Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 77
Filtrar
1.
Indian J Psychiatry ; 66(Suppl 2): S283-S303, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38445283

RESUMO

This clinical practice guide traces the role of art and creativity in mental health and well-being. This is a difficult task since the evidence from research spans a wide variety of fine art forms and different aspects of creativity. Hence, we have tried to combine both evidence-based research as well as our clinical experience and practice in the field of arts in utilizing creative pursuits as a life skill and a well-being initiative. The focus of the guidelines is preventive and promotional with relevance to mental health. We also hope that this should be a beginning in encouraging psychiatrists in India to use art-based therapies in their clinical practice. This will further our knowledge of how arts can be a therapeutic intervention as well as a well-being tool. It will also build on the evidence base on how art impacts our mental health. Creativity is undeniably one of humanity's most valued traits; the capacity to produce new ideas, innovations, and art is perhaps the most striking characteristic of the human brain. "Art" has evolved, and what is art, has been redefined over human history. The domain of "art" refers to the diverse range of activities that often use imagination to express ideas and feelings. Whilst the boundaries of what constitutes art or creativity may sometimes appear esoteric, we still can identify a range of creative pursuits: visual, musical, verbal, literary, dance, or creative pursuits related to our body movements and a range of forms of newer integrated forms and those that use technology are recognized as art forms. As in most ancient traditions, in India, we have a plethora of fine art traditions many of which have a highly systematic practice around their learning. We believe this is an asset that we need to nurture and celebrate. We begin by tracing the footsteps of Indian fine arts being a mental health promotional tool in ancient India. We then proceed to describe the scope of creative pursuits for different populations and its relevance in school and child mental health. We offer suggestions as to how creative art forms can be utilized in a practical way in daily life, schools, and care of the elderly. It is to be noted that the entire focus here is the process of creativity and not the completed product or the achievement related to the same. Hence, it is relevant to each one of us and to anyone who wishes to be healthy.

2.
PLoS Negl Trop Dis ; 18(3): e0012028, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452055

RESUMO

BACKGROUND: India is going through the maintenance phase of VL elimination programme which may be threatened by the persistence of hidden parasite pools among asymptomatic leishmanial infection (ALI) and PKDL. The present work was designed to determine the burden of VL, PKDL, and ALI and to assess the role of treatment of ALI in maintaining post-elimination phase. METHODS AND FINDING: The study was undertaken in Malda district, West Bengal, India during October 2016 to September 2021. Study areas were divided into 'Study' and 'Control' arms. VL and PKDL cases of both the arms were diagnosed by three active mass surveys with an interval of one year and treated as per National guideline. ALI of 'Study' arm was treated like VL. ALI of 'Control' arm was followed up to determine their fate. Fed sand-fly pools were analysed for parasitic DNA. No significant difference was noted between the incidence of VL and PKDL in both the arms. Incidence of ALI declined sharply in 'Study' arm but an increasing trend was observed in 'Control' arm. Significantly higher rate of sero-conversion was noted in 'Control' arm and was found to be associated with untreated ALI burden. Parasitic DNA was detected in 22.8% ALI cases and 2.2% sand-fly pools. CONCLUSION: Persistence of a significant number of PKDL and ALI and ongoing transmission, as evidenced by new infection and detection of leishmanial DNA in vector sand-flies, may threaten the maintenance of post-elimination phase. Emphasis should be given for elimination of pathogen to prevent resurgence of VL epidemics.


Assuntos
Leishmania donovani , Leishmaniose Cutânea , Leishmaniose Visceral , Phlebotomus , Psychodidae , Animais , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/complicações , Areia , Psychodidae/parasitologia , Infecções Assintomáticas/epidemiologia , Índia/epidemiologia , DNA , Leishmaniose Cutânea/epidemiologia
3.
Br J Psychiatry ; 224(5): 150-156, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38344814

