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1.
Braz. j. biol ; 84: e256190, 2024. tab, graf, mapas
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1364523

RESUMO

Particulate matter (PM) is a major air pollutant causing serious health problems. The aim of the present study was to find out concentration of PM in ambient air and its associated health risk in Haripur city, Pakistan. Twenty-three samples were taken at various educational institutes, hospitals, recreational areas and industries in Haripur city. Concentration of PM2.5 (µg/m3) and PM10 (µg/m3) was measured with Youngteng YT-HPC 3000A portable PM counter. The results revealed that values of both PM2.5 and PM10 were above the permissible limits (35 µg/m3 for PM2.5 and 150 µg/m3 for PM10) set by Environmental Protection Agency Pakistan (Pak-EPA) in all the educational institutes, hospitals, recreational areas and industries investigated. Furthermore, significant (p<0.05) variation was found in the concentration of both PM2.5 and PM10 in all the educational institutes, hospitals, recreational areas, and industries studied. The concentration of PM2.5 was positively correlated with the concentration of PM10 in all the sampling sites. Therefore, from 1-14 scale standard of health index, the values of PM2.5 and PM10 exhibited that the ambient air quality of Haripur city Pakistan is under high risk. If the regulatory authorities such as Environmental Protection Agency, Health Department and Local Government monitor PM pollution in different settings of Haripur city, then a decrease can be possible in the pollution level. The remedies that can be taken to overcome the problem of ambient air pollution such as PM are plantation of trees at the sites where there are higher levels of air pollutants and use of masks on personal protection basis along with implementation of pollution control system in industries of Hattar Industrial Estate Haripur city, Pakistan.


O material particulado (MP) é um importante poluente do ar que causa sérios problemas de saúde. O objetivo do presente estudo foi descobrir a concentração de MP no ar ambiente e sua associação com o risco à saúde na cidade de Haripur, Paquistão. Vinte e três amostras foram coletadas em várias instituições de ensino, hospitais, áreas recreativas e indústrias na cidade de Haripur. A concentração de MP2,5 (µg/m3) e MP10 (µg/m3) foi medida por meio do contador de MP portátil Youngteng YT-HPC 3000A. Os resultados revelaram que os valores de MP2,5 e MP10 estavam acima dos limites permitidos (35 µg/m3 para MP2,5 e 150 µg/m3 para MP10) estabelecidos pela Agência de Proteção Ambiental do Paquistão (Pak-EPA) em todas as instituições de ensino, hospitais, áreas recreativas e indústrias investigadas. Além disso, foi encontrada variação significativa (p < 0,05) na concentração de MP2,5 e MP10 em todos os locais estudados. A concentração de MP2,5 correlacionou-se positivamente com a concentração de MP10 em todos os locais de amostragem. Portanto, a partir da escala padrão 1-14 do índice de saúde, os valores de MP2,5 e MP10 mostraram que a qualidade do ar ambiente na cidade de Haripur, Paquistão, está sob alto risco. Se as autoridades reguladoras, como a Pak-EPA, o Departamento de Saúde e o governo local, monitorarem a poluição por MP em diferentes configurações da cidade de Haripur, pode ser que haja uma diminuição no nível de poluição. As medidas que podem ser tomadas para superar o problema da poluição do ar ambiente, como o MP, são o plantio de árvores nos locais onde há maiores níveis de poluentes atmosféricos, o uso de máscaras e a implantação de sistema de controle de poluição nas propriedades industriais de Hattar, na cidade Haripur, Paquistão.


Assuntos
Risco à Saúde Humana , Poluentes Atmosféricos , Poluição do Ar , Material Particulado , Paquistão
2.
Braz. j. biol ; 84: e253106, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345544

RESUMO

Abstract This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabe's (LM), Willmott's index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.


