Herlyn-Werner-Wunderlinch: An unusual presentation in a patient with Prader-Willi syndrome.

Herlyn-Werner-Wunderlich syndrome is an uncommon urogenital anomaly defined by uterus didelphys, obstructed hemi-vagina and unilateral renal anomalies. The most common clinical presentation is dysmenorrhoea following menarche, but it can also present as pain and an abdominal mass. Prader-Willi syndrome is a rare neuroendocrine genetic syndrome. Hypothalamic dysfunction is common and pituitary hormone deficiencies including hypogonadism are prevalent. We report the case of a 33-year-old female with Prader-Willi syndrome who was referred to the Gynaecology clinic due to vaginal bleeding and abdominal pain. Abdominal ultrasound revealed a haematometra and haematocolpos and computed tomography showed a uterus malformation and a right uterine cavity occupation (hematometra) as well as right kidney agenesis. Vaginoscopy and hysteroscopy were performed under general anaesthesia, finding a right bulging vaginal septum and a normal left cervix and hemiuterus. Septotomy was performed with complete haematometrocolpos drainage. The association of the two syndromes remains unclear.

Preclinical safety evaluation of the ethanolic extract from campomanesia guazumifolia (cambess.) O. Berg fruits peels in rats.

The toxicological potential of the ethanolic extract from Campomanesia guazumifolia (EECG), a species traditionally recognised for its antidiabetic, anti-inflammatory and hypercholesterolemic properties, was investigated in acute and subacute toxicity models in rats. In the acute toxicity test, 2000 mg/kg of EECG was administered orally in female rats, while male and female rats received 250, 500 or 750 mg/kg of EECG for the subacute toxicity test. No evidence of toxicity was observed in the animals acutely exposed, indicating that the LD50 is above 2000 mg/kg. However, repeated exposure to this extract resulted in alterations in important biochemical parameters indicative of hepatic and renal toxicity, including AST, ALT, creatinine, urea, and cholesterol. Additionally, some hematological parameters were also changed by the treatment. EECG demonstrated low toxicological potential. Nevertheless, given the observed changes in liver and kidney enzymes, further investigations into the protective effects of this extract following repeated administration are warranted.

Maternal-fetal safety evaluation of an aqueous extract of Casearia sylvestris leaves in rats.

BACKGROUND: This study evaluated the maternal, embryotoxic, and teratogenic effects of the aqueous extract of Casearia sylvestris (AECS), a species listed in the Unique Health System of Brazil, and widely used for treating several conditions, such as diarrhea, wounds, pain, and ulcers. METHODS: Pregnant rats were daily treated orally with 0, 175, 350, or 700 mg/kg/body weight of AECS, from gestational day (GD) 6 to 15 (organogenesis period). On GD 20, the pregnant rats were euthanized, and the litters submitted to an assessment of fetal development. RESULTS: No clinical signs of toxicity were observed in the dams during the treatment. In the embryo-fetal development study, a significant increase in the basal zone height of the placenta was observed in the intermediate dose group. Furthermore, there was a significant increase in the relative anogenital distance measurement of female fetuses in the lowest and intermediate dose groups. Although no visceral abnormalities were observed in the treated-fetuses, skeletal anomalies evidenced by changes in the ossification of the sternum and the presence of supernumerary ribs were found in the intermediate and high dose groups. CONCLUSION: In conclusion, the treatment with AECS during organogenesis at this dose level had detrimental effects on the normal development of fetuses.

Análise da situação vacinal contra Papilomavírus Humano entre estudantes de medicina de uma universidade pública federal / Human papillomavirus among medical students at a federal public university

