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1.
Medicine (Baltimore) ; 103(27): e38813, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968472

RESUMO

Simulation-based training (SBT) has emerged as a transformative approach in medical education, significantly enhancing healthcare professionals' learning experience and clinical competency. This article explores the impact of SBT, tracing its historical development and examining the various types of simulations utilized today, including high-fidelity mannequins, virtual reality environments, standardized patients, and hybrid simulations. These methods offer a safe and controlled environment for students to practice and hone technical and non-technical skills, ultimately improving patient safety and clinical outcomes. The benefits of SBT are manifold, including enhanced skill acquisition, error reduction, and the opportunity for repeated practice without risk to actual patients. Immediate feedback and structured debriefing further solidify learning, making Simulation an invaluable tool in medical education. However, the implementation of SBT is challenging. It requires substantial financial investment, specialized equipment, and trained faculty. Additionally, there are concerns about the realism of simulations and the transferability of skills to real-world clinical settings. Despite these challenges, numerous case studies and empirical research underscore the effectiveness of SBT compared to traditional methods. Looking ahead, advancements in technology, such as artificial intelligence and improved virtual reality applications, promise to enhance the efficacy and accessibility of simulation training. The integration of Simulation with other training modalities and its adoption in diverse global contexts highlight its potential to revolutionize medical education worldwide. This article affirms the crucial role of SBT in preparing the next generation of healthcare professionals and its ongoing evolution driven by technological innovations.


Assuntos
Competência Clínica , Educação Médica , Treinamento por Simulação , Humanos , Treinamento por Simulação/métodos , Educação Médica/métodos , Realidade Virtual , Manequins
2.
Medicine (Baltimore) ; 103(24): e38560, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875433

RESUMO

Hypertension, a prevalent chronic condition characterized by elevated blood pressure, is a significant global health burden, contributing to approximately 7.5 million premature deaths annually. While existing literature predominantly focuses on conventional treatment modalities, this paper offers unique insights into dependable approaches to hypertension management. Drawing upon epidemiological data, it highlights the increasing prevalence of hypertension across diverse populations, emphasizing demographic disparities and regional variations. This article underscores the need for tailored interventions considering individual risk profiles and socioeconomic determinants. Beyond conventional lifestyle modifications and pharmacological therapies, it explores emerging trends such as mindfulness-based interventions and integrative medicine in hypertension management. Additionally, it discusses the role of digital health technologies and telemedicine in enhancing patient engagement and remote monitoring, optimizing treatment outcomes. Furthermore, the paper addresses the evolving landscape of personalized medicine and genomic advancements in predicting individual responses to antihypertensive therapies, advocating for precision medicine approaches. This paper advocates for a holistic and patient-centered approach to hypertension management by offering a comprehensive overview of established and emerging strategies. It underscores the importance of interdisciplinary collaboration, continuous education, and innovative research endeavors to address the multifaceted challenges posed by hypertension and improve global cardiovascular health outcomes.


Assuntos
Hipertensão , Telemedicina , Humanos , Hipertensão/terapia , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Medicina de Precisão/métodos , Atenção Plena/métodos , Medicina Integrativa/métodos , Estilo de Vida
4.
Arch Orthop Trauma Surg ; 144(6): 2609-2617, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700676

RESUMO

PURPOSE: This study employs both the fragility index (FI) and fragility quotient (FQ) to assess the level of robustness in the cervical disc arthroplasty (CDA) literature. We hypothesize that dichotomous outcomes involving CDA would exhibit statistical vulnerability. METHODS: A PubMed search was conducted to evaluate dichotomous data for randomized controlled trials (RCTs) in CDA literature from 2000 to 2023. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by the study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. RESULTS: Of the 1561 articles screened, 111 met the search criteria, with 35 RCTs evaluating CDA included for analysis. Six hundred and ninety-three outcome events with 130 significant (P < 0.05) outcomes and 563 nonsignificant (P ≥ 0.05) outcomes were identified. The overall FI and FQ for all 693 outcomes were 5 (IQR 3-7) and 0.019 (IQR 0.011-0.043). Fragility analysis of statistically significant outcomes and nonsignificant outcomes both revealed an FI of 5. All of the studies reported loss to follow-up (LTF) data where 65.7% (23) did not report or reported an LTF greater or equal to 5. CONCLUSIONS: The literature regarding CDA RCTs lacks statistical robustness and may misrepresent the conclusions with the sole use of the P value. By implementing the FI and FQ along with the P value, we believe the interpretation and contextualization of the clinical data surrounding CDA will be better understood.