Resumo Este estudo teve como objetivo desenvolver e avaliar modelos baseados em dados para previsão da produção florestal em diferentes cenários de mudanças climáticas na divisão florestal Gallies do distrito de Abbottabad, Paquistão. Os modelos Random Forest (RF) e Kernel Ridge Regression (KRR) foram desenvolvidos e avaliados usando dados de produção de duas espécies (pinheiro-azul e abeto-prateado) como uma variável objetiva e dados climáticos (temperatura, umidade, precipitação e velocidade do vento) como preditivos variáveis. A precisão da previsão de ambos os modelos foi avaliada por meio de erro quadrático médio (RMSE), erro absoluto médio (MAE), coeficiente de correlação (r), erro quadrático médio relativo (RRMSE), Legates-McCabe's (LM), índice de Willmott (WI) e métricas Nash-Sutcliffe (NSE). No geral, o modelo RF superou o modelo KRR devido à sua maior precisão na previsão do rendimento florestal. O estudo recomenda fortemente que o modelo RF seja aplicado em outras regiões do país para previsão do crescimento e produtividade florestal, o que pode ajudar no manejo e planejamento futuro da produtividade florestal no Paquistão.


Assuntos
Mudança Climática , Paquistão
3.
Braz. j. biol ; 84: e253107, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355911

RESUMO

Abstract Life cycle assessment was carried out for a conventional wooden furniture set produced in Mardan division of the Khyber Pakhtunkhwa province of Pakistan during 2018-19. Primary data regarding inputs and outputs were collected through questionnaire surveys from 100 conventional wooden furniture set manufacturers, 50 in district Mardan and 50 in district Swabi. In the present study, cradle-to-gate life cycle assessment approach was applied for a functional unit of one conventional wooden furniture set. Production weighted average data were modelled in the environmental impacts modelling software i.e., SimaPro v.8.5. The results showed that textile used in sofa set, wood preservative for polishing and preventing insects attack and petrol used in generator had the highest contribution to all the environmental impact categories evaluated. Total cumulative energy demand for wooden furniture set manufactured was 30,005 MJ with most of the energy acquired from non-renewable fossil fuel resources.


Resumo A abordagem de avaliação do ciclo de vida foi realizada para um conjunto de móveis de madeira convencional produzido na divisão Mardan da província de Khyber Pakhtunkhwa do Paquistão durante 2018-19. Os dados primários sobre entradas e saídas foram coletados por meio de pesquisas por questionário de 100 fabricantes de conjuntos de móveis de madeira convencionais, 50 no distrito de Mardan e 50 no distrito de Swabi. No presente estudo, a abordagem de avaliação do ciclo de vida do berço ao portão foi aplicada para uma unidade funcional de um conjunto de móveis de madeira convencional. Os dados da média ponderada da produção foram modelados no software de modelagem de impactos ambientais, isto é, SimaPro v.8.5. Os resultados mostraram que os têxteis usados ​​no conjunto de sofás, o preservativo de madeira para polir e prevenir o ataque de insetos e a gasolina usada no gerador tiveram a maior contribuição em todas as categorias de impacto ambiental avaliadas. A demanda total acumulada de energia para o conjunto de móveis de madeira fabricado foi de 30.005 MJ, com a maior parte da energia adquirida de recursos de combustíveis fósseis não renováveis.


Assuntos
Meio Ambiente , Decoração de Interiores e Mobiliário , Paquistão
4.
Braz. j. biol ; 83: e246002, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285612

RESUMO

Abstract Economic valuation of ecosystem services is a new concept in forest management. Economic valuation provides basis for payment for ecosystem services (PES). Therefore, objective of this study was to evaluate eco-tourism and carbon stock services of the Maindam valley, District Swat, Pakistan. For the carbon stock calculation, a sample size of 155 plots of 0.1 hectare (Ha) was taken using preliminary survey at 95% confidence interval and 10% allowable error. The data for tourism services was collected from owners of all the hotels, 100 tourists and key informants of the area at 10% sampling intensity on pretested questionnaire for twenty years period (1997-2017). Results showed that Miandam valley has carbon stock worth US$ 16,306,000 while the value of eco-tourism was US$ 1,578,458 on annual basis. The results also showed that trend of tourism has drastically declined after the 9/11 incident for foreigners and locals and the situation was further deteriorated during the era of Talibanization or militancy from 2008-2011. This study recommends implementation of PES strategy at the rate of 5%, thus a total of US$ 78,922 can be earned from eco-tourism and carbon crediting in the study area annually, which could play important role in sustainable forest management.


