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1.
Patient Educ Couns ; 125: 108290, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38714007

RESUMO

OBJECTIVE: Electronic clinical decision support tools (eCDSTs) are interventions designed to facilitate clinical decision-making using targeted medical knowledge and patient information. While eCDSTs have been demonstrated to improve quality of care, there is a paucity of research relating to the acceptability of eCDSTs in primary care from the patients' perspective. This study aims to summarize current evidence relating to primary care patients' perceptions and experiences on the use of eCDSTs by their clinician to provide care. METHODS: Four databases (Medline, Embase, CINAHL and Cochrane Library) were searched for qualitative and quantitative studies with outcomes relating to patients' perceptions of the use of clinician-facing or shared-eCDSTs. Data extraction and critical appraisal using the Johanna Briggs Institute Critical Appraisal checklists were carried out independently by reviewers. Qualitative and quantitative outcomes were synthesized independently. We used Richardson et al. 'Patient Evaluation of Artificial Intelligence (AI) in Healthcare' framework for qualitative analysis. FINDINGS: 20 papers were included for synthesis. eCDSTs were generally well-regarded by patients. The key facilitators for use were promoting informed decision-making, prompting discussions, aiding clinical decision-making, and enabling information sharing. Key barriers for use were lack of holistic care, 'medicalized' language, and confidentiality concerns. CONCLUSION: Our study identified important aspects to consider in the development of future eCDSTs. Patients were generally positive regarding the use of eCDSTs; however, patient's perspectives should be included from the conception of new eCDSTs to ensure recommendations align with the needs of patients and clinicians. PRACTICE IMPLICATIONS: The study results contribute to ensuring the acceptability of eCDSTs for patients and their unique needs. Encouragement is given for future development to adopt and build upon these findings. Additional research focusing on patients' perceptions of using eCDSTs for specific health conditions is deemed necessary.

2.
Angew Chem Int Ed Engl ; : e202401261, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687258

RESUMO

Aggregation is a conventional method to enhance the quantum yields (QYs) of pure organic luminophores due to the restriction of intramolecular motions (RIM). However, how to realize RIM in metal-organic frameworks (MOFs) is still unclear and challenging. In this work, the ligand meta-anchoring strategy is first proposed and proved to be an effective and systematic approach to restrict the intramolecular motions of MOFs for the QY improvement. By simply shifting the substituent position in the ligand from para to meta, the QY of the resulting MOF is significantly enhanced by eleven-fold. The value is even higher than that of ligand aggregates, demonstrating the strong RIM effect of this ligand meta-anchoring strategy. The introduction of co-ligand induces the appearance of visible yellow room temperature phosphorescence with a lifetime of 222 ms due to the QY enhancement and the charge transfer between the donor and accepter units. The present work thus broadens the understanding of the RIM mechanism from a new perspective, develops a novel method to realize RIM and expands the applicable objects from pure organic materials to organic-inorganic hybrid materials.

3.
Elife ; 122024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457350

RESUMO

Studies of climate variation commonly rely on chemical and isotopic changes recorded in sequentially produced growth layers, such as in corals, shells, and tree rings, as well as in accretionary deposits-ice and sediment cores, and speleothems. Oxygen isotopic compositions (δ18O) of tooth enamel are a direct method of reconstructing environmental variation experienced by an individual animal. Here, we utilize long-forming orangutan dentitions (Pongo spp.) to probe recent and ancient rainfall trends on a weekly basis over ~3-11 years per individual. We first demonstrate the lack of any consistent isotopic enrichment effect during exclusive nursing, supporting the use of primate first molar teeth as environmental proxies. Comparisons of δ18O values (n=2016) in twelve molars from six modern Bornean and Sumatran orangutans reveal a high degree of overlap, with more consistent annual and bimodal rainfall patterns in the Sumatran individuals. Comparisons with fossil orangutan δ18O values (n=955 measurements from six molars) reveal similarities between modern and late Pleistocene fossil Sumatran individuals, but differences between modern and late Pleistocene/early Holocene Bornean orangutans. These suggest drier and more open environments with reduced monsoon intensity during this earlier period in northern Borneo, consistent with other Niah Caves studies and long-term speleothem δ18O records in the broader region. This approach can be extended to test hypotheses about the paleoenvironments that early humans encountered in southeast Asia.


