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The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.
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OBJECTIVE: The aim of this study was to develop and validate a clinical prediction model to predict overall survival in patients with nonmetastatic, resected gallbladder cancer (GBC). BACKGROUND: Although several tools are available, no optimal method has been identified to assess survival in patients with resected GBC. METHODS: Data from a Dutch, nation-wide cohort of patients with resected GBC was used to develop a prediction model for overall survival. The model was internally validated and a cohort of Australian GBC patients who underwent resection was used for external validation. The performance of the American Joint Committee on Cancer (AJCC) staging system and the present model were compared. RESULTS: In total, 446 patients were included; 380 patients in the development cohort and 66 patients in the validation cohort. In the development cohort median survival was 22 months (median follow-up 75 months). Age, T/N classification, resection margin, differentiation grade, and vascular invasion were independent predictors of survival. The externally validated C-index was 0.75 (95%CI: 0.69-0.80), implying good discriminatory capacity. The discriminative ability of the present model after internal validation was superior to the ability of the AJCC staging system (Harrell C-index 0.71, [95%CI: 0.69-0.72) vs. 0.59 (95% CI: 0.57-0.60)]. CONCLUSION: The proposed model for the prediction of overall survival in patients with resected GBC demonstrates good discriminatory capacity, reasonable calibration and outperforms the authoritative AJCC staging system. This model can be a useful tool for physicians and patients to obtain information about survival after resection and is available from https:// gallbladderresearch.shinyapps.io/Predict_GBC_survival/.
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Neoplasias da Vesícula Biliar , Humanos , Prognóstico , Estadiamento de Neoplasias , Modelos Estatísticos , AustráliaRESUMO
BACKGROUND: The multidisciplinary management of patients with brain metastases consists of surgical resection, radiation treatment and systemic treatment. Tailoring and timing these treatment modalities is challenging. This study presents real-world data from consecutively treated patients and assesses the impact of all treatment strategies and their relation with survival. The aim is to provide new insights to improve multidisciplinary decisions towards individualized treatment strategies in patients with brain metastases. METHODS: A retrospective consecutive cohort study was performed. Patients with brain metastases were included between June 2018 and May 2020. Brain metastases of small cell lung carcinoma were excluded. Overall survival was analyzed in multivariable models. RESULTS: 676 patients were included in the study, 596 (88%) received radiotherapy, 41 (6%) awaited the effect of newly started or switched systemic treatment and 39 (6%) received best supportive care. Overall survival in the stereotactic radiotherapy group was 14 months (IQR 5-32) and 32 months (IQR 11-43) in patients who started or switched systemic treatment and initially did not receive radiotherapy. In patients with brain metastases without options for local or systemic treatment best supportive care was provided, these patients had an overall survival of 0 months (IQR 0-1). Options for systemic treatment, Karnofsky Performance Score ≥ 70 and breast cancer were prognostic for a longer overall survival, while progressive extracranial metastases and whole-brain-radiotherapy were prognostic for shorter overall survival. CONCLUSIONS: Assessing prognosis in light of systemic treatment options is crucial after the diagnosis of brain metastasis for the consideration of radiotherapy versus best supportive care.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Estudos Retrospectivos , Estudos de Coortes , Prognóstico , Neoplasias Encefálicas/cirurgia , Neoplasias Pulmonares/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.
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Povo Asiático/estatística & dados numéricos , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Esofágicas/patologia , Mucina-1/metabolismo , Neoplasias Gástricas/patologia , População Branca/estatística & dados numéricos , Idoso , Carcinoma de Células em Anel de Sinete/etnologia , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/terapia , Estudos de Coortes , Terapia Combinada , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Taxa de SobrevidaRESUMO
The authors would like to correct the error in the publication of the original article. The surname and given names of the authors were swapped in the "Acknowledgements". The corrected detail is given below.