Resumo A valoração econômica dos serviços ecossistêmicos é um novo conceito no manejo florestal. A avaliação econômica fornece base para o pagamento por serviços ecossistêmicos (PES). Portanto, o objetivo deste estudo foi avaliar o ecoturismo e os serviços de estoque de carbono do vale de Miandam, distrito Swat, Paquistão. Para o cálculo do estoque de carbono, um tamanho de amostra de 155 parcelas de 0,1 hectare (ha) foi tirado, usando pesquisa preliminar com intervalo de confiança de 95% e erro admissível de 10%. Os dados para serviços de turismo foram coletados de proprietários de todos os hotéis, 100 turistas e informantes-chave da área em 10% de intensidade de amostragem em questionário pré-testado para um período de 20 anos (1997-2017). Os resultados mostraram que o vale de Miandam tem estoque de carbono no valor de US$ 16.306.000, enquanto o valor do ecoturismo foi de US$ 1.578.458 anualmente. Os resultados também mostraram que a tendência do turismo diminuiu drasticamente para estrangeiros e locais após o incidente de 11 de Setembro, e a situação se agravou ainda mais durante a era da talibanização ou militância de 2008-2011. Este estudo recomenda a implementação da estratégia de PES na taxa de 5%, portanto um total de US$ 78.922 pode ser ganho com ecoturismo e crédito de carbono na área de estudo anualmente, o que pode desempenhar um papel importante no manejo florestal sustentável.


Assuntos
Ecossistema , Conservação dos Recursos Naturais , Paquistão , Carbono/análise , Florestas
5.
Eur Rev Med Pharmacol Sci ; 26(22): 8370-8375, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36459020

RESUMO

OBJECTIVE: The dopamine receptor 2 (DRD2) binds dopamine in both central tissues (e.g., basal ganglia, pituitary gland) and peripheral tissues (e.g., adrenal gland, kidneys, intestine) and mediates dopamine actions in cognition, emotional processing, and prolactin-secretion inhibition and stimulation, and in DRD2-/- knockout mice insulin secretion is impaired. Variants in or around the DRD2 gene have been implicated in major depressive disorder (MDD), schizophrenia, obesity, and type 2 diabetes (T2D) but not in comorbid MDD-T2D patients; DRD2 agonists (e.g., bromocriptine) are approved treatments in T2D. This study aimed to detect whether the DRD2 gene plays a role in T2D, MDD, and T2D-MDD comorbidity in Italian families. SUBJECTS AND METHODS: In 212 Italian families with T2D and MDD, we investigated the presence of linkage and linkage disequilibrium of variants in the DRD2 gene with T2D and/or MDD. A test was considered statistically significant if p was <0.05. RESULTS: We found 3 novel variants (rs6276, rs35608204, and rs1800499) significantly linked to and/or associated with the risk of T2D and 1 novel variant (rs112646785) significantly linked and associated to the comorbidity of T2D and MDD. CONCLUSIONS: This is the first study to link and associate DRD2 variants with the comorbidity of T2D and MDD.