When an animal drinks water, two naturally occurring variants of oxygen ­ known as oxygen-18 and oxygen-16 ­ are incorporated into its growing teeth. The ratio of these variants in water changes with temperature, rainfall and other environmental conditions and therefore can provide a record of the climate during an animal's life. Teeth tend to be well preserved as fossils, which makes it possible to gain insights into this climate record even millions of years after an animal's death. Orangutans are highly endangered great apes that today live in rainforests on the islands of Borneo and Sumatra. During a period of time known as the Pleistocene (around 2.6 million years to 12,000 years ago), these apes were more widely spread across Southeast Asia. Climate records from this area in the time before human-induced climate change are somewhat limited. Therefore, fossilized orangutan teeth offer a possible way to investigate past seasonal rainfall patterns and gain insight into the kind of environments early humans would have encountered. To address this question, Smith et al. measured oxygen-18 and oxygen-16 variants in thin slices of modern-day orangutan teeth using a specialized analytical system. This established that the teeth showed seasonal patterns consistent with recent rainfall trends, and that the ratio of these oxygen variants did not appear to be impacted by milk intake in young orangutans. These findings indicated that the oxygen variants could be a useful proxy for predicting prehistoric weather patterns from orangutan teeth. Further measurements of teeth from fossilized Sumatran orangutans showed broadly similar rainfall patterns to those of teeth from modern-day orangutans. On the other hand, fossilized teeth from Borneo suggested that the environment used to be drier, with less intense wet seasons. The approach developed by Smith et al. provides an opportunity for scientists to leverage new fossil discoveries as well as existing collections to investigate past environments. This could allow future research into how climate variation may have influenced the spread of early humans through the region, as well as the evolution of orangutans and other endangered animals.


Assuntos
Hominidae , Pongo abelii , Dente , Animais , Humanos , Pongo pygmaeus , Sudeste Asiático
4.
Small Methods ; : e2400003, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552251

RESUMO

Lead-free low-dimensional organic-inorganic metal halides have gained increasing attention in a wide range of applications due to their low toxicity, outstanding optical performance, and structural tunability. In this work, a general method of incorporating organic molecule into sodium antimony bromides is introduced. The 1D Na3SbBr6(C2H6OS)6 and Na3SbBr6(C4H8OS)6 single crystals exhibit bright yellow and orange emission with PL peaks at 610 and 664 nm, and high photoluminescence quantum yields (PLQYs) of 85% and 60%, respectively. These two compounds can be reversibly converted into each other by the removal and addition of the organic components. Their exceptional luminescent performance enables them to be used as solid-state phosphors for the fabrication of yellow and orange down-conversion LEDs. A white LED with a high color rendering index (CRI) of 95 is also fabricated by using Na3SbBr6(C2H6OS)6 as the yellow phosphor. The universality of this method is demonstrated by synthesizing other members of this family with diverse A-groups, including methylammonium (MA) and formamidinium (FA). This work provides an effective strategy for the development of diverse lead-free and high-performance organic-inorganic hybrid materials and indicates these organic-inorganic hybrid compounds are promising luminescent materials for lighting or displays.

5.
medRxiv ; 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38405702

RESUMO

Dysfunction of endothelial insulin delivery to muscle associates with insulin resistance. CD36, a fatty acid transporter and modulator of insulin signaling is abundant in endothelial cells, especially in capillaries. Humans with inherited 50% reduction in CD36 expression have endothelial dysfunction but whether it is associated with insulin resistance is unclear. Using hyperinsulinemic/euglycemic clamps in Cd36-/- and wildtype mice, and in 50% CD36 deficient humans and matched controls we found that Cd36-/- mice have enhanced systemic glucose disposal despite unaltered transendothelial insulin transfer and reductions in microvascular perfusion and blood vessel compliance. Partially CD36 deficient humans also have better glucose disposal than controls with no capillary recruitment by insulin. CD36 knockdown in primary human-derived microvascular cells impairs insulin action on AKT, endothelial nitric oxide synthase, and nitric oxide release. Thus, insulin resistance of microvascular function in CD36 deficiency paradoxically associates with increased glucose utilization, likely through a remodeling of muscle gene expression.

6.
EClinicalMedicine ; 69: 102457, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361989

RESUMO

Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. Findings: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference -0.6%, 95% CI -3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. Interpretation: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. Funding: The National Institute for Health Research Health Technology Assessment programme.