Assuntos
Vértebras Cervicais , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Vértebras Cervicais/cirurgia , Artroplastia/métodos , Artroplastia/estatística & dados numéricos , Substituição Total de Disco/métodos , Degeneração do Disco Intervertebral/cirurgia , Interpretação Estatística de Dados
5.
Immunity ; 57(7): 1514-1532.e15, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38788712

RESUMO

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic cell death (ICD). Although the catalytic function of RIPK1 is required to trigger cell death, its non-catalytic scaffold function mediates strong pro-survival signaling. Accordingly, cancer cells can hijack RIPK1 to block necroptosis and evade immune detection. We generated a small-molecule proteolysis-targeting chimera (PROTAC) that selectively degraded human and murine RIPK1. PROTAC-mediated depletion of RIPK1 deregulated TNFR1 and TLR3/4 signaling hubs, accentuating the output of NF-κB, MAPK, and IFN signaling. Additionally, RIPK1 degradation simultaneously promoted RIPK3 activation and necroptosis induction. We further demonstrated that RIPK1 degradation enhanced the immunostimulatory effects of radio- and immunotherapy by sensitizing cancer cells to treatment-induced TNF and interferons. This promoted ICD, antitumor immunity, and durable treatment responses. Consequently, targeting RIPK1 by PROTACs emerges as a promising approach to overcome radio- or immunotherapy resistance and enhance anticancer therapies.


Assuntos
Morte Celular Imunogênica , Proteólise , Proteína Serina-Treonina Quinases de Interação com Receptores , Transdução de Sinais , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Humanos , Animais , Camundongos , Proteólise/efeitos dos fármacos , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Morte Celular Imunogênica/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Necroptose/imunologia , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Camundongos Endogâmicos C57BL , Antineoplásicos/farmacologia , Imunoterapia/métodos
6.
Trop Med Infect Dis ; 9(5)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38787029

RESUMO

Childhood undernutrition is a major issue in low- and middle-income countries, affecting the health, well-being, and educational outcomes of schoolchildren. This study aimed to assess the prevalence and associated factors of stunting, wasting, and underweight among schoolchildren in peri-urban areas in the south-eastern part of Tanzania. A cross-sectional study was conducted involving 930 children aged 6-12 years from four primary schools from July to August 2019. The WHO Anthro Survey Analyzer was employed to estimate the prevalence of stunting, wasting, and underweight, while logistic regression analyses examined sociodemographic background, malaria infection, anaemia, anthropometric measures, and dietary diversity score as potential factors. The prevalence of stunting, wasting, underweight, overweight, and obesity was 11.8%, 4.3%, 3.9%, 11.1%, and 2.0%, respectively. Overall, 1.5% of the children had malaria, as determined by rapid diagnostic tests, and 0.4% had severe anaemia. Univariate analysis indicated higher odds of undernutrition among children aged 9-12 compared to their younger peers. Stunting was more common among children with low and medium dietary diversity. Anaemia was found in 11.2% of schoolchildren, and severe anaemia was associated with wasting. Multivariate analysis revealed that age and low dietary diversity were significantly associated with undernutrition. These findings emphasise the need for school-based health and nutrition programmes targeting children beyond the age of 5 to improve their nutritional status and mitigate potential adverse effects on health, cognition, and academic achievement. Regular assessment of the nutritional status of schoolchildren is warranted.

