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Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second-line treatment for ITP. Real-world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real-world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing.
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Aminopiridinas , Morfolinas , Púrpura Trombocitopênica Idiopática , Piridinas , Humanos , Pessoa de Meia-Idade , Feminino , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Masculino , Espanha , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Idoso , Morfolinas/uso terapêutico , Morfolinas/efeitos adversos , Estudos Retrospectivos , Adulto , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Oxazinas/uso terapêutico , Oxazinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: The association between use of antipsychotics and COVID-19 outcomes is inconsistent, which may be linked to use of these drugs in age-related diseases. Furthermore, there is little evidence regarding their effect in the nongeriatric population. We aim to assess the association between antipsychotic use and risk of disease progression and hospitalization due to COVID-19 among the general population, stratifying by age. METHODS: We conducted a population-based, multiple case-control study to assess risk of hospitalization, with cases being patients with a PCR(+) test who required hospitalization and controls being individuals without a PCR(+) test; and risk of progression to hospitalization, with cases being the same as those used in the hospitalization substudy and controls being nonhospitalized PCR(+) patients. We calculated adjusted odds-ratios (aOR) and 95% confidence intervals (CI), both overall and stratified by age. RESULTS: Antipsychotic treatment in patients younger than 65 years was not associated with a higher risk of hospitalization due to COVID-19 (aOR 0.94 [95%CI = 0.69-1.27]) and disease progression among PCR(+) patients (aOR 0.96 [95%CI = 0.70-1.33]). For patients aged 65 years or older, however, there was a significant, increased risk of hospitalization (aOR 1.58 [95% CI = 1.38-1.80]) and disease progression (aOR 1.31 [95% CI = 1.12-1.55]). CONCLUSIONS: The results of our large-scale real-world data study suggest that antipsychotic use is not associated with a greater risk of hospitalization due to COVID-19 and progression to hospitalization among patients younger than 65 years. The effect found in the group aged 65 years or older might be associated with off-label use of antipsychotics.
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Antipsicóticos , COVID-19 , Hospitalização , Humanos , Antipsicóticos/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , COVID-19/epidemiologia , Estudos de Casos e Controles , Hospitalização/estatística & dados numéricos , Fatores Etários , Adulto , Progressão da Doença , Idoso de 80 Anos ou mais , Tratamento Farmacológico da COVID-19 , Pacientes AmbulatoriaisRESUMO
BackgroundBy mid-September 2023, several event notifications related to cryptosporidiosis had been identified from different regions in Spain. Therefore, a request for urgent notification of cryptosporidiosis cases to the National Surveillance Network was launched.AimWe aimed at assessing the extent of the increase in cases, the epidemiological characteristics and the transmission modes and compared to previous years.MethodsWe analysed data on case notifications, outbreak reports and genotypes focusing on June-October 2023 and compared the results to 2016-2022.ResultsIn 2023, 4,061 cryptosporidiosis cases were notified in Spain, which is an increase compared to 2016-2022. The cumulative incidence was 8.3 cases per 100,000 inhabitants in 2023, sixfold higher than the median of 1.4 cases per 100,000 inhabitants 2016-2022. Almost 80% of the cases were notified between June and October. The largest outbreaks were related to contaminated drinking water or swimming pools. Cryptosporidium hominis was the most common species in the characterised samples (115/122), and the C. hominis IfA12G1R5 subtype, previously unusual in Spain, was detected from 76 (62.3%) of the 122 characterised samples.ConclusionsA substantial increase in cryptosporidiosis cases was observed in 2023. Strengthening surveillance of Cryptosporidium is essential for prevention of cases, to better understand trends and subtypes circulating and the impact of adverse meteorological events.
