTIVE: The Mini International Neuropsychiatric Interview (MINI) is one of the most used instruments for the assessment of Mental Disorders, playing an essential role in psychiatric research and in clinical and hospital practice. Despite this, the accuracy of the MINI, when used by a psychiatrist, is poorly studied, particularly in relation to Bipolar Disorder (BD). The early diagnosis of BD and Major Depressive Disorder (MDD) is extremely important, as it provides an opportunity for intervention that can reduce the impact on the patient's daily life and functionality. As such, this study assesses the suitability of MINI for diagnosing BD or MDD in a sample of patients with mood disorders. METHOD: Agreement between the MINI and the clinical interview was assessed in a sample of 347 outpatients by calculating Cohen's kappa, sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve (AUC). RESULTS: The sample consisted of 347 patients with mood disorders. 279 were women (80.40%), 105 (30.3%) were diagnosed with MDD and 242 (69.7%) with BD from the assessment performed in the clinical interview. In the MINI assessment, 97 individuals (28%) were classified with a diagnosis of MDD and 250 (72%) with BD. We found a sensitivity of 87.2% and specificity of 62.8% for the MINI in the diagnosis of BD and a Cohen's kappa between the MINI and the clinical interview of 0.51. The AUC was 0.75. CONCLUSIONS: MINI has greater sensitivity (87.2%) for the diagnosis of BD and greater specificity (87.2%) for the diagnosis of MDD. In addition, the moderate Cohen kappa (0.51) and AUC (0.75) values between the MINI and the clinical interview are acceptable when considering most available psychiatric diagnostic tools.

Residual contamination in antineoplastic drug packaging.

INTRODUCTION: The handling of antineoplastic drugs should follow strict supervision and safety rules to minimize the occupational exposure risks to professionals involved. The external surface contamination of drug vials is recognized as a health risk. So, our goal was to determine if there is residual contamination on the vials and containers surface of the antineoplastic drugs doxorubicin (DOX) and cyclophosphamide (CP). METHODS: A cross-sectional study was conducted. Samples were collected using a uniform sampling procedure on the inner surfaces of the packages/boxes and the outer surfaces of the vials. The analyzes were executed by high-performance liquid chromatography/mass spectrometry (UHPLC-MS/MS). RESULTS: A total of 209 samples were analyzed, 66 of CP and 143 of DOX. CP levels were detected in nine samples (13.63%), three were below the lower limit of quantification (LLQ) and the other six had contamination levels ranging from 1.24 to 28.04 ng/filter. DOX levels were detected in 36 samples (25.17%), two were below the LLQ and the others had levels between 1.32 and 664.84 ng/filter. The majority of samples with residual contamination were in vials (80.0%), however, boxes also showed contamination. CONCLUSIONS: The results revealed the presence of residual contamination in the vials and packages of CP and DOX drugs. Although the residues found in each sample are small, special care should be taken in the handling and disposal of the antineoplastic drugs. The use of personal protective equipment is fundamental while handling the vials and packaging of cytotoxic drugs.

Poor nutritional status of fifteen-year-old or younger adolescent mothers enhances the risk of small-for-gestational-age newborns

Introduction: To analyze the factors (socio-demographic, clinical, prenatal care, delivery, postpartum data and anthropometric measures) associated with the birth of small for gestational age newborns.Methods: A cross-sectional study was performed with 15 years old or younger postpartum adolescents divided into small-for-gestational-age newborn (SGA) and non-small-for-gestational age newborn groups (NSGA). Socio-demographic, clinical, prenatal care, delivery, postpartum data and anthropometric measures (triceps skinfold (TS), and mid-arm circumference, (MAC)) were collected.Results: 8,153 women gave birth at the obstetric ward and 364 (4.46%) ≤ 15 years old adolescents were enrolled in the study. The proportion of SGA newborns was 34.61%. The SGA group attended fewer prenatal visits (p = 0.037), had a higher prevalence of nutritional status classified as "very low weight" (p < 0.001) and vaginal delivery (p = 0.023), compared to the NSGA group. The nutritional status and vaginal delivery remained significant even after adjustment for confounders. The prevalence risk for SGA birth was 30% higher in the group of mothers with nutritional status classified as "very low weight" (odds ratio 1.30, 95% confidence interval 1.13 to 1.50) (p < 0.001).Conclusions: 15.4% of adolescents ≤ 15 years of age had an arm circumference compatible with the "very low weight" condition, demonstrating the high prevalence of poor maternal nutritional status in this group. The birth of SGA among adolescents ≤ 15 years of age is independently associated with maternal nutritional status classified as "very low weight" by the mid-arm circumference measures (MAC).