7.
Medicine (Baltimore) ; 103(20): e38199, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758874

RESUMO

Sexually transmitted diseases (STDs) pose a significant global health challenge with far-reaching social, economic, and public health implications. These infections have haunted humanity from ancient times to today, transcending geographical boundaries and cultural contexts. This article explores the multifaceted landscape of STDs, delving into their epidemiology, pathophysiology, clinical manifestations, and global response strategies. The global prevalence of STDs is staggering, with millions of new cases reported annually. Prominent among these infections is HIV/AIDS, which remains a major global health crisis, affecting over 38 million people worldwide. Additionally, bacterial STDs like chlamydia, gonorrhea, and syphilis continue to pose significant health risks, with millions of new cases reported yearly. Beyond the physical manifestations, STDs have profound social and economic implications. They can result in severe reproductive health issues, stigma, discrimination, and psychological distress, burdening healthcare systems and affecting individuals' quality of life. The global response to STDs has been multifaceted, with international organizations and governments implementing various prevention and control strategies, including sexual education programs and scaling up access to testing and treatment. However, challenges persist, including disparities in healthcare access, sociocultural factors influencing transmission, and evolving pathogens with increasing resistance to treatment. Through case studies and real-world examples, we illuminate the human stories behind the statistics, highlighting the lived experiences of individuals grappling with STDs and the complex interplay of factors shaping their journeys. Ultimately, this review calls for continued research, innovative strategies, and sustained global commitment to mitigating the burden of STDs and promoting sexual health and well-being for all.


Assuntos
Saúde Global , Infecções Sexualmente Transmissíveis , Humanos , Infecções Sexualmente Transmissíveis/epidemiologia , Efeitos Psicossociais da Doença , Prevalência , Estigma Social
8.
J Cross Cult Gerontol ; 39(2): 173-188, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710976

RESUMO

Reduced social support has been associated with presence of depression and reduced quality of life among older adults. The relationships may be better understood by exploring the interactions of individual domains among the constructs. This cross-sectional survey involved a consecutive sample of 206 (116 females and 90 males) older adults living in a Southern Nigeria community. The Multidimensional Scale of Perceived Social Support, Geriatric Depression Scale, and World Health Organization Quality of Life-OLD Questionnaire, were used to measure social support, depression, and quality of life respectively. Data was analyzed using frequency counts, percentages, mean, standard deviation, multiple regression and Spearman rank-order correlation coefficient, at 0.05 alpha level. Prevalence rate of depression among participants was 45.5%. Social support was perceived to be low by 37.4% of participants with the lowest mean social support score coming from friends domain. Participants' quality of life was generally fairly good (> 60%) with the lowest scores coming from the intimacy domain. Significant correlations between social support domains and each of quality of life (p < 0.05) and depression were respectively positive and negative; but weakest for the friend and strongest for significant others domains. All quality of life domains were significantly correlated with social support except the death and dying domain. All the domains of social support (family and significant other) were significant predictors of depression except the friend domain. Significant others around individual older adults particularly those with depression ought to be educated on the importance of their roles. Stakeholders including healthcare providers may create and support programmes for improved social networking for the older adults in order to enhance their general wellbeing and quality of life.


Assuntos
Depressão , Qualidade de Vida , Apoio Social , Humanos , Qualidade de Vida/psicologia , Feminino , Masculino , Estudos Transversais , Nigéria/epidemiologia , Idoso , Depressão/psicologia , Depressão/epidemiologia , Inquéritos e Questionários , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Prevalência , Avaliação Geriátrica
9.
J Chem Theory Comput ; 20(9): 3976-3992, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38708963

RESUMO

Recent studies have shown that metal-organic frameworks (MOFs) have potential as thermoelectric materials, and the topic has received increasing attention. The main motivation for this project is to further our knowledge of thermoelectric properties in MOFs and find which available self-consistent-charge density functional tight binding (SCC-DFTB) method can best predict (at least trends in) the electronic properties of MOFs at a lower computational cost than standard density functional theory (DFT). In this work, the electronic properties of monolayer, serrated, AA-stacked, and/or AB-stacked Zn3C6O6, Cd3C6O6, Zn-NH-MOF─for which no previous calculations of thermoelectric performance exist─and Ni3(HITP)2 MOFs are modeled with DFT-PBE, DFT-HSE06, GFN1-xTB, GFN2-xTB, and DFTB-3ob/mio. The band structures, density of states, and their relative orbital contributions, as well as the electrical conductivity, Seebeck coefficient, and power factor, are compared across methods and geometries. Our results suggest that GFN-xTB is adequate to predict the MOFs' band structure shape and density of states but not band gap. Our calculations further indicate that Zn3C6O6, Cd3C6O6, and Zn-NH-MOF have higher power factor values than Ni3(HITP)2, one of the highest performing synthesized MOFs, and are therefore promising for thermoelectric applications.

