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OBJECTIVE: To evaluate the impact of double embryo vitrification on clinical outcomes. METHODS: This retrospective cohort study included data from January 2013 to March 2021. The study group included women aged 33.3±5.7 years with double-vitrified embryos (n=381), while the control group included women aged 32.1±6.7 years with embryos vitrified once (n=780), all transferred at the blastocyst stage. The primary endpoint was live birth rate (LBR), and secondary endpoints included percent positive ßHCG test, clinical/ongoing pregnancy rates, miscarriage/biochemical pregnancy rates and birthweight. RESULTS: LBR was significantly lower in double-vitrified embryos (30.2%) than in embryos vitrified once (45.6%, p<.05). Similarly, double-vitrified embryos were associated with significantly lower positive ßHCG tests (46% vs. 63.3%, p<.05) and clinical (34.9% vs. 52.2%, p<.05) and ongoing pregnancy (31.3% vs. 47.3%, p<.05) rates compared to embryos vitrified once. However, biochemical pregnancy (double vitrified: 24.1% vs. vitrified once: 17.9%, p>.05) and miscarriage rates (double vitrified: 10.2% vs. vitrified once: 9.4%, p>.05), as well as mean birthweight (double-vitrified embryos: 2950g vs. embryos vitrified once: 2837g, p>.05) did not differ significantly between two groups. On a secondary comparison, amongst double-vitrified embryos, the subgroup that was cultured for more than 24 hours between warming and second vitrification achieved significantly higher positive ßHCG tests (49%) and clinical pregnancy (38%) rates, compared to embryos re-vitrified on the same day of warming (31.8% and 20.5%, respectively, p<.05). Nevertheless, LBR did not differ significantly amongst these study-group embryos (embryos that remained in culture for more than 24 hours: 32.2% vs. embryos that were re-vitrified on warming day: 20.5%, p>.05). CONCLUSIONS: Double vitrification of embryos adversely affects clinical outcomes. However, it represents a valuable option concerning embryo wastage, with acceptable success rates.
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Criopreservação , Transferência Embrionária , Vitrificação , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Transferência Embrionária/métodos , Transferência Embrionária/estatística & dados numéricos , Resultado da Gravidez/epidemiologia , Taxa de Gravidez , Fertilização in vitro/métodos , Coeficiente de Natalidade , Nascido Vivo/epidemiologiaRESUMO
Introduction Dysphagia is a significant but underrecognized clinical issue in the intensive care unit (ICU), and it is associated with various complications. Despite its clinical importance, there is limited research and no Greek ICU-specific guidelines for managing dysphagic patients. Additionally, only a few ICUs in Greece have dysphagia specialists, specifically speech-language pathologists (SLPs) providing their expertise. Objective Τo identify the current practices for dysphagia management (screening, assessment, treatment) and gain insight into ICU directors' awareness/perceptions of the prevalence, complications, and risk of dysphagia. Materials and Methods We identified 138 Greek ICUs. Data were collected from ICU (including pediatric and neonatal) directors, working in public and private hospitals, via a 24-item, anonymous online questionnaire, within a 4-month period. Results Our survey was completed by 45 ICU directors. Most participants (84.4%) reported that dysphagia is a relevant clinical problem in their ICU, and 51.1% estimated a frequency rate < 20%. Non-instrumental approaches are mainly utilized to screen and diagnose dysphagia, whereas enteral nutrition and diet modifications are used to manage dysphagia. Additionally, 64.4% of ICU directors agreed that SLPs are essential for the management of dysphagic patients, and 66.7%, that awareness of dysphagia in their ICU could be increased. Conclusion The current study documented the methods and approaches used to manage dysphagic patients in Greek ICUs. The ICU directors seem to recognize the clinical significance of dysphagia and its complications. According to our findings, the employment of SLPs could result in a more comprehensive and intensive approach and improve the quality of care for these patients.