Medical Residents, the Group and the Formation of Professional Identity During the COVID-19 Pandemic / Médicos residentes, o grupo e a formação da identidade profissional durante a pandemia do COVID-19

Abstract Residency is still considered the gold standard for quality medical training, and acquiring a professional identity as a specialist is one of its central elements. Residents obtain this identity through both the educational environment and direct interaction with peers and supervisors. However, modifications in health care and educational routines during the recent coronavirus disease 2019 (COVID-19) pandemic have significantly impaired these channels. This study is part of a qualitative research project to analyze professional identity formation in a medical residency program in obstetrics and gynecology at a public hospital in southern Brazil. The authors conducted 28 semi-structured interviews with medical residents and preceptors, as well as a focus group with the residents, which was recorded, transcribed, and analyzed in an effort to construct major analytical categories. Restricted movement and physical contact have forced the use of alternative means of interpersonal interaction, such as communication through social media or instant messaging applications. This has also affected educational activities, such as morning rounds, lectures, and seminars. These changes represent a significant impact, especially in Brazil, where physical proximity is an important cultural feature, even in the work and school environments. We speculate that this new type of virtual interaction will also affect the formation of professional identity among obstetrician-gynecologists. These findings suggest that medical residency programs should be attentive to changes in resident training to ensure that the specialist profile and the expected skills, which are consolidated over many years, are not lost.

Resumo A residência médica ainda é considerada o padrão-ouro para a formação médica de qualidade, sendo o processo de construção da identidade profissional de um médico especialista um de seus elementos centrais. Os residentes obtêm essa identidade, entre outros fatores, por meio do ambiente educacional e da interação direta com colegas e supervisores. No entanto, as modificações nas rotinas assistenciais e educacionais durante a recente pandemia de coronavirus disease 2019 (Covid-19) prejudicaram significativamente esses canais. Este estudo faz parte de um projeto de pesquisa qualitativa com o objetivo de analisar a formação da identidade profissional em um programa de residência médica em ginecologia e obstetrícia em um hospital público do sul do Brasil. Os autores realizaram 28 entrevistas semiestruturadas com médicos residentes e preceptores, bem como um grupo focal com residentes. Tanto as entrevistas como as reuniões com o grupo focal foram gravadas, transcritas e analisadas no esforço de construir categorias analíticas. Foi identificado que o movimento restrito e o contato físico forçaram o uso de meios alternativos de interação interpessoal, como a comunicação por meio de mídias sociais ou aplicativos de mensagens instantâneas. Isso também afetou as atividades educacionais, como as rounds, palestras e seminários. Essas mudanças representam um impacto significativo, principalmente no Brasil, onde a proximidade física é uma importante característica cultural, mesmo em ambientes de trabalho e de estudo. Conjectura-se que esse novo tipo de interação virtual também afetará a formação da identidade profissional entre os ginecologistas-obstetras. Esses achados sugerem que os programas de residência médica devem estar atentos às mudanças na formação dos residentes para garantir que o perfil do especialista e as competências esperadas, consolidadas ao longo de muitos anos, não sejam perdidos.

Voice, Speech, and Clinical Aspects During Pregnancy: A Longitudinal Study.

BACKGROUND: Pregnancy involves anatomical, physiological, and metabolic changes in a woman's body. However, the effects of these changes on the voice remains unclear, particularly regarding the clinical characteristics. OBJECTIVES: We aimed to evaluate changes in vocal and speech acoustic measures and the relationship between them and clinical aspects in women during pregnancy. METHOD: A prospective, longitudinal study was carried out with 41 low risk, adult, pregnant women, followed for prenatal care. Demographic and anthropometric data as well as lifestyle habits and health conditions were collected. Voice recordings of sustained vowels, and automatic and spontaneous speech were held over each trimester and analyzed by PRAAT®to evaluate acoustic, aerodynamic, and articulatory measures. RESULTS: There were no changes in fundamental frequency, jitter, shimmer, and harmony to noise ratio during pregnancy. Maximum phonation time (MPT), pause rate, and pause duration reduced at the end of pregnancy. MPT was lower in sedentary pregnant women. The fundamental frequency peak rate was higher in eutrophic participants and lower in the third trimester in women with BMI ≥25 kg/m2. Pause rate was higher in pregnant women with BMI ≥25 kg/m2. There was no relationship between sleep quality, reflux, and vocal symptoms and acoustic and aerodynamic measures. CONCLUSIONS: Differences were shown in MPT and temporal pause measurements during pregnancy. Acoustic measurements did not change. There was a relationship between acoustic and aerodynamic measures and clinical variables (BMI, physical activity, and body mass gain).

