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Physical inactivity is a global public health challenge, and effective, large-scale interventions are needed. We examined the effectiveness of a population-wide mobile health (mHealth) intervention in Singapore, National Steps Challenge Season 3 (NSC3) and 2 booster challenges (Personal Pledge and Corporate Challenge). The study includes 411,528 participants. We used regression discontinuity design and difference-in-difference with fixed-effects regression to examine the association of NSC3 and the additional booster challenges on daily step counts. Participants tended to be female (58.5%), with an average age of 41.5 years (standard deviation, 13.9) and body mass index (weight (kg)/height (m)2) of 23.8 (standard deviation, 4.5). We observed that NSC3 was associated with a mean increase of 1,437 steps (95% confidence interval (CI): 1,408, 1,467) per day. Enrollments in Personal Pledge and Corporate Challenge were associated with additional mean increases of 1,172 (95% CI: 1,123, 1,222) and 896 (95% CI: 862, 930) steps per day, respectively. For NSC3, the associated mean increase in the step counts across different sex and age groups varied, with greater increases for female participants and those in the oldest age group. We provide real-world evidence suggesting that NSC3 was associated with improvements in participants' step counts. Results suggest NSC3 is an effective and appealing population-wide mHealth physical activity intervention.
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Exercício Físico , Telemedicina , Humanos , Adulto , Feminino , Estudos de Coortes , Índice de Massa Corporal , Comportamento SedentárioRESUMO
BACKGROUND: Nurturing effective physician-patient relationships is essential to the provision of patient-centred care. Palliative care physicians may apply boundary-crossings or breaches in professional standards to nurture effective physician-patient relationships. Being highly individualized and shaped by the physician's narratives, clinical experience, and contextual considerations, boundary-crossings are susceptible to ethical and professional violations. To better appreciate this concept, we employ the Ring Theory of Personhood (RToP) to map the effects of boundary-crossings on the physician's belief systems. METHODS: As part of the Tool Design SEBA methodology, a Systematic Evidence-Based Approach (SEBA) guided systematic scoping review was employed to guide the design of a semi-structured interview questionnaire with palliative care physicians. The transcripts were simultaneously content and thematically analysed. The themes and categories identified were combined using the Jigsaw Perspective and the resulting domains formed the basis for the discussion. RESULTS: The domains identified from the 12 semi-structured interviews were catalysts and boundary-crossings. Boundary-crossings attempt to address threats to a physician's belief systems (catalysts) and are highly individualized. Employ of boundary-crossings depend on the physician's sensitivity to these 'catalysts', their judgement and willingness to act, and their ability to balance various considerations and reflect on their actions and their ramifications. These experiences reshape belief systems, understandings of boundary-crossings and may influence decision-making and practice, underscoring the potential for greater professional breaches when unchecked. CONCLUSION: Underlining its longitudinal effects, the Krishna Model underscores the importance of longitudinal support, assessment and oversight of palliative care physicians, and lays the foundation for a RToP-based tool to be employed within portfolios.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Médicos , Humanos , Cuidados Paliativos , Relações Médico-PacienteRESUMO
BACKGROUND: A nurse's role in caring for the dying is fraught with ethical, professional, and psychosocial challenges that impact how they perceive their roles as professionals. When unsupported, nurses caring for the dying experience burnout, career dissatisfaction and leave the profession. Better understanding of how caring for the dying affects the professional identity formation (PIF) of nurses will guide efforts to better support nurses. METHODS: Guided by new data on the subject, we adopt the theoretical lens of the Ring Theory of Personhood (RToP) to evaluate how caring for the dying impacts the values, beliefs, principles, professional identities and personhood of nurses. We employ Krishna's Systematic Evidence-Based Approach (SEBA) to guide the design and piloting of the semi-structured interview tool. RESULTS: Analysis of interviews with eight senior nurses in Supportive, Palliative and Oncology care revealed three domains: Identity 1) Formation; 2) Conflict and 3) Refinement. Identity Formation occurs early in a nurse's career, upon entering a new specialist field, and at the start of Supportive, Palliative and Oncology care. Identity Formation reveals significant changes to how self-concepts of professional identities are tied to individual concepts of personhood. Caring for the dying, however, resulted in Conflicts between values, beliefs, and principles within regnant concepts of personhood and their professional duties. These conflicts are captured as conflicts within ('disharmony') and/or between ('dyssynchrony') the rings of the RToP. These conflicts can result in changes to self-concepts of personhood and professional identities. Identity Refinement sees experience and timely support helping nurses attenuate the impact of difficult experiences. This reduces the risk of burnout and mitigates changes to their professional identities. Identity Refinement helps them develop a 'rooted identity' which remains relatively consistent in the face of adversity. CONCLUSIONS: Ongoing Identity Construction amongst nurses, particularly in caring for the dying, underscore the host organisation's role in ensuring structured, longitudinal, accessible, and personalised assessments and support of nurses, especially when they are prone to dyssynchrony and disharmony whilst caring for the terminally ill. Further study into assessment methods and the role of the environment is critical.