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BACKGROUND AND AIMS: Clinicopathological characteristics of gastric cancer (GC) are changing, especially in the West with a decreasing incidence of distal, intestinal-type tumours and the corresponding increasing proportion of tumours with Laurén diffuse or WHO poorly cohesive (PC) including signet ring cell (SRC) histology. To accurately assess the behaviour and the prognosis of these GC subtypes, the standardization of pathological definitions is needed. METHODS: A multidisciplinary expert team belonging to the European Chapter of International Gastric Cancer Association (IGCA) identified 11 topics on pathological classifications used for PC and SRC GC. The topics were debated during a dedicated Workshop held in Verona in March 2017. Then, through a Delphi method, consensus statements for each topic were elaborated. RESULTS: A consensus was reached on the need to classify gastric carcinoma according to the most recent edition of the WHO classification which is currently WHO 2010. Moreover, to standardize the definition of SRC carcinomas, the proposal that only WHO PC carcinomas with more than 90% poorly cohesive cells having signet ring cell morphology have to be classified as SRC carcinomas was made. All other PC non-SRC types have to be further subdivided into PC carcinomas with SRC component (< 90% but > 10% SRCs) and PC carcinomas not otherwise specified (< 10% SRCs). CONCLUSION: The reported statements clarify some debated topics on pathological classifications used for PC and SRC GC. As such, this consensus classification would allow the generation of evidence on biological and prognostic differences between these GC subtypes.
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Carcinoma de Células em Anel de Sinete/classificação , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , HumanosAssuntos
Apêndice/diagnóstico por imagem , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Detecção Precoce de Câncer/métodos , Achados Incidentais , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics.
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Síndrome do Cabeceio/epidemiologia , Pesquisa , Animais , Epilepsia Generalizada/epidemiologia , Epilepsia Generalizada/parasitologia , Epilepsia Generalizada/prevenção & controle , Parasitologia de Alimentos , Humanos , Metagenômica , Síndrome do Cabeceio/parasitologia , Síndrome do Cabeceio/prevenção & controle , Oncocercose/epidemiologia , Oncocercose/parasitologia , Oncocercose/prevenção & controle , Simuliidae/patogenicidade , Uganda/epidemiologiaRESUMO
OBJECTIVE: The impact of childhood trauma (CT) on brain-derived neurotrophic factor (BDNF) and cytokines levels remains unclear. We investigated the association between CT and changes in BDNF and cytokines plasma levels in children. METHOD: We recruited 36 children with trauma (CT+) and 26 children without trauma (CT-). The presence of CT was based on a clinical interview and by Criteria A of DSM-IV criteria for PTSD. Blood samples were drawn from all children to assess BDNF and cytokines. ancova was performed with psychiatric symptoms and BMI as covariates to evaluate group differences in plasma levels. RESULTS: CT+ showed increased levels of BDNF and TNF-α after excluding children with history of inflammatory disease (P<0.05) when compared with those CT-. IL-12p70, IL-6, IL-8, IL-10, and IL-1ß levels were not statistically different between groups. CONCLUSION: CT+ showed increased BDNF and proinflammatory cytokines levels. The increase in BDNF levels may be an attempt to neutralize the negative effects of CT, while an increase in TNF-a levels be associated with a proinflammatory state after CT. How these changes associated with trauma relate to other biological changes and illness trajectory later in life remain to be further studied.
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Fator Neurotrófico Derivado do Encéfalo/sangue , Maus-Tratos Infantis/psicologia , Citocinas/sangue , Transtornos de Estresse Pós-Traumáticos , Fator de Necrose Tumoral alfa/sangue , Biomarcadores/sangue , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Inflamação/sangue , Masculino , Psicopatologia , Transtornos de Estresse Pós-Traumáticos/sangue , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologiaRESUMO
Following studies on the transmission of Onchocerca volvulus (Leuckart) by Simulium sanctipauli Vajime & Dunbar (Diptera, Simuliidae) in Upper Denkyira District in Ghana in 2001 and 2002 (Kutin et al., Med Vet Ent 18:167-173, 2004), further assessments were carried out in 2006 and 2013/2014 to determine whether transmission parameters had changed since community-directed ivermectin treatment (CDTI) began in 1999. There were no marked changes of the transmission intensities in 2006. Only slight, but non-significant, reductions were observed in infection rates of parous flies with larval stages (L1-L3) of O. volvulus from 44.1 % (of 1672 parous flies) in 2001/2002 to 42.1 % (506) in 2006 and from 6.5 to 5.9 % of flies carrying infective larvae in their heads. This suggested that there was an ongoing transmission in the area and the parasite reservoir in the human population was still high. Unexpectedly, further assessments conducted in October 2013 and March and October 2014 revealed that the vector S. sanctipauli had apparently disappeared and transmission had ceased, probably as a result of intensified gold mining activities along the rivers Ofin and Pra. The water of both rivers was extremely turbid, heavily loaded with suspended solids, probably preventing the development of blackfly larvae. Some breeding and biting of Simulium yahense Vajime & Dunbar was observed in a small tributary of the Pra, the Okumayemfuo, which is not affected by gold mining. However, the infection rate of flies was low, only 3.7 % of 163 parous flies were infected with first stage (L1) larvae of O. volvulus.