7.
HIV Med ; 25(1): 95-106, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37670375

RESUMO

BACKGROUND: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. METHODS: Older (>50 years) and younger (<50 years) people with HIV and older HIV-negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi-squared/Fisher's exact/Kruskal-Wallis tests. RESULTS: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV-negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2 ). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14-0.52) than controls, but male sex (OR 2.45; 95% CI 1.20-4.50) and high waist-to-hip ratio (OR 3.04; 95% CI 1.74-5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV-related variables. CONCLUSIONS: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV-related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care.


Assuntos
Técnicas de Imagem por Elasticidade , Fígado Gorduroso , Infecções por HIV , Papaver , Humanos , Masculino , Idoso , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/patologia , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/patologia , Fígado/diagnóstico por imagem , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Obesidade/complicações , Obesidade/epidemiologia , Técnicas de Imagem por Elasticidade/efeitos adversos
8.
Ann Vasc Surg ; 99: 320-331, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37866676

RESUMO

BACKGROUND: Since its introduction, thoracic endovascular aortic repair (TEVAR) has revolutionized the treatment of type B aortic dissections (TBADs). However, the proximal aspect of the aortic pathology treated may infringe on the origin of the left subclavian artery or even more proximally. Hence, to ensure durable outcomes, the origin of these vessels needs to be covered, but an extra-anatomical bypass is required to perfuse vital branches, known as aortic arch debranching. This series aims to describe and delineate the disparities of aortic arch debranching during TEVAR for TBAD. METHODS: A retrospective review and analysis of a multicenter international database was conducted to identify patients with TBAD treated with TEVAR between 2005 and 2021. Data analyzed included patient demographics, disease characteristics, operative characteristics, and postoperative outcomes with follow-up on mortality and reintervention. All statistical analyses were carried out using IBM SPSS 26. Patient survival was calculated using a Kaplan-Meier survival analysis, and a P value of less than 0.05 was considered statistically significant. RESULTS: A total of 58 patients were included in the analysis, of which 27 (46.6%) presented with complicated disease and 31 were uncomplicated, of which 10 (17.2%) were classed as high risk and 21 (36.2%) low risk. Zone 2 was the most common proximal landing zone for the stent graft. Left subclavian artery bypass was performed selectively (26%), with 1 stroke occurring, likely due to embolic reasons. A further 6 underwent more proximal aortic debranching before TEVAR (10%) and was a significant risk factor for mortality and the number of stents deployed. The overall rates of reintervention and mortality were 17.2% (n = 10) and 29.3% (n = 17). CONCLUSIONS: Aortic arch debranching and TEVAR for TBAD is associated with significant mortality. Future developments to treat aortic arch pathology could incorporate branched graft devices, eliminating the need for debranching, improving stroke rates, and reducing future reinterventions.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Correção Endovascular de Aneurisma , Prótese Vascular , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Resultado do Tratamento , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Stents , Fatores de Risco , Estudos Retrospectivos
9.
Digit Health ; 9: 20552076231212286, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025097

RESUMO

Objective: This study aims to explore young people's perspectives of emerging technologies and health systems research in an adolescent health community of practice. Methods: The context of this integrated knowledge translation study is the Wellbeing Health & Youth Centre of Research Excellence in Adolescent Health. A theory-building, non-systematic review was conducted to examine the concepts and interrelationships of emerging technologies associated with digital innovation and health systems. This typology informed the design of an online workshop with young people to explore their views, concerns, and ideas about health systems research. Results: A digital innovation typology was identified to differentiate and explain emerging technology concepts and interrelationships that can be applied to the health systems context. Aligned with this typology, youth perspectives about digital health challenges and opportunities were identified to support future research, policy, and practice. Conclusion: The integrated findings from this study can assist the navigation of complex emerging technologies, and the negotiation of equitable health systems research, between youth and adult stakeholders. Further, with these typology-related resources, mutual learning and the public involvement of young people in health systems research and priority setting agendas can be supported.