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Esgotamento Profissional , Neoplasias , Humanos , Pessoalidade , Pesquisa Qualitativa , Singapura , Doente TerminalRESUMO
BACKGROUND: Mentoring's pivotal role in nurturing professional identity formation (PIF) owes much to its combined use with supervision, coaching, tutoring, instruction, and teaching. However the effects of this combination called the 'mentoring umbrella' remains poorly understood. This systematic scoping review thus aims to map current understanding. METHODS: A Systematic Evidence-Based Approach guided systematic scoping review seeks to map current understanding of the 'mentoring umbrella' and its effects on PIF on medical students and physicians in training. It is hoped that insights provided will guide structuring, support and oversight of the 'mentoring umbrella' in nurturing PIF. Articles published between 2000 and 2021 in PubMed, Scopus, ERIC and the Cochrane databases were scrutinised. The included articles were concurrently summarised and tabulated and concurrently analysed using content and thematic analysis and tabulated. The themes and categories identified were compared with the summaries of the included articles to create accountable and reproducible domains that guide the discussion. RESULTS: A total of 12201 abstracts were reviewed, 657 full text articles evaluated, and 207 articles included. The three domains identified were definitions; impact on PIF; and enablers and barriers. The mentoring umbrella shapes PIF in 3 stages and builds a cognitive base of essential knowledge, skills and professional attitudes. The cognitive base informs thinking, conduct and opinions in early supervised clinical exposure in Communities of practice (COP). The COPs' individualised approach to the inculcation of desired professional characteristics, goals, values, principles and beliefs reshapes the individual's identity whilst the socialisation process sees to their integration into current identities. CONCLUSION: The mentoring umbrella's provides personalised longitudinal support in the COP and socialisation process. Understanding it is key to addressing difficulties faced and ensuring holistic and timely support.