10.
Am J Trop Med Hyg ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593792

RESUMO

In Nigeria, mass drug administration (MDA) for schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) has often been coordinated with other programs that receive greater external funding. As these programs reach stop MDA milestones, SCH and STH programs will likely need to transition implementation, or "mainstream," to domestic support. A mixed-methods study was conducted in four districts before (2021) and after (2022) mainstreaming to evaluate its impact on MDA coverage. Household surveys were done in 30 villages per district pre- and post-mainstreaming. All selected communities were eligible for STH treatment; around a third were eligible for SCH treatment. Mass drug administration was primarily conducted in schools. A total of 5,441 school-aged children were included in pre-mainstreaming and 5,789 were included in post-mainstreaming. Mass drug administration coverage was heterogeneous, but overall, mebendazole coverage declined nonsignificantly from 81% pre-mainstreaming to 76% post-mainstreaming (P = 0.09); praziquantel coverage declined significantly from 73% to 55% (P = 0.008). Coverage was significantly lower among unenrolled children or those reporting poor school attendance in nearly every survey. For the qualitative component, 173 interviews and 74 focus groups were conducted with diverse stakeholders. Respondents were deeply pessimistic about the future of MDA after mainstreaming and strongly supported a gradual transition to full government ownership. Participants formulated recommendations for effective mainstreaming: clear budget allocation by governments, robust and targeted training, trust building, and comprehensive advocacy. Although participants lacked confidence that SCH and STH programs could be sustained after reductions in external support, initial results indicate that MDA coverage can remain high 1 year into mainstreaming.

12.
Medicine (Baltimore) ; 103(13): e37396, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552097

RESUMO

A thyroid storm is a life-threatening endocrine emergency characterized by severe hyperthyroidism and many systemic manifestations. Prompt recognition and treatment are essential for patient survival. This study evaluates the utility of existing diagnostic criteria and scoring systems for thyroid storm. A comprehensive literature review encompassed articles published up to December 2023. Various diagnostic criteria and scoring systems, such as the Burch-Wartofsky Point Scale and the Japanese Thyroid Association criteria, were critically assessed based on their sensitivity, specificity, and clinical applicability. Our findings reveal that existing diagnostic criteria and scoring systems, although valuable tools, exhibit limitations. They may lack sensitivity in identifying milder cases of thyroid storm or fail to differentiate it from other critical conditions. Furthermore, some criteria rely heavily on subjective clinical Judgment, which can vary among healthcare providers. Future research should focus on refining existing criteria and developing more objective and universally applicable diagnostic tools to address these limitations. Incorporating advanced laboratory markers and modern imaging techniques may enhance diagnostic accuracy. Additionally, a standardized scoring system approach could improve clinical practice consistency. In conclusion, while current diagnostic criteria and scoring systems provide a foundation for identifying thyroid storm, their utility has shortcomings. Advancements in diagnostic methods and a collaborative effort to establish standardized criteria are imperative to enhance the accuracy and reliability of thyroid storm diagnosis, ultimately improving patient outcomes.


Assuntos
Crise Tireóidea , Humanos , Crise Tireóidea/diagnóstico , Crise Tireóidea/tratamento farmacológico , Reprodutibilidade dos Testes
13.
Nephrology (Carlton) ; 29(6): 311-324, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38403867

RESUMO

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.


Assuntos
Consenso , Hiperpotassemia , Humanos , Hiperpotassemia/epidemiologia , Hiperpotassemia/terapia , Hiperpotassemia/diagnóstico , Ásia/epidemiologia , Fatores de Risco , Potássio/sangue , Silicatos/uso terapêutico , Silicatos/efeitos adversos
14.
Heliyon ; 10(4): e25934, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38384510

RESUMO

The railway industry has witnessed increasing adoption of digital technologies, known as Railway 4.0, that is revolutionizing operations, infrastructure, and transportation systems. However, developing countries face challenges in keeping pace with these technological advancements. With limited research on Railway 4.0 adoption in developing countries, this study was motivated to investigate the awareness, readiness, and challenges faced by railway professionals towards implementing Railway 4.0 technologies. The aim was to assess the level of awareness and preparedness and identify the key challenges influencing Railway 4.0 adoption in Nigeria's railway construction industry. A questionnaire survey (was distributed to professionals in the railway construction sector to gather their perspectives on awareness of, preparation for, and challenges associated with the use of Railway 4.0 technologies. The results revealed that awareness of Railway 4.0 technologies was moderate, while readiness was low among the professionals. Using exploratory factor analysis, 10 underlying challenge constructs were identified including lack of technical know-how, resistance to change, infrastructure limitations, and uncertainty about benefits, amongst others. Partial Least Square Structural Equation Modelling (PLS-SEM) confirmed these constructs, with reliability and availability, lack of technical know-how, lack of training and resources, and uncertainties in benefit and gains having significant influence on awareness and readiness. The study concludes that focused efforts in training, infrastructure improvement, supportive policies, and communicating the advantages of Railway 4.0 are critical to drive adoption in Nigeria and other developing economies. The findings provide insights into tailoring Railway 4.0 implementation strategies for developing contexts.