RESUMO

BACKGROUND: Enduring ethnic inequalities exist in mental healthcare. The COVID-19 pandemic has widened these. AIMS: To explore stakeholder perspectives on how the COVID-19 pandemic has increased ethnic inequalities in mental healthcare. METHOD: A qualitative interview study of four areas in England with 34 patients, 15 carers and 39 mental health professionals from National Health Service (NHS) and community organisations (July 2021 to July 2022). Framework analysis was used to develop a logic model of inter-relationships between pre-pandemic barriers and COVID-19 impacts. RESULTS: Impacts were largely similar across sites, with some small variations (e.g. positive service impacts of higher ethnic diversity in area 2). Pre-pandemic barriers at individual level included mistrust and thus avoidance of services and at a service level included the dominance of a monocultural model, leading to poor communication, disengagement and alienation. During the pandemic remote service delivery, closure of community organisations and media scapegoating exacerbated existing barriers by worsening alienation and communication barriers, fuelling prejudice and division, and increasing mistrust in services. Some minority ethnic patients reported positive developments, experiencing empowerment through self-determination and creative activities. CONCLUSIONS: During the COVID-19 pandemic some patients showed resilience and developed adaptations that could be nurtured by services. However, there has been a reduction in the availability of group-specific NHS and third-sector services in the community, exacerbating pre-existing barriers. As these developments are likely to have long-term consequences for minority ethnic groups' engagement with mental healthcare, they need to be addressed as a priority by the NHS and its partners.


Assuntos
COVID-19 , Serviços Comunitários de Saúde Mental , Pesquisa Qualitativa , Humanos , COVID-19/etnologia , Serviços Comunitários de Saúde Mental/organização & administração , Inglaterra , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Etnicidade/psicologia , Etnicidade/estatística & dados numéricos , Grupos Minoritários/psicologia , SARS-CoV-2 , Disparidades em Assistência à Saúde/etnologia , Medicina Estatal , Minorias Étnicas e Raciais , Idoso
4.
BMJ Ment Health ; 26(1)2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37463794

RESUMO

BACKGROUND: Long-standing ethnic inequalities in access and mental healthcare were worsened by the COVID-19 pandemic. OBJECTIVES: Stakeholders coproduced local and national implementation plans to improve mental healthcare for people from minority ethnic groups. METHODS: Experience-based codesign conducted in four areas covered by National Health Service (NHS) mental health trusts: Coventry and Warwickshire, Greater Manchester, East London and Sheffield. Data were analysed using an interpretivist-constructivist approach, seeking validation from participants on their priority actions and implementation plans. Service users (n=29), carers (n=9) and health professionals (n=33) took part in interviews; focus groups (service users, n=15; carers, n=8; health professionals, n=24); and codesign workshops (service users, n=15; carers, n=5; health professionals, n=21) from July 2021 to July 2022. FINDINGS: Each study site identified 2-3 local priority actions. Three were consistent across areas: (1) reaching out to communities and collaborating with third sector organisations; (2) diversifying the mental healthcare offer to provide culturally appropriate therapeutic approaches and (3) enabling open discussions about ethnicity, culture and racism. National priority actions included: (1) co-ordination of a national hub to bring about system level change and (2) recognition of the centrality of service users and communities in the design and provision of services. CONCLUSIONS: Stakeholder-led implementation plans highlight that substantial change is needed to increase equity in mental healthcare in England. CLINICAL IMPLICATIONS: Working with people with lived experience in leadership roles, and collaborations between NHS and community organisations will be essential. Future research avenues include comparison of the benefits of culturally specific versus generic therapeutic interventions.


Assuntos
COVID-19 , Etnicidade , Humanos , Medicina Estatal , Pandemias , COVID-19/epidemiologia , Inglaterra , Acesso aos Serviços de Saúde
5.
Int J Soc Psychiatry ; 69(4): 994-1003, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36645032

