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1.
Immunity ; 56(12): 2816-2835.e13, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38091953

RESUMO

Cancer cells can evade natural killer (NK) cell activity, thereby limiting anti-tumor immunity. To reveal genetic determinants of susceptibility to NK cell activity, we examined interacting NK cells and blood cancer cells using single-cell and genome-scale functional genomics screens. Interaction of NK and cancer cells induced distinct activation and type I interferon (IFN) states in both cell types depending on the cancer cell lineage and molecular phenotype, ranging from more sensitive myeloid to less sensitive B-lymphoid cancers. CRISPR screens in cancer cells uncovered genes regulating sensitivity and resistance to NK cell-mediated killing, including adhesion-related glycoproteins, protein fucosylation genes, and transcriptional regulators, in addition to confirming the importance of antigen presentation and death receptor signaling pathways. CRISPR screens with a single-cell transcriptomic readout provided insight into underlying mechanisms, including regulation of IFN-γ signaling in cancer cells and NK cell activation states. Our findings highlight the diversity of mechanisms influencing NK cell susceptibility across different cancers and provide a resource for NK cell-based therapies.


Assuntos
Neoplasias Hematológicas , Neoplasias , Humanos , Células Matadoras Naturais , Neoplasias/genética , Apresentação de Antígeno , Genômica , Citotoxicidade Imunológica/genética , Linhagem Celular Tumoral
2.
Sensors (Basel) ; 23(6)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36991755

RESUMO

The exponentially growing concern of cyber-attacks on extremely dense underwater sensor networks (UWSNs) and the evolution of UWSNs digital threat landscape has brought novel research challenges and issues. Primarily, varied protocol evaluation under advanced persistent threats is now becoming indispensable yet very challenging. This research implements an active attack in the Adaptive Mobility of Courier Nodes in Threshold-optimized Depth-based Routing (AMCTD) protocol. A variety of attacker nodes were employed in diverse scenarios to thoroughly assess the performance of AMCTD protocol. The protocol was exhaustively evaluated both with and without active attacks with benchmark evaluation metrics such as end-to-end delay, throughput, transmission loss, number of active nodes and energy tax. The preliminary research findings show that active attack drastically lowers the AMCTD protocol's performance (i.e., active attack reduces the number of active nodes by up to 10%, reduces throughput by up to 6%, increases transmission loss by 7%, raises energy tax by 25%, and increases end-to-end delay by 20%).

3.
Blood ; 135(9): 597-609, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-31830245

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy has proven effective in relapsed and refractory B-cell malignancies, but resistance and relapses still occur. Better understanding of mechanisms influencing CAR T-cell cytotoxicity and the potential for modulation using small-molecule drugs could improve current immunotherapies. Here, we systematically investigated druggable mechanisms of CAR T-cell cytotoxicity using >500 small-molecule drugs and genome-scale CRISPR-Cas9 loss-of-function screens. We identified several tyrosine kinase inhibitors that inhibit CAR T-cell cytotoxicity by impairing T-cell signaling transcriptional activity. In contrast, the apoptotic modulator drugs SMAC mimetics sensitized B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma cells to anti-CD19 CAR T cells. CRISPR screens identified death receptor signaling through FADD and TNFRSF10B (TRAIL-R2) as a key mediator of CAR T-cell cytotoxicity and elucidated the RIPK1-dependent mechanism of sensitization by SMAC mimetics. Death receptor expression varied across genetic subtypes of B-cell malignancies, suggesting a link between mechanisms of CAR T-cell cytotoxicity and cancer genetics. These results implicate death receptor signaling as an important mediator of cancer cell sensitivity to CAR T-cell cytotoxicity, with potential for pharmacological targeting to enhance cancer immunotherapy. The screening data provide a resource of immunomodulatory properties of cancer drugs and genetic mechanisms influencing CAR T-cell cytotoxicity.