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Abstract Introduction Dysphagia is a significant but underrecognized clinical issue in the intensive care unit (ICU), and it is associated with various complications. Despite its clinical importance, there is limited research and no Creek ICU-specific guidelines for managing dysphagic patients. Additionally, only a few ICUs in Greece have dysphagia specialists, specifically speech-language pathologists (SLPs) providing their expertise. Objective To identify the current practices for dysphagia management (screening, assessment, treatment) and gain insight into ICU directors' awareness/perceptions of the prevalence, complications, and risk of dysphagia. Materials and Methods We identified 138 Creek ICUs. Data were collected from ICU (including pediatric and neonatal) directors, working in public and private hospitals, via a 24-item, anonymous online questionnaire, within a 4-month period. Results Our survey was completed by 45 ICU directors. Most participants (84.4%) reported that dysphagia is a relevant clinical problem in their ICU, and 51.1 % estimated a frequency rate < 20%. Non-instrumental approaches are mainly utilized to screen and diagnose dysphagia, whereas enteral nutrition and diet modifications are used to manage dysphagia. Additionally, 64.4% of ICU directors agreed that SLPs are essential for the management of dysphagic patients, and 66.7%, that awareness of dysphagia in their ICU could be increased. Conclusion The current study documented the methods and approaches used to manage dysphagic patients in Creek ICUs. The ICU directors seem to recognize the clinical significance of dysphagia and its complications. According to our findings, the employment of SLPs could result in a more comprehensive and intensive approach and improve the quality of care for these patients.
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Leishmania infantum, the causative agent of American Visceral Leishmaniasis (VL), is known for its ability to modulate the host immune response to its own favor. Ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase) represents a family of enzymes that hydrolyze nucleotides and are involved in nucleotide-dependent biological processes. L. infantum has two ENTPDases, namely LiNTPDase1 and LiNTPDase2. Here, we used genetic tools to overexpress or abolish the expression of LiNTPDase1 and -2 to assess their role in parasite growth in culture and macrophage infection. While LiNTPDase1 or 2-overexpressing clones showed no morphological or growth changes in promastigotes, LiNTPDase2 overexpression increased macrophage adhesion and infection by 50% and 30%, respectively. The individual LiNTPDase1 and 2 knockout mutants showed lag in growth profile, which was reversed by the addition of adenine and guanine to the culture media. Moreover, the morphology of the knockout mutants even in supplemented media was changed to an amastigote-like form. The double knockout of both genes was lethal and a mechanism of compensation of deletion of one isoform was detected in these mutants. Correspondingly, the absence of LiNTPDase1 or LiNTPDase2 led to a dramatic reduction in in vitro infection (â¼90%). Interestingly, nitric oxide production was decreased in both knockout mutants during infection, which suggests that both LiNTPDases can inhibit macrophage responses against the parasite. Overall, our results show important roles of LiNTPDase1 and -2 concerning in vitro macrophage infection and reinforce their use as potential targets to control Leishmania infections.
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Leishmania infantum , Leishmaniose Cutânea , Leishmaniose Visceral , Parasitos , Animais , Óxido Nítrico/metabolismo , Leishmaniose Visceral/parasitologia , Macrófagos , Parasitos/metabolismoRESUMO
Aspergillosis is a fungal infection caused by Aspergillus species, which is contracted through spores that colonize the respiratory tract, causing rhinosinusitis and pulmonary infections. Oral aspergillosis is rare and, when present, may cause soft tissue and bone destruction, generally in immunodeficient patients. Mandibular Aspergillus osteomyelitis is even rarer, with few cases reported in the literature. A 57-year-old Caucasian woman was referred for the evaluation of painful recurrent swelling in the anterior mandibular alveolar ridge, with purulent drainage, previously treated with multiple surgical debridement procedures and antibiotics without success. The patient was otherwise systemically healthy. Surgical debridement was performed and histopathological examination showed osteomyelitis associated with Aspergillus species. Therapy with oral itraconazole (400 mg per day) was administered for 3 months, resulting in complete resolution. No recurrence was detected after 15 years of follow-up. The patient was rehabilitated with dental implants. In conclusion, non-bacterial microorganisms, such as Aspergillus, should be considered in cases of mandibular osteomyelitis that do not heal after surgical debridement and antibiotic therapy.