Medical Residents, the Group and the Formation of Professional Identity During the COVID-19 Pandemic.

Residency is still considered the gold standard for quality medical training, and acquiring a professional identity as a specialist is one of its central elements. Residents obtain this identity through both the educational environment and direct interaction with peers and supervisors. However, modifications in health care and educational routines during the recent coronavirus disease 2019 (COVID-19) pandemic have significantly impaired these channels. This study is part of a qualitative research project to analyze professional identity formation in a medical residency program in obstetrics and gynecology at a public hospital in southern Brazil. The authors conducted 28 semi-structured interviews with medical residents and preceptors, as well as a focus group with the residents, which was recorded, transcribed, and analyzed in an effort to construct major analytical categories. Restricted movement and physical contact have forced the use of alternative means of interpersonal interaction, such as communication through social media or instant messaging applications. This has also affected educational activities, such as morning rounds, lectures, and seminars. These changes represent a significant impact, especially in Brazil, where physical proximity is an important cultural feature, even in the work and school environments. We speculate that this new type of virtual interaction will also affect the formation of professional identity among obstetrician-gynecologists. These findings suggest that medical residency programs should be attentive to changes in resident training to ensure that the specialist profile and the expected skills, which are consolidated over many years, are not lost.

A residência médica ainda é considerada o padrão-ouro para a formação médica de qualidade, sendo o processo de construção da identidade profissional de um médico especialista um de seus elementos centrais. Os residentes obtêm essa identidade, entre outros fatores, por meio do ambiente educacional e da interação direta com colegas e supervisores. No entanto, as modificações nas rotinas assistenciais e educacionais durante a recente pandemia de coronavirus disease 2019 (Covid-19) prejudicaram significativamente esses canais. Este estudo faz parte de um projeto de pesquisa qualitativa com o objetivo de analisar a formação da identidade profissional em um programa de residência médica em ginecologia e obstetrícia em um hospital público do sul do Brasil. Os autores realizaram 28 entrevistas semiestruturadas com médicos residentes e preceptores, bem como um grupo focal com residentes. Tanto as entrevistas como as reuniões com o grupo focal foram gravadas, transcritas e analisadas no esforço de construir categorias analíticas. Foi identificado que o movimento restrito e o contato físico forçaram o uso de meios alternativos de interação interpessoal, como a comunicação por meio de mídias sociais ou aplicativos de mensagens instantâneas. Isso também afetou as atividades educacionais, como as rounds, palestras e seminários. Essas mudanças representam um impacto significativo, principalmente no Brasil, onde a proximidade física é uma importante característica cultural, mesmo em ambientes de trabalho e de estudo. Conjectura-se que esse novo tipo de interação virtual também afetará a formação da identidade profissional entre os ginecologistas-obstetras. Esses achados sugerem que os programas de residência médica devem estar atentos às mudanças na formação dos residentes para garantir que o perfil do especialista e as competências esperadas, consolidadas ao longo de muitos anos, não sejam perdidos.

Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression.

BACKGROUND: The protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway regulates early follicular activation and follicular pool maintenance in female germline cells. Fragile X mental retardation 1 (FMR1) regulates folliculogenesis and it is variably expressed in patients with Premature Ovary Insufficiency. FMR1 expression is supposed to be linked to AKT/mTOR signaling in an ovarian response dependent manner as demonstrated in recent in vitro and in vivo studies in the female germline in vitro and in vivo. METHODS: We evaluated changes in the expression of AKT/mTOR signaling pathway genes by real time PCR in the peripheral blood of 74 patients with Premature Ovarian Insufficiency and 56 fertile controls and correlated their expression with FMR1 expression. RESULTS: Expression of the genes AKT1, TSC2, mTOR, and S6K was significantly more abundant in patients with POI than in the controls. For AKT1, TSC2 and mTOR, gene expression was not affected by FMR1-CGG repeat number in the 5´-untranslated region. FMR1 and S6K expression levels, however, were significantly upregulated in patients with POI and an FMR1 premutation. Independent of a premutation, expression of mTOR, S6K, and TSC2 was significantly correlated with that of FMR1 in all patients. Furthermore, when grouped according to ovarian reserve, this effect remained significant only for mTOR and S6K, with higher significance note in patients with Premature Ovarian Insufficiency than in the controls. CONCLUSIONS: In Premature ovarian insufficiency patients, activation of AKT/mTOR signaling pathway is remarkable and putatively pathognomonic. Additionally, it seems to be triggered by an FMR1/mTOR/S6K linkage mechanism, most relevant in premutation carriers.