10.
Pacing Clin Electrophysiol ; 46(12): 1465-1471, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37910470

RESUMO

BACKGROUND: Permanent pacemaker (PPM) implantation is a well-established treatment for symptomatic sinus node dysfunction (SND). The optimal timing of this intervention is unclear, with atrioventricular blocks often prioritized in resource stressed waiting lists due to mortality concerns. METHODS: Mortality data was compared between patients receiving elective outpatient (OP) PPM implantation, and those presenting to hospital for urgent inpatient (IP) management for symptomatic SND. Survival analysis was conducted using Kaplan-Meier plots and compared using the log-rank test. Univariable and multivariable Cox regression, as well as propensity score matching analyses were performed to assess the prognostic effect on 30-day and 1-year all-cause mortality of inpatient implant. RESULTS: Of the 1269 patients identified with isolated SND, 740 (58%) had PPMs implanted on an OP and 529 (42%) on an IP basis. Mortality was significantly worse in patients where management was driven by hospital admission on an urgent basis (Log-Rank χ2 = 21.6, p < 0.001) and remained an independent predictor of 1-year all-cause mortality (HR 3.40, 95% CI 1.97-5.86, p < 0.001) on multivariable analysis. CONCLUSIONS: SND is predominantly a disease associated with ageing and comorbid populations, where avoidance of deconditioning, hospitalization acquired infections, and polypharmacy is advantageous. Admission avoidance is therefore the preferable strategy.


Assuntos
Bloqueio Atrioventricular , Marca-Passo Artificial , Humanos , Síndrome do Nó Sinusal/terapia , Marca-Passo Artificial/efeitos adversos , Pacientes Ambulatoriais , Hospitalização
11.
Nat Commun ; 14(1): 7757, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012222

RESUMO

Metal-organic framework (MOF) is a class of porous materials providing an excellent platform for engineering heterogeneous catalysis. We herein report the design of MOF Zr-PZDB consisting of Zr6-clusters and PZDB (PZDB = 4,4'-(phenazine-5,10-diyl)dibenzoate) linkers, which served as the heterogeneous donor catalyst for enhanced electron donor-acceptor (EDA) photoactivation. The high local concentration of dihydrophenazine active centers in Zr-PZDB can promote the EDA interaction, therefore resulting in superior catalytic performance over homogeneous counterparts. The crowded environment of Zr-PZDB can protect the dihydrophenazine active center from being attacked by radical species. Zr-PZDB efficiently catalyzes the Minisci-type reaction of N-heterocycles with a series of C-H coupling partners, including ethers, alcohols, non-activated alkanes, amides, and aldehydes. Zr-PZDB also enables the coupling reaction of aryl sulfonium salts with heterocycles. The catalytic activity of Zr-PZDB extends to late-stage functionalization of bioactive and drug molecules, including Nikethamide, Admiral, and Myristyl Nicotinate. Systematical spectroscopy study and analysis support the EDA interaction between Zr-PZDB and pyridinium salt or aryl sulfonium salt, respectively. Photoactivation of the MOF-based EDA adduct triggers an intra-complex single electron transfer from donor to acceptor, giving open-shell radical species for cross-coupling reactions. This research represents the first example of MOF-enabled heterogeneous EDA photoactivation.

12.
Sci Rep ; 13(1): 18994, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923825

RESUMO

Natural killer (NK) cell subsets with adaptive properties are emerging as regulators of vaccine-induced T and B cell responses and are specialized towards antibody-dependent functions contributing to SARS-CoV-2 control. Although HIV-1 infection is known to affect the NK cell pool, the additional impact of SARS-CoV-2 infection and/or vaccination on NK cell responses in people living with HIV (PLWH) has remained unexplored. Our data show that SARS-CoV-2 infection skews NK cells towards a more differentiated/adaptive CD57+FcεRIγ- phenotype in PLWH. A similar subset was induced following vaccination in SARS-CoV-2 naïve PLWH in addition to a CD56bright population with cytotoxic potential. Antibody-dependent NK cell function showed robust and durable responses to Spike up to 148 days post-infection, with responses enriched in adaptive NK cells. NK cell responses were further boosted by the first vaccine dose in SARS-CoV-2 exposed individuals and peaked after the second dose in SARS-CoV-2 naïve PLWH. The presence of adaptive NK cells associated with the magnitude of cellular and humoral responses. These data suggest that features of adaptive NK cells can be effectively engaged to complement and boost vaccine-induced adaptive immunity in potentially more vulnerable groups such as PLWH.