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OBJECTIVE: To investigate factors that influence or promote disbelief and negative attitudes toward COVID-19. METHODS: This was cross-sectional study involving 544 males and females ≥ 18 years of age in Greece between December of 2020 and January of 2021. All participants were informed about the purpose of the study, protection of anonymity, and volunteer participation. Participants completed an online anonymous 40-item questionnaire. Analysis of data included the identification of correlations and use of t-tests and ANOVA. RESULTS: The level of knowledge regarding COVID-19 transmission routes, manifestations, and prevention was high in our sample. Women appeared to have a more positive attitude toward COVID-19 prevention and management than did men (p = 0.032 and p = 0.018, respectively). Younger people (18-30 years of age) seemed to deny the validity of scientific data and mass media reports about ways to deal with the pandemic more commonly than did those > 30 years of age (p = 0.003 and p = 0.001, respectively). People who resided in cities more commonly believed in scientific announcements than did those living in villages (p = 0.029). CONCLUSIONS: In order to minimize cases of denial of and disbelief in COVID-19 and to promote vaccination, a series of actions are required. Governments should implement a series of measures to contain the disease, taking into consideration the psychological and social aspects of those policies.
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COVID-19 , Adulto , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pandemias/prevenção & controle , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
Abstract Introduction Anatomical variations of the nasal cavity and of the paranasal sinuses are frequently encountered and play an important role in dysfunctional drainage of sinuses. However, it is not clear in the literature whether they predispose to sinus pathology. Objectives The aim of the present review is to summarize the understanding of the association between anatomical variations of the sinonasal area and sinus pathology. Data Synthesis The present review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We performedathorough research on PubMed from October2004 until May 2020 byusing the search terms paranasal sinus anatomical variations and sinus disease, sinusitis, and mucosal disease. Thirty studies were eligible and were included in the analysis. Overall, the studies encompassed a total of 6,999 patients included in the present review. In many studies, it has been statistically established that certain anatomical variations increase the risk of sinus disease. On the other hand, the rest of the collected studies failed to show any statistically significant correlation between anatomical variants and sinus pathology. Conclusion The present study highlights the possible correlation between some anatomical variations of the sinonasal area and pathologies of the paranasal sinuses. Careful assessment and computed tomography (CT) in patients with chronic rhinosinusitis is needed, especially in those undergoing endoscopic surgery, to identify and treat anatomical variations in the paranasal sinuses that may be correlated with rhinosinusitis. Due to contradictory results in the literature, further research is needed to elucidate the effects of anatomical variants of the sinonasal area.
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Introduction Anatomical variations of the nasal cavity and of the paranasal sinuses are frequently encountered and play an important role in dysfunctional drainage of sinuses. However, it is not clear in the literature whether they predispose to sinus pathology. Objectives The aim of the present review is to summarize the understanding of the association between anatomical variations of the sinonasal area and sinus pathology. Data Synthesis The present review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We performed a thorough research on PubMed from October 2004 until May 2020 by using the search terms paranasal sinus anatomical variations and sinus disease , sinusitis , and mucosal disease . Thirty studies were eligible and were included in the analysis. Overall, the studies encompassed a total of 6,999 patients included in the present review. In many studies, it has been statistically established that certain anatomical variations increase the risk of sinus disease. On the other hand, the rest of the collected studies failed to show any statistically significant correlation between anatomical variants and sinus pathology. Conclusion The present study highlights the possible correlation between some anatomical variations of the sinonasal area and pathologies of the paranasal sinuses. Careful assessment and computed tomography (CT) in patients with chronic rhinosinusitis is needed, especially in those undergoing endoscopic surgery, to identify and treat anatomical variations in the paranasal sinuses that may be correlated with rhinosinusitis. Due to contradictory results in the literature, further research is needed to elucidate the effects of anatomical variants of the sinonasal area.
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ABSTRACT Objective: To investigate factors that influence or promote disbelief and negative attitudes toward COVID-19. Methods: This was cross-sectional study involving 544 males and females ≥ 18 years of age in Greece between December of 2020 and January of 2021. All participants were informed about the purpose of the study, protection of anonymity, and volunteer participation. Participants completed an online anonymous 40-item questionnaire. Analysis of data included the identification of correlations and use of t-tests and ANOVA. Results: The level of knowledge regarding COVID-19 transmission routes, manifestations, and prevention was high in our sample. Women appeared to have a more positive attitude toward COVID-19 prevention and management than did men (p = 0.032 and p = 0.018, respectively). Younger people (18-30 years of age) seemed to deny the validity of scientific data and mass media reports about ways to deal with the pandemic more commonly than did those > 30 years of age (p = 0.003 and p = 0.001, respectively). People who resided in cities more commonly believed in scientific announcements than did those living in villages (p = 0.029). Conclusions: In order to minimize cases of denial of and disbelief in COVID-19 and to promote vaccination, a series of actions are required. Governments should implement a series of measures to contain the disease, taking into consideration the psychological and social aspects of those policies.