Ovarian Tissue Culture to Preserve Fertility in Transgender Male Patients after Hormonal Treatment / Cultura de tecido ovariano para preservação da fertilidade em pacientes transexuais masculinos após tratamento hormonal

Abstract Objective To evaluate the reproductive and histological characteristics of fresh cultured ovarian tissue from transgender male patients. Methods An in vitro pilot study in which samples were collected during sex reassignment surgery for transgender male patients. The ovarian cortex was cut into fragments of 2 mm, 3mm, and 4 mm, and placed in a 96-well plate suitable for cultivation at days 0, 2, 4, 6, and 8, when the histology was analyzed. Results Stromal hyperplasia was observed in all samples, and it was not associated with the obtainment of primordial or primary follicles. Peripheral reduction in cell count was also a recurrent finding. Primordial and primary follicles were identified with a heterogeneous pattern in fragments from the same patient and from different patients, and follicles in more advanced stages of development (secondary and antral) were not found. There was an association between the diameter of the ovarian fragments and the identification of primary follicles (p=0.036). The number of days in culture was associated with histological signs of tissue damaging in the fragments (p=0.002). The total number of follicles identified in the samples with 2mm in diameter was significantly lower than in those that measured 4mm in diameter (p=0.031). Conclusion A diameter of 4mm is suitable for ovarian tissue culture with the benefit of ease of handling. Even after prolonged exposure to testosterone, the ovarian fragments presented primordial and primary follicles, maintaining viability throughout the days they were exposed to the culture. Freezing the ovarian cortex of transgender patients who will undergo surgery for gender reassignment would be an interesting option, in the future, for the preservation of fertility.

Resumo Objetivo Avaliar as características reprodutivas e histológicas de tecido ovariano cultivado a fresco de pacientes transexuais masculinos. Métodos Estudo experimental in vitro e piloto, no qual amostras foram coletadas durante a cirurgia de redesignação de sexo para pacientes transexuais masculinos. O córtex ovariano foi cortado em fragmentos de 2mm, 3mm, e 4mm, e colocado em placa de 96 poços própria para cultivo nos dias 0, 2, 4, 6 e 8, quando a histologia foi analisada. Resultados Hiperplasia estromal foi observada em todas as amostras, e não esteve associada à obtenção de folículos primordiais ou primários. A redução periférica no número de células também foi um achado recorrente. Folículos primordiais e primários foramidentificados com padrão heterogêneo emfragmentos domesmo paciente e em fragmentos de pacientes diferentes, não sendo encontrados folículos em estágios mais avançados de desenvolvimento (secundários e antrais). Houve associação entre o diâmetro dos fragmentos ovarianos e a identificação dos folículos primários (p=0,036). O número de dias de cultura esteve associado a sinais histológicos de lesão tecidual nos fragmentos (p=0,002). O número total de folículos identificados nas amostras de 2mm de diâmetro foi significativamente menor do que nas de 4mm de diâmetro (p=0,031). Conclusão O diâmetro de 4mm parece ser mais adequado para a cultura de tecido ovariano com a vantagem de fácil manejo. Mesmo após exposição prolongada à testosterona, os fragmentos ovarianos apresentavam folículos primordiais e primários, e manteve a viabilidade ao longo dos dias de exposição à cultura. No futuro, o congelamento da cortical do ovário de pacientes transgêneros que se submeterão à cirurgia de redesignação sexual poderia ser uma opção interessante para a preservação da fertilidade.

Ovarian Tissue Culture to Preserve Fertility in Transgender Male Patients after Hormonal Treatment.