Assuntos
Citotoxicidade Imunológica/imunologia , Resistencia a Medicamentos Antineoplásicos/imunologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Linfócitos T Citotóxicos/imunologia , Linhagem Celular Tumoral , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Testes Imunológicos de Citotoxicidade/métodos , Humanos , Ativação Linfocitária/imunologia , Linfoma Difuso de Grandes Células B/imunologia , Receptores de Antígenos Quiméricos
4.
Am J Hematol ; 97(5): 562-573, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35132679

RESUMO

There are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686). Patients received four 21-day cycles of RsqVd and could then receive either another 4 cycles of RsqVd or undergo autologous stem cell transplant. Postinduction/posttransplant, patients received lenalidomide maintenance, with bortezomib included for high-risk patients. The primary endpoint was overall response rate (ORR) after 4 cycles of RsqVd. Eighty-eight patients were enrolled and 84 treated across the two studies; median age was 64.7 (CTI study) and 60.0 years (DFCI study), and 59% and 57% had stage II-III disease. Pooled ORR after 4 cycles in evaluable patients was 93.5%, including 48.1% complete or very good partial responses (CTI study: 91.9%, 59.5%; DFCI study: 95.0%, 37.5%), and in the all-treated population was 85.7% (44.0%). Patients received a median of 4 (CTI study) and 8 (DFCI study) RsqVd cycles; 60% and 31% of patients (CTI study) and 33% and 51% of patients (DFCI study) underwent transplant or received further RsqVd induction, respectively. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Humanos , Quimioterapia de Indução , Lenalidomida/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estudos Prospectivos
5.
Sensors (Basel) ; 21(5)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801361

RESUMO

This paper presents an algorithm for segmentation and shape analysis of erythrocyte images collected using an optical microscope. The main objective of the proposed approach is to compute statistical object values such as the number of erythrocytes in the image, their size, and width to height ratio. A median filter, a mean filter and a bilateral filter were used for initial noise reduction. Background subtraction using a rolling ball filter removes background irregularities. Combining the distance transform with the Otsu and watershed segmentation methods allows for initial image segmentation. Further processing steps, including morphological transforms and the previously mentioned segmentation methods, were applied to each segmented cell, resulting in an accurate segmentation. Finally, the noise standard deviation, sensitivity, specificity, precision, negative predictive value, accuracy and the number of detected objects are calculated. The presented approach shows that the second stage of the two-stage segmentation algorithm applied to individual cells segmented in the first stage allows increasing the precision from 0.857 to 0.968 for the artificial image example tested in this paper. The next step of the algorithm is to categorize segmented erythrocytes to identify poorly segmented and abnormal ones, thus automating this process, previously often done manually by specialists. The presented segmentation technique is also applicable as a probability map processor in the deep learning pipeline. The presented two-stage processing introduces a promising fusion model presented by the authors for the first time.


Assuntos
Algoritmos , Microscopia , Eritrócitos , Processamento de Imagem Assistida por Computador
6.
Chem Res Toxicol ; 33(6): 1292-1311, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31884781

RESUMO

The optoelectrical and magnetic characteristics of naturally existing iron-based nanostructures, especially hematite and magnetite nanoparticles (H-NPs and M-NPs), gained significant research interest in various applications, recently. The main purpose of this Review is to provide an overview of the utilization of H-NPs and M-NPs in various environmental remediation. Iron-based NPs are extensively explored to generate green energy from environmental friendly processes such as water splitting and CO2 conversion to hydrogen and low molecular weight hydrocarbons, respectively. The latter part of the Review provided a critical overview to use H-NPs and M-NPs for the detection and decontamination of inorganic and organic contaminants to counter the environmental pollution and toxicity challenge, which could ensure environmental sustainability and hygiene. Some of the future perspectives are comprehensively presented in the final portion of the script, optimiztically, and it is supported by some relevant literature surveys to predict the possible routes of H-NPs and M-NPs modifications that could enable researchers to use these NPs in more advanced environmental applications. The literature collection and discussion on the critical assessment of reserving the environmental sustainability challenges provided in this Review will be useful not only for experienced researchers but also for novices in the field.


Assuntos
Recuperação e Remediação Ambiental , Compostos Férricos , Óxido Ferroso-Férrico , Nanoestruturas , Poluição Ambiental/prevenção & controle , Compostos Férricos/química , Óxido Ferroso-Férrico/química , Nanoestruturas/química , Energia Renovável
7.
Int J Cancer ; 144(6): 1356-1366, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30125350