RESUMO

BACKGROUND: A range of evidence for the effectiveness of one-to-one peer support in mental health services is emerging. Levels of engagement with peer support vary with limited studies showing few individual participant characteristics predicting engagement. Implementation factors that might predict engagement have not been considered. METHODS: Data were analysed from the intervention arm of the ENRICH trial of one-to-one peer support for discharge from acute psychiatric inpatient care. Two outcomes were considered: (1) a measure of 'engaged with peer worker'; (2) number of face-to-face contacts with peer worker post-discharge. Two sets of independent variables were analysed against each outcome: (1) pre-randomisation participant characteristics; (2) implementation factors measured pre-discharge. Analyses used logistic and zero-inflated negative binomial regression models according to outcome structure. RESULTS: Data were analysed for 265 participants randomised to peer support who had a known peer worker. Non-heterosexual participants had increased odds of engaging with peer support compared to heterosexual participants, OR = 4.38 (95% CI: 1.13, 16.9, p = .032). Longer duration of first contact with peer worker (OR = 1.03, 95% CI: 1.00, 1.04, p < .001) and more relationship building activities in the first contact (OR = 1.4, 95% CI: 1.13, 1.85, p = .004) were associated with greater odds of engaging with peer support. Analysis of number of contacts post-discharge showed consistent findings. CONCLUSIONS: Implementation of peer support should include a focus on relationship building in the first session of peer support. The potential for peer support to break down barriers to accessing mental health services experienced by people from marginalised communities warrants further investigation.


Assuntos
Serviços de Saúde Mental , Alta do Paciente , Humanos , Assistência ao Convalescente , Pacientes Internados , Aconselhamento
6.
Stat Methods Med Res ; 32(1): 88-99, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36266972

RESUMO

Covariate adjusted response adaptive designs are developed with ordinal categorical responses for phase III clinical trial involving multiple treatments. Stochastic ordering principle is used to order the treatments according to effectiveness and consequently allocation functions are developed by combining the cumulative odds ratios suitably. The performance of the proposed designs is investigated through relevant exact as well as large sample measures. To investigate the performance in a real situation, a real clinical trial involving lung cancer patients is further redesigned using the proposed allocation design.


Assuntos
Projetos de Pesquisa , Humanos , Razão de Chances
7.
J Stat Theory Pract ; 17(1): 13, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36533269

RESUMO

In this paper, stein-type two-stage sampling procedure is carried out for fixed accuracy confidence interval estimation of the common variance ( σ 2 ) parameter corresponding to multivariate normal distribution with autoregressive covariance structure of order 1. Related asymptotics are obtained and simulation results are presented.

8.
J Pers Med ; 12(6)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35743652

RESUMO

Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote carcinogenesis. An example is the enhanced risk for several types of cancer in patients with CF, especially cancers of the GI tract. CFTR also acts as a tumor suppressor in diverse sporadic epithelial cancers in many tissues, primarily due to the silencing of CFTR expression via multiple mechanisms, but especially due to epigenetic regulation. This review provides an update on the latest research linking CFTR-deficiency to GI cancers, in both CF patients and in sporadic GI cancers, with a particular focus on cancer of the intestinal tract. It will discuss changes in the tissue landscape linked to CFTR-deficiency that may promote cancer development such as breakdowns in physical barriers, microbial dysbiosis and inflammation. It will also discuss molecular pathways and mechanisms that act upstream to modulate CFTR expression, such as by epigenetic silencing, as well as molecular pathways that act downstream of CFTR-deficiency, such as the dysregulation of the Wnt/ß-catenin and NF-κB signaling pathways. Finally, it will discuss the emerging CFTR modulator drugs that have shown promising results in improving CFTR function in CF patients. The potential impact of these modulator drugs on the treatment and prevention of GI cancers can provide a new example of personalized cancer medicine.