RESUMO Objetivo: Investigar fatores que influenciam ou promovem a descrença e atitudes negativas em relação à COVID-19. Métodos: Estudo transversal envolvendo 544 homens e mulheres com ≥ 18 anos de idade na Grécia entre dezembro de 2020 e janeiro de 2021. Todos os participantes foram informados sobre o objetivo do estudo, proteção do anonimato e participação voluntária. Os participantes responderam a um questionário on-line anônimo com 40 itens. A análise dos dados incluiu a identificação de correlações e o uso de testes t e ANOVA. Resultados: O nível de conhecimento sobre as vias de transmissão, manifestações e prevenção da COVID-19 foi alto em nossa amostra. As mulheres pareceram ter uma atitude mais positiva em relação à prevenção e manejo da COVID-19 do que os homens (p = 0,032 e p = 0,018, respectivamente). As pessoas mais jovens (18-30 anos de idade) pareceram negar mais a validade dos dados científicos e reportagens da mídia sobre as formas de lidar com a pandemia do que aquelas com > 30 anos de idade (p = 0,003 e p = 0,001, respectivamente). As pessoas que residiam em cidades grandes acreditavam mais nos pronunciamentos científicos do que as que residiam em vilas (p = 0,029). Conclusões: Para minimizar o número de casos de negação e descrença em relação à COVID-19 e promover a vacinação, é necessária uma série de ações. Os governos devem implementar uma série de medidas para conter a doença, levando em consideração os aspectos psicológicos e sociais dessas políticas.
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Abstract Aim: The study aimed to investigate the effects of the somatotype components on handball. Methods: The sample consisted of 60 elite junior handball players. Somatotype was evaluated using the Heath & Carter method. The kinetic performance trials of the handball athletes were running speed performance over 5 m 10 m and 20 m sprints, sit and reach, standing long jump (SLJ), ball velocity, and maximum aerobic power. For the data analyses, we used Pearson correlation and multiple linear regression. Results: The endomorphic component correlated positive with all three sprint times (5 m, 10 m και 30 m sprints) (r = 0.315, p = 0.014; r = 0.367, p = 0.004; r = 0.358, p = 0.005 respectively) while negative with SLJ (r = -0.418, p = 0.001) και maximum aerobic power (r = -0.322, p = 0.012). The mesomorphic component had a positive correlation with ball velocity (r = 0.260, p = 0.045) and negative relation with SLJ (r = -0.261, p = 0.044). The ectomorphic component exhibited a negative correlation only with ball velocity (r = -0.260, p = 0.045). The ordinary least square regression models found that endomorphy and ectomorphy were prognostic factors and predicted worse performance in all of the examined motor performance indices except ball velocity and 5 m sprint, while mesomorphy was a predictor of worse performance in SLJ. Conclusions: In conclusion, according to the findings of this study, somatotype components play an important role in performance-related parameters.
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Poly(A) Binding Proteins (PABPs) are major eukaryotic RNA-binding proteins (RBPs) with multiple roles associated with mRNA stability and translation and characterized mainly from multicellular organisms and yeasts. A variable number of PABP homologues are seen in different organisms however the biological reasons for multiple PABPs are generally not well understood. In the unicellular Leishmania, dependent on post-transcriptional mechanisms for the control of its gene expression, three distinct PABPs are found, with yet undefined functional distinctions. Here, using RNA-immunoprecipitation sequencing analysis we show that the Leishmania PABP1 preferentially associates with mRNAs encoding ribosomal proteins, while PABP2 and PABP3 bind to an overlapping set of mRNAs distinct to those enriched in PABP1. Immunoprecipitation studies combined to mass-spectrometry analysis identified RBPs differentially associated with PABP1 or PABP2, including RBP23 and DRBD2, respectively, that were investigated further. Both RBP23 and DRBD2 bind directly to the three PABPs in vitro, but reciprocal experiments confirmed preferential co-immunoprecipitation of PABP1, as well as the EIF4E4/EIF4G3 based translation initiation complex, with RBP23. Other RBP23 binding partners also imply a direct role in translation. DRBD2, in contrast, co-immunoprecipitated with PABP2, PABP3 and with RBPs unrelated to translation. Over 90% of the RBP23-bound mRNAs code for ribosomal proteins, mainly absent from the transcripts co-precipitated with DRBD2. These experiments suggest a novel and specific route for translation of the ribosomal protein mRNAs, mediated by RBP23, PABP1 and the associated EIF4E4/EIF4G3 complex. They also highlight the unique roles that different PABP homologues may have in eukaryotic cells associated with mRNA translation.