OBJETIVO: Analisar a situação vacinal contra o papilomavírus humano entre estudantes da Faculdade de Medicina da Universidade Federal de Juiz de Fora. MÉTODOS: Trata-se de um estudo observacional transversal, que visa identificar e analisar as características e variáveis que se relacionam com a situação vacinal contra o papilomavírus humano de discentes da Faculdade de Medicina da Universidade Federal de Juiz de Fora. Os dados foram coletados por meio de questionários online padronizados. RESULTADOS: Entre os participantes, 176 (49,2%) alegaram serem vacinados contra o vírus e receberam, no mínimo, uma dose da vacina. Dentre os pesquisados, 74 (20,7%) estudantes declararam terem tomado 3 doses, enquanto 89 (24,9%) tomaram 2 e 13 (3,6%) tomaram apenas 1 dose. Com relação aos vacinados na faixa etária abrangida pela rede pública, 62 (17,3%) são do sexo feminino (9-14 anos) e 12 (3,4%) são do sexo masculino (11-14 anos). Sobre os discentes que já apresentaram alguma lesão pelo vírus, 66,66% não foram vacinados. CONCLUSÃO:Com o presente estudo, foi possível evidenciar que, assim como ocorre com a população brasileira em geral, a situação vacinal contra o papilomavírus humano entre estudantes da Faculdade de Medicina da Universidade Federal de Juiz de Fora está aquém do esperado. O principal motivo relatado para a não vacinação foi não fazer parte da faixa etária incluída na vacinação da rede pública. Constatou-se também que a prevalência de lesão por Papilomavírus Humano em vacinados foi menor que nos não vacinados, enfatizando a necessidade da vacina para prevenção de lesões causadas pelo vírus (AU).

OBJECTIVE: Analyze the vaccination status against the human papillomavirus among students at the School of Medicine of the Federal University of Juiz de Fora. METHODS: It is an observational cross-sectional study that aims to identify and analyze the characteristics and variables that relate to the vaccination status against the human papillomavirus of students at the School of Medicine of the Federal University of Juiz de Fora. The data were collected using standardized online questionnaires. RESULTS: Among the participants, 176 (49.2%) claimed to have been vaccinated against the virus and had received at least one dose of the vaccine. Among those surveyed, 74 (20.7%) students reported having taken 3 doses, while 89 (24.9%) took 2 and 13 (3.6%) took only 1 dose. Regarding the vaccinated in the age group covered by the public network, 62 (17.3%) are female (9-14 years old) and 12 (3.4%) are male (11-14 years old). A total of 66.66% of the students who have already had some injury by the virus, were not vaccinated. CONCLUSION: This study showed that, as with the Brazilian population in general, the vaccination status against human papillomavirus among students at the School of Medicine of the Federal University of Juiz de Fora is below expectations. The main reason reported for non-vaccination was not being part of the age group included in the vaccination of the public network. It was also found that the prevalence of lesions by Human Papillomavirus in vaccinated was lower than in non-vaccinated, emphasizing the need for the vaccine to prevent lesions caused by the virus (AU).

Proceso de actualización de la Agenda Nacional de Investigación Salud Pública 2021-2022 / Update process of the National Agenda for Public Health Research 2021-2022

INTRODUCCIÓN: Una Agenda Nacional de Investigación en Salud Pública (ANISP) participativa y con priorización temática constituye un elemento estratégico para generar recomendaciones y políticas públicas basadas en evidencia, que impacten positivamente en la salud de las poblaciones y permitan lograr los objetivos sanitarios. En la actualización de la ANISP participaron la Dirección de Investigación en Salud (DIS) del Ministerio de Salud de la Nación (MSAL), a través de la Red Ministerial de Investigación en Salud (REMINSA), y actores de los niveles gubernamentales provinciales y nacionales pertenecientes a los sectores público, privado, de la salud, académico y de investigación. Se adaptó la herramienta original propuesta por la Organización Panamericana de la Salud, utilizada en el proceso en 2019. La actualización abarcó diferentes etapas. La selección de los temas contó con la legitimidad, reconocimiento y participación de los actores vinculados a la salud, a la gestión gubernamental y privada y a la investigación científica; se trabajó de manera federal y transversal, por consenso con las redes provinciales y un Comité Central Asesor en el MSAL. A partir de los lineamientos preliminares obtenidos, se elaboró una encuesta en línea semiestructurada, que fue distribuida a todos los actores federales y recibió 431 respuestas. El proceso resultó en 55 lineamientos priorizados, divididos en 6 áreas temáticas y 33 subtemas, seleccionados por votación según importancia, impacto y factibilidad

Update process ofthe National Agenda for Public Health Research 2021-2022 / Proceso de actualización de la agenda nacional de investigación en salud pública 2021-2022