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Tutoria , Médicos , Estudantes de Medicina , Humanos , Mentores/educação , Identificação Social , Estudantes de Medicina/psicologiaRESUMO
BACKGROUND: Despite a global call for action and growing burden of non-communicable diseases (NCD) associated with physical inactivity, effective interventions to increase community-wide physical activity (PA) remain few. NCDs accounted for 80% of Singapore's disease burden (2015) and yet 40% of Singaporeans did not meet minimum recommended weekly PA despite evidence of the benefits to cardiorespiratory health, diabetes and cancer prevention. METHODS: A large-scale public health intervention was initiated in 2015 to increase population-level PA through incidental daily walking. Intervention components included fitness trackers, redeemable rewards and gamification, implemented in a mutually-reinforcing manner within an eco-system supportive of PA and informed by real-time data analytics. Mean daily step count at baseline and post-intervention were compared across periods, and the influence of participant sub-groups characteristics on overall results, using significance tests. Standards for Reporting on Implementation Studies (StaRI) were adhered to. RESULTS: Intervention reach increased fourfold from 129,677 participants in wave 1 (2015-16) to 690,233 in wave 3 (2017-18) amounting to a total of 1,184,410 Step Challenge participations. Mean days of fitness tracker use increased from 2.4 to 5.0 days/week among participants completing the Challenge in wave 1 and from 5.3 to 6.0 days/week in wave 3. The mean number of daily steps between pre-Challenge and Challenge periods increased by 4163 (sd=1360; p< 0.001) in wave 1, by 2242 (sd=334; p< 0.001) in wave 2 and by 1645 steps/day (sd=54; p< 0.001) in wave 3. Mean daily step increases between wave 1 and 3 also suggest that incidental PA was maintained, a finding supported by a 2017 national population survey showing that incidental PA among adults increased from 5% in 2010 to 14% in 2017 while moderate-intensity PA increased from 5 to 10% over the same period. CONCLUSION: Population-level PA was effectively increased through multi-level interventions integrating technology, behavioural economics, gamification, marketing, communications and community linkages within a supportive context- and climate-appropriate environment. Responsive data analytics were instrumental to strengthen implementation by tailoring modalities that maximise effectiveness at population-level. Further analyses are needed to explore potential barriers, challenges or unmet needs in sub-groups with lower uptake to tailor future interventions for greater reach and impact.
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Exercício Físico , Motivação , Adulto , Monitores de Aptidão Física , Humanos , Tecnologia , CaminhadaRESUMO
PROBLEM: In the Katherine region, Northern Territory, barriers to eye care for Aboriginal and Torres Strait Islander people include unclear eye care referral processes, challenges coordinating patient eye care between various providers, complex socioeconomic determinants and a lengthy outpatient ophthalmology waiting list. DESIGN: Mixed methods participatory approach using a regional needs analysis, clinical file audit and stakeholder survey, to develop, implement and monitor quality improvement strategies. SETTING: Collaboration with Aboriginal Community Controlled Health Services and regional eye care stakeholders in the Katherine region. KEY MEASURES FOR IMPROVEMENT: Clinical audit data captured frequency and rates of primary eye checks, ophthalmology referrals and spectacle prescriptions. A survey was developed and applied to assess stakeholder perspectives of regional eye care systems. STRATEGY FOR CHANGE: Quality improvement strategies informed by regional data (clinical audits and survey) included increasing service delivery to match eye care needs, primary eye care training for Aboriginal Community Controlled Health Services staff, updating Aboriginal Community Controlled Health Services primary care templates and forming a regional eye care coalition group. EFFECTS OF CHANGE: Post-implementation, rates and frequency of recorded optometry examinations, number of spectacles prescribed and rates of annual dilated fundus examinations for patients with diabetes increased. There was a decrease in the number of patients with diabetes who had never had an eye examination. Eye care stakeholders perceived a marked improvement in the effectiveness of the regional eye care system. LESSONS LEARNT: Our findings highlight the importance of engaging services and stakeholders to ensure a systems approach that is evidence-informed, contextually appropriate and reflects commitment to improved eye health outcomes.
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Serviços de Saúde Comunitária/organização & administração , Promoção da Saúde/métodos , Serviços de Saúde do Indígena/organização & administração , Havaiano Nativo ou Outro Ilhéu do Pacífico/educação , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Optometria/educação , Melhoria de Qualidade/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Serviços de Saúde Comunitária/estatística & dados numéricos , Feminino , Serviços de Saúde do Indígena/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Northern Territory , Melhoria de Qualidade/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
Spontaneous folding of a polypeptide chain into a knotted structure remains one of the most puzzling and fascinating features of protein folding. The folding of knotted proteins is on the timescale of minutes and thus hard to reproduce with atomistic simulations that have been able to reproduce features of ultrafast folding in great detail. Furthermore, it is generally not possible to control the topology of the unfolded state. Single-molecule force spectroscopy is an ideal tool for overcoming this problem: by variation of pulling directions, we controlled the knotting topology of the unfolded state of the 52-knotted protein ubiquitin C-terminal hydrolase isoenzyme L1 (UCH-L1) and have therefore been able to quantify the influence of knotting on its folding rate. Here, we provide direct evidence that a threading event associated with formation of either a 31 or 52 knot, or a step closely associated with it, significantly slows down the folding of UCH-L1. The results of the optical tweezers experiments highlight the complex nature of the folding pathway, many additional intermediate structures being detected that cannot be resolved by intrinsic fluorescence. Mechanical stretching of knotted proteins is also of importance for understanding the possible implications of knots in proteins for cellular degradation. Compared with a simple 31 knot, we measure a significantly larger size for the 52 knot in the unfolded state that can be further tightened with higher forces. Our results highlight the potential difficulties in degrading a 52 knot compared with a 31 knot.