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Criptosporidiose , Cryptosporidium , Surtos de Doenças , Criptosporidiose/epidemiologia , Humanos , Espanha/epidemiologia , Cryptosporidium/isolamento & purificação , Cryptosporidium/genética , Masculino , Incidência , Adulto , Feminino , Pré-Escolar , Surtos de Doenças/estatística & dados numéricos , Adolescente , Pessoa de Meia-Idade , Criança , Lactente , Idoso , Adulto Jovem , Genótipo , Vigilância da População , Água Potável/parasitologia , Piscinas , Notificação de Doenças/estatística & dados numéricos , Recém-Nascido , Fezes/parasitologiaRESUMO
OBJECTIVES: To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. METHODS: We conducted a multiple population-based case-control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. RESULTS: ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69-0.89] and aOR = 0.80 [95%CI 0.72-0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52-0.98] and aOR = 0.69 [95%CI 0.52-0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82-0.94] and aOR = 0.92 [95%CI 0.86-0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61-0.85]), mortality (aOR = 0.59 [95%CI 0.38-0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79-0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60-0.95]), mortality (aOR = 0.36 [95%CI 0.17-0.75]) and disease progression (aOR = 0.73 [95%CI 0.56-0.95]). CONCLUSION: This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.
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Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , COVID-19 , Hospitalização , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Masculino , Feminino , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , Antagonistas de Receptores de Angiotensina/uso terapêutico , Idoso , Estudos de Casos e Controles , Anti-Hipertensivos/uso terapêutico , Espanha/epidemiologia , Hipertensão/tratamento farmacológico , Idoso de 80 Anos ou mais , Progressão da DoençaRESUMO
BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.
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Ginecologia/educação , Oncologistas/educação , Europa (Continente) , Feminino , HumanosRESUMO
A scaffold hopping strategy, including intellectual property availability assessment, was successfully applied for the discovery of novel PI3K inhibitors. Compounds were designed based on the chemical structure of the lead compound ETP-46321, a potent PI3K inhibitor, previously reported by our group. The new generated compounds showed good in vitro potency and selectivity, proved to inhibit potently the phosphorylation of AKTSer473 in cells and demonstrated to be orally bioavailable, thus becoming potential back-up candidates for ETP-46321.
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Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/metabolismo , Administração Oral , Animais , Química Farmacêutica , Avaliação Pré-Clínica de Medicamentos , Meia-Vida , Imidazóis/química , Imidazóis/metabolismo , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazinas/química , Pirazinas/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismoRESUMO
The involvement of the phosphoinositide 3-kinases (PI3Ks) in several diseases, especially in the oncology area, has singled it as one of the most explored therapeutic targets in the last two decades. Many different inhibitor classes have been developed by the industry and academia with a diverse selectivity profile within the PI3K family. In the present manuscript we report a further exploration of our lead PI3K inhibitor ETP-46321 (Martínez González et al., 2012)1 by the application of a conformational restriction strategy. For that purpose we have successfully synthesized novel tricyclic imidazo[1,2-a]pyrazine derivatives as PI3K inhibitors. This new class of compounds had enable the exploration of the solvent-accessible region within PI3K and resulted in the identification of molecule 8q with the best selectivity PI3Kα/δ isoform profile in vitro, and promising in vivo PK data.
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Imidazóis/química , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/química , Pirazinas/química , Animais , Meia-Vida , Humanos , Imidazóis/síntese química , Imidazóis/farmacocinética , Concentração Inibidora 50 , Camundongos , Microssomos Hepáticos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacocinética , Pirazinas/síntese química , Pirazinas/farmacocinética , Relação Estrutura-AtividadeRESUMO
Despite the ecological and evolutionary importance of nectar, mechanisms controlling its synthesis and secretion remain largely unknown. It is widely believed that nectar is 'secreted phloem sap', but current research reveals a biochemical complexity that is unlikely to stem directly from the phloem. We used the short daily peak in production of extrafloral nectar by Acacia cornigera to investigate metabolic and proteomic dynamics before, during and after 2 h of diurnal secretion. Neither hexoses nor dominating nectar proteins (nectarins) were detected in the phloem before or during nectar secretion, excluding the phloem as the direct source of major nectar components. Enzymes involved in the anabolism of sugars, amino acids, proteins, and nectarins, such as invertase, ß-1,3-glucanase and thaumatin-like protein, accumulated in the nectary directly before secretion and diminished quantitatively after the daily secretion process. The corresponding genes were expressed almost exclusively in nectaries. By contrast, protein catabolic enzymes were mainly present and active after the secretion peak, and may function in termination of the secretion process. Thus the metabolic machinery for extrafloral nectar production is synthesized and active during secretion and degraded thereafter. Knowing the key enzymes involved and the spatio-temporal patterns in their expression will allow elucidation of mechanisms by which plants control nectar quality and quantity.