RESUMEN INTRODUCCIÓN : Una Agenda Nacional de Investigación en Salud Pública (ANISP) participativa y con priorización temática constituye un elemento estratégico para generar recomendaciones y políticas públicas basadas en evidencia, que imparten positivamente en la salud de las poblaciones y permitan lograr los objetivos sanitarios. En la actualización de la ANISP participaron la Dirección de Investigación en Salud (DIS) del Ministerio de Salud de la Nación (MSAL), a través de la Red Ministerial de Investigación en Salud (REMINSA), y actores de los niveles gubernamentales provinciales y nacionales pertenecientes a los sectores público, privado, de la salud, académico y de investigación. Se adaptó la herramienta original propuesta por la Organización Panamericana de la Salud, utilizada en el proceso en 2019. La actualización abarcó diferentes etapas. La selección de los temas contó con la legitimidad, reconocimiento y participación de los actores vinculados a la salud, a la gestión gubernamental y privada y a la investigación científica; se trabajó de manera federal y transversal, por consenso con las redes provinciales y un Comité Central Asesor en el MSAL. A partir de los lineamientos preliminares obtenidos, se elaboró una encuesta en línea semiestructurada, que fue distribuida a todos los actores federales y recibió 431 respuestas. El proceso resultó en 55 lineamientos priorizados, divididos en 6 áreas temáticas y 33 subtemas, seleccionados por votación según importancia, impacto y factibilidad.

ABSTRACT INTRODUCTION : A participatory National Public Health Research Agenda (ANISP) with thematic prioritization is a strategic element to generóte evidence-based recommendations and public policies that have a positive impact on the health of populations and enable to achieve health objectives. The Directorate of Health Research (DIS) ofthe Argentine Ministry of Health (MSAL), through the Ministerial NetWork of Health Research (REMINSA), along with adors from the provincial and national government levels belonging to public, privóte, health, academic and research sectors participated in the update of the ANISP. They adapted the original tooI proposed by the Pan American Health Organizatlon and used in the process in 2019. The update included different stages. The selection ofthe topics had the legitimacy, recognition and participation ofthe actors involved, related to health, to government and privóte management and to scientific research; the work was conducted in a federal and transversal manner by consensus with the provincial networks and a Central Advisory Committee in the MSAL. Based on the preliminary guidelines obtained, a semi-structured online survey was developed and distributed to all federal actors, receiving 431 responses. The process resulted in 55 priorilized guidelines, divided into 6 thematic oreas and 33 sub-themes, selected by voting according to importance, impact and feasibility.

Tumor de Células Gigantes em porção anterolateral de costela / Giant Cell Tumor in anterolateral rib portion

RESUMO: O Tumor de Células Gigantes é uma neoplasia osteolítica benigna, porém agressiva, ricamente vascularizada e com numerosas células gigantes com atividade osteoclástica. Ocorre mais frequentemente nas epífises de ossos longos e raramente acomete as costelas (cerca de 1% dos casos). A apresentação deste tumor em porção anterolateral de arco costal é extremamente rara em comparação com a região posterior. O presente relato descreve o caso de uma paciente que apresentava uma tumoração dolorosa em parede torácica anterolateral esquerda, de crescimento insidioso. Exames de imagem revelaram uma lesão insuflativa em 10º arco costal esquerdo (4,2 x 3,5 cm), com áreas de calcificação interior. A paciente foi submetida a tratamento cirúrgico, com ressecção ampla do tumor, englobando 9º, 10º e 11º arcos costais e uma porção do diafragma. O diagnóstico definitivo de tumor de células gigantes se deu pela imunohistoquímica da peça cirúrgica. Este relato permite fornecer bases para o estudo das possibilidades terapêuticas desta patologia em localizações atípicas, reforçando que a exérese em bloco com margens amplas destes tumores promove uma menor chance de recidiva local. (AU)

ABSTRACT: Giant Cell Tumor is a benign but aggressive osteolytic neoplasm, richly vascularized and with numerous giant cells with osteoclastic activity. It often occurs in long bone epiphyses and rarely affects the ribs (about 1% of cases). The presentation of this tumor in the anterolateral portion of the costal arch is extremely rare compared to the posterior region. The present report describes the case of a patient who had a painful tumor on the left anterolateral chest wall, of insidious growth. Imaging exams revealed an insufflating lesion in the 10th left costal arch (4.2 x 3.5 cm), with areas of interior calcification. The patient underwent surgical treatment, with wide resection of the tumor, comprising 9th, 10th and 11th ribs and a portion of the diaphragm. The definitive diagnosis of giant cell tumor was made by immunohistochemistry of the surgical specimen. This report provides a basis for studying the therapeutic possibilities of this pathology in atypical locations, reinforcing that the block excision with wide margins of these tumors promotes a lower chance of local recurrence. (AU)

High frequency of HPV genotypes 59, 66, 52, 51, 39 and 56 in women from Western Mexico.