9.
BMC Psychiatry ; 22(1): 373, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650562

RESUMO

BACKGROUND: Peer workers are increasingly employed in mental health services to use their own experiences of mental distress in supporting others with similar experiences. While evidence is emerging of the benefits of peer support for people using services, the impact on peer workers is less clear. There is a lack of research that takes a longitudinal approach to exploring impact on both employment outcomes for peer workers, and their experiences of working in the peer worker role. METHODS: In a longitudinal mixed methods study, 32 peer workers providing peer support for discharge from inpatient to community mental health care - as part of a randomised controlled trial - undertook in-depth qualitative interviews conducted by service user researchers, and completed measures of wellbeing, burnout, job satisfaction and multi-disciplinary team working after completing training, and four and 12 months into the role. Questionnaire data were summarised and compared to outcomes for relevant population norms, and changes in outcomes were analysed using paired t-tests. Thematic analysis and interpretive workshops involving service user researchers were used to analysis interview transcripts. A critical interpretive synthesis approach was used to synthesise analyses of both datasets. RESULTS: For the duration of the study, all questionnaire outcomes were comparable with population norms for health professionals or for the general population. There were small-to-medium decreases in wellbeing and aspects of job satisfaction, and increase in burnout after 4 months, but these changes were largely not maintained at 12 months. Peer workers felt valued, empowered and connected in the role, but could find it challenging to adjust to the demands of the job after initial optimism. Supervision and being part of a standalone peer worker team was supportive, although communication with clinical teams could be improved. CONCLUSIONS: Peer workers seem no more likely to experience negative impacts of working than other healthcare professionals but should be well supported as they settle into post, provided with in-work training and support around job insecurity. Research is needed to optimise working arrangements for peer workers alongside clinical teams.


Assuntos
Esgotamento Profissional , Transtornos Mentais , Serviços de Saúde Mental , Humanos , Satisfação no Emprego , Transtornos Mentais/psicologia , Transtornos Mentais/terapia , Grupo Associado , Inquéritos e Questionários
10.
Biom J ; 64(1): 165-185, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34585751

RESUMO

Compromising ethics and precision in the context of a multiarmed clinical trial, an optimal order adjusted response adaptive design is proposed for survival outcomes subject to independent random censoring. The operating characteristics of the proposed design and the follow-up inference are studied both theoretically as well as empirically and are compared with those of the competitors. Applicability of the developed design is further illustrated through redesigning a real clinical trial with survival responses.


Assuntos
Projetos de Pesquisa
11.
J Biopharm Stat ; 31(6): 809-827, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34464231

RESUMO

In clinical trials, fixed randomizations in a prefixed proportion (e.g. 1:1 or 2:1 for two treatment trials) may be adopted to allocate the entering patients among the competing treatments. However, such an allocation procedure ignores the knowledge obtained from the accrued information on the performance of the treatments until that point. However, while allocating, a fixed randomization may favor the most and the least effective treatments in a prefixed manner, and hence becomes instrumental to induce a conflict with the "individual ethics" requirement. Adaptive allocation designs are considered instead, for their ability to dynamically settle the issue of running randomization towards the treatment doing better - all using the available data but with a scope to compromise in statistical precision. Although most of the developments are pertinent to binary, continuous and survival responses, ordinal categorical responses are natural outcomes in many disciplines of clinical trials like Orthopedics and Ophthalmology. Therefore, to balance between ethics and precision in the context of a multi-treatment clinical trial producing ordinal categorical responses, an optimal response adaptive design is derived by minimizing a measure of "precision" subject to constrained number of "failures" ensuring higher number of assignments to the "best" treatment. Related design and inference-based characteristics are extensively studied - both theoretically and empirically. Further, the practical applicability of the developed design is envisaged through re-designing of a real clinical trial, where the responses are immediate and are measured in ordinal categorical scale.


Assuntos
Projetos de Pesquisa , Humanos , Distribuição Aleatória , Resultado do Tratamento
12.
Cells ; 10(2)2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673061

RESUMO

This report describes novel thiol-modified N-acetylmannosamine (ManNAc) analogs that extend metabolic glycoengineering (MGE) applications of Ac5ManNTGc, a non-natural monosaccharide that metabolically installs the thio-glycolyl of sialic acid into human glycoconjugates. We previously found that Ac5ManNTGc elicited non-canonical activation of Wnt signaling in human embryoid body derived (hEBD) cells but only in the presence of a high affinity, chemically compatible scaffold. Our new analogs Ac5ManNTProp and Ac5ManNTBut overcome the requirement for a complementary scaffold by displaying thiol groups on longer, N-acyl linker arms, thereby presumably increasing their ability to interact and crosslink with surrounding thiols. These new analogs showed increased potency in human neural stem cells (hNSCs) and human adipose stem cells (hASCs). In the hNSCs, Ac5ManNTProp upregulated biochemical endpoints consistent with Wnt signaling in the absence of a thiol-reactive scaffold. In the hASCs, both Ac5ManNTProp and Ac5ManNTBut suppressed adipogenic differentiation, with Ac5ManNTBut providing a more potent response, and they did not interfere with differentiation to a glial lineage (Schwann cells). These results expand the horizon for using MGE in regenerative medicine by providing new tools (Ac5ManNTProp and Ac5ManNTBut) for manipulating human stem cells.