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Insetos Vetores/parasitologia , Inseticidas/farmacologia , Ivermectina/farmacologia , Onchocerca volvulus/fisiologia , Oncocercose/transmissão , Simuliidae/parasitologia , Animais , Cruzamento , Feminino , Geografia , Gana/epidemiologia , Humanos , Larva , Oncocercose/prevenção & controle , RiosRESUMO
OBJECTIVE: Early-onset bipolar (BP) disorder and other poor prognosis characteristics are more prevalent in patients from the United States than from the Netherlands and Germany (abbreviated as Europe). We explored the impact of parental loading for affective illness on onset and other characteristics of BP disorder. METHOD: Parental history for unipolar (UP) and bipolar (BP) depression and course of illness characteristics were obtained from self-report in adults (average age 42) with BP disorder. Illness characteristics were examined by χ2 and multinomial logistic regression in relationship to the degree of parental loading: i) both parents negative; ii) one UP disorder; iii) one with BP disorder; and iv) both affected. RESULTS: After controlling for many poor prognosis factors, compared with those from Europe, patients from the United States had more iii) one parent with BP disorder and iv) both parents affected. An early age of onset of BP disorder was independently associated with this increased parental loading for affective disorder. CONCLUSION: Parental history of BP disorder and both parents with a mood disorder were more common in the United States than Europe and were associated with an early onset of bipolar disorder and other poor prognosis characteristics. These findings deserve replication and exploration of the potential mechanisms involved and their therapeutic implications.
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Sintomas Afetivos , Transtorno Bipolar , Filho de Pais com Deficiência/psicologia , Pais/psicologia , Adulto , Sintomas Afetivos/diagnóstico , Sintomas Afetivos/etnologia , Idade de Início , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/etnologia , Transtorno Bipolar/psicologia , Comparação Transcultural , Transtorno Depressivo , Saúde da Família/etnologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Países Baixos/epidemiologia , Prevalência , Prognóstico , Escalas de Graduação Psiquiátrica , Fatores de Risco , Autorrelato , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: We discuss the rationale behind staging systems described specifically for bipolar disorders. Current applications, future directions and research gaps in clinical staging models for bipolar disorders are outlined. METHOD: We reviewed the literature pertaining to bipolar disorders, focusing on the first episode onwards. We systematically searched data on staging models for bipolar disorders and allied studies that could inform the concept of staging. RESULTS: We report on several dimensions that are relevant to staging concepts in bipolar disorder. We consider whether staging offers a refinement to current diagnoses by reviewing clinical studies of treatment and functioning and the potential utility of neurocognitive, neuroimaging and peripheral biomarkers. CONCLUSION: Most studies to date indicate that globally defined late-stage patients have a worse overall prognosis and poorer response to standard treatment, consistent with patterns for end-stage medical disorders. We believe it is possible at this juncture to speak broadly of 'early'- and 'late'-stage bipolar disorder. Next steps require further collaborative efforts to consider the details of preillness onset and intermediary stages, and how many additional stages are optimal.