BACKGROUND: Human papillomavirus infection is an important factor associated with cervical cancer (CC) development. The prevalence and genotype distribution vary greatly worldwide. Examining local epidemiological data constitutes an important step towards the development of vaccines to prevent CC. In this work, we studied the prevalence of HPV genotypes in women from Western Mexico with the COBAS 4800 and/or Linear Array Genotyping Test (LA). METHODS: The samples analysed in this study represent a population from Western Mexico, which includes six different states. Our approach was first to test for HPV in cervical samples from women who attended their health clinic for routine gynaecological studies (open-population, n = 3000) by utilizing COBAS 4800. Afterwards, 300 of the HPV-positive samples were randomly selected to be genotyped with LA; finally, we genotyped samples from women with cervical intraepithelial neoplasia grade 1 (CIN 1, n = 71) and CC (n = 96) with LA. Sociodemographic data of the diverse groups were also compared. RESULTS: The overall HPV prevalence among the open-population of women as determined by COBAS 4800 was 12.1% (n = 364/3000). Among the HPV-positive samples, single infections (SI) with HPV16 were detected in 12.4% (n = 45/364), SI with HPV18 were detected in 1.4%, and infection with at least one of the genotypes included in the high-risk HPV pool was detected in 74.5% of the cases. LA analysis of the samples showed that in addition to HPV genotypes 16 and 18, there was a high prevalence of HPV genotypes 59, 66, 52, 51, 39 and 56 in women from Western Mexico. With respect to the sociodemographic data, we found statistically significant differences in the number of pregnancies, the use of hormonal contraceptives and tobacco intake. CONCLUSIONS: Our data indicate that there is a high prevalence of HPV genotypes which are not covered by the vaccines currently available in Mexico; therefore, it is necessary to include HPVs 59, 66, 51, 39 and 56 in the design of future vaccines to reduce the risk of CC development. It is also essential to emphasize that the use of hormonal contraceptives and tobacco smoking are risk factors for CC development in addition to the presence of HPV.

Delineating the motor phenotype of SGCE-myoclonus dystonia syndrome.

OBJECTIVE: To perform phenotype and genotype characterization in myoclonus-dystonia patients and to validate clinical rating tools. METHOD: Two movement disorders experts rated patients with the Burke-Fahn-Marsden and Unified-Myoclonus rating scales using a video-recording protocol. Clinimetric analysis was performed. SGCE mutations were screened by Sanger sequencing and multiplex ligation-dependent probe amplification. RESULTS: 48 patients were included and 43/48 rated. Mean age at assessment was 12.9±10.5 years (range 3-51) and 88% were ≤18 years of age. Myoclonus was a universal sign with a rostro-caudal severity-gradient. Myoclonus increased in severity and spread to lower limbs during action tests. Stimulus-evoked myoclonus was observed in 86.8% cases. Dystonia was common but mild. It had a focal distribution and was action-induced, causing writer's cramp (69%) and gait dystonia (34%). The severity of both myoclonus and dystonia had a strong impact on hand writing and walking difficulties. The Unified Myoclonus Rating scale showed the best clinimetric properties for the questionnaire, action myoclonus and functional subscales, and exceeded the Burke-Fahn-Marsden scale in its utility in assessing functional impairment in MDS patients. Twenty-one different SGCE mutations were identified in 45/48 patients, eleven being novel (most prevalent p. Val187*, founder mutation in Canary Islands). CONCLUSION: This study quantifies the severity of the motor phenotype in SGCE-myoclonus dystonia syndrome, with a special focus on children, and identifies disabilities in gross and fine motor tasks that are essential for childhood development. Our results contribute to the knowledge of SGCE-related MDS in the early stage of evolution, where disease-modifying therapies could be initiated in order to prevent long-term social and physical burdens.