Assuntos
Adipócitos/metabolismo , Diferenciação Celular/fisiologia , Glicoconjugados/metabolismo , Células-Tronco/metabolismo , Hexosaminas/metabolismo , Humanos , Ácido N-Acetilneuramínico/metabolismo , Compostos de Sulfidrila/metabolismo
13.
Mol Biol Rep ; 48(1): 897-914, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33400075

RESUMO

Enhanced metastasis and disease recurrence accounts for the high mortality rates associated with cancer. The process of Epithelial-Mesenchymal Transition (EMT) contributes towards the augmentation of cancer invasiveness along with the gain of stem-like and the subsequent drug-resistant behavior. Apart from the well-established transcriptional regulation, EMT is also controlled post-transcriptionally by virtue of alternative splicing (AS). Numerous genes including Fibroblast Growth Factor receptor (FGFR) as well as CD44 are differentially spliced during this trans-differentiation process which, in turn, governs cancer progression. These splicing alterations are controlled by various splicing factors including ESRP, RBFOX2 as well as hnRNPs. Here, we have depicted the mechanisms governing the splice isoform switching of FGFR and CD44. Moreover, the role of the splice variants generated by AS of these gene transcripts in modulating the metastatic potential and stem-like/chemoresistant behavior of cancer cells has also been highlighted. Additionally, the involvement of splicing factors in regulating EMT/invasiveness along with drug-resistance as well as the metabolic properties of the cells has been emphasized. Tumorigenesis is accompanied by a remodeling of the cellular splicing profile generating diverse protein isoforms which, in turn, control the cancer-associated hallmarks. Therefore, we have also briefly discussed about a wide variety of genes which are differentially spliced in the tumor cells and promote cancer progression. We have also outlined different strategies for targeting the tumor-associated splicing events which have shown promising results and therefore this approach might be useful in developing therapies to reduce cancer aggressiveness in a more specific manner.


Assuntos
Carcinogênese/genética , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/genética , Receptores de Hialuronatos/genética , Recidiva Local de Neoplasia/genética , Neoplasias/genética , Receptores de Fatores de Crescimento de Fibroblastos/genética , Processamento Alternativo , Antineoplásicos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Metástase Linfática , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
14.
BJPsych Bull ; 45(1): 22-27, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32605689

RESUMO

AIMS AND METHOD: To compare differences in clozapine doses and plasma levels between Bangladeshi and White British patients. Following ethical approval we identified all current Bangladeshi and White British patients on clozapine maintenance in an east London clinic. We carried out univariate and multivariate regression analyses to examine associations between clozapine doses and ethnicity, age, gender, smoking status and weight. We also compared plasma clozapine levels of the two groups. RESULTS: On univariate analysis White British patients had on average 85 mg higher doses than Bangladeshi patients (P = 0.004). Older age, male gender and smoking were also associated with higher dose. On multivariate analysis only age and smoking status remained significant. A greater proportion of Bangladeshi patients had high plasma clozapine levels compared with White British (30.76% v. 20.75%), although the difference was not statistically significant. CLINICAL IMPLICATIONS: Our findings point to the need for the broadening of data collection on ethnic differences in clozapine prescribing within big data-sets such as Prescribing Observatory for Mental Health (POM-UK). Ethnopharmacological variations can inform more person-centred guidance on prescribing.