6.
Methods ; 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36436760

RESUMO

Context Sleep screening is an important tool for both healthcare and neuroscientific research. Automatic sleep scoring is an alternative to the time-consuming gold-standard manual scoring procedure. Objective Recently there have seen promising results on automatic stage scoring by extracting spatio-temporal features via deep neural networks from electroencephalogram (EEG). However, such methods fail to consistently yield good performance due to a missing piece in data representation: the medical criterion of the sleep scoring task on top of EEG features. We argue that capturing stage-specific features that satisfy the criterion of sleep medicine is non-trivial for automatic sleep scoring. Method This paper considers two criteria: Transient stage marker and Overall profile of EEG features, then we propose a physiologically meaningful framework for sleep stage scoring via mixed deep neural networks. The framework consists of two sub-networks: feature extraction networks, constructed in consideration of the physiological characteristics of sleep, and an attention-based scoring decision network. Moreover, we quantize the framework for potential use under an IoT setting. Results For proof-of-concept, the performance of the proposed framework is demonstrated by introducing multiple sleep datasets with the largest comprising 42,560 hours recorded from 5,793 subjects. From the experiment results, the proposed method achieves a competitive stage scoring performance, especially for Wake, N2, and N3, with higher F1 scores of 0.92, 0.86, and 0.88, respectively. Moreover, the feasibility analysis of framework quantization provides a potential for future implementation in the edge computing field and clinical settings.

7.
Blood ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36399701

RESUMO

Graft vs. host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, Interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating safety and efficacy of a novel recombinant human Interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD (NCT02406651; https://clinicaltrials.gov/ct2/show/NCT02406651). The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. 19/27 patients (70%; 80% CI: 56-79) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders exhibited a distinct fecal microbiota composition characterized by expansion of commensal anaerobes, which correlated with increased overall microbial α-diversity, suggesting improvement of GVHD-associated dysbiosis. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This work was supported by funding from Evive Biotech., The Society of Memorial Sloan Kettering Cancer Center, and the National Institutes of Health.

8.
Mymensingh Med J ; 31(4): 1057-1067, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36189552

RESUMO

The outcomes of acute coronary syndromes (ACS) vary internationally, given regional differences in patient co-morbidities, access to health care, interventional procedures and adherence to guideline-based management practices. This study aimed to identify the predictors of mortality from a large ACS registry of patients admitted to a tertiary care cardiac centre in Dhaka, Bangladesh. This was a hospital record based retrospective cross sectional observational study that included all patients presenting with ACS to Ibrahim Cardiac Hospital and Research Institute, Dhaka, Bangladesh from January 2013 to December 2013. Data were collected from cardiac catheterization laboratory database and hospital discharge records. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 16.0. A p value <0.05 was considered statistically significant. Ethical approval was obtained by Institutional Review Board of the hospital. A total of 1914 ACS patients were studied: 39.8% presented with ST-elevation myocardial infarction (STEMI), 39.7% with non-ST-elevation myocardial infarction (NSTEMI) and 20.5% with unstable angina (UA). There were 146 in-hospital deaths (7.6%). Mortality was highest among STEMI patients (10.5%), followed by NSTEMI (8.1%) and UA (1.03%). The mean age of expired patients was significantly higher than that of those who survived (64.82±12.14 years vs. 57.32±11.99 years; p<0.001). Male patients were 71.4%, with no significant gender differences observed between expired and surviving groups. Age >50 years {odds ratio (OR) 2.56, p=0.005}, chronic kidney disease (CKD) (OR 2.1, p<0.001), shock (OR 16.82, p<0.001), left ventricular failure (LVF) (OR 2.43, p<0.001) and STEMI (OR 1.92, p=0.002) were independent predictors of mortality among ACS patients. Although diabetes per se was not associated with mortality (OR 1.3; 95% CI=0.89-1.91; p=0.169), uncontrolled diabetes defined as HbA1c levels ≥7.5% had significant risk of mortality (OR 51.4, p<0.001). ACS patients who did not undergo angiography (OR 16.4; p<0.001) or PCI (OR 18.9; p<0.001) had greater risk of mortality. ACS patients complicated with shock, LVF, uncontrolled diabetes and CKD had increased risk of in-hospital mortality. Improved outcomes may be likely with prompt angiography and PCI during index admission. This study is a preliminary initiative, and prospective multi-centre registries with nation-wide involvement are warranted.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Infarto do Miocárdio com Supradesnível do Segmento ST , Síndrome Coronariana Aguda/terapia , Idoso , Angina Instável , Bangladesh/epidemiologia , Estudos Transversais , Hemoglobina A Glicada , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
9.
Med Eng Phys ; 108: 103876, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36195370