Assuntos
COVID-19 , Infecções por HIV , HIV-1 , Vacinas , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Células Matadoras Naturais , Anticorpos , Infecções por HIV/complicações , Anticorpos Antivirais
13.
ACS Nano ; 17(21): 21182-21194, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37901961

RESUMO

The technology of aggregation-induced emission (AIE) presents a promising avenue for fluorescence imaging-guided photodynamic cancer therapy. However, existing near-infrared AIE photosensitizers (PSs) frequently encounter limitations, including tedious synthesis, poor tumor retention, and a limited understanding of the underlying molecular biology mechanism. Herein, an effective molecular design paradigm of anion-π+ interaction combined with the inherently crowded conformation that could enhance fluorescence efficacy and reactive oxygen species generation was proposed through a concise synthetic method. Mechanistically, upon photosensitization, the Hippo signaling pathway contributes to the death of melanoma cells and promotes the nuclear location of its downstream factor, yes-associated protein, which regulates the transcription and expression of apoptosis-related genes. The finding in this study would trigger the development of high-performance and versatile AIE PSs for precision cancer therapy based on a definite regulatory mechanism.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Via de Sinalização Hippo , Medicina de Precisão , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
14.
Int J Biol Macromol ; 253(Pt 5): 127136, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37776932

RESUMO

Chronic pain management poses a formidable challenge to healthcare, exacerbated by current analgesic options' limitations and adverse effects. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, has emerged as a promising target for novel analgesics. However, safety and tolerability concerns have constrained the development of TRPV1 modulators. In this study, we explored marine-derived natural products as a source of potential TRPV1 modulators using high-throughput dye-uptake assays. We identified chrexanthomycins, a family of hexacyclic xanthones, exhibited potent TRPV1 inhibitory effects, with compounds cC and cF demonstrating the most significant activity. High-resolution patch-clamp assays confirmed the direct action of these compounds on the TRPV1 channel. Furthermore, in vivo assays revealed that cC and cF effectively suppressed capsaicin-induced pain sensation in mice, comparable to the known TRPV1 inhibitor, capsazepine. Structural-activity relationship analysis highlighted the importance of specific functional groups in modulating TRPV1 activity. Our findings underscore the therapeutic potential of chrexanthomycins and pave the way for further investigations into marine-derived TRPV1 modulators for pain management.


Assuntos
Antineoplásicos , Produtos Biológicos , Camundongos , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Capsaicina/farmacologia , Proteínas de Transporte , Canais de Cátion TRPV/fisiologia
16.
HIV Med ; 24(12): 1198-1209, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37644705

RESUMO

BACKGROUND: Anticholinergic medications (ACMs) are associated with poorer age-related outcomes, including falls and frailty. We investigate associations between ACM use and recurrent falls and frailty among older (aged ≥50 years) people with HIV in the POPPY study. METHODS: Anticholinergic potential of co-medications at study entry was coded using the anticholinergic burden score, anticholinergic risk score, and Scottish Intercollegiate Guidelines Network score; drugs scoring ≥1 on any scale were defined as ACM. Associations with recurrent falls (two or more falls in the previous 28 days) and frailty (modified Fried's) were assessed using logistic regression adjusting for (1) possible demographic/lifestyle confounders and (2) clinical factors and depressive symptoms (Patient Health Questionnaire-9). RESULTS: ACM use was reported by 193 (28%) of 699 participants, with 64 (9%) receiving two or more ACM; commonly prescribed ACMs were codeine (12%), citalopram (12%), loperamide (9%), and amitriptyline (7%). Falls were reported in 63/673 (9%), and 126/609 (21%) met the frailty criteria. Both recurrent falls and frailty were more common in ACM users than in non-users (recurrent falls: 17% in users vs. 6% in non-users, p < 0.001; frailty: 32% vs. 17%, respectively, p < 0.001). Use of two or more ACMs was associated with increased odds of falls after adjustment for demographic/lifestyle factors (odds ratio [OR] 4.53; 95% confidence interval [CI] 2.06-9.98) and for clinical factors (OR 3.58; 95% CI 1.37-9.38). Similar albeit weaker associations were seen with frailty (OR 2.26; 95% CI 1.09-4.70 and OR 2.12; 95% CI 0.89-5.0, respectively). CONCLUSIONS: ACM are commonly prescribed for people living with HIV, and evidence exists for an association with recurrent falls and frailty. Clinicians should be alert to this and reduce ACM exposure where possible.


Assuntos
Fragilidade , Infecções por HIV , Humanos , Fragilidade/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Fatores de Risco , Antagonistas Colinérgicos/efeitos adversos
17.
Angew Chem Int Ed Engl ; 62(36): e202307251, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37428447

RESUMO

A unique benzannulation strategy for regioselective de novo synthesis of densely functionalized phenols is described. Through metal-mediated formal [2+2+1+1] cycloaddition of two different alkynes and two molecules of CO, a series of densely functionalized phenols were obtained. The benzannulation strategy allows efficient regioselective installation up to five different substituents on a phenol ring. The resulting phenols have a substitution pattern different from those obtained from Dötz and Danheiser benzannulations.