OBJECTIVE: To evaluate the reproductive and histological characteristics of fresh cultured ovarian tissue from transgender male patients. METHODS: An in vitro pilot study in which samples were collected during sex reassignment surgery for transgender male patients. The ovarian cortex was cut into fragments of 2 mm, 3 mm, and 4 mm, and placed in a 96-well plate suitable for cultivation at days 0, 2, 4, 6, and 8, when the histology was analyzed. RESULTS: Stromal hyperplasia was observed in all samples, and it was not associated with the obtainment of primordial or primary follicles. Peripheral reduction in cell count was also a recurrent finding. Primordial and primary follicles were identified with a heterogeneous pattern in fragments from the same patient and from different patients, and follicles in more advanced stages of development (secondary and antral) were not found. There was an association between the diameter of the ovarian fragments and the identification of primary follicles (p = 0.036). The number of days in culture was associated with histological signs of tissue damaging in the fragments (p = 0.002). The total number of follicles identified in the samples with 2 mm in diameter was significantly lower than in those that measured 4 mm in diameter (p = 0.031). CONCLUSION: A diameter of 4 mm is suitable for ovarian tissue culture with the benefit of ease of handling. Even after prolonged exposure to testosterone, the ovarian fragments presented primordial and primary follicles, maintaining viability throughout the days they were exposed to the culture. Freezing the ovarian cortex of transgender patients who will undergo surgery for gender reassignment would be an interesting option, in the future, for the preservation of fertility.

OBJETIVO: Avaliar as características reprodutivas e histológicas de tecido ovariano cultivado a fresco de pacientes transexuais masculinos. MéTODOS: Estudo experimental in vitro e piloto, no qual amostras foram coletadas durante a cirurgia de redesignação de sexo para pacientes transexuais masculinos. O córtex ovariano foi cortado em fragmentos de 2 mm, 3 mm, e 4 mm, e colocado em placa de 96 poços própria para cultivo nos dias 0, 2, 4, 6 e 8, quando a histologia foi analisada. RESULTADOS: Hiperplasia estromal foi observada em todas as amostras, e não esteve associada à obtenção de folículos primordiais ou primários. A redução periférica no número de células também foi um achado recorrente. Folículos primordiais e primários foram identificados com padrão heterogêneo em fragmentos do mesmo paciente e em fragmentos de pacientes diferentes, não sendo encontrados folículos em estágios mais avançados de desenvolvimento (secundários e antrais). Houve associação entre o diâmetro dos fragmentos ovarianos e a identificação dos folículos primários (p = 0,036). O número de dias de cultura esteve associado a sinais histológicos de lesão tecidual nos fragmentos (p = 0,002). O número total de folículos identificados nas amostras de 2 mm de diâmetro foi significativamente menor do que nas de 4 mm de diâmetro (p = 0,031). CONCLUSãO: O diâmetro de 4 mm parece ser mais adequado para a cultura de tecido ovariano com a vantagem de fácil manejo. Mesmo após exposição prolongada à testosterona, os fragmentos ovarianos apresentavam folículos primordiais e primários, e manteve a viabilidade ao longo dos dias de exposição à cultura. No futuro, o congelamento da cortical do ovário de pacientes transgêneros que se submeterão à cirurgia de redesignação sexual poderia ser uma opção interessante para a preservação da fertilidade.

Semen Analysis of Total Motile Sperm Count Based on the 1999 and 2010 WHO Criteria.

OBJECTIVE: Approximately 15% of the couples suffer from infertility. Half of the cases of infertility are due to male factors. Several sperm function tests have been proposed to evaluate male fertility, but sperm analysis is still the first and most important diagnostic test for male infertility. The prognostic value of semen characteristics such as concentration, morphology and motility markers are often confused with male infertility. Evaluation of seminal parameters and classification for normality remains a frequent topic of discussion. METHODS: This study evaluated 477 semen samples from men undergoing investigation or infertility treatment between 2011 and 2015. RESULTS: The spermograms of 401 patients were deemed abnormal based on the 1999 World Health Organization (WHO) criteria; the number changed to 223 when the spermograms were assessed based on the 2010 WHO criteria and to 200 when Total Motile Sperm Count (TMSC) was used as the criterion. Sperm morphology was the item in the criteria that most significantly changed spermogram classification. Normality parameters became less rigid from 1999 to 2010, thereby significantly changing the proportion of individuals no longer described as infertile/subfertile. CONCLUSIONS: The classification based on TMSC could not differentiate between fertile and infertile subjects for not taking sperm morphology into account. Nevertheless, it may be helpful in cases where intrauterine insemination is indicated.

FMR1 and AKT/mTOR Signaling in Human Granulosa Cells: Functional Interaction and Impact on Ovarian Response.