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Acacia/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Néctar de Plantas/metabolismo , Acacia/enzimologia , Glucana 1,3-beta-Glucosidase/genética , Glucana 1,3-beta-Glucosidase/metabolismo , Especificidade de Órgãos , Floema/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteólise , Proteoma/análise , Proteômica , Especificidade da Espécie , Fatores de Tempo , beta-Frutofuranosidase/genética , beta-Frutofuranosidase/metabolismoRESUMO
INTRODUCTION: The management of infections in war wounds is a problem aggravated by the presence of multiresistant bacteria and requires a combined approach with surgery. Literature has identified the risks and patterns of antibiotic resistance in previous armed conflicts, but the Russian-Ukrainian conflict has required the study of specific bacterial resistance patterns. METHODS: We included war-injured patients from the Russian-Ukrainian conflict transferred for treatment to the General Defense Hospital of Zaragoza from May 2022 to October 2023. Epidemiological data, factors related to the injury, presence of infection and microbiological results were collected; These data were subsequently analyzed statistically. RESULTS: Fifty-three patients were included in the study, with a mean age of 35.6 years; 83% were injured by an explosive mechanism and all received antibiotic therapy prior to transfer. Seventeen patients had skin, soft tissue or joint infection. Correlation was demonstrated with the presence of bone lesion (p 0.03), skin coverage defect (p 0.000) and presence of foreign bodies (p 0.006). Nine patients had monomicrobial cultures, and the most frequently isolated microorganisms were Gram negative bacilli (GNB) and Staphylococcus aureus. Virtually all GNB presented some resistance mechanism. CONCLUSION: Our work shows the correlation of war wound infection with the presence of foreign bodies and affected tissues. Likewise, the presence of polymicrobial wounds is emphasized, with a predominance of GNB and multidrug-resistant S. aureus.
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BACKGROUND AND AIM: Increased mortality during the COVID-19 pandemic is not explained exclusively by COVID-19 infection and its complications. We analysed non-COVID-19 causes of mortality in a population analysis based on data from the Spanish National Institute of Statistics. METHODS: Using monthly mortality data in Spain (January 2010-December 2020), we analysed deaths associated with cancer, blood, endocrine, mental, nervous, cardiovascular, respiratory and digestive diseases and explored the COVID-19 impact using a difference-in-difference strategy. We calculated monthly interannual variations in mortality and computed percentage change in terms of the log of deaths in month h of year t minus the log of deaths in month h in the previous year t-1. RESULTS: In 2020 in Spain, mortality increased 17.9% compared with 2019. COVID-19 was the leading cause of death (n=60 358), followed by ischaemic heart disease (n=29 654). Throughout 2020, monthly interannual variations in cardiovascular mortality showed an average upward trend of 1.7%, while digestive, cancer and blood diseases showed a downward trend. CONCLUSIONS: During the COVID-19 pandemic in Spain in 2020, excess mortality was primarily related to cardiovascular mortality while mortality associated with digestive, cancer and blood diseases was reduced.