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Leishmania/metabolismo , Proteínas de Ligação a Poli(A)/metabolismo , Proteínas de Protozoários/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Ribossômicas/metabolismo , Leishmania/genética , Proteínas de Ligação a Poli(A)/genética , Ligação Proteica , Biossíntese de Proteínas , Proteínas de Protozoários/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteínas Ribossômicas/genéticaRESUMO
OBJECTIVE: The objective of the study was to estimate the effects of synbiotics on laboratory, macroscopic, and histopathologic features in dextran sulfate sodium (DSS) experimental colitis. MATERIALS AND METHODS: A total of 40 Wistar rats received 5% of DSS in their drinking water for 8 days to induce ulcerative colitis (UC). Eight rats were sacrificed to confirm the presence of UC. The remaining rats were randomly assigned to two groups: the synbiotics group, which received synbiotics once per day and the control group, which received tap water for another 8 days. RESULTS: On the 8th day of DSS administration animals developed UC with bloody diarrhea. In the majority of the hematologic variables studied (hemoglobin [HB], red blood cells, platelets, mean corpuscular volume, and mean corpuscular HB), in bodyweight and histopathologic colitis score there was no significant difference between groups. However, the synbiotics group, compared to control, presented a significantly greater colon length on the 4th day, significantly increased hematocrit (HT) on the 8th day, and a significantly decreased number of myeloperoxidase positive cells on the 8th day. Furthermore, there was a trend toward histopathological and clinical improvement. CONCLUSIONS: Administration of synbiotics in the experimental UC results in an attenuation of mucosal inflammatory neutrophil infiltration and an increase in HT.
OBJETIVO: Estimar los efectos de los simbióticos en la colitis experimental causada por dextrano sulfato de sodio (DSS). MATERIAL Y MÉTODOS: Cuarenta ratas Wistar recibieron DSS al 5% en su agua de beber por 8 días para inducir colitis ulcerosa (CU). Ocho ratas fueron sacrificadas para confirmar la presencia de CU. Las ratas restantes fueron asignadas aleatoriamente a dos grupos: un grupo que recibió simbióticos una vez al día y un grupo control que recibió agua del grifo por 8 días. RESULTADOS: En el octavo día de la administración de DSS los animales desarrollaron CU con diarrea sanguinolenta. En la mayoría de las variables hematológicas estudiadas (hemoglobina, glóbulos rojos, plaquetas, volumen corpuscular medio, hemoglobina corpuscular media), en el peso corporal y en la clasificación histopatológica de la CU no hubo diferencias significativas entre los grupos. Sin embargo, el grupo con simbióticos, en comparación con el grupo control, presentó una longitud del colon más larga en el cuarto día, un hematocrito muy aumentado en el octavo día y un número de células mieloperoxidasa positivas significativamente reducido en el octavo día. Además, hubo una tendencia hacia un mejoramiento histopatológico y clínico. CONCLUSIONES: La administración de simbióticos en la CU experimental tiene como resultado una atenuación de la infiltración inflamatoria de neutrófilos de la mucosa y un aumento del hematocrito.