RESUMO

Renal cell cancer (RCC) has become a prototype example of the extensive intratumor heterogeneity and clonal evolution of human cancers. However, there is little direct evidence on how the genetic heterogeneity impacts on drug response profiles of the cancer cells. Our goal was to determine how genomic clonal evolution impacts drug responses. Finding from our study could help to define the challenge that clonal evolution poses on cancer therapy. We established multiple patient-derived cells (PDCs) from different tumor regions of four RCC patients, verified their clonal relationship to each other and to the uncultured tumor tissue by genome sequencing. Furthermore, comprehensive drug-sensitivity testing with 460 oncological drugs was performed on all PDC clones. The PDCs retained many cancer-specific copy number alterations and mutations in driver genes such as VHL, PBRM1, PIK3C2A, KMD5C and TSC2 genes. The drug testing highlighted vulnerability in the PDCs toward approved RCC drugs, such as the mTOR-inhibitor temsirolimus, but also novel sensitivities were uncovered. The individual PDC clones from different tumor regions in a patient showed distinct drug-response profiles, suggesting that genomic heterogeneity contributes to the variability in drug responses. Studies of multiple PDCs from a patient with cancer are informative for elucidating cancer heterogeneity and for the determination on how the genomic evolution is manifested in cancer drug responsiveness. This approach could facilitate tailoring of drugs and drug combinations to individual patients.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Evolução Clonal , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Renais/tratamento farmacológico , Células 3T3 , Adulto , Idoso , Animais , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Técnicas de Cocultura , Variações do Número de Cópias de DNA , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Cultura Primária de Células , Células Tumorais Cultivadas
8.
Parasitology ; 146(2): 129-141, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30068403

RESUMO

Parasites reside inside or outside their hosts and get host nutrition and blood. Here, we have emphasized economic losses in cattle caused by parasitic diseases due to ecto- and endo- parasites (flies, ticks, mites and helminths). We have outlined different methods/models including economic evaluation techniques and dynamic analysis as a major class, used for the calculation of economic losses caused by parasites in cattle. According to already conducted studies, a decrease in production is mentioned in quantity and percentage while financial losses are expressed in the form of account with respect to per head, herd or for the specific study area. The parasites cause the reduced production and financial losses due to control, treatment and mortality costs. We calculated the average decrease in milk production and organ condemnation as 1.16 L animal-1 day-1 and 12.95%, respectively, from overall cattle parasitic infections. Moreover, the average calculated financial and percentage losses were US$ 50.67 animal-1 year-1 and 17.94%, respectively. Economically important parasitic diseases mentioned here are caused by specific spp. of protozoans and helminths according to data collected from the literature. Protozoan diseases include tick-borne diseases, coccidiosis, neosporosis, trypanosomiasis and cryptosporidiosis. Losses due to tick-borne infections were encountered for decreased milk production, mortality, treatment and control. Losses from coccidiosis were due to decreased weight gain, treatment costs and mortality. While abortion losses were encountered in neosporosis. Trypanosomiasis caused losses due to a decrease in milk yield. Moreover, only diagnostic (conventional or molecular techniques) cost was taken into account for cryptosporidiosis. Economically important nematode parasites are Oesophagostomum spp., Cooperia spp., Trichostrongylus spp., Strongyloides spp., Ostertagia spp. and Haemonchus placei. Due to the zoonotic importance of echinococcosis, Echinococcus granulosus is the most economically important cestode parasite. Losses caused by echinococcosis were due to organ condemnation, carcass weight loss and decreases hide value, milk production and fecundity. While, fascioliasis is one of the most economically important trematodal disease, which causes cirrhosis of the liver due to parasite migration, and thus, the organ becomes inedible. So, it would be helpful for farmers and researchers to approach these methods/models for calculation of parasitic losses and should adopt suitable measures to avoid long-term economic losses.


Assuntos
Doenças dos Bovinos/economia , Ectoparasitoses/veterinária , Modelos Econômicos , Doenças Parasitárias em Animais/economia , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Análise Custo-Benefício , Ectoparasitoses/economia , Helmintíase Animal/economia , Software , Processos Estocásticos
9.
Sensors (Basel) ; 19(3)2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30744032

RESUMO

Hard exudates are one of the most characteristic and dangerous signs of diabetic retinopathy. They can be marked during the routine ophthalmological examination and seen in color fundus photographs (i.e., using a fundus camera). The purpose of this paper is to introduce an algorithm that can extract pathological changes (i.e., hard exudates) in diabetic retinopathy. This was a retrospective, nonrandomized study. A total of 100 photos were included in the analysis-50 sick and 50 normal eyes. Small lesions in diabetic retinopathy could be automatically diagnosed by the system with an accuracy of 98%. During the experiments, the authors used classical image processing methods such as binarization or median filtration, and data was read from the d-Eye sensor. Sixty-seven patients (39 females and 28 males with ages ranging between 50 and 64) were examined. The results have shown that the proposed solution accuracy level equals 98%. Moreover, the algorithm returns correct classification decisions for high quality images and low quality samples. Furthermore, we consider taking retina photos using mobile phones rather than fundus cameras, which is more practical. The paper presents an innovative approach. The results are introduced and the algorithm is described.