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COVID-19 , Causas de Morte , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Espanha/epidemiologia , Causas de Morte/tendências , Masculino , Feminino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , SARS-CoV-2 , Idoso , Pessoa de Meia-Idade , Pandemias , Neoplasias/mortalidade , Fatores de Tempo , AdultoRESUMO
OBJECTIVE: To evaluate the prognostic value of tumor volume on preoperative MRI in endometrial cancer (EC) patients and its association with adverse prognostic factors and survival. METHODS: A retrospective observational study with 127 consecutive patients with endometrioid EC was carried out between 2016 and 2021 at Juan Ramón Jiménez University Hospital, Huelva (Spain). All patients underwent preoperative magnetic resonance imaging (MRI) for local staging. The tumor volume was analyzed on MRI by two different methods: by measuring the three maximum diameters of the tumor according to an ellipse formula and by manual region of interest in different sections; the ratio between tumor volume and uterus volume was also calculated as a third tool. The relationships between volume, prognostic factors, and survival were analyzed. RESULTS: A total of 127 patients with endometroid EC underwent preoperative MRI and were included in the study. Tumor volume was significantly higher for deep myometrial invasion, cervical stromal involvement, infiltrated serosa, lymph node metastases, high-grade EC, and lymphovascular space involvement, advanced FIGO stage, and High Recurrence Risk Group (P < 0.001). ROC curves showed that tumor volume greater than 25 cm3 predicts lymph node metastases. Volume index greater than 17 cm3 was associated with reduced disease-free survival (P < 0.001) and overall survival (P < 0.003). Multivariate analysis showed that the greatest tumor volume had an independent impact on recurrence (odds ratio [OR]1.019, 95% confidence interval [CI] 1.005-1.032) and survival (OR 1.027, 95% CI 1.009-1.046). CONCLUSIONS: This study shows an important correlation between tumor volume on MRI and poor prognostic factors. Preoperative tumor volume on MRI is a valuable biomarker to be considered for management of EC.
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Carcinoma Endometrioide , Neoplasias do Endométrio , Feminino , Humanos , Metástase Linfática , Carga Tumoral , Prognóstico , Neoplasias do Endométrio/patologia , Carcinoma Endometrioide/diagnóstico por imagem , Carcinoma Endometrioide/patologia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
Objective: To evaluate whether the introduction of tumor volume as new parameter in the MRI assessment could improve both concordance between preoperative and postoperative staging, and the identification of histological findings. Methods: A retrospective observational study with 127 patients with endometrial cancer (EC) identified between 2016 and 2021 at the Juan Ramon Jimenez University Hospital, Huelva (Spain) was carried out. Tumor volume was measured in three ways. Analyses of Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) were performed. Results: Although preoperative MRI had an 89.6% and 66.7% sensitivity for the detection of deep mucosal invasion and cervical stroma infiltration, preoperative assessment had an intraclass correlation coefficient of 0.517, underestimating tumor final stage in 12.6% of cases, with a poor agreement between preoperative MRI and postoperative staging (κ=0.082) and low sensitivity (14.3%) for serosa infiltration. The cut-off values for all three volume parameters had good/excellent AUC (0.73-0.85), with high sensitivity (70-83%) and specificity (64-84%) values for all histopathological variables. Excellent/good agreement was found all volume parameters for the identification of deep myometrial invasion (0.71), cervical stroma infiltration (0.80), serosa infiltration (0.81), and lymph node metastases (0.81). Conclusion: Tumor volume measurements have good predictive capacity to detect histopathological findings that affect final tumor staging and might play a crucial role in the preoperative assessment of patients with endometrial cancer in the future.
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PIM kinases have become targets of interest due to their association with biochemical mechanisms affecting survival, proliferation and cytokine production. 1,2,3-Triazolo[4,5-b]pyridines were identified as PIM inhibitors applying a scaffold hopping approach. Initial exploration around this scaffold and X-ray crystallographic data are hereby described.
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Desenho de Fármacos , Modelos Moleculares , Inibidores de Proteínas Quinases/síntese química , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Piridinas/síntese química , Triazóis/síntese química , Ativação Enzimática/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Concentração Inibidora 50 , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Piridinas/química , Piridinas/farmacologia , Triazóis/química , Triazóis/farmacologiaRESUMO
Phosphoinositide-3-kinase (PI3K) is an important target for cancer therapeutics due to the deregulation of its signaling pathway in a wide variety of human cancers. We describe herein a novel series of imidazo[1,2-a]pyrazines as PI3K inhibitors.