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Redobramento de Proteína , Desdobramento de Proteína , Ubiquitina Tiolesterase/química , Pinças Ópticas , Imagem Individual de MoléculaRESUMO
We determine whether age is a prognostic factor for surgical outcomes of external dacryocystorhinostomy (Ex-DCR). This retrospective cohort study conducted at Tilganga Institute of Ophthalmology (Kathmandu, Nepal) compared pediatric Ex-DCR procedures (age ≤ 15 years) to adult Ex-DCR procedures (age > 15 years) and was performed between January 2013 and December 2013, with a minimum follow-up period of 6 months. Primary outcome measure was rate of success, defined as complete resolution of subjective symptom(s) of epiphora (subjective success), combined with patent lacrimal passage on syringing (anatomical success) at last follow-up visit. Other outcome measures included clinical presentation, diagnosis, intraoperative complications and post-operative complications. In total, 154 Ex-DCR procedures were included, with an age range of 8 months to 81 years (mean age 36.4 ± 21.0 years). In all, 38 pediatric Ex-DCR procedures were compared to 116 adult procedures. Success rates were 97% in the pediatric group and 95% in the adult group, with no clinically or statistically significant difference in success rate or complication rate between groups (p > 0.05). Our study yielded high success rates of Ex-DCR in both pediatric and adult age groups suggesting that Ex-DCR remains an optimal treatment choice for all age groups. With no difference in surgical outcomes between pediatric and adult patients, including complication rate, we conclude that age is not a prognostic factor for Ex-DCR failure. We do not recommend adjuvant therapy for pediatric patients.
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Dacriocistorinostomia , Obstrução dos Ductos Lacrimais/terapia , Ducto Nasolacrimal/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dacriocistorinostomia/métodos , Feminino , Humanos , Lactente , Complicações Intraoperatórias , Obstrução dos Ductos Lacrimais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ducto Nasolacrimal/fisiopatologia , Nepal , Complicações Pós-Operatórias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: DDX5/p68 RNA helicase is a member of the DEAD (Asp-Glu-Ala-Asp) box proteins. Apart from RNA unwinding, DDX5 is an important transcriptional factor and co-activator in cell proliferation and differentiation. FINDINGS: Here, we have characterised the role of DDX5 in adipogenesis in 3T3-L1 cells using siRNA mediated suppression. Transient inhibition of Ddx5 mRNA expression at the start of adipogenesis impairs the differentiation programme even when DDX5 expression is restored later in adipogenesis. However transient suppression of Ddx5 at the later stages of adipogenesis do not impair adipogenesis or triglyceride accumulation suggesting Ddx5 expression is dispensable in a mature adipocyte. CONCLUSION: These results implicate DDX5 as a crucial factor involved in the complex transcriptional cascade of events that regulate adipogenesis and essential to the initiation of adipogenesis.