Assuntos
Técnicas de Diagnóstico Oftalmológico/instrumentação , Exsudatos e Transudatos/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Retina/diagnóstico por imagem , Telemedicina/instrumentação , Algoritmos , Retinopatia Diabética/diagnóstico por imagem , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
East Mediterr Health J ; 23(3): 131-142, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28493259

RESUMO

The Atlas project on substance use is a global WHO project that aims to collect and disseminate data on resources for the prevention and treatment of substance use disorders. Information on resources available in the WHO Eastern Mediterranean Region was first published in 2012. The Atlas questionnaire was updated in 2014 and data were collected in all WHO Member States. All countries of the Region submitted the Atlas questionnaire. This report presents the latest key information on resources for the prevention and treatment of substance use disorders in the Eastern Mediterranean Region based on the responses of the countries to the questionnaire. Current estimates show that the burden attributable to drug use disorders in the Region is high. Health system resources for the prevention and treatment of substance use disorders vary across countries, but are generally still insufficient to provide adequate care and treatment for people with these disorders. Countries need to strengthen prevention and treatment of substance use disorders, particularly by increasing coverage of treatment interventions.


Assuntos
Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Humanos , Região do Mediterrâneo/epidemiologia , Inquéritos e Questionários , Organização Mundial da Saúde
12.
East Mediterr Health J ; 23(3): 129-130, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30378673

RESUMO

Substance use is a public health problem worldwide. According to United Nations Office on Drugs and Crime (UNODC) estimates, there has been an increase of more than 10% over recent years in cannabis use in 9 countries in the Region; while the prevalence of opiate use in Afghanistan, the Islamic Republic of Iran and Pakistan is among the highest in the world. The estimated prevalence for drug dependence in the North Africa and Middle East region is 0.29%, which is 1.3 times higher than the global prevalence. Emergencies and civil unrest are known as important factors in the exacerbation of the situation.


Assuntos
Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Fortalecimento Institucional , Humanos , Região do Mediterrâneo/epidemiologia , Prevalência , Saúde Pública , Transtornos Relacionados ao Uso de Substâncias/etnologia
13.
Bioinformatics ; 31(23): 3815-21, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26254433

RESUMO

MOTIVATION: Most data analysis tools for high-throughput screening (HTS) seek to uncover interesting hits for further analysis. They typically assume a low hit rate per plate. Hit rates can be dramatically higher in secondary screening, RNAi screening and in drug sensitivity testing using biologically active drugs. In particular, drug sensitivity testing on primary cells is often based on dose-response experiments, which pose a more stringent requirement for data quality and for intra- and inter-plate variation. Here, we compared common plate normalization and noise-reduction methods, including the B-score and the Loess a local polynomial fit method under high hit-rate scenarios of drug sensitivity testing. We generated simulated 384-well plate HTS datasets, each with 71 plates having a range of 20 (5%) to 160 (42%) hits per plate, with controls placed either at the edge of the plates or in a scattered configuration. RESULTS: We identified 20% (77/384) as the critical hit-rate after which the normalizations started to perform poorly. Results from real drug testing experiments supported this estimation. In particular, the B-score resulted in incorrect normalization of high hit-rate plates, leading to poor data quality, which could be attributed to its dependency on the median polish algorithm. We conclude that a combination of a scattered layout of controls per plate and normalization using a polynomial least squares fit method, such as Loess helps to reduce column, row and edge effects in HTS experiments with high hit-rates and is optimal for generating accurate dose-response curves. CONTACT: john.mpindi@helsinki.fi. AVAILABILITY AND IMPLEMENTATION: Supplementary information: R code and Supplementary data are available at Bioinformatics online.