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Imidazóis/química , Imidazóis/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Pirazinas/química , Pirazinas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Imidazóis/metabolismo , Camundongos , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazinas/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The sequence and chronology of the main biochemical changes occurring in the cytoplasm of bovine oocytes during the in vitro maturation process were tracked by Raman microscopy applied to cells previously subjected to enzymatic digestion of the zona pellucida. Specific spectral markers for proteins, lipids and carbohydrates were used to evaluate the developmental status of the ooplasm at four different times. Spectral changes revealed that lipid accumulation was dominant during the first six hours of culture while protein content reached the average levels characteristic of mature oocytes within the last four hours of the maturation process. A time-dependent decrease in carbohydrates was also observed. Finally, the carbohydrate-to-protein (P1037/P1002) ratio proved to be sensitive enough to determine the cytoplasmic maturation state of bovine oocytes and promises to be useful in future research aimed at optimizing culture conditions through the promotion of protein accumulation in the ooplasm.
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Microscopia , Oócitos , Animais , Carboidratos/análise , Bovinos , Citoplasma , Microscopia/veterinária , Oócitos/química , Oócitos/metabolismo , OogêneseRESUMO
BACKGROUND: Vaccine hesitancy decreases adult vaccination coverage and has been recognized by WHO as a major health threat. Primary care physicians (PCP) play a key role in vaccination by giving vaccine counselling to their patients. The aim of this systematic review is to identify the knowledge, beliefs, attitudes and barriers (KBAB) associated with own vaccination and patient recommendation in primary care physicians. METHODS: MEDLINE/PubMed, EMBASE and Cochrane Library databases were used to search and identify relevant studies based on their title and abstract. In the next step, the full text of each previously selected article was read for eligibility. Articles were selected by two independent reviewers and data extraction was performed using tables. The following information was extracted: methodological characteristics, demographic factors, professional characteristics, and intrinsic or extrinsic factors influencing vaccination or recommendation. RESULTS: Our search yielded 41 eligible papers, data-sources, previous practices, belief in the effectiveness or safety of the vaccine, perceived risk, and trust in health authorities were all shown to be related to own vaccination and patient recommendation. CONCLUSION: Internet is the main source of information for PCP related to vaccine hesitancy. It is therefore essential to increase the presence and access to pro-vaccination content in this area. In addition, involving PCP in the establishment of vaccination recommendations could improve their credibility in the institutions. On the other hand, training in communication skills and establishing reminder systems could reflect higher vaccination coverage among their patients.
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Médicos de Atenção Primária , Vacinas , Adulto , Humanos , Vacinação , Confiança , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Hemimegalencephaly (HME) is a developmental abnormality of the central nervous system (CNS) which may present as either a syndromic or isolated case. Here, we present two cases of early prenatal diagnosis of HME. Prenatal CNS ultrasound and MRI in the first case revealed ventricular asymmetry, midline shift with displacement of the occipital lobe across the midline, large dilatation mainly at the posterior horn of the left lateral ventricle, and a head circumference in the 90th percentile without involvement of the brain stem and cerebellum, as well as abdominal lymphangioma. Right hemispherectomy was performed at 3 months of age due to intractable seizures. The pathological specimen showed findings characteristic of HME, including a disorganized cytoarchitecture with lack of neuronal lamination, focal areas of polymicrogyria, and neuronal heterotopias with dysplastic cells. In the second case, 2D and 3D neurosonography demonstrated similar findings (asymmetry of cerebral hemispheres, midline shift, and dilation of the posterior horn of the left lateral cerebral ventricle). Posterior fossa structures were unremarkable. HME was diagnosed and the pregnancy was terminated. Autopsy findings confirmed the diagnosis of HME.