We aimed to determine whether a functional link with impact on female ovarian reserve exists between FMR1 expression and expression ratios of AKT/mTOR signaling genes in human granulosa cells in vivo, as suggested from prior in vitro data. Three hundred and nine women, who were classified as normal (NOR; n = 225) and poor (POR; n = 84) responders based on their ovarian reserve, were recruited during stimulation for assisted reproductive techniques. Expressions of FMR1 and of key genes of the AKT/mTOR and AKT/FOXO1/3 signaling pathways were comparatively analyzed in their granulosa cells. FMR1 expression in granulosa cells of NOR and POR correlated significantly with AKT1, TSC2, mTOR, and S6K expression. No correlation was found between FMR1 and FOXO1 in all, and FOXO3 expression in POR, patients. AKT1 expression was significantly higher and FOXO1 expression lower in POR samples, whereas AKT1 expression was lower and FOXO1 expression was higher in NOR samples. In human native granulosa cells, FMR1 expression significantly correlated with the expression of key genes of the AKT/mTOR signaling pathway, but not with the FOXO1/3 signaling pathway. Our data point to a functional link between FMR1 expression and expression of the AKT/mTOR signaling pathway genes controlling human follicular maturation.

Occupational exposure assessment in professionals who manipulate and administer antineoplastic drugs in a university hospital in Southern Brazil.

INTRODUCTION: Our goal was to demonstrate the effects of occupational exposure to antineoplastic drugs on oxidative stress parameters and DNA damage in health professionals who manipulate and administer antineoplastic drugs in a University Hospital in Southern Brazil. METHODS: The case-control study with a longitudinal design, involved 64 individuals, 29 of them pharmacists, pharmacy technicians and nurses who were occupationally exposed to antineoplastic drugs and 35 professionals who were not exposed. Gene mutations were determined by micronucleus from salivary fluid; DNA damage by comet assay and oxidative stress parameters in whole blood were also evaluated. RESULTS: All workers exposed to antineoplastic drugs used personal protective equipment (PPE). It was demonstrated that the total nonprotein thiol and thiobarbituric acid reactive substances levels showed interaction between group and time, with higher levels one week after handling/administration of antineoplastic drugs in the exposed group (GEE, p ≤ 0.0001 and p = 0,013, respectively). Additionally, there was a group effect on the activities of the catalase and glutathione peroxidase antioxidant enzymes (GEE, p = 0.027 and p ≤ 0.0001, respectively), and workers occupationally exposed to antineoplastic drugs had higher enzyme activities compared to those not exposed. No genotoxic damage was demonstrated through the evaluated parameters. CONCLUSIONS: Despite the correct use of PPE, professionals occupationally exposed to antineoplastic drugs were more susceptible to oxidative stress than those not exposed. The evaluation of the studied parameters is especially important for the definition of conducts and practices in the area, always in search of guaranteeing the establishment of a rational policy to protect workers' health.

Non-invasive Embryo Assessment: Altered Individual Protein Profile in Spent Culture Media from Embryos Transferred at Day 5.

In order to improve ART outcome, non-invasive embryo assessment is gaining more and more attention. Therefore, the aim of this study is to determine the consecutive implantation potential via the secretome between blastocysts with or without implantation and to analyse possible interactions between these differentially expressed proteins. In this prospective study, 69 spent culture media from blastocysts transferred at day 5 were collected from patients undergoing IVF/ICSI treatment in a single IVF centre between April 2015 and November 2018 after informed consent and analysed individually. Exclusion criteria were the absence of informed consent, PCOS, endometriosis and maternal age > 42 years. Dependent on the treatment outcome, media were subsequently divided into two groups: from embryos who implanted successfully (n = 37) and from embryos without implantation (n = 32). Ninety-two proteins were measured simultaneously using the proximity extension assay (PEA) technology with the Olink® CVD III panel employing oligonucleotide-labelled antibodies. Statistical analysis was performed using the Kolmogorov-Smirnov test, Student's t test, the Mann-Whitney U test and Fisher's exact test. Media from implanted blastocysts showed significantly higher expression of EPHB4, ALCAM, CSTB, BMH, TIMP4, CCL24, SELE, FAS, JAM-A, PON3, PDGF-A, vWF and PECAM-1 compared with media from blastocysts without subsequent implantation. The highest relative expression change could be demonstrated for PECAM-1 and TIMP4. PECAM-1, SELE and vWF were co-expressed. Especially EPHB 4, SELE, ALCAM, MCP-1, CCL24, FAS, JAM-A and PDGF-A have already been described in early embryonic development and metabolism. Therefore, these proteins together with PECAM-1 indicate possible biomarkers for non-invasive embryo assessment in the future. However, due to the innovative methodology, defining a threshold for the use as biomarkers remains to be assessed.

Factors Influencing Success Rate of Intracytoplasmic Sperm Injection with Azoospermic Male Patients.