Assuntos
Antineoplásicos/farmacologia , Interpretação Estatística de Dados , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala/métodos , Neoplasias da Próstata/tratamento farmacológico , Algoritmos , Relação Dose-Resposta a Droga , Humanos , Masculino , Distribuição Normal , Células Tumorais Cultivadas
14.
Int J Cancer ; 136(11): 2535-45, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25359680

RESUMO

Hormonal therapies targeting androgen receptor (AR) are effective in prostate cancer (PCa), but often the cancers progress to fatal castrate-resistant disease. Improved understanding of the cellular events during androgen deprivation would help to identify survival and stress pathways whose inhibition could synergize with androgen deprivation. Toward this aim, we performed an RNAi screen on 2,068 genes, including kinases, phosphatases, epigenetic enzymes and other druggable gene targets. High-content cell spot microarray (CSMA) screen was performed in VCaP cells in the presence and absence of androgens with detection of Ki67 and cleaved ADP-ribose polymerase (cPARP) as assays for cell proliferation and apoptosis. Thirty-nine candidate genes were identified, whose silencing inhibited proliferation or induced apoptosis of VCaP cells exclusively under androgen-deprived conditions. One of the candidates, HSPB (heat shock 27 kDa)-associated protein 1 (HSPBAP1), was confirmed to be highly expressed in tumor samples and its mRNA expression levels increased with the Gleason grade. We found that strong HSPBAP1 immunohistochemical staining (IHC) was associated with shorter disease-specific survival of PCa patients compared with negative to moderate staining. Furthermore, we demonstrate that HSPBAP1 interacts with AR in the nucleus of PCa cells specifically during androgen-deprived conditions, occupies chromatin at PSA/klk3 and TMPRSS2/tmprss2 enhancers and regulates their expression. In conclusion, we suggest that HSPBAP1 aids in sustaining cell viability by maintaining AR signaling during androgen-deprived conditions.


Assuntos
Androgênios/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Biblioteca Gênica , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Interferente Pequeno/metabolismo , Receptores Androgênicos/metabolismo , Análise de Sobrevida , Análise Serial de Tecidos
15.
Eur Arch Psychiatry Clin Neurosci ; 265(6): 471-81, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25421792

RESUMO

Psychotic symptoms are more common in general population than validated diagnosis of psychosis. There is evidence to suggest that these symptoms, hallucinations, paranoia, elated mood, thought insertion, are part of a spectrum of psychosis and may have association with the same risk factors that determine development of psychosis. These symptoms have an association with exposure to psychological trauma, post-traumatic stress disorder, anxiety and depression. The aim of this study was to explore the prevalence of psychotic symptoms in the population affected by a natural disaster, earthquake in this case and possible correlates of these symptoms. We conducted a cross-sectional survey of a population sample affected by the disaster, comprising of 1,291 individuals, 18 months after 2005 earthquake in Northern Pakistan and Kashmir to look at the prevalence of these symptoms and their correlates. Screening Instrument for Traumatic Stress in Earthquake Survivors and Self-Reporting Questionnaire and Psychosis Screening Questionnaire were used as tools. We examined association between the symptoms of anxiety, depression, PTSD and psychotic symptoms. We performed logistic regression analysis where hallucinations and delusions were dependent variables and demographic and trauma exposure variables were independent variables. The prevalence of psychotic symptoms ranged between 16.8 and 30.4 %. They were directly correlated with symptoms of post-traumatic stress disorder as well as concurrent symptoms of anxiety and depression. Lower level of education had a strong association in all the regression models. For hallucinations, living in a joint family had a negative association and participation in rescue, history of exposure to previous trauma and past psychiatric history had positive association. Paranoia was associated with female gender. Any psychiatric symptom was associated death of a family member, history of past psychiatric illness and living in a tent at the time of interview. Pattern of association of psychotic symptoms is consistent with prior literature and can be understood in the light of stress vulnerability model.