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Colite Ulcerativa/terapia , Hematócrito , Infiltração de Neutrófilos , Simbióticos/administração & dosagem , Animais , Peso Corporal , Colite Ulcerativa/sangue , Colite Ulcerativa/enzimologia , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana , Contagem de Eritrócitos , Índices de Eritrócitos , Microbioma Gastrointestinal , Hemoglobina A/análise , Masculino , Neutrófilos/enzimologia , Tamanho do Órgão , Peroxidase/análise , Contagem de Plaquetas , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
BACKGROUND: Cooperation in public health and in oncology in particular, is currently a major issue for the island of Martinique, given its geopolitical position in the Caribbean region. The region of Martinique shares certain public health problems with other countries of the Caribbean, notably in terms of diagnostic and therapeutic management of patients with cancer. We present here a roadmap of cooperation priorities and activities in cancer surveillance and oncology in Martinique. MAIN BODY: The fight against cancer is a key public health priority that features high on the regional health policy for Martinique. In the face of these specific epidemiological conditions, Martinique needs to engage in medical cooperation in the field of oncology within the Caribbean, to improve skills and knowledge in this field, and to promote the creation of bilateral relations that will help to improve cancer management in an international healthcare environment. CONCLUSIONS: These collaborative exchanges will continue throughout 2020 and will lead to the implementation of mutual research projects across a larger population basin, integrating e-health approaches and epidemiological e-cohorts.
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Neoplasias/diagnóstico , Vigilância da População/métodos , Saúde Pública/métodos , Atenção à Saúde/métodos , Atenção à Saúde/tendências , Humanos , Cooperação Internacional , Martinica/epidemiologia , Oncologia/métodos , Neoplasias/epidemiologia , Saúde Pública/estatística & dados numéricos , Nações Unidas/organização & administração , Nações Unidas/tendênciasRESUMO
OBJECTIVE: To explore the effect of early-onset preeclampsia on the blood pressure of offspring during the first month of life. STUDY DESIGN: This prospective case-control study included 106 neonates of mothers with early-onset preeclampsia (developing at <34 weeks of gestation) and 106 infants of normotensive mothers, matched 1-to-1 for sex and gestational age. Serial blood pressure measurements were obtained on admission, daily for the first postnatal week, and then weekly up to the fourth week of life. RESULTS: There were no differences in blood pressure values on admission and the first day of life between cases and controls. Conversely, infants exposed to preeclampsia had significantly higher systolic (SBP), diastolic (DBP), and mean blood pressure (MBP) on the subsequent days up to the fourth postnatal week (P <.001-.033). Multiple regression analyses with adjustment for sex, gestational age, antenatal corticosteroid use, and maternal antihypertensive medication use confirmed the foregoing findings (P <.001-.048). Repeated-measures ANOVA also identified preeclampsia as a significant determinant of trends in SBP, DBP, and MBP during the first month of life (F = 16.2, P < .001; F = 16.4, P < .001; and F = 17.7, P < .001, respectively). CONCLUSIONS: Infants of mothers with early-onset preeclampsia have elevated blood pressure values throughout the neonatal period compared with infants born to normotensive mothers.
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Diástole/fisiologia , Hipertensão/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Sístole/fisiologia , Adulto , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVE: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. STUDY DESIGN: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year. RESULTS: We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not. CONCLUSIONS: Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.
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Colangite Esclerosante/sangue , Colangite Esclerosante/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , gama-Glutamiltransferase/sangue , Adolescente , Análise de Variância , Biomarcadores/sangue , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Testes de Função Hepática , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Falha de Tratamento , Resultado do TratamentoRESUMO
Bottom trawlers land around 19 million tons of fish and invertebrates annually, almost one-quarter of wild marine landings. The extent of bottom trawling footprint (seabed area trawled at least once in a specified region and time period) is often contested but poorly described. We quantify footprints using high-resolution satellite vessel monitoring system (VMS) and logbook data on 24 continental shelves and slopes to 1,000-m depth over at least 2 years. Trawling footprint varied markedly among regions: from <10% of seabed area in Australian and New Zealand waters, the Aleutian Islands, East Bering Sea, South Chile, and Gulf of Alaska to >50% in some European seas. Overall, 14% of the 7.8 million-km2 study area was trawled, and 86% was not trawled. Trawling activity was aggregated; the most intensively trawled areas accounting for 90% of activity comprised 77% of footprint on average. Regional swept area ratio (SAR; ratio of total swept area trawled annually to total area of region, a metric of trawling intensity) and footprint area were related, providing an approach to estimate regional trawling footprints when high-resolution spatial data are unavailable. If SAR was ≤0.1, as in 8 of 24 regions, there was >95% probability that >90% of seabed was not trawled. If SAR was 7.9, equal to the highest SAR recorded, there was >95% probability that >70% of seabed was trawled. Footprints were smaller and SAR was ≤0.25 in regions where fishing rates consistently met international sustainability benchmarks for fish stocks, implying collateral environmental benefits from sustainable fishing.