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Adipogenia , RNA Helicases DEAD-box/metabolismo , Células-Tronco Mesenquimais/enzimologia , Células 3T3-L1 , Adipócitos/enzimologia , Animais , RNA Helicases DEAD-box/genética , Expressão Gênica , Técnicas de Silenciamento de Genes , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C3HAssuntos
Exercício Físico , Promoção da Saúde/métodos , Telemedicina , Adulto , Exercício Físico/psicologia , Humanos , Aplicativos Móveis , Motivação , Singapura , SmartphoneRESUMO
BACKGROUND: The widespread use of physical activity trackers enables the collection of high-resolution health data, such as hourly step counts, to evaluate health promotion programmes. We aim to investigate how participants meet their daily step goals. METHODS: We used 24-h steps data from the National Steps ChallengeTM Season 3, wherein participants were rewarded with vouchers when achieving specified goals of 5000, 7500, and 10,000 steps per day. We extracted data from 3075 participants' including a total of 52,346 participant-days. We modelled the hourly step counts using a two-part model, in which the distribution for step counts was allowed to depend on the sum of step counts up to the previous hour and participant demographics. RESULTS: Participants have a mean age of 44.2 years (standard deviation = 13.9), and 40.4% are males. We show that on weekdays, the hourly mean step counts among participants aged 60 and above are higher than participants aged 30 to 59 from the start of the day till 6 p.m. We also find that participants who accumulate at least 7000 steps by 7 p.m. are associated with higher success of achieving 10,000 steps. CONCLUSIONS: We provide recommendations on the hourly targets to achieve daily goals, based on different participants' characteristics. Future studies could experimentally test if prompts and nudges at the recommended times of day could promote reaching step goals.
The National Steps ChallengeTM is a nationwide physical activity programme in Singapore that encourages participants to exercise more. We used daily step data from over 3000 adult participants to investigate how different types of participants met their daily step goals. We found that participants who had taken at least 7000 steps by 7 p.m. were more likely to achieve 10,000 steps by the end of the day. Based on our analysis, we propose specific recommendations for hourly targets based on characteristics such as age and sex. Our study provides a better understanding of the population's physical activity levels which will enable people to be given targeted recommendations based on their own characteristics that might facilitate them more easily meeting their exercise goals.
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PURPOSE: Breast cancer is a major cause of cancer-related mortality among African women. The adoption of molecular genomic technologies in the management of cancer cases is limited in Africa. To provide much-needed insights on the feasibility and utility of such precision medicine paradigms in Africa, we conducted a prospective, non-interventional study involving combined tissue and plasma Next-generation sequencing (NGS)-based testing in cancer patients in Ghana. METHODS: We recruited 20 newly diagnosed, histologically confirmed, treatment-naïve women with metastatic breast cancer at the Cape Coast Teaching Hospital in Ghana. Tissue (NGS) and cell-free DNA (cfDNA) liquid biopsy analysis were ordered on all 20 patients. RESULTS: All 20/20 (100 %) liquid biopsy samples were acceptable for analysis, whereas only 6/20 (30 %) passed quality control for tissue NGS testing. Liquid biopsy detected 42 cfDNA mutations in 17/20 patients. Of the 17 patients, 3 (17.6 %) had mutations previously associated with African ancestry, including BRCA1 p.K719E, ARAF p.S262I and GATA3 p.G125dup. Eight potentially actionable alterations specific to breast cancer were found in 6/17 (35.3 %) liquid biopsy samples, while potentially actionable mutations non-specific to breast cancer were detected in 12/17 (70.6 %). Tissue biopsy analysis detected mutations in all 6 patients tested, with 3/6 (50 %) patients presenting potentially actionable mutations relevant to breast cancer. CONCLUSION: Liquid biopsy detected multiple additional actionable variants in Ghanaian women with breast cancer. Plasma cfDNA analysis featured fewer variations in sample preparation which is a key consideration in resource-limited settings. Liquid biopsy presents a great opportunity to improve cancer care in Africa.