Assuntos
Terremotos/estatística & dados numéricos , Alucinações/epidemiologia , Transtornos Paranoides/epidemiologia , Transtornos Psicóticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adolescente , Adulto , Idoso , Ansiedade/epidemiologia , Comorbidade , Depressão/epidemiologia , Desastres/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Sobreviventes/estatística & dados numéricos , Adulto Jovem
16.
BMC Psychiatry ; 15: 232, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26428314

RESUMO

BACKGROUND: In humanitarian settings common mental disorders (depression, anxiety disorders, posttraumatic stress disorder) are highly prevalent. The World Health Organization (WHO) has developed Problem Management Plus (PM+), a 5-session, individual psychological intervention program, delivered by paraprofessionals that addresses common mental disorders in people in communities affected by adversity. The objectives of this study are to test effectiveness and cost-effectiveness of the locally adapted PM+ compared to Treatment as usual (TAU) in Peshawar District, Pakistan. METHODS: A randomised controlled trial will be conducted in 346 primary care attendees in 3 health care centres in Peshawar District, Pakistan. After informed consent, primary care attendees with high levels of psychological distress according to the General Health Questionnaire-12 (GHQ-12) and functional impairment (WHO Disability Assessment Schedule 2.0 (WHODAS)) will be assigned to PM+ (n = 173) or TAU (n = 173). At baseline, 1 week and 3 months following PM+, independent assessors will assess psychological distress with the Hospital Anxiety and Depression Scale (HADS), and functional disability with the WHODAS. Secondary outcomes are posttraumatic stress disorder (PTSD) symptoms, and client-perceived priority problems. Further, cost-effectiveness will be assessed using the Service Receipt Inventory (SRI). DISCUSSION: If proven effective, PM+ will be rolled out to other areas for further adaptation and testing in diverse humanitarian settings. TRIAL REGISTRATION: ACTRN12614001235695. Registered 26 November 2014. Australian New Zealand Clinical Trials Registry.


Assuntos
Psicoterapia/métodos , Estresse Psicológico/terapia , Adolescente , Adulto , Altruísmo , Transtornos de Ansiedade/economia , Transtornos de Ansiedade/etiologia , Análise Custo-Benefício , Aconselhamento/economia , Transtorno Depressivo/economia , Transtorno Depressivo/etiologia , Feminino , Humanos , Masculino , Paquistão , Atenção Primária à Saúde/economia , Psicoterapia/economia , Transtornos de Estresse Pós-Traumáticos/economia , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico/economia
17.
Cochrane Database Syst Rev ; (9): CD010625, 2015 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-26397173

RESUMO

BACKGROUND: Psychosis is three times more common in people with an intellectual disability than in those without an intellectual disability. A low intelligence quotient (IQ) is a defining characteristic for intellectual disability and a risk factor for poor outcome in psychosis. Clozapine is recommended for treatment-resistant psychosis. The effect of psychotropic medication can be different in people with intellectual disability; for example, they may be more prone to side effects. People with an intellectual disability and psychosis form a special subgroup and we wanted to examine if there is randomised controlled trial (RCT) data in this population to support the use of clozapine. OBJECTIVES: To determine the effects of clozapine for treating adults with a dual diagnosis of intellectual disability and psychosis. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Embase and eight other databases up to December 2014. We also searched two trials registers, the Cochrane Schizophrenia Group's Register of Trials, and contacted the manufacturers of clozapine. SELECTION CRITERIA: RCTs that assessed the effects of clozapine, at any dose, for treating adults (aged 18 years and over) with a dual diagnosis of intellectual disability and psychotic disorder, compared with placebo or another antipsychotic medication. DATA COLLECTION AND ANALYSIS: Three review authors independently screened all titles, abstracts and any relevant full-text reports against the inclusion criteria. MAIN RESULTS: Of the 1224 titles and abstracts screened, we shortlisted 38 full-text articles, which we subsequently excluded as they did not meet the inclusion criteria. These studies were not RCTs. Consequently, no studies are included in this Cochrane review. AUTHORS' CONCLUSIONS: There are currently no RCTs that assess the efficacy and side effects of clozapine in people with intellectual disabilities and psychoses. Given the use of clozapine in this vulnerable population, there is an urgent need for a RCT of clozapine in people with a dual diagnosis of intellectual disability and psychosis to fill the evidence gap.