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Transtorno Bipolar/diagnóstico , Comitês Consultivos , Biomarcadores/sangue , Transtorno Bipolar/sangue , Progressão da Doença , Humanos , Índice de Gravidade de Doença , Sociedades MédicasRESUMO
To prevent duodenal and ampullary cancer in familial adenomatous polyposis (FAP) patients, a diagnosis of high grade dysplasia (HGD) plays an important role in the clinical management. Previous research showed that FAP patients are both over- and undertreated after a misdiagnosis of HGD, indicating unwarranted variation. We aimed to investigate the laboratory variation in dysplasia grading of duodenal adenomas and explore possible explanations for this variation. We included data from all Dutch pathology laboratories between 1991 and 2020 by retrieving histology reports from upper endoscopy specimens of FAP patients from the Dutch nationwide pathology databank (PALGA). Laboratory variation was investigated by comparing standardized proportions of HGD. To describe the degree of variation between the laboratories a factor score was calculated. A funnel plot was used to identify outliers. A total of 3050 specimens from 25 laboratories were included in the final analyses. The mean observed HGD proportion was 9.4%. The top three HGD-diagnosing laboratories diagnosed HGD 3.9 times more often than the lowest three laboratories, even after correcting for case-mix. No outliers were identified. Moderate laboratory variation was found in HGD diagnoses of duodenal tissue of FAP patients after adjusting for case-mix. Despite the fact that no outliers were observed, there may well be room for quality improvement. Concentration of these patients in expertise centers may decrease variation. To further reduce unwarranted variation, we recommend (inter)national guidelines to become more uniform in their recommendations regarding duodenal tissue sampling and consequences of HGD diagnoses.
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Adenoma , Polipose Adenomatosa do Colo , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Neoplasias Duodenais , Humanos , Ampola Hepatopancreática/patologia , Laboratórios , Polipose Adenomatosa do Colo/diagnóstico , Adenoma/patologia , Neoplasias Duodenais/patologiaRESUMO
BACKGROUND: Colorectal, endometrial and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC). The aim of the present study was to establish whether carriers of mutations in mismatch repair genes MLH1, MSH2 or MSH6 are at increased risk of urinary bladder cancer. METHODS: Carriers and first degree relatives of 95 families with a germline mutation in the MLH1 (n=26), MSH2 (n=43), or MSH6 (n=26) gene were systematically questioned about the occurrence of carcinoma. The cumulative risk of cancer occurring before the age of 70 years (CR70) was compared to the CR70 of the general Dutch population. Microsatellite instability (MSI) testing and/or immunohistochemistry (IHC) for mismatch repair proteins was performed on bladder tumour tissue. RESULTS: Bladder cancer was diagnosed in 21 patients (90% men) from 19 Lynch syndrome families (2 MLH1, 15 MSH2, and 4 MSH6). CR70 for bladder cancer was 7.5% (95% CI 3.1% to 11.9%) for men and 1.0% (95% CI 0% to 2.4%) for women, resulting in relative risks for mutation carriers and first degree relatives of 4.2 (95% CI 2.2 to 7.2) for men and 2.2 (95% CI 0.3 to 8.0) for women. Men carrying an MSH2 mutation and their first degree relatives were at highest risks: CR70 for bladder and upper urinary tract cancer being 12.3% (95% CI 4.3% to 20.3%) and 5.9% (95% CI 0.7% to 11.1%). Bladder cancer tissue was MSI positive in 6/7 tumours and loss of IHC staining was found in 14/17 tumours, indicating Lynch syndrome aetiology. CONCLUSION: Patients with Lynch syndrome carrying an MSH2 mutation are at increased risk of urinary tract cancer including bladder cancer. In these cases surveillance should be considered.