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BACKGROUND: People with diabetic foot ulcers (DFU) are at risk of major amputation, which is associated with a high mortality rate (exceeding 50% at five years) and reduced quality of life. We hypothesise that flap reconstruction of diabetic foot ulcers improves patient outcomes in comparison to standard treatment modalities including major amputation. METHODS: MEDLINE, EMBASE, the Cochrane Library and grey literature were searched on 9 th February 2022. Comparative and single-arm studies reporting outcomes of DFU treated with local, regional or free flaps including function, limb loss, mortality, and flap failure were included. Risk of bias was assessed and meta-analysis of proportions was performed. RESULTS: 3,878 records were retrieved, of which 45 met the inclusion criteria, including 1,681 patients who underwent flap reconstruction of DFU. Free flaps were most commonly performed (n = 1,257, 72%). Only one study utilised a verified functional outcome measure. At 12 months, the mortality rate was 6.35% (95% C.I. 3.89 - 10.20), limb loss rate was 11.39% (95% C.I. 7.02 - 17.96) and the free flap failure rate was 9.95% (95% C.I. 8.19 - 12.05). All studies were at high risk of bias. A comparative meta-analysis of interventions was not performed due to study method and outcome heterogeneity. CONCLUSIONS: There is short-term evidence that flap reconstruction (including microsurgical transfer) has low mortality, limb loss and flap failure rates. However, there are limited high-quality comparative studies, and uncertainty remains regarding the outcome of DFU flap reconstruction in comparison to other treatments.
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PURPOSE: To use optical coherence tomography angiography (OCTA) parameters from both the retinal and choroidal microvasculature to detect the presence and severity of diabetic retinopathy (DR). METHOD: This is a cross-sectional case-control study. OCTA parameters from retinal vasculature, fovea avascular zone (FAZ) and choriocapillaris were evaluated from 3×3 mm2 fovea-centred scans. Areas under the receiver operating characteristic (ROC) curve were used to compare the discriminative power on the presence of diabetes mellitus (DM), the presence of DR and need for referral: group 1 (no DM vs DM no DR), group 2 (no DR vs any DR) and group 3 (non-proliferative DR (NPDR) vs proliferative DR (PDR)). RESULTS: 35 eyes from 27 participants with no DM and 132 eyes from 75 with DM were included. DR severity was classified into three groups: no DR group (62 eyes), NPDR (51 eyes), PDR (19 eyes). All retinal vascular parameters, FAZ parameters and choriocapillaris parameters were strongly altered with DR stages (p<0.01), except for the deep plexus FAZ area (p=0.619). Choriocapillaris parameters allowed to better discriminate between no DM versus DM no DR group compared with retinal parameters (areas under the ROC curve=0.954 vs 0.821, p=0.006). A classification model including retinal and choroidal microvasculature significantly improved the discrimination between DR and no DR compared with each parameter separately (p=0.029). CONCLUSIONS: Evaluating OCTA parameters from both the retinal and choroidal microvasculature in 3×3 mm scans improves the discrimination of DM and early DR.
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Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Estudos de Casos e Controles , Angiofluoresceinografia/métodos , Estudos Transversais , Benchmarking , Vasos Retinianos , Corioide/irrigação sanguínea , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: There remains uncertainty regarding optimal definitive management for malignant posterior circulation infarcts (MPCI). While guidelines recommend neurosurgery for malignant cerebellar infarcts that are refractory to medical therapy, concerns exist about the functional outcome and quality of life after decompressive surgery. OBJECTIVE: This study aims to evaluate the outcomes of surgical intervention compared to medical therapy in MPCI. METHODS: In this systematic review, MEDLINE, Embase and Cochrane databases were searched from inception until 2 April 2021. Studies were included if they involved posterior circulation strokes treated with neurosurgical intervention and reported mortality and functional outcome data. Data were collected according to PRISMA guidelines. RESULTS: The search yielded 6677 studies, of which 31 studies (comprising 723 patients) were included for analysis. From the included studies, we found that surgical therapy led to significant differences in mortality and functional outcomes in patients with severe disease. Neurological decline and radiological criteria were often used to decide the timing for surgical intervention, as there is currently limited evidence for preventative neurosurgery. There is also limited evidence for the superiority of one surgical modality over another. CONCLUSION: For patients with MPCI who are clinically stable at the time of presentation, in terms of mortality and functional outcome, surgical therapy appears to be equivocal to medical therapy. Reliable evidence is lacking, and further prospective studies are rendered.