Introduction Azoospermia affects about 1% of men, of whom up to 15% inquire about infertility treatment. Information about predictive factors for these couples is very limited. Patients, Materials and Methods We performed a retrospective analysis of the clinical records of 118 cycles of intracytoplasmic sperm injection treatment after testicular sperm extraction for male azoospermia carried out between January 2008 and October 2015. Of those, 66 were first, 35 second, and 17 third cycles. Statistical significance was set at p < 0.05. Predictive factors for successful pregnancy were evaluated and included male/female age, male/female body mass index, male/female nicotine use, and histological results of testes biopsies. Results Embryo quality and the number of embryos transferred were positively associated with pregnancy success (p = 0.003). Males whose partners conceived had a significantly lower body mass index than those whose partners did not conceive (p = 0.023). Neither female weight nor age nor smoking status of the male or female were significant factors. In cases with tubular atrophy ≥ SIGG grade 4 the chance of pregnancy was poor, irrespective of the existence of mature sperm and the number of cycles performed. Conclusion Overweight male patients should be advised about weight reduction prior to treatment, and counseling about success rates should include histological and sperm-positive biopsy results.

In vitro maturation of immature oocytes from ovarian tissue prior to shipment to a cryobank.

PURPOSE: Female fertility preservation prior to gonadotoxic therapies can be achieved by the cryopreservation of ovarian cortical tissue. Immature oocytes may be recovered during the preparation, matured in vitro and lead to live births, thereby providing an additional option for fertility preservation. The purpose of this study was to test the feasibility of this approach in a setting with unilateral biopsy of a small piece of ovarian tissue and minimal tissue preparation prior to shipment to an external cryobank. METHODS: A prospective observational clinical study in an academic center was performed from January 2018 through December 2019. Ovarian tissue was obtained laparoscopically. Immature oocytes were recovered by minimal preparation of the tissue before shipment to an external cryobank for cryopreservation. In vitro maturation was performed on recovered immature oocytes. RESULTS: Twelve patients were enrolled. Immature oocytes could be recovered for all. The maturation rate was 38.9% (n = 14/36). Metaphase II (MII) were either directly used for intracytoplasmic sperm injection (ICSI) with a fertilization rate of 66.6% (n = 4/6) or vitrified (n = 8). PNs were cryopreserved (n = 4). Vitrified MII were warmed with a post-warming vitality rate of 75.0% (n = 3/4) and used for ICSI with a fertilization rate of 33.3% (n = 1/3). CONCLUSIONS: Immature oocytes can be successfully retrieved from ovarian tissue through minimal tissue preparation prior to shipment to a cryobank, matured in vitro, fertilized and cryopreserved for potential future fertility treatments. The total number of oocytes available for fertility preservation can be increased even without controlled ovarian stimulation in a situation where only ovarian biopsy for cryopreservation is performed. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00013170. Registered 11 December 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013170 .

Desempenho acadêmico de doutores egressos do Programa de Pós-Graduação em Medicina: Ciências Médicas da Faculdade de Medicina da UFRGS / Academic performance of doctoral graduates from the Graduate Program in Medicine: Medical Sciences at UFRGS School of Medicine

Introdução: embora, no Brasil, muito tenha sido feito para estimular a criação e manutenção de programas de pós-graduação ainda há carência de meios para avaliar e para mensurar a evolução profissional dos egressos. O objetivo é compreender a trajetória dos Doutores formados pelo Programa de Pós-Graduação em Medicina Ciências Médicas (PPGCM), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS) e propor um índice de desempenho acadêmico e de inserção profissional. Métodos: foi realizado um estudo transversal. Foram coletados dados dos Currículos Lattes dos egressos de doutorado do Programa de Pós-Graduação em Medicina: Ciências Médicas (PPGCM), no período de 1987 a 2014. Foram extraídos apenas os dados pertinentes a sua origem, curso de graduação e de mestrado, produção intelectual, inserção acadêmica e a posição profissional. Resultados: foram analisados 324 doutores egressos, 221 eram graduados em Medicina. Foram utilizadas as variáveis: graduação em medicina, vínculo laboral em universidade pública, exerce atividade como orientador em nível de doutorado, exerce atividade como orientador em nível de mestrado, bolsista de produtividade em pesquisa do CNPq e possui registro do índice H no currículo Lattes. O coeficiente de determinação (R2) demonstrou que as variáveis incluídas no modelo explicam 99% do modelo hierárquico. Conclusão: os resultados demonstram que os egressos têm contribuído para a construção de conhecimento qualificado disseminado em jornais de circulação internacional, formação de recursos humanos, interagir e criar parcerias em seu ambiente de trabalho, gerenciar e repassar o conhecimento, bem como para fomentar o conhecimento na área das ciências médicas com relevância regional, nacional e internacional. (AU)