RESUMO

Wearable human activity recognition systems (HAR) using inertial measurement units (IMU) play a key role in the development of smart rehabilitation systems. Training of a HAR system with patient data is costly, time-consuming, and difficult for the patients. This study proposes a new scheme for the optimal design of HARs with minimal involvement of the patients. It uses healthy subject data for optimal design for a set of activities used in the rehabilitation of PD1 patients. It maintains its performance for individual PD subjects using a single session data collection and an adaptation procedure. In the optimal design, several classifiers (i.e. NM, k-NN, MLP with RBF as a hidden layer, and multistage RBF SVM) were investigated. Features were signal-based in the time, frequency, and time-frequency domains. Double-stage feature extraction by PCA and fisher technique was used. The optimal design reached a recall of 95% on healthy subjects using only two sensors on the left thigh and forearm. Implementing the adaptation procedure on two PD subjects, the performance was maintained above 80%. Post analysis on the performance of the adapted HAR showed a slight drop in precision (above 87% to above 81%) for activities that was performed in sitting condition.


Assuntos
Telerreabilitação , Dispositivos Eletrônicos Vestíveis , Algoritmos , Atividades Humanas , Humanos
10.
Histopathology ; 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221864

RESUMO

Squamous cell carcinoma (SCC) is the most common malignant tumour of the penis. The 2022 WHO classification reinforces the 2016 classification and subclassifies precursor lesions and tumours into human papillomavirus (HPV)-associated and HPV-independent types. HPV-associated penile intraepithelial neoplasia (PeIN) is a precursor lesion of invasive HPV- associated SCC, whereas differentiated PeIN is a precursor lesion of HPV-independent SCC. Block-type positivity of p16 immunohistochemistry is the most practical daily utilised method to separate HPVassociated from HPVindependent penile SCC. If this is not feasible, the term SCC, not otherwise specified (NOS) is appropriate. Certain histologies that were previously classified as "subtypes" are now grouped, and coalesced as "patterns", under the rubric of usual type SCC and verrucous carcinoma (e.g. usual-type SCC includes pseudohyperplastic and acantholytic/pseudoglandular carcinoma, and carcinoma cuniculatum is included as a pattern of verrucous carcinoma). If there is an additional component of the usual type of invasive SCC (formerly termed hybrid histology), the tumour would be a mixed carcinoma (e.g. carcinoma cuniculatum or verrucous carcinoma with usual invasive SCC); in such cases, reporting of the relative percentages in mixed tumours may be useful. The consistent use of uniform nomenclature and reporting of percentages will inform the refinement of future reporting classification schemes and guidelines/recommendations. The classification of scrotal tumours is provided for the first time in the fifth edition of the WHO Blue book, and it follows the schema of penile cancer classification for both precursor lesions and the common SCC of the scrotum. Basal cell carcinoma of the scrotum may have a variable clinical course and finds a separate mention.

11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 1113-1116, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36085834

RESUMO

Cancer is one of the deadliest diseases worldwide. Accurate diagnosis and classification of cancer subtypes are indispensable for effective clinical treatment. Promising results on automatic cancer subtyping systems have been published recently with the emergence of various deep learning methods. However, such automatic systems often overfit the data due to the high dimensionality and scarcity. In this paper, we propose to investigate automatic subtyping from an unsupervised learning perspective by directly constructing the underlying data distribution itself, hence sufficient data can be generated to alleviate the issue of overfitting. Specifically, we bypass the strong Gaussianity assumption that typically exists but fails in the unsupervised learning subtyping literature due to small-sized samples by vector quantization. Our proposed method better captures the latent space features and models the cancer subtype manifestation on a molecular basis, as demonstrated by the extensive experimental results.