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Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of lipids and immune cells in plaques built up inside artery walls. Docosahexaenoic acid (DHA, 22:6n-3), an omega-3 polyunsaturated fatty acid (PUFA), which exerts anti-inflammatory and antioxidant properties, has long been purported to be of therapeutic benefit to atherosclerosis patients. However, large clinical trials have yielded inconsistent data, likely due to variations in the formulation, dosage, and bioavailability of DHA following oral intake. To fully exploit its potential therapeutic effects, we have developed an injectable liposomal DHA formulation intended for intravenous administration as a plaque-targeted nanomedicine. The liposomal formulation protects DHA against chemical degradation and increases its local concentration within atherosclerotic lesions. Mechanistically, DHA liposomes are readily phagocytosed by activated macrophages, exert potent anti-inflammatory and antioxidant effects, and inhibit foam cell formation. Upon intravenous administration, DHA liposomes accumulate preferentially in atherosclerotic lesional macrophages and promote polarization of macrophages towards an anti-inflammatory M2 phenotype, resulting in attenuation of atherosclerosis progression in both ApoE-/- and Ldlr-/- experimental models. Plaque composition analysis demonstrates that liposomal DHA inhibits macrophage infiltration, reduces lipid deposition, and increases collagen content, thus improving the stability of atherosclerotic plaques against rupture. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) further reveals that DHA liposomes can partly restore the complex lipid profile of the plaques to that of early-stage plaques. In conclusion, DHA liposomes offer a promising approach for applying DHA to stabilize atherosclerotic plaques and attenuate atherosclerosis progression, thereby preventing atherosclerosis-related cardiovascular events.
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Aterosclerose , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/metabolismo , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácidos Docosa-Hexaenoicos/farmacologia , Lipossomos/uso terapêutico , Aterosclerose/metabolismo , Anti-Inflamatórios/uso terapêutico , Apolipoproteínas E/genéticaRESUMO
Poorer outcomes have been reported with COVID-19 and influenza coinfections. As the COVID-19 pandemic rages on, protection against influenza by vaccination is becoming increasingly important. This study examines how COVID-19 has influenced influenza vaccination intentions from a global perspective. A literature search was conducted on Embase, PubMed, and CNKI from 1 January 2019 to 31 December 2021 for articles reporting rates of influenza vaccination pre-COVID-19 (19/20 season), and intention and/or uptake of influenza vaccination post-COVID-19 (20/21 season). The changes in vaccination intention and reasons for changes were reported. Subgroup analyses were performed by region, gender, age, and occupation. Newcastle Ottawa Scale was used for quality assessment of the articles. Twenty-seven studies with 39,193 participants were included. Among 22 studies reporting intention to vaccinate in 20/21, there was increased intention to vaccinate (RR 1.50, 95% CI 1.32−1.69, p < 0.001) regardless of age, gender, and occupation. The remaining five studies reporting vaccination intention and uptake in 20/21 showed a similar increase (RR 1.68, 95%CI 1.20−2.36). Important determinants include historical vaccine acceptance, and perception of influenza severity and vaccine safety. The COVID-19 pandemic has increased intention to vaccinate against influenza internationally. The pandemic could be a window of opportunity to promote influenza vaccination and decrease vaccine hesitancy.