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Doenças Fetais/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Ecoencefalografia , Feminino , Hemisferectomia , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/patologia , Malformações do Desenvolvimento Cortical/cirurgia , Gravidez , Segundo Trimestre da Gravidez , Resultado do TratamentoRESUMO
The vibrational study of the pyraclostrobin (methyl N-(2-{[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}phenyl) N-methoxycarbamate) molecule, a synthetic fungicide for agricultural uses, was performed. Pyraclostrobin belongs to the strobilurin family and acts by inhibiting the fungus respiratory chain at the level of Complex III, becoming an excellent agent for preventive, curative and eradicative activities against a wide range of fungal plant pathogens. However, its presence needs to be monitored to avoid the excessive and/or improper use that may compromise human or environmental health. The FTIR and Raman spectra of pyraclostrobin in pure solid state were recorded and compared with those obtained from both the substance in CH2Cl2 solution and in an agricultural commercial product (Comet® BASF). The spectral analysis was complemented with quantum-chemical calculations at the DFT level (B3LYP/6-311G*) for the predictions of the molecular geometry and its vibrational behavior. The high flexibility of the molecule was explored by performing potential energy scans on several dihedral angles and the results suggested that the main conformer of pyraclostrobin is that possessing the ortho-substituted benzene ring in perpendicular orientation regarding the plane that contains the ether group and the pyrazole ring, although the presence of a second preferred conformation in the experimental vibrational spectra was not ruled out. Among the many vibrational bands of pyraclostrobin that were well identified in the spectrum of the composite product for agricultural use, the one located at 936 cm-1 stood out. This signal was assigned to a vibration of the pyrazole ring and promised to be a good candidate as marker of the presence of the fungicide in complex matrixes.
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Fungicidas Industriais , Vibração , Humanos , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , EstrobilurinasRESUMO
PURPOSE: Genomic cancer risk assessment (GCRA) is standard-of-care practice that uses genomic tools to identify individuals with increased cancer risk, enabling screening for early detection and cancer prevention interventions. GCRA is not available in most of Mexico, where breast cancer (BC) is the leading cause of cancer death and ovarian cancer has a high mortality rate. METHODS: Guided by an implementation science framework, we piloted the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) intervention, combining GCRA training, practice support, and low-cost BRCA1/2 (BRCA) gene testing at four centers in Mexico. The RE-AIM model was adapted to evaluate GRACIAS intervention outcomes, including reach, the proportion of new patients meeting adapted National Comprehensive Cancer Network criteria who participated in GCRA. Barriers to GCRA were identified through roundtable sessions and semistructured interviews. RESULTS: Eleven clinicians were trained across four sites. Mean pre-post knowledge score increased from 60% to 67.2% (range 53%-86%). GCRA self-efficacy scores increased by 31% (95% CI, 6.47 to 55.54; P = .02). Participant feedback recommended Spanish content to improve learning. GRACIAS promoted reach at all sites: 77% in Universidad de Guadalajara, 86% in Instituto Nacional de Cancerología, 90% in Tecnológico de Monterrey, and 77% in Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Overall, a pathogenic BRCA variant was identified in 15.6% (195 of 1,253) of patients. All trainees continue to provide GCRA and address barriers to care. CONCLUSION: We describe the first project to use implementation science methods to develop and deliver an innovative multicomponent implementation intervention, combining low-cost BRCA testing, comprehensive GCRA training, and practice support in Mexico. Scale-up of the GRACIAS intervention will promote risk-appropriate care, cancer prevention, and reduction in related mortality.
Assuntos
Neoplasias da Mama , Genômica , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Feminino , Genes BRCA1 , Humanos , México , Medição de RiscoRESUMO
The present study focused on the effects of a subchronic melatonin treatment on locomotor activity and cortisol plasma levels in goldfish. We compared two different administration routes: peripheral (10 microg/g body weight) versus central (1 microg/microl) injections of melatonin for 7 or 4 days, respectively. Daily locomotor activity, including both diurnal and nocturnal activities, food anticipatory activity and circulating cortisol at 11:00 (under 24 h of food deprivation and 17 h postinjection) were significantly reduced after repeated intraperitoneal injections with melatonin for 7 days, but not after intracerebroventricular treatment. Taking in mind the anoretic effect of melatonin in this species, we investigated if such feeding reduction is directly responsible for the reduction in motor activity induced by melatonin treatment. Food restriction (50%) for 10 days did not significantly modify either daily locomotor activity or plasma cortisol levels in goldfish, indicating that the peripheral action of melatonin diminishing locomotor activity in goldfish is not a direct consequence of its anoretic action. In summary, our results indicate that, as previously described in other vertebrate species, melatonin can regulate locomotor activity and cortisol levels in goldfish, suggesting a sedative effect of this hormone in this teleost.