Assuntos
Neoplasias , Transcriptoma , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Distribuição Normal , Aprendizado de Máquina não Supervisionado
12.
World J Gastroenterol ; 28(32): 4620-4634, 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36157930

RESUMO

BACKGROUND: Pancreatic cancer is the most aggressive cancer type. Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients. AIM: To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation (ID: C5EOSEW5050ESA trademarked as Nuva-staticTM), and gemcitabine combination on pancreatic xenograft model. METHODS: Mice were randomly divided into six groups of 6 mice each (n = 6) and given different treatments for 28 d. The study design consisted of a 2 x 3 factorial treatment structure, with gemcitabine (yes/no) by oral (at 1200 and 400 mg/kg per day). Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice. C5EOSEW5050ESA (200 or 400 mg/kg per day) was administered orally, while gemcitabine (10 mg/kg per 3 d) was given intraperitoneally either alone or in combination treatment. Histopathological analyses of vital organs, tumour tissues, and incidence of lethality were analysed. Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67, respectively. RESULTS: No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group. C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment. Remarkably, a comparably greater response in a reduction in tumour growth, Ki-67 protein expression, and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents. CONCLUSION: These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment. Thus, this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.


Assuntos
Orthosiphon , Neoplasias Pancreáticas , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Desoxicitidina/análogos & derivados , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Xenoenxertos , Humanos , Antígeno Ki-67/metabolismo , Camundongos , Camundongos Nus , Necrose , Orthosiphon/metabolismo , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Prehosp Emerg Care ; : 1-7, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36053543

RESUMO

OBJECTIVE: The Hunter-8 prehospital stroke scale predicts large vessel occlusion in hyperacute ischemic stroke patients (LVO) at hospital admission. We wished to test its performance in the hands of paramedics as part of a prehospital triage algorithm. We aimed to determine (a) the proportion of patients identified by the Hunter-8 algorithm, receiving reperfusion therapies, (b) whether a call to stroke team improved this, and (c) performance for LVO detection using an expanded LVO definition. METHODS: A prehospital workflow combining pre-morbid functional status, time from symptom onset, and the Hunter-8 scale was implemented from July 2019. A telephone call to the stroke team was prompted for potential treatment candidates. Classic LVO was defined as a proximal middle cerebral artery (MCA-M1), terminal internal carotid artery, or tandem occlusion. Extended LVO added proximal MCA-M2 and basilar occlusions. RESULTS: From July 2019 to April 2021, there were 363 Hunter-8 activations, 320 analyzed: 181 (56.6%) had confirmed ischemic strokes, 13 (4.1%) transient ischemic attack, 91 (28.5%) stroke mimics, and 35 (10.9%) intracranial hemorrhage. Fifty-two patients (16.3%) received reperfusion therapies, 35 with Hunter-8 ≥ 8. The stroke doctor changed the final destination for 76 patients (23.7%), and five received reperfusion therapies. The AUCs for classic and extended LVO were 0.73 (95% CI 0.66-0.79) and 0.72 (95% CI 0.65-0.77), respectively. CONCLUSION: The Hunter-8 workflow resulted in 28.7% of confirmed ischemic stroke patients receiving reperfusion therapies, with no secondary transfers to the comprehensive stroke center. The role of communication with stroke team needs to be further explored.

14.
Blood ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36095841

RESUMO

The standard primary treatment for acute graft vs host disease (GVHD) requires prolonged, high dose systemic corticosteroids (SCS) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low risk (LR) GVHD that is very likely to respond to SCS. We hypothesized that itacitinib, a selective JAK1 inhibitor, would effectively treat LR GVHD without SCS. We treated 70 patients with LR GVHD in a multicenter, phase 2 trial (NCT03846479) with 28 days of itacitinib 200 mg/day (responders could receive a second 28-day cycle) and compared their outcomes to 140 contemporaneous, matched control patients treated with SCS. More patients responded to itacitinib within 7 days (81% vs 66%, p=0.02) and response rates at day 28 were very high for both groups (89% vs 86%, p=0.67) with few symptomatic flares (11% vs 12%, p=0.88). Fewer itacitinib treated patients developed a serious infection within 90 days (27% vs 42%, p=0.04) due to fewer viral and fungal infections. Grade ≥3 cytopenias were similar between groups except for less severe leukopenia with itacitinib (16% vs 31%, p=0.02). No other grade ≥3 adverse events occurred in >10% of itacitinib treated patients. There were no significant differences between groups at 1-year for non-relapse mortality (4% vs 11%, p=0.21), relapse (18% vs 21%, p=0.64), chronic GVHD (28% vs 33%, p=0.33) or survival (88% vs 80%, p=0.11). Itacitinib monotherapy seems to be a safe and effective alternative to SCS treatment for LR GVHD that deserves further investigation.