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BACKGROUND: The mechanisms through which drug-cue-induced negative affective states are involved in relapse have not been defined. We tested the hypothesis that in individuals having developed a dorsolateral striatum (DLS)-dependent cue-controlled cocaine-seeking habit, the loss of the opportunity to enact the drug-seeking response during abstinence results in an urge to act that exacerbates relapse severity mediated by negative urgency. METHODS: Eighty-seven male Sprague Dawley rats were trained to seek cocaine under the influence of the conditioned reinforcing properties of drug-paired cues or not. We investigated whether the tendency to relapse depended on the aversive state of withdrawal or instead on the loss of opportunity to perform the ingrained drug-seeking response after periods of abstinence. The striatal locus of control over cocaine seeking at baseline and relapse was investigated using in situ hybridization of the cellular activity marker C-fos and assessment of the sensitivity of instrumental drug seeking to dopamine receptor blockade in the dorsomedial striatum-dependent goal-directed and DLS-dependent habit systems. RESULTS: The development of a DLS-dependent cue-controlled cocaine-seeking habit prior to abstinence resulted in a marked increase in drug seeking at relapse, which was not motivated by a cocaine withdrawal state and was no longer dependent on the DLS habit system. Instead, it reflected the emergence of negative urgency caused by the prevention of the performance of the habit during abstinence and underpinned by transient engagement of the goal-directed system. CONCLUSIONS: These results show that ingrained cue-controlled drug-seeking habits increase the pressure to relapse.
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Transtornos Relacionados ao Uso de Cocaína , Cocaína , Animais , Cocaína/farmacologia , Sinais (Psicologia) , Comportamento de Procura de Droga/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Recidiva , AutoadministraçãoRESUMO
Background Evidence of scaled-up physical activity interventions is scarce. This study evaluates the uptake, engagement, and effectiveness of one such intervention program. Methods and Results The program was open to individuals aged ≥17 years in Singapore. The main intervention components comprised device-based daily physical activity recording paired with step count goals and financial rewards. According to the different reward opportunities, we divided the evaluation period (August 2017 to June 2018) into the baseline monitoring phase, the main challenge phase, and the maintenance phase. Uptake was assessed by the number of individuals registered, and engagement by the step recording duration after registration. The effectiveness was defined as changes in mean daily step count from baseline to the main challenge phase and the maintenance phase. A total of 696 907 participants registered, including more Singapore citizens (versus noncitizens), women, and younger (aged 17-39 years) individuals. The evaluation of engagement and effectiveness included 421 388 (60.5%) participants who provided plausible characteristic information and step count data. The median duration of engagement was 74 (IQR, 14-149) days. Compared with the baseline of 7509 (SD, 3467) steps, mean daily step count increased by 1579 (95% CI, 1564-1594) steps during the main challenge phase and 934 (95% CI, 916-952) steps during the maintenance phase. Greater engagement and activity increase were found in participants who are citizens, women, aged ≥40 years, non-obese, and using separate wearables (versus smartphones). Conclusions Mobile health physical activity interventions can successfully reach a large population and be effective in increasing physical activity, despite declining program engagement over time.
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Exercício Físico , Telemedicina , Adulto , Feminino , Humanos , Recompensa , Singapura/epidemiologia , SmartphoneRESUMO
Objectives: Hospital outbreaks of SARS-CoV-2 infection are dreaded but preventable catastrophes. We review the literature to examine the pattern of SARS-CoV-2 transmission in hospitals and identify potential vulnerabilities to mitigate the risk of infection. Methods: Three electronic databases (PubMed, Embase and Scopus) were searched from inception to July 27, 2021 for publications reporting SARS-CoV-2 outbreaks in hospital. Relevant articles and grey literature reports were hand-searched. Results: Twenty-seven articles that described 35 SARS-CoV-2 outbreaks were included. Despite epidemiological investigations, the primary case could not be identified in 37% of outbreaks. Healthcare workers accounted for 40% of primary cases (doctors 17%, followed by ancillary staff 11%). Mortality among infected patients was approximately 15%. By contrast, none of the infected HCWs died. Several concerning patterns were identified, including infections involving ancillary staff and healthcare worker infections from the community and household contacts. Conclusion: Continuous efforts to train-retrain and enforce correct personal protective equipment use and regular routine screening tests (especially among ancillary staff) are necessary to stem future hospital outbreaks of SARS-CoV-2.