18.
Macromol Biosci ; 23(8): e2300068, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37315231

RESUMO

A bottom-up approach to fabricating monodisperse, two-component polymersomes that possess phase-separated ("patchy") chemical topology is presented. This approach is compared with already-existing top-down preparation methods for patchy polymer vesicles, such as film rehydration. These findings demonstrate a bottom-up, solvent-switch self-assembly approach that produces a high yield of nanoparticles of the target size, morphology, and surface topology for drug delivery applications, in this case patchy polymersomes of a diameter of ≈50 nm. In addition, an image processing algorithm to automatically calculate polymersome size distributions from transmission electron microscope images based on a series of pre-processing steps, image segmentation, and round object identification is presented.


Assuntos
Nanopartículas , Polímeros , Sistemas de Liberação de Medicamentos , Microscopia , Solventes
19.
Asian Cardiovasc Thorac Ann ; 31(7): 633-643, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37264635

RESUMO

BACKGROUND: Endovascular aortic repair (EVAR) has become the preferred treatment for abdominal aortic aneurysm (AAA). Its main aim is to seal the perfusion of the aneurysmal sac and, thus, induce sac regression and subsequent aortic remodelling. Aneurysmal sac regression has been linked to the short- and long-term clinical outcomes post-EVAR. It has also been shown to be influenced by endograft device choice, with several of these available commercially. This review summarises and discusses current evidence on the influence of pre- and intraoperative factors on sac regression. Additionally, this review aims to highlight the device-specific variations in sac regression to provide an overall holistic approach to treating AAAs with EVAR. METHODS: A comprehensive literature search was conducted using multiple electronic databases to identify and extract relevant data. RESULTS: Female sex, >70 mm original sac diameters, higher pre-procedural fibrinogen levels, smoking and low intra-aneurysmal pressure were found to positively impact sac regression. Whereas renal impairment, ischemic heart disease, high intra-aneurysmal pressure and aneurysm neck thrombus negatively influenced sac regression. Patent lumbar arteries, age, statins and hypercholesterolaemia displayed conflicting evidence regarding sac regression. Regarding the EVAR endografts compared, newer generation devices such as the Anaconda mainly showed the most optimal results. CONCLUSION: Sac regression following EVAR in AAA is an important prognostic factor for morbidity and mortality. Nevertheless, several pre- and intraoperative factors can have an influence on sac regression. Therefore, it is necessary to take them into account when assessing AAA patients for EVAR to optimise outcomes. The choice of EVAR stent-graft can also affect sac regression, with evidence suggesting that the Fenestrated Anaconda is associated with the most favourable results.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Feminino , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Demografia , Estudos Retrospectivos , Fatores de Risco , Prótese Vascular , Endoleak/etiologia
20.
Expert Rev Med Devices ; 20(8): 643-650, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313606

RESUMO

INTRODUCTION: Endovascular aneurysm repair (EVAR) has rapidly become the preferred management of abdominal aortic aneurysm (AAA). Sac regression status post-EVAR has been linked to clinical outcomes as well as the choice of EVAR device. The aim of this narrative review is to investigate the relationship between sac regression and clinical outcomes post-EVAR in AAA. Another aim is to compare sac regression achieved with the main EVAR devices. AREAS COVERED: We carried out a comprehensive literature search on multiple electronic databases. Sac regression was usually defined as a decrease in the sac diameter (>10 mm) over follow-up. This revealed that individuals who had sac regression post-EVAR had significantly lower mortality, and higher event-free survival rates. Further, lower rates of endoleak and reintervention were observed in patients with regressing aneurysm sacs. Sac regression patients also had significantly lower odds of rupture compared to counterparts with stable or expanded sacs. The choice of EVAR device was also shown to impact regression, with the Fenestrated Anaconda showing favorable results. EXPERT OPINION: Sac regression post-EVAR in AAA is an important prognostic factor as it translates to improved mortality and morbidity. Therefore, this relationship must be seriously taken into consideration during follow-up.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Aneurisma da Aorta Abdominal/cirurgia , Endoleak , Correção Endovascular de Aneurisma , Resultado do Tratamento , Fatores de Risco , Estudos Retrospectivos , Prótese Vascular
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