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Neoplasias Colorretais Hereditárias sem Polipose/complicações , Predisposição Genética para Doença , Proteína 2 Homóloga a MutS/genética , Neoplasias da Bexiga Urinária/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Carcinoma/complicações , Carcinoma/genética , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/metabolismo , Mutação , Proteínas Nucleares/metabolismo , Linhagem , Fatores de Risco , Neoplasias da Bexiga Urinária/complicações , UrotélioRESUMO
As part of a continuous, standardized programme of monitoring the Leishmania vectors in German military camps in northern Afghanistan between 2007 and 2009, a detailed taxonomic analysis of the endemic sandfly fauna, as sampled using light and odour-baited traps, was conducted. Of the 10 sandfly species that were recorded, six may serve as enzootic and/or zooanthroponotic vectors of parasites causing human leishmaniasis. The use of a simple DNA-'barcoding' technique based on the mitochondrial cyt b gene, to identify the collected sandflies to species level, revealed (1) a clear discrimination between the potential vector species, (2) clustering of species within most subgenera, and (3) particularly high heterogeneity within the subgenus Paraphlebotomus (Phlebotomus alexandri being grouped with Ph. papatasi rather than with other Paraphlebotomus species). The data also indicate a high level of genetic heterogeneity within the subgenus Sergentomyia but close similarity between Sergentomyia sintoni and Sergentomyia murgabiensis. The morphological similarity of many medically important sandflies can make species identification difficult, if not impossible. The new DNA-barcoding techniques may provide powerful discriminatory tools in the future.
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Código de Barras de DNA Taxonômico/métodos , Insetos Vetores/classificação , Psychodidae/classificação , Afeganistão , Animais , Citocromos b/genética , DNA Mitocondrial/genética , Feminino , Humanos , Insetos Vetores/anatomia & histologia , Insetos Vetores/genética , Leishmaniose/transmissão , Masculino , Psychodidae/anatomia & histologia , Psychodidae/genéticaRESUMO
Although approximately 40% of all the people blinded by Onchocerca volvulus are Nigerians, almost nothing was known about the various cytospecies of the blackfly vectors present in Nigeria until 1981. The activation of the Nigerian National Onchocerciasis Control Programme in 1986 (and that programme's initiation of mass distributions of ivermectin in 1991) provided a significant stimulus to understand the biology of the Nigerian vectors but the exploration of any possible differences between the cytospecies has been hampered by a lack of accessible taxonomic information. This review attempts to satisfy that need. There are nine different cytoforms reliably recorded from Nigeria (Simulium damnosum s.s. Nile form, S. damnosum s.s. Volta form, S. sirbanum Sirba form, S. sirbanum Sudanense form, S. soubrense Beffa form, S. squamosum A, S. squamosum B, S. squamosum C and S. yahense typical form), and three more are known from surrounding countries and might be reasonably expected to occur in Nigeria. All of these cytospecies are presumed to be vectors, although there have been almost no identifications of the vectors of O. volvulus in Nigeria. The biogeographical distribution of the cytoforms is broadly similar to that known in other parts of West Africa (although many of the cytoforms remain insufficiently studied). The physico-chemical hydrology of the Nigerian breeding sites of the cytospecies does not, however, correspond to that seen elsewhere in West Africa, and it is not clear whether this might be related to differences in the cytoforms. An illustrated cytotaxonomic key is presented to facilitate and encourage future studies.
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Insetos Vetores/classificação , Simuliidae/classificação , Animais , Humanos , Insetos Vetores/genética , Nigéria/epidemiologia , Oncocercose/epidemiologia , Oncocercose/transmissão , Relações entre Irmãos , Simuliidae/genéticaRESUMO
A Bacterial Artificial Chromosome (BAC) library was made from wild-caught Simulium squamosum, which is an important vector of human onchocerciasis. The library is composed of 12,288 BACs, with an average insert size of 128 kb, and is expected to contain ~1.54 GB of cloned DNA. Random BAC-end sequencing generated over 95 kb of DNA sequence data from which putative S. squamosum gene sequences and novel repetitive DNA families were identified, including DNA transposons, retrotransposons and simple sequence repeats (SSRs). The sequence survey also provided evidence of DNA of microbial origin, and dissection of sample blackflies indicated that some of those used to prepare the library were likely to be parasitized by the mermithid Isomermis lairdi. Hybridisations with a set of three independent blackfly single-copy genes and two Wolbachia genes suggest that the library provides around 13-fold coverage of the S. squamosum genome and about 12-fold coverage of its Wolbachia endosymbiont.