15.
Bioengineering (Basel) ; 7(4)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182731

RESUMO

Comprehensive analysis of the glycoproteome is critical due to the importance of glycosylation to many aspects of protein function. The tremendous complexity of this post-translational modification, however, makes it difficult to adequately characterize the glycoproteome using any single method. To overcome this pitfall, in this report we compared three glycoproteomic analysis methods; first the recently developed N-linked glycans and glycosite-containing peptides (NGAG) chemoenzymatic method, second, solid-phase extraction of N-linked glycoproteins (SPEG), and third, hydrophilic interaction liquid chromatography (HILIC) by characterizing N-linked glycosites in the secretome of Chinese hamster ovary (CHO) cells. Interestingly, the glycosites identified by SPEG and HILIC overlapped considerably whereas NGAG identified many glycosites not observed in the other two methods. Further, utilizing enhanced intact glycopeptide identification afforded by the NGAG workflow, we found that the sugar analog 1,3,4-O-Bu3ManNAc, a "high flux" metabolic precursor for sialic acid biosynthesis, increased sialylation of secreted proteins including recombinant human erythropoietin (rhEPO).

16.
J Cell Physiol ; 235(11): 7696-7708, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32324275

RESUMO

Cancer is referred to as the "Emperor of all maladies" accounting for the second-highest mortality rates worldwide. Major factors associated with cancer lethality are uncontrolled proliferation, metastasis, and frequent recurrence. The conventional therapeutic drugs used in cancer therapy have been associated with numerous damaging side-effects that call for the use of alternative therapeutic options. The natural plant compounds (NPCs) have been found to be effective against diverse groups of diseases including cancer. Among the different types, the polyphenolic phytochemicals like curcumin, (-)epigallocatechin-3-gallate, Resveratrol, and nimbolide which are predominant parts of daily dietary intake have proved their potency in reducing the aggressive properties of cancer. Here, we have highlighted the mechanisms through which these NPCs influence growth, metastatic potential, and the drug-resistant behavior of different cancer types. Moreover, we have also emphasized on their function as modulators of the immune system as well as the metabolic properties of the tumor. The role of these phytochemicals in reducing cancer progression has been highlighted when administered unaided or in combination with similar group of compounds. Moreover, their ability to enhance the drug-sensitivity of cancer cells which accounts for their use in combination with conventional chemotherapeutics has also been discussed in this article. Therefore, co-administration of these phytochemicals with chemically similar group members or with conventional chemotherapeutics may prove to be an effective treatment strategy for cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Humanos , Neoplasias/patologia , Compostos Fitoquímicos/farmacologia , Polifenóis/farmacologia
17.
Life Sci ; 246: 117400, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32032645

RESUMO

AIMS: Comparative sub-acute toxicity, including tolerance and dependence potential of fentanyl and its three novel and potent analogues was determined in mice. MAIN METHODS: Comparative sub-acute (21 d, intraperitoneal; 1/10 LD50) toxicity of fentanyl and its three novel analogues viz., N-(1-(2-phenoxyethyl)-4-piperidinyl) propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) was determined in mice. Animals were observed for additional seven days to assess the recovery. The brain, liver and kidney toxicity was assessed on the basis of various biochemical, oxidative, histological, and neuroadaptive markers. The expression levels of key neuronal markers associated with drug tolerance and dependence were investigated by western blot and immunohistochemistry. KEY FINDINGS: Fentanyl and its analogues caused abnormal levels of liver and kidney specific biomarkers in plasma. Brain malondialdehyde (MDA) levels were raised by all the treatments and kidney MDA level by analogue 6 (21 d). Reduced glutathione levels in brain, liver, and kidney were diminished by all the treatments (21 & 28 d) and a significant change in the levels of antioxidant enzymes was also produced mainly after 21 d. The deleterious effects of fentanyl and its analogues were further substantiated by corresponding histopathological changes in brain, liver and kidney (21 & 28 d). These compounds were also found to produce neuroadaptive changes as evidenced by the increased expression levels of c-Fos, glucocorticoid receptor, N-methyl-d-aspartate receptor1 and µ-opioid receptor (21 & 28 d). SIGNIFICANCE: Three novel analogues of fentanyl were envisaged to have alternative therapeutic potentials. However, their comparative sub-acute toxicity revealed undesirable side effects, thereby masking their therapeutic ability.