15.
Cell ; 185(20): 3705-3719.e14, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36179667

RESUMO

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteroides , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Meropeném , Camundongos , Mucinas/metabolismo , Muco/metabolismo , Polissacarídeos/metabolismo , Xilose
16.
Adv Mater ; 34(47): e2206884, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36134538

RESUMO

Solution-processed photodetectors based on colloidal quantum dots (CQDs) are promising candidates for short-wavelength infrared light sensing applications. Present-day CQD photodetectors employ a CQD active layer sandwiched between carrier-transport layers in which the electron-transport layer (ETL) is composed of metal oxides. Herein, a new class of ETLs is developed using n-type CQDs, finding that these benefit from quantum-size effect tuning of the band energies, as well as from surface ligand engineering. Photodetectors operating at 1450 nm are demonstrated using CQDs with tailored functionalities for each of the transport layers and the active layer. By optimizing the band alignment between the ETL and the active layer, CQD photodetectors that combine a low dark current of ≈1 × 10-3 mA cm-2 with a high external quantum efficiency of ≈66% at 1 V are reported, outperforming prior reports of CQD photodetectors operating at >1400 nm that rely on metal oxides as ETLs. It is shown that stable CQD photodetectors rely on well-passivated CQDs: for ETL CQDs, a strongly bound organic ligand trans-4-(trifluoromethyl)cinnamic acid (TFCA) provides improved passivation compared to the weakly bound inorganic ligand tetrabutylammonium iodide (TBAI). TFCA suppresses bias-induced ion migration inside the ETL and improves the operating stability of photodetectors by 50× compared to TBAI.

17.
Sci Rep ; 12(1): 16343, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175472

RESUMO

Multifocal microscopy enables high-speed three-dimensional (3D) volume imaging by using a multifocal grating in the emission path. This grating is typically designed to afford a uniform illumination of multifocal subimages for a single emission wavelength. Using the same grating for multicolor imaging results in non-uniform subimage intensities in emission wavelengths for which the grating is not designed. This has restricted multifocal microscopy applications for samples having multicolored fluorophores. In this paper, we present a multicolor multifocal microscope implementation which uses a Spatial Light Modulator (SLM) as a single multifocal grating to realize near-uniform multifocal subimage intensities across multiple wavelength emission bands. Using real-time control of an in-situ-optimized SLM implemented as a multifocal grating, we demonstrate multicolor multifocal 3D imaging over three emission bands by imaging multicolored particles as well as Escherichia coli (E. coli) interacting with human liver cancer cells, at [Formula: see text] multicolor 3D volumes per second acquisition speed. Our multicolor multifocal method is adaptable across SLM hardware, emission wavelength band locations and number of emission bands, making it particularly suited for researchers investigating fast processes occurring across a volume where multiple species are involved.


Assuntos
Infecções por Escherichia coli , Microscopia , Escherichia coli , Corantes Fluorescentes , Humanos , Iluminação
18.
Nano Lett ; 22(16): 6802-6807, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35969869

RESUMO

Infrared photodetection enables depth imaging techniques such as structured light and time-of-flight. Traditional photodetectors rely on silicon (Si); however, the bandgap of Si limits photodetection to wavelengths shorter than 1100 nm. Photodetector operation centered at 1370 nm benefits from lower sunlight interference due to atmospheric absorption. Here, we report 1370 nm-operating colloidal quantum dot (CQD) photodetectors and evaluate their outdoor performance. We develop a surface-ligand engineering strategy to tune the electronic properties of each CQD layer and fabricate photodetectors in an inverted (PIN) architecture. The strategy enables photodetectors with an external quantum efficiency of 75% and a low dark current (1 µA/cm2). Outdoor testing demonstrates that CQD-based photodetectors combined with a 10 nm-line width bandpass filter centered at 1370 nm achieve over 2 orders of magnitude (140× at incident intensity 1 µW/cm2) higher signal-to-background ratio than do Si-based photodetectors that use an analogous bandpass filter centered at 905 nm.