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Cromossomos Artificiais Bacterianos/genética , Vetores de Doenças , Biblioteca Genômica , Oncocercose/transmissão , Simuliidae/genética , Animais , Sequência de Bases , Mapeamento Cromossômico , Clonagem Molecular , Genes de Insetos/genética , Humanos , Repetições de Microssatélites/genética , Oncocercose/parasitologia , Simuliidae/crescimento & desenvolvimento , Manejo de Espécimes/métodos , Wolbachia/genéticaRESUMO
Patients with subarachnoid hemorrhage (SAH) who are using antiplatelet drugs prior to their hemorrhage, often receive platelet transfusions to reverse antiplatelet effects prior to life-saving surgical interventions. However, little is known about the effect of platelet transfusion on patient outcome in these patients. The aim of this study is to investigate the effect of platelet transfusion on clinical outcome in patients with aneurysmal SAH (aSAH) who use antiplatelet agents. Consecutive adult patients with an aSAH admitted between 2011 and 2015 to the Academic Medical Center (Amsterdam, the Netherlands) were included. Demographic characteristics and in-hospital complications were compared and clinical outcome was assessed after six months. Multivariable logistic regression analysis was performed to correct for confounding variables. A total of 364 patients with an aSAH were included. Thirty-eight (10%) patients underwent platelet transfusion during admission. Patients receiving platelet transfusion had worse clinical outcome (modified Rankin Scale score 4-6) at six months compared to patients without platelet transfusion (65% versus 32%, odds ratio 4.0, 95% confidence interval:1.9-8.1). Multivariable logistic regression analysis showed that platelet transfusion during admission was associated with unfavorable clinical outcome after six months; adjusted for age, treatment modality, modified Fisher and WFNS on admission (adjusted odds ratio 3.3, 95% confidence interval: 1.3-8.4). In this observational study, platelet transfusion was associated with poor clinical outcome at six months after correcting for confounding influences. In aSAH patients who need surgical treatment at low risk of bleeding, the indication for platelet transfusion needs careful weighing of the risk-benefit-balance.
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Transfusão de Plaquetas/efeitos adversos , Medição de Risco , Hemorragia Subaracnóidea/cirurgia , Lesão Pulmonar Aguda/etiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/etiologia , Trombose/etiologia , Reação Transfusional/etiologia , Resultado do TratamentoRESUMO
INTRODUCTION: Tumor-targeted imaging is a promising technique for the detection of lymph node metastases (LNM) and primary tumors. It remains unclear which biomarker is the most suitable target to distinguish malignant from healthy tissue in esophageal adenocarcinoma (EAC). OBJECTIVE: We performed an immunohistochemistry study to identify viable tumor markers for tumor-targeted imaging of EAC. METHODS: We used samples from 72 patients with EAC to determine the immunohistochemical expression of ten potential tumor biomarkers for EAC (carbonic anhydrase IX [CA-IX], carcinoembryonic antigen [CEA], hepatic growth factor receptor, epidermal growth factor receptor, epithelial membrane antigen [EMA], epithelial cell adhesion molecule [EpCAM], human epidermal growth factor receptor 2 [HER-2], urokinase plasminogen activator receptor, vascular endothelial growth factor-A [VEGF-A], and VEGF receptor 2). Immunohistochemistry was performed on tissue microarrays of LNM (n = 48), primary EACs (n = 62), fibrotic tissues (n = 11), nonmalignant lymph nodes (n = 24), and normal esophageal and gastric tissues (n = 40). Tumor marker staining was scored on intensity and percentage of positive cells. RESULTS: EMA and EpCAM showed strong expression in LNM (> 95%) and primary EACs (> 95%). Significant expression was also observed for LNM and EAC using VEGF-A (85 and 92%), CEA (68 and 54%), and CA-IX (4 and 34%). The other tumor biomarkers showed expression of 0-15% for LNM and primary EAC. Except for VEGF-A, nonmalignant lymph node staining was scored as slight or absent. CONCLUSIONS: High expression rates and correlation between LNM in EAC combined with low expression rates in healthy lymph nodes and esophagus tissues were observed for EpCAM and CEA, meaning these are promising targets for tumor-targeted imaging approaches for lymph nodes in patients with EAC.