15.
Curr Cardiol Rep ; 26(4): 211-220, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38342801

RESUMO

PURPOSE OF REVIEW: The surgical management of symptomatic peripheral artery disease (PAD) has changed in the last few decades. Improvement in endovascular technology has resulted in more complex lesion once reserved for open surgery being addressed in an endovascular fashion. Even with these advances, there are lesions and patients that are better managed with an open surgical procedure. The aim of this review is to describe the most commonly performed open surgical procedures for PAD. RECENT FINDINGS: The recently published Best Endovascular versus Best Surgical Therapy (BEST-CLI) trial was an international, prospective, randomized controlled trial that aimed to investigate which revascularization (endovascular vs. surgical bypass) approach was superior for limb salvage. The evidence supports an open surgical bypass as an initial approach. The advancements made in the surgical management of PAD have provided options for patients who were once deemed poor surgical candidates. The goal continues to be utilization of the best available tools to address patient disease. In this current era, it is important to be familiar with the open surgical therapies.


Assuntos
Procedimentos Endovasculares , Doença Arterial Periférica , Humanos , Estudos Prospectivos , Isquemia/terapia , Resultado do Tratamento , Doença Arterial Periférica/cirurgia , Salvamento de Membro , Fatores de Risco , Estudos Retrospectivos , Extremidade Inferior/irrigação sanguínea
16.
Artigo em Inglês | MEDLINE | ID: mdl-38395024

RESUMO

Peripartum cardiomyopathy (PPCM) causes pregnancy-associated heart failure, typically during the last month of pregnancy, and up to 6 months post-partum, in women without known cardiovascular disease. PPCM is a global disease, but with a significant geographical variability within and between countries. Its true incidence in Africa is still unknown because of the lack of a PPCM population-based study. The variability in the epidemiology of PPCM between and within countries could be due to differences in the prevalence of both genetic and non-genetic risk factors. Several risk factors have been implicated in the aetiopathogenesis of PPCM over the years. Majority of patients with PPCM present with symptoms and signs of congestive cardiac failure. Diagnostic work up in PPCM is prompted by strong clinical suspicion, but Echocardiography is the main imaging technique for diagnosis. The management of PPCM involves multiple disciplines - cardiologists, anaesthetists, intensivists, obstetricians, neonatologists, and the prognosis varies widely.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Complicações Cardiovasculares na Gravidez , Transtornos Puerperais , Gravidez , Humanos , Feminino , Período Periparto , Países em Desenvolvimento , Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Cardiomiopatias/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/epidemiologia , Transtornos Puerperais/terapia , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/epidemiologia , Complicações Cardiovasculares na Gravidez/terapia
17.
Sci Adv ; 10(3): eadn3478, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38232169

RESUMO

Data science is assuming a pivotal role in guiding reaction optimization and streamlining experimental workloads in the evolving landscape of synthetic chemistry. A discipline-wide goal is the development of workflows that integrate computational chemistry and data science tools with high-throughput experimentation as it provides experimentalists the ability to maximize success in expensive synthetic campaigns. Here, we report an end-to-end data-driven process to effectively predict how structural features of coupling partners and ligands affect Cu-catalyzed C-N coupling reactions. The established workflow underscores the limitations posed by substrates and ligands while also providing a systematic ligand prediction tool that uses probability to assess when a ligand will be successful. This platform is strategically designed to confront the intrinsic unpredictability frequently encountered in synthetic reaction deployment.