Introduction: Although, in Brazil, much has been done to encourage the creation and maintenance of graduate programs, there remains a lack of means to assess and measure the professional outcomes of graduates. The objective is to understand the trajectory of doctoral graduates from the Graduate Program in Medicine: Medical Sciences (PPGCM), School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), and propose an index for academic performance and professional placement. Methods: A cross-sectional study was conducted. Data available at CV Lattes database of the National Council for Scientific and Technological Development (CNPq) were collected on doctoral graduates from the PPGCM, from 1987 to 2014. Only data pertaining to their origin, undergraduate and master's degrees, intellectual output, academic performance, and professional placement were retrieved. Results: Data on 324 doctoral graduates were analyzed, 221 had graduated in medicine. Undergraduate degree, employment at a public university, working as a doctoral-level advisor, working as a master's-level advisor, CNPq research productivity grantee, and having a recorded h-index in the Lattes curriculum were collected. The coefficient of determination (R 2 ) demonstrated that the variables included in the model explain 99% of the hierarchical model. Conclusion: The results show that the graduates have contributed to developing qualified knowledge disseminated in international newspapers, training human resources, interacting and creating partnerships in the workplace, managing and passing on knowledge, as well as fostering knowledge in the area of medical sciences with regional, national, and international relevance. (AU)

Endometrial expression of receptivity markers subject to ovulation induction agents.

PURPOSE: Implantation rates differ according to ovulation induction agents in ART. This study investigates the different local endometrial effects of LH- versus hCG-induced ovulation. METHODS: Endometrial stromal cells from healthy patients were cultured with hCG or LH in different concentrations, supplemented with 250 ng/mL hCG and progesterone after 2 and 5 days. In addition after decidualization induction, cells were treated with hCG (50 or 250 ng/mL) or LH (10 or 50 ng/mL) for 3 days. Receptivity markers expression was evaluated by real-time quantitative PCR on day 3 and 6. RESULTS: On day 3, non-decidualized cells treated with LH showed an increased expression of IGFBP1, IL-8 and CXCL12 compared to hCG. The expression pattern changed on day 6, where cells treated with hCG showed higher expression of implantation markers compared to LH-treated cells. Furthermore, on day 3, decidualized cells treated with hCG250 showed an increased IL8 and CXCL12 expression compared to LH10. CONCLUSIONS: LH seems to modulate the local endometrial expression of receptivity markers earlier compared to hCG; however, the effect is not sustained over time in cells without prior decidualization. Though, in decidualized cells, pattern changed and an earlier positive effect of hCG was shown on IL-8 and CXCL12.

Assessment of the psychometric properties of the 17- and 6-item Hamilton Depression Rating Scales in major depressive disorder, bipolar depression and bipolar depression with mixed features.

Assessing therapeutic response in depression requires scales that adequately measure the core symptoms of depressive symptomatology. The main goal of this study was to assess the psychometric properties of the 17-item Hamilton Depression Rating Scale (HAM-D17) and the 6-item Hamilton Depression Rating Scale (HAM-D6) in patients with Major Depressive Disorder (MDD), bipolar depression and bipolar depression with mixed features. We conducted a reanalysis of a pragmatic clinical trial in an outpatient clinic for mood disorders that included eight weeks of follow-up. A Mokken analysis was performed to evaluate the unidimensionality of the HAM-D17 and HAM-D6, and the Spearman correlation was used to assess concurrent validity between the HAM-D17, the HAM-D6 and quality of life scale (SF-36 and WHOQOL-BREF) scores. A total of 237 patients with a mean age of 40.2 years (±11.7) were included. According to the DSM-IV criteria, 58 (24.5%) were diagnosed with MDD and 73 (30.8%) were diagnosed with bipolar depression. Bipolar depression with mixed features was diagnosed in 106 (44.7%) patients according to the DSM-IV and supplemented by the Cincinnati criteria. Only the HAM-D6 scale proved to be unidimensional, showing strong homogeneity for evaluating MDD, moderate homogeneity for bipolar depression and weak homogeneity for bipolar depression with mixed features. Both the HAM-D17 and the HAM-D6 had inverse, significant correlations at baseline with SF-36 and WHOQOL-BREF scores. This is the first study to include bipolar depression patients with mixed features in an assessment of HAM-D6 unidimensionality.