Genes and Variants Underlying Human Congenital Lactic Acidosis-From Genetics to Personalized Treatment.

Congenital lactic acidosis (CLA) is a rare condition in most instances due to a range of inborn errors of metabolism that result in defective mitochondrial function. Even though the implementation of next generation sequencing has been rapid, the diagnosis rate for this highly heterogeneous allelic condition remains low. The present work reports our group's experience of using a clinical/biochemical analysis system in conjunction with genetic findings that facilitates the taking of timely clinical decisions with minimum need for invasive procedures. The system's workflow combines different metabolomics datasets and phenotypic information with the results of clinical exome sequencing and/or RNA analysis. The system's use detected genetic variants in 64% of a cohort of 39 CLA-patients; these variants, 14 of which were novel, were found in 19 different nuclear and two mitochondrial genes. For patients with variants of unknown significance, the genetic analysis was combined with functional genetic and/or bioenergetics analyses in an attempt to detect pathogenicity. Our results warranted subsequent testing of antisense therapy to rescue the abnormal splicing in cultures of fibroblasts from a patient with a defective GFM1 gene. The discussed system facilitates the diagnosis of CLA by avoiding the need to use invasive techniques and increase our knowledge of the causes of this condition.

E6/E7 and E6* From HPV16 and HPV18 Upregulate IL-6 Expression Independently of p53 in Keratinocytes.

Keratinocyte infection with high-risk human papillomavirus genotypes has been linked to cancer development. In cervix, the alpha HPV16 and HPV18 have been reported as the mayor causative agents of cervical cancer. Oncogenic progression and chronic inflammation are closely related processes, with IL-6 as one of the main pro-inflammatory cytokines involved. However, there are limited studies about the regulation of IL-6 by low and high risk HPVs and the HPV proteins implicated in this modulation. In this work, we report the overexpression of IL-6 in HPV infected cervical cancer derived cell lines (HeLa and SiHa) compared to non-tumorigenic keratinocytes (HaCaT), and in Cervical Intraepithelial Neoplasia grade 1 HPV16 and HPV18 positive cervical samples compared to HPV negative samples without lesions. Moreover, we generated HaCaT keratinocytes that express E5, E6, and E7 from high risk (16 or 18) or low risk (62 and 84) HPVs. E5 proteins do not modify IL-6 expression, while E7 modestly increase it. Interestingly, E6 proteins in HaCaT cells upregulate IL-6 mRNA expression and protein secretion. Indeed, in HaCaT cells that express high risk HPV16E6 or HPV18E6 proteins, only the truncated E6* isoforms were expressed, showing the stronger IL-6 overexpression, while in HaCaT cells that express low risk HPV62 and HPV84 full length E6 proteins, IL-6 was also upregulated but not so drastically. Since HaCaT cells have a mutated p53 form that is not degraded by the introduction of E6 or E6/E7, it seems that E6/E7 regulate IL-6 by an additional mechanism independent of p53. In addition, basal keratinocytes showed a strong expression of IL-6R using immunohistochemistry, suggesting an autocrine mechanism over proliferative cells. Altogether, IL-6 cytokine expression in keratinocytes is upregulated by E6 and E7 proteins from HPVs 16, 18, 62, and 84, especially by high risk HPV16 and HPV18 E6*, which may contribute to promote a pro-inflammatory and highly proliferative microenvironment that can persist over time and lead to cervical tumorigenesis.

Cross-hybridization between HPV genotypes in the Linear Array Genotyping Test confirmed by Next-Generation Sequencing.