Assuntos
Fentanila/toxicidade , Animais , Biomarcadores/análise , Western Blotting , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dano ao DNA/efeitos dos fármacos , Fentanila/análogos & derivados , Glutationa/análise , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/análise , Camundongos , Estresse Oxidativo/efeitos dos fármacos
18.
Stat Methods Med Res ; 29(3): 827-836, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31072189

RESUMO

A multi-treatment response adaptive procedure is developed considering "comparison with the best" philosophy of multiple comparison procedures for clinical trials with ordinal categorical responses, when there is no shared control. For each response category, we arbitrarily create two outcome groups; one by combining the categories more favorable to it and the other by merging the categories at most as favorable to it and hence define the odds (i.e. cumulative odds). Pairwise ratios of such odds (i.e. cumulative odds ratios) based on pairs of treatments are combined conveniently to derive a measure of relative superiority and hence the allocation probability functions. For practical implementation, we suggest response-adaptive randomization (RAR), that is, update the allocation probabilities dynamically using the available allocation and response information to favor the treatment doing better. Empirical as well as large sample properties following the randomization are investigated in detail. Moreover, a real clinical trial with trauma patients is redesigned using the proposed RAR to envisage practical applicability.


Assuntos
Projetos de Pesquisa , Humanos , Probabilidade , Distribuição Aleatória
19.
Life Sci ; 228: 98-111, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31051153

RESUMO

AIMS: Protective efficacy of N­acetylcysteine (NAC) was assessed against sub-acute diisopropyl phosphorofluoridate (DFP) poisoning in mice. MAIN METHODS: Mice were allocated into nine groups of six each: vehicle control; DFP (0.125 LD50 ≈ 0.483 mg/kg bwt, s.c.); DFP + Atropine (ATR, 10 mg/kg bwt, i.p., 0 min); DFP + Pralidoxime (2-PAM, 30 mg/kg bwt, i.m., 0 min); DFP + NAC (150 mg/kg bwt, i.p., -60 min); DFP + ATR + NAC; DFP + 2-PAM + NAC; DFP + ATR + 2-PAM; and DFP + ATR + 2-PAM + NAC. Animals received various treatments for 21 d daily. Plasma butyrylcholinesterase (BChE) was measured after 7, 14 and 21 d of exposure. Brain acetylcholinesterase (AChE) and reduced glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD) were measured (brain, liver and kidney) after 21 d of exposure. Histopathology, immunohistochemistry, and Western blot for inducible nitric oxide synthase (iNOS) and c-fos were also performed. KEY FINDINGS: DFP significantly reduced BChE and AChE levels. Diminished GSH, CAT, SOD (brain and liver), GPx, GR, and elevated MDA (Brain) levels were also observed. DFP caused notable histopathology (brain, liver and kidney) and over expression of iNOS, and c-fos proteins (brain). NAC enhanced the protective efficacy of ATR and 2-PAM in most parameters, without any appreciable protection in iNOS and c-fos expression. SIGNIFICANCE: NAC as an adjunct with ATR and 2-PAM, exhibited marked beneficial effects against sub-acute DFP poisoning, indicating its possible implications in the management of OP poisoning.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Isoflurofato/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Acetilcolinesterase/análise , Animais , Encéfalo/patologia , Butirilcolinesterase/sangue , Catalase/análise , Glutationa/análise , Glutationa Peroxidase/análise , Glutationa Redutase/análise , Rim/patologia , Fígado/patologia , Masculino , Malondialdeído/análise , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/análise
20.
BJPsych Bull ; 43(3): 106-111, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30693856

RESUMO

Aims and methodThe Tower Hamlets Crisis House (voluntary sector), in partnership with the local home treatment team, offers a brief residential alternative to psychiatric hospital admission. Here, we review clinician-reported (Health of the Nation Outcome Scales; HoNOS) and patient-reported (DIALOG) outcome scores collected from successive admissions between June 2015 and December 2016, to assess the effectiveness of the service model. We identified 153 successive admissions, and of these, 85 (55.6%) and 91 (59.5%) patients completed both admission and discharge DIALOG and HoNOS questionnaires, respectively. We analysed ten out of twelve HoNOS domains and eight patient-reported outcome measure DIALOG domains. RESULTS: We found a statistically significant improvement in nine out of ten domains of HoNOS and three out of eight domains of DIALOG.Clinical implicationsA partnership between a home treatment team and crisis house can result in positive outcomes for patients, as determined by both clinicians and patients.Declaration of interestNone.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...