18.
Nurs Inq ; 31(1): e12562, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37211658

RESUMO

With this paper, we walk out some central ideas about posthumanisms and the ways in which nursing is already deeply entangled with them. At the same time, we point to ways in which nursing might benefit from further entanglement with other ideas emerging from posthumanisms. We first offer up a brief history of posthumanisms, following multiple roots to several points of formation. We then turn to key flavors of posthuman thought to differentiate between them and clarify our collective understanding and use of the terms. This includes considerations of the threads of transhumanism, critical posthumanism, feminist new materialism, and the speculative, affirmative ethics that arise from critical posthumanism and feminist new materialism. These ideas are fruitful for nursing, and already in action in many cases, which is the matter we occupy ourselves with in the final third of the paper. We consider the ways nursing is already posthuman-sometimes even critically so-and the speculative worldbuilding of nursing as praxis. We conclude with visions for a critical posthumanist nursing that attends to humans and other/more/nonhumans, situated and material and embodied and connected, in relation.


Assuntos
Feminismo , Humanismo , Humanos
19.
J Clin Invest ; 134(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-37934611

RESUMO

BACKGROUNDPhase 1 study of ATRinhibition alone or with radiation therapy (PATRIOT) was a first-in-human phase I study of the oral ATR (ataxia telangiectasia and Rad3-related) inhibitor ceralasertib (AZD6738) in advanced solid tumors.METHODSThe primary objective was safety. Secondary objectives included assessment of antitumor responses and pharmacokinetic (PK) and pharmacodynamic (PD) studies. Sixty-seven patients received 20-240 mg ceralasertib BD continuously or intermittently (14 of a 28-day cycle).RESULTSIntermittent dosing was better tolerated than continuous, which was associated with dose-limiting hematological toxicity. The recommended phase 2 dose of ceralasertib was 160 mg twice daily for 2 weeks in a 4-weekly cycle. Modulation of target and increased DNA damage were identified in tumor and surrogate PD. There were 5 (8%) confirmed partial responses (PRs) (40-240 mg BD), 34 (52%) stable disease (SD), including 1 unconfirmed PR, and 27 (41%) progressive disease. Durable responses were seen in tumors with loss of AT-rich interactive domain-containing protein 1A (ARID1A) and DNA damage-response defects. Treatment-modulated tumor and systemic immune markers and responding tumors were more immune inflamed than nonresponding.CONCLUSIONCeralasertib monotherapy was tolerated at 160 mg BD intermittently and associated with antitumor activity.TRIAL REGISTRATIONClinicaltrials.gov: NCT02223923, EudraCT: 2013-003994-84.FUNDINGCancer Research UK, AstraZeneca, UK Department of Health (National Institute for Health Research), Rosetrees Trust, Experimental Cancer Medicine Centre.


Assuntos
Morfolinas , Neoplasias , Pirimidinas , Sulfonamidas , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Indóis , Inflamação/tratamento farmacológico , Genômica , Proteínas Mutadas de Ataxia Telangiectasia/genética
20.
Am J Clin Exp Urol ; 11(6): 559-577, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148930

RESUMO

Lower urinary tract dysfunction (LUTD) encompasses a range of debilitating conditions that affect both sexes and different age groups. Understanding the underlying neurobiological mechanisms contributing to LUTD has emerged as a critical avenue for the development of targeted therapeutic strategies. Brain-derived neurotrophic factor (BDNF), a prominent member of the neurotrophin family, has attracted attention due to its multiple roles in neural development, plasticity, and maintenance. This review examines the intricate interplay between neurobiological factors and LUTD, focusing on the central involvement of BDNF. The review emphasizes the bidirectional relationship between LUTD and BDNF and explores how LUTD-induced neural changes may affect BDNF dynamics and vice versa. Growth factor therapy and the combined administration of controlled release growth factors and stem cells are minimally invasive treatment strategies for neuromuscular injury. Among the many growth factors and cytokines, brain-derived neurotrophic factor (BDNF) plays a prominent role in neuromuscular repair. As an essential neurotrophin, BDNF is involved in the modulation of neuromuscular regeneration through tropomyosin receptor kinase B (TrkB). Increasing BDNF levels facilitates the regeneration of the external urethral sphincter and contributes to the regulation of bladder contraction. Treatments targeting the BDNF pathway and sustained release of BDNF may become novel treatment options for urinary incontinence and other forms of lower urinary tract dysfunction. This review discusses the applications of BDNF and the theoretical basis for its use in the treatment of lower urinary tract dysfunction, including urinary incontinence (UI), overactive bladder (OAB), and benign prostatic hyperplasia (BPH), and in the clinical diagnosis of bladder dysfunction.

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