BACKGROUND: Linear Array Genotyping Test (LA) is one of the gold standards used for Human Papillomavirus (HPV) genotyping, however, since its launching in 2006, new HPV genotypes are still being characterized with the use of high specificity techniques such as Next-Generation Sequencing (NGS). Derived from a previous study of the IMSS Research Network on HPV, which suggested that there might be cross-reaction of some HPV genotypes in the LA test, the aim of this study was to elucidate this point. METHODS: Double stranded L1 fragments (gBlocks) from different HPVs were used to perform LA test, additionally, 14 HPV83+ and 26 HPV84+ cervical samples determined with LA, were individually genotyped by NGS. RESULTS: From the LA HPV83+ samples, 64.3% were truly HPV83+, while 42.9% were found to be HPV102+. On the other hand, 69.2% of the LA HPV84+ samples were HPV84+, while 3.8, 11.5 and 30.8% of the samples were indeed HPV 86, 87 and 114 positive, respectively. Additionally, novel nucleotide changes in L1 gene from HPV genotypes 83, 84, 87, 102 and 114 were determined in Mexican cervical samples, some of them lead to changes in the protein sequence. CONCLUSIONS: We demonstrated that there is cross-hybridization between alpha3-HPV genotypes 86, 87 and 114 with HPV84 probe in LA strips and between HPV102 with HPV83 probe; this may be causing over or under estimation in the prevalence of these genotypes. In the upcoming years, a switch to more specific and sensitive genotyping methods that detect a broader spectrum of HPV genotypes needs to be implemented.

Benefits of fasting abbreviation with carbohydrates and omega-3 infusion during cabg: a double-blind controlled randomized trial

Abstract Objective: To assess postoperative clinical data considering the association of preoperative fasting with carbohydrate (CHO) loading and intraoperative infusion of omega-3 polyunsaturated fatty acids (ω-3 PUFA). Methods: 57 patients undergoing coronary artery bypass grafting (CABG) were randomly assigned to receive 12.5% maltodextrin (200 mL, 2 h before anesthesia), (CHO, n=14); water (200 mL, 2 h before anesthesia), (control, n=14); 12.5% maltodextrin (200 mL, 2 h before anesthesia) plus intraoperative infusion of ω-3 PUFA (0.2 g/kg), (CHO+W3, n=15); or water (200 mL, 2 h before anesthesia) plus intraoperative infusion of ω-3 PUFA (0.2 g/kg), (W3, n=14). The need for vasoactive drugs was analyzed, in addition to postoperative inflammation and metabolic control. Results: There were two deaths (3.5%). Patients in CHO groups presented a lower incidence of hospital infection (RR=0.29, 95% CI 0.09-0.94; P=0.023), needed fewer vasoactive drugs during surgery and ICU stay (P<0.05); and had better blood glucose levels in the first six hours of recovery (P=0.015), requiring less exogenous insulin (P=0.018). Incidence of postoperative atrial fibrillation (POAF) varied significantly among groups (P=0.009). Subjects who receive ω-3 PUFA groups had fewer occurrences of POAF (RR=4.83, 95% CI 1.56-15.02; P=0.001). Patients in the W3 group had lower ultrasensitive-CRP levels at 36 h postoperatively (P=0.008). Interleukin-10 levels varied among groups (P=0.013), with the highest levels observed in the postoperative of patients who received intraoperative infusion of ω-3 PUFA (P=0.049). Conclusion: Fasting abbreviation with carbohydrate loading and intraoperative infusion of ω-3 PUFA is safe and supports faster postoperative recovery in patients undergoing on-pump CABG.

Benefits of Fasting Abbreviation with Carbohydrates and Omega-3 Infusion During CABG: a Double-Blind Controlled Randomized Trial.

OBJECTIVE: To assess postoperative clinical data considering the association of preoperative fasting with carbohydrate (CHO) loading and intraoperative infusion of omega-3 polyunsaturated fatty acids (ω-3 PUFA). METHODS: 57 patients undergoing coronary artery bypass grafting (CABG) were randomly assigned to receive 12.5% maltodextrin (200 mL, 2 h before anesthesia), (CHO, n=14); water (200 mL, 2 h before anesthesia), (control, n=14); 12.5% maltodextrin (200 mL, 2 h before anesthesia) plus intraoperative infusion of ω-3 PUFA (0.2 g/kg), (CHO+W3, n=15); or water (200 mL, 2 h before anesthesia) plus intraoperative infusion of ω-3 PUFA (0.2 g/kg), (W3, n=14). The need for vasoactive drugs was analyzed, in addition to postoperative inflammation and metabolic control. RESULTS: There were two deaths (3.5%). Patients in CHO groups presented a lower incidence of hospital infection (RR=0.29, 95% CI 0.09-0.94; P=0.023), needed fewer vasoactive drugs during surgery and ICU stay (P<0.05); and had better blood glucose levels in the first six hours of recovery (P=0.015), requiring less exogenous insulin (P=0.018). Incidence of postoperative atrial fibrillation (POAF) varied significantly among groups (P=0.009). Subjects who receive ω-3 PUFA groups had fewer occurrences of POAF (RR=4.83, 95% CI 1.56-15.02; P=0.001). Patients in the W3 group had lower ultrasensitive-CRP levels at 36 h postoperatively (P=0.008). Interleukin-10 levels varied among groups (P=0.013), with the highest levels observed in the postoperative of patients who received intraoperative infusion of ω-3 PUFA (P=0.049). CONCLUSION: Fasting abbreviation with carbohydrate loading and intraoperative infusion of ω-3 PUFA is safe and supports faster postoperative recovery in patients undergoing on-pump CABG.

Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.

The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging. Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%). Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II. Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4). Overall, 27 variants were identified, 12 of which are novel. The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.

Preoperative carbohydrate load and intraoperatively infused omega-3 polyunsaturated fatty acids positively impact nosocomial morbidity after coronary artery bypass grafting: a double-blind controlled randomized trial.

BACKGROUND: A strategy of limited preoperative fasting, with carbohydrate (CHO) loading and intraoperative infusion of omega-3 polyunsaturated fatty acids (ω-3 PUFA), has seldom been tried in cardiovascular surgery. Brief fasting, followed by CHO intake 2 h before anesthesia, may improve recovery from CABG procedures and lower perioperative vasoactive drug requirements. Infusion of ω-3 PUFA may reduce occurrences of postoperative atrial fibrillation (POAF) and shorten hospital stays. The aim of this study was to assess morbidity (especially POAF) in ICU patients after coronary artery bypass grafting (CABG)/cardiopulmonary bypass (CPB) in combination, if preoperative fasts are curtailed in favor of CHO loading, and ω-3 PUFA are infused intraoperatively. METHODS: Fifty-seven patients undergoing CABG were randomly assigned to receive 12.5% maltodextrin (200 ml, 2 h before anesthesia), without infusing ω-3 PUFA (CHO, n = 14); water (200 ml, 2 h before anesthesia), without infusing ω-3 PUFA (controls, n = 14); 12.5% maltodextrin (200 ml, 2 h before anesthesia) plus intraoperative ω-3 PUFA (0.2 mcg/kg) (CHO + W3, n = 15); or water (200 ml, 2 h before anesthesia) plus intraoperative ω-3 PUFA (0.2 mcg/kg) (W3, n = 14). Perioperative clinical variables and mortality were analyzed, examining the incidence of POAF, as well as the need for inotropic vasoactive drugs during surgery and in ICU. RESULTS: Two deaths occurred (3.5%), but there were no instances of bronchoaspiration and mediastinitis. Neither ICU stays nor total postoperative stays differed by group (P > 0.05). Patients given preoperative CHO loads (CHO and CHO + W3 groups) experienced fewer instances of hospital infection (RR = 0.29, 95%CI 0.09-0.94; P = 0.023) and were less reliant on vasoactive amines during surgery (RR = 0.60, 95% CI 0.38-0.94; P = 0.020). Similarly, the number of patients requiring vasoactive drugs while recovering in ICU differed significantly by group (P = 0.008), showing benefits in patients given CHO loads. The overall incidence of POAF was 29.8% (17/57), differing significantly by group (P = 0.009). Groups given ω-3 PUFA (W3 and CHO + W3 groups) experienced significantly fewer instances of POAF (RR = 4.83, 95% CI 1.56-15.02; P = 0.001). CONCLUSION: Preoperative curtailment of fasting was safe in this cohort. When implemented in conjunction with CHO loading and infusion of ω-3 PUFA during surgery, expedited recovery from CABG with CPB was observed. TRIAL REGISTRATION: NCT: 03017001.