Assuntos
Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Deficiência Intelectual/psicologia , Transtornos Psicóticos/tratamento farmacológico , Adulto , Humanos
18.
Sensors (Basel) ; 14(6): 11031-44, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24955946

RESUMO

With the rapid increase in computational power of mobile devices the amount of ambient intelligence-based smart environment systems has increased greatly in recent years. A proposition of such a solution is described in this paper, namely real time monitoring of an electrocardiogram (ECG) signal during everyday activities for identification of life threatening situations. The paper, being both research and review, describes previous work of the authors, current state of the art in the context of the authors' work and the proposed aforementioned system. Although parts of the solution were described in earlier publications of the authors, the whole concept is presented completely for the first time along with the prototype implementation on mobile device-a Windows 8 tablet with Modern UI. The system has three main purposes. The first goal is the detection of sudden rapid cardiac malfunctions and informing the people in the patient's surroundings, family and friends and the nearest emergency station about the deteriorating health of the monitored person. The second goal is a monitoring of ECG signals under non-clinical conditions to detect anomalies that are typically not found during diagnostic tests. The third goal is to register and analyze repeatable, long-term disturbances in the regular signal and finding their patterns.


Assuntos
Computadores de Mão , Diagnóstico por Computador/métodos , Eletrocardiografia Ambulatorial/métodos , Frequência Cardíaca Fetal/fisiologia , Software , Telemedicina/métodos , Interface Usuário-Computador , Diagnóstico por Computador/instrumentação , Diagnóstico Precoce , Eletrocardiografia Ambulatorial/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Polymers (Basel) ; 16(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38475263

RESUMO

This study focuses on evaluating the fatigue life performance of 3D-printed polymer composites produced through the fused deposition modelling (FDM) technique. Fatigue life assessment is essential in designing components for industries like aerospace, medical, and automotive, as it provides an estimate of the component's safe service life during operation. While there is a lack of detailed research on the fatigue behaviour of 3D-printed polymer composites, this paper aims to fill that gap. Fatigue tests were conducted on the 3D-printed polymer composites under various loading conditions, and static (tensile) tests were performed to determine their ultimate tensile strength. The fatigue testing load ranged from 80% to 98% of the total static load. The results showed that the fatigue life of the pressed samples using a platen press was significantly better than that of the non-pressed samples. Samples subjected to fatigue testing at 80% of the ultimate tensile strength (UTS) did not experience failure even after 1 million cycles, while samples tested at 90% of UTS failed after 50,000 cycles, with the failure being characterized as splitting and clamp area failure. This study also included a lap shear analysis of the 3D-printed samples, comparing those that were bonded using a two-part Araldite glue to those that were fabricated as a single piece using the Markforged Mark Two 3D printer. In summary, this study sheds light on the fatigue life performance of 3D-printed polymer composites fabricated using the FDM technique. The results suggest that the use of post-printing platen press improved the fatigue life of 3D-printed samples, and that single printed samples have better strength of about 265 MPa than adhesively bonded samples in which the strength was 56 MPa.

20.
East Mediterr Health J ; 30(5): 369-379, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38874297

RESUMO

Background: The increasing emergencies and humanitarian challenges have worsened the mental health condition of women in the Eastern Mediterranean Region. Aim: To assess the prevalence, determinants and interventions to address mental health among women in fragile and humanitarian settings in the Eastern Mediterranean Region. Methods: Using the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines, we reviewed 59 peer-reviewed published studies (PubMed, IMEMR) and grey literature (WHO/IRIS) from January 2001 to February 2023, focusing on women's mental health in the Eastern Mediterranean Region. We then conducted a descriptive analysis of the sociodemographic characteristics. Results: Among the 59 studies reviewed, only 13 of the 48 peer-reviewed studies focused primarily on women's mental health, 11 grey literature records mostly presented grouped regional data, 11 of the 25 studies on mental health among migrants were about those taking refuge in high-income countries. The average prevalence of mental disorders from 32 cross-sectional studies on women aged 12-75 years was 49%, average prevalence of anxiety was 68%, post-traumatic stress disorder was 52%, and depression was 43%. Women exhibited higher level depression than men. Age, educational disparities, and limited access to services were important risk factors for mental health disorder. Several promising interventions emerged. Conclusion: More efforts should be made to provide customized, context-specific solutions to the mental health challenges of women in humanitarian and fragile settings in the Eastern Mediterranean Region, including allocation of more resources to mental health programmes, addressing barriers, enhancing mental health surveillance, and reduction of stigma.


Assuntos
Transtornos Mentais , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Região do Mediterrâneo/epidemiologia , Transtornos Mentais/epidemiologia , Saúde Mental/estatística & dados numéricos , Oriente Médio/epidemiologia , Prevalência , Saúde da Mulher
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