19.
Transplant Cell Ther ; 28(10): 681-693, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35853610

RESUMO

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin (ATG), grade 3-4 aGvHD (28% versus 39%, P = .001), stage 3-4 lower gastrointestinal (GI) tract aGvHD (14% versus 21%, P = .01), and chronic GI GvHD (21% versus 31%, P = .006) were less common after Haplo/PTCy transplantation. In patients with grade 2-4 aGvHD, cGvHD rate after Haplo/PTCY was also lower (hazard ratio [HR] = .4, P < .001) in comparison with MUD/conventional transplantation without ATG in the nonmyeloablative conditioning setting. Irrespective of the use of ATG, non-relapse mortality rate was lower (HR = .6, P = .01) after Haplo/PTCy transplantation, except for transplants that were from a female donor into a male recipient. In patients with cGvHD, irrespective of ATG use, Haplo/PTCy transplantation had lower non-relapse mortality rates (HR = .6, P = .04). Mortality rate was higher (HR = 1.6, P = .03) during, but not after (HR = .9, P = .6) the first 6 months after cGvHD diagnosis. Our results suggest that PTCy-based GvHD prophylaxis mitigates the development of GI GvHD and may translate into lower GvHD-related non-relapse mortality rate.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Estudos Retrospectivos
20.
Transplant Cell Ther ; 28(10): 695.e1-695.e10, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35902049

RESUMO

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is increasing in patients undergoing HLA-matched sibling (MSD) or unrelated (MUD) donor hematopoietic cell transplantation (HCT), but data about its comparative efficacy against the traditional GVHD prophylaxis are scarce. Two broad questions assessed in this study were (a) comparison of PTCy-based GVHD prophylaxis versus Tac/MTX (without ATG) in the MSD and (b) comparison of PTCy-based GVHD prophylaxis versus Tac/MTX (with ATG) in the MUD group. This retrospective single-center study analyzed the outcomes of 964 patients who received Tac/MTX (n = 578) versus PTCy-based (n = 386) GVHD prophylaxis. All MUD recipients in the Tac/MTX group also received ATG; thus separate analyses were conducted for MSD (n = 412) and MUD (n = 552) cohorts. In the MUD cohort, 306 patients received Tac/MTX/ATG and 246 received PTCy-based GVHD prophylaxis. In the MSD cohort, 272 received Tac/MTX and 140 received PTCy-based prophylaxis. Both PTCy groups included somewhat older patients than the Tac/MTX groups and more patients had myeloid malignancy (85%-90% versus 59%-64%, respectively). A majority of patients in all groups received myeloablative conditioning and peripheral blood graft. Both PTCy groups had a significantly delayed neutrophil engraftment, higher risk of hemorrhagic cystitis, and higher risk of bacterial infections than the Tac/MTX groups. The risks of viral infections and related deaths were significantly higher in Tac/MTX group in the MUD cohort. In multivariate analysis, the risk of grade III-IV acute GVHD was similar in PTCy and Tac/MTX groups in both MSD and MUD cohorts, but the risk of chronic GVHD was significantly lower with PTCy in the MSD cohort. PTCy was associated with a significantly lower risk of non-relapse mortality and better progression-free survival in the MUD. PTCy was associated with improved GVHD-free relapse-free survival in both MSD and MUD groups. Our data suggest a benefit of using PTCy-based GVHD prophylaxis in both MSD (versus Tac/MTX) and MUD (versus Tac/MTX/ATG) HCT.


Assuntos
Doença Enxerto-Hospedeiro , Tacrolimo , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Tacrolimo/uso terapêutico
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