Experiência paterna no primeiro ano de vida da criança: revisão integrativa de pesquisas qualitativas / Paternal experience during the child's first year of life: integrative review of qualitative research

As transformações sociais têm suscitado a reflexão sobre o papel paterno e apontado para novas paternidades, caracterizadas pelo envolvimento mais efetivo do pai no cotidiano familiar e nos cuidados com a criança. A presente revisão integrativa de pesquisas qualitativas teve como objetivo sintetizar as evidencias da literatura sobre a experiência paterna ao longo do primeiro ano de vida da(o) filha(o), com atenção às questões de gênero. Vinte e três artigos integram este estudo. Observou-se que os pais vivenciaram interações positivas com seus bebês e, ainda, almejaram mais tempo e espaço para se dedicarem à família. No entanto, a desigualdade entre os gêneros, a contínua exigência da provisão financeira do lar e sua inaptidão para o momento da amamentação impediram que houvesse maior envolvimento paterno. Concluiu-se que o movimento das novas paternidades faz-se presente na vivência do pai e as tendências contemporâneas de gênero são desafios no apoio à parentalidade.

Social transformations have raised reflection about the paternal role and pointed to new fatherhoods, characterized by more effective involvement of the father in the family routine and in childcare. The present integrative review of qualitative studies aimed to synthetize the literature evidence about fatherhood experience throughout the first year of the child's life, attentive to gender questions. Twenty three studies integrated this review. It was observed that fathers had positive experience with their babies and, still, craved for more time and space to dedicate to the family. However, inequality between genders, continuous requirement of financial provision at home and their inaptitude for breastfeeding moment impeded more paternal involvement. We concluded that new fatherhoods movement is present in the father experience and contemporary gender tendencies are challenges for parenting support.

Hígado graso agudo del embarazo / Acute fatty liver of pregnancy

El hígado graso agudo del embarazo es una complicación infrecuente, pero potencialmente mortal, que puede ocurrir durante el tercer trimestre de embarazo. Fue descrito por Sheehan en 1940 e inicialmente se pensó que era inevitablemente un trastorno mortal. Sin embargo, el diagnóstico precoz y la finalización inmediata de la gestación han mejorado el pronóstico de esta patología, y hoy en día la mortalidad materna es la excepción y no la regla, pudiendo conseguirse en la mayoría de los casos una completa recuperación de la paciente. Presentamos el caso de una paciente de 28 años, con una gestación gemelar bicorial biamniótica, que durante la semana 38 de gestación desarrolló esta patología de forma aguda (AU)

Acute fatty liver of pregnancy is a rare but life-threatening complication that can occur during the third trimester. This complication was described by Sheehan in 1940 and was initially thought to be fatal in all cases. However, early diagnosis and immediate pregnancy termination have improved the prognosis of this disease. Maternal mortality is now the exception and not the rule, and complete recovery is usually achieved. We report the case of a 28-year-old patient with a diamniotic dichorionic twin gestation who developed acute fatty liver of pregnancy in week 38 (AU)

Tratamiento del embarazo ectópico cervical con metotrexato y rescate con leucovorina / Treatment of cervical pregnancy with methotrexate and folnic acid

Objetivo. Presentar dos casos de gestación ectópica cervical tratados en forma exitosa con metotrexato sistémico. Sujetos y métodos. Dos pacientes (28 y 35 años de edad) portadoras de una gestación ectópica cervical. Intervenciones: Régimen a días alternos de metotrexato 1mg/kg (días 1, 3, 5 y 7) con rescate de leucovorina (días 2, 4, 6 y 8). Punto final (resultado que se midió): éxito del tratamiento conservador de una gestación ectópica cervical. Resultados. Los dos casos de gestación ectópica cervical fueron exitosamente tratados y la capacidad reproductiva preservada. Conclusiones. El tratamiento conservador de la gestación ectópica con metotrexato sistémico es seguro y coste-efectivo (AU)

Objective. To present two cases of cervical ectopic pregnancy successfully treated with systemic methotrexate. Subjects and methods. Two women with a cervical ectopic pregnancy. Interventions: alternative day regime of methotrexate 1mg/kg (days 1,3,5 and 7) with folinic acid rescue (days 2, 4, 6, and 8). End points: successful treatment. Results. Two cases of ectopic cervical pregnancy were successfully treated and preserved their reproductive capability. Conclusions. Conservative medical treatment of cervical ectopic pregnancy with systemic methotrexate is safe and effective (AU)

Array-CGH in patients with Kabuki-like phenotype: identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration.

BACKGROUND: Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. METHODS: We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. RESULTS: No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. CONCLUSION: Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.