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Pesqueiros/estatística & dados numéricos , Alaska , Animais , Austrália , Biodiversidade , Chile , Ecossistema , Invertebrados/fisiologia , Nova Zelândia , Oceanos e Mares , Alimentos Marinhos/estatística & dados numéricosRESUMO
Oropouche fever is an emerging zoonotic disease caused by Oropouche virus (OROV), an arthropod transmitted Orthobunyavirus circulating in South and Central America. During the last 60 years, more than 30 epidemics and over half a million clinical cases attributed to OROV infection have been reported in Brazil, Peru, Panama, Trinidad and Tobago. OROV fever is considered the second most frequent arboviral febrile disease in Brazil after dengue fever. OROV is transmitted through both urban and sylvatic transmission cycles, with the primary vector in the urban cycle being the anthropophilic biting midge Culicoides paraensis. Currently, there is no evidence of direct human-to-human OROV transmission. OROV fever is usually either undiagnosed due to its mild, self-limited manifestations or misdiagnosed because its clinical characteristics are similar to dengue, chikungunya, Zika and yellow fever, including malaria as well. At present, there is no specific antiviral treatment, and in the absence of a vaccine for effective prophylaxis of human populations in endemic areas, the disease prevention relies solely on vector control strategies and personal protection measures. OROV fever is considered to have the potential to spread across the American continent and under favorable climatic conditions may expand its geographic distribution to other continents. In view of OROV's emergence, increased interest for formerly neglected tropical diseases and within the One Health concept, the existing knowledge and gaps of knowledge on OROV fever are reviewed.
Assuntos
Infecções por Arbovirus/epidemiologia , Infecções por Arbovirus/virologia , Arbovírus , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Zoonoses , Animais , Infecções por Arbovirus/diagnóstico , Infecções por Arbovirus/transmissão , Arbovírus/classificação , Arbovírus/genética , Arbovírus/patogenicidade , Vetores Artrópodes/virologia , América Central/epidemiologia , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/transmissão , Gerenciamento Clínico , Surtos de Doenças , Humanos , América do Sul/epidemiologiaRESUMO
The Poly-A Binding Protein (PABP) is a conserved eukaryotic polypeptide involved in many aspects of mRNA metabolism. During translation initiation, PABP interacts with the translation initiation complex eIF4F and enhances the translation of polyadenylated mRNAs. Schematically, most PABPs can be divided into an N-terminal RNA-binding region, a non-conserved linker segment and the C-terminal MLLE domain. In pathogenic Leishmania protozoans, three PABP homologues have been identified, with the first one (PABP1) targeted by phosphorylation and shown to co-immunoprecipitate with an eIF4F-like complex (EIF4E4/EIF4G3) implicated in translation initiation. Here, PABP1 phosphorylation was shown to be linked to logarithmic cell growth, reminiscent of EIF4E4 phosphorylation, and coincides with polysomal association. Phosphorylation targets multiple serine-proline (SP) or threonine-proline (TP) residues within the PABP1 linker region. This is an essential protein, but phosphorylation is not needed for its association with polysomes or cell viability. Mutations which do impair PABP1 polysomal association and are required for viability do not prevent phosphorylation, although further mutations lead to a presumed inactive protein largely lacking phosphorylated isoforms. Co-immunoprecipitation experiments were carried out to investigate PABP1 function further, identifying several novel protein partners and the EIF4E4/EIF4G3 complex, but no other eIF4F-like complex or subunit. A novel, direct interaction between PABP1 and EIF4E4 was also investigated and found to be mediated by the PABP1 MLLE binding to PABP Interacting Motifs (PAM2) within the EIF4E4 N-terminus. The results shown here are consistent with phosphorylation of PABP1 being part of a novel pathway controlling its function and possibly translation in Leishmania.
Assuntos
Leishmania infantum/metabolismo , Iniciação Traducional da Cadeia Peptídica/fisiologia , Proteínas de Ligação a Poli(A)/metabolismo , Proteínas de Protozoários/metabolismo , Motivos de Aminoácidos , Leishmania infantum/genética , Fosforilação/fisiologia , Proteínas de Ligação a Poli(A)/genética , Proteínas de Protozoários/genéticaRESUMO
Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of "resistance" related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined.