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1.
Hippocampus ; 34(2): 100-122, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38145465

RESUMEN

In this study, we aimed to understand the contributions of hippocampal anteroposterior subregions (head, body, tail) and subfields (cornu ammonis 1-3 [CA1-3], dentate gyrus [DG], and subiculum [Sub]) and encoding strategies to the age-related verbal memory decline. Healthy participants were administered the California Verbal Learning Test-II to evaluate verbal memory performance and encoding strategies and underwent 4.7 T magnetic resonance imaging brain scan with subsequent hippocampal subregions and subfields manual segmentation. While total hippocampal volume was not associated with verbal memory performance, we found the volumes of the posterior hippocampus (body) and Sub showed significant effects on verbal memory performance. Additionally, the age-related volume decline in hippocampal body volume contributed to lower use of semantic clustering, resulting in lower verbal memory performance. The effect of Sub on verbal memory was statistically independent of encoding strategies. While total CA1-3 and DG volumes did not show direct or indirect effects on verbal memory, exploratory analyses with DG and CA1-3 volumes within the hippocampal body subregion suggested an indirect effect of age-related volumetric reduction on verbal memory performance through semantic clustering. As semantic clustering is sensitive to age-related hippocampal volumetric decline but not to the direct effect of age, further investigation of mechanisms supporting semantic clustering can have implications for early detection of cognitive impairments and decline.


Asunto(s)
Envejecimiento Saludable , Longevidad , Adulto , Humanos , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Memoria , Región CA3 Hipocampal , Imagen por Resonancia Magnética/métodos
2.
Allergy ; 79(5): 1317-1328, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38462795

RESUMEN

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.


Asunto(s)
Anafilaxia , Humanos , Anafilaxia/epidemiología , Anafilaxia/etiología , Anafilaxia/terapia , Niño , Masculino , Femenino , Preescolar , Asia/epidemiología , Adolescente , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/terapia , Lactante , Alérgenos/inmunología , Manejo de la Enfermedad , Epinefrina/uso terapéutico , Epinefrina/administración & dosificación , Sistema de Registros
3.
Int Arch Allergy Immunol ; 185(1): 43-55, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37899044

RESUMEN

INTRODUCTION: Atopic dermatitis (AD) is characterized by an impaired epidermal barrier, which could be associated with sensitization to food allergens (FAs) and/or inhaled allergens and contribute to the severity of AD. However, no clinical guidance has been established for evaluations of food sensitization (FS) in AD patients. This study investigated how AD severity and epidermal barrier impairment are associated with FS and factors that can predict FS in children with AD. METHODS: This cross-sectional study included 100 children (12-60 months) diagnosed with AD. AD severity was determined using the Scoring Atopic Dermatitis (SCORAD) index. FS was evaluated by measuring serum-specific IgE antibodies against 31 FAs using an immunoblotting method. Epidermal barrier impairment was assessed by measuring transepidermal water loss (TEWL) and stratum corneum hydration (SCH) levels. RESULTS: 90% of participants were sensitized to at least one tested FA, with cow's milk, egg white, beef, almond, egg yolk, and peanut being the most common. Children with moderate-severe AD had lower SCH levels than those with mild AD. Children with AD who were sensitized to >10 FAs had significantly higher TEWL and lower SCH levels, compared with those sensitized to 1-4 FAs and 5-10 FAs. The SCORAD score and SCH level in lesional skin provided moderately predictive value for sensitization to FAs in children with AD. CONCLUSION: FS is common in children with AD and closely associate with AD severity as well as epidermal barrier impairment. Evaluations of FS should be considered for children with moderate to severe AD and/or low SCH levels.


Asunto(s)
Dermatitis Atópica , Hipersensibilidad a los Alimentos , Niño , Femenino , Animales , Bovinos , Humanos , Estudios Transversales , Alérgenos , Gravedad del Paciente , Agua
4.
Symbiosis ; 92(3): 439-451, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38666134

RESUMEN

Symbiosis can benefit hosts in numerous ways, but less is known about whether interactions with hosts benefit symbionts-the smaller species in the relationship. To determine the fitness impact of host association on symbionts in likely mutualisms, we conducted a meta-analysis across 91 unique host-symbiont pairings under a range of spatial and temporal contexts. Specifically, we assess the consequences to symbiont fitness when in and out of symbiosis, as well as when the symbiosis is under suboptimal or varying environments and biological conditions (e.g., host age). We find that some intracellular symbionts associated with protists tend to have greater fitness when the symbiosis is under stressful conditions. Symbionts of plants and animals did not exhibit this trend, suggesting that symbionts of multicellular hosts are more robust to perturbations. Symbiont fitness also generally increased with host age. Lastly, we show that symbionts able to proliferate in- and outside host cells exhibit greater fitness than those found exclusively inside or outside cells. The ability to grow in multiple locations may thus help symbionts thrive. We discuss these fitness patterns in light of host-driven factors, whereby hosts exert influence over symbionts to suit their own needs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13199-024-00984-6.

5.
J Neurosci Res ; 101(3): 367-383, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36478439

RESUMEN

The ability to recognize others' emotions is vital to everyday life. The goal of this study was to assess which emotions show age-related decline in recognition accuracy of facial emotional expressions across the entire adult lifespan and how this process is related to cognitive empathy (Theory of Mind [ToM]), alexithymia traits, and amygdala subnuclei volumes in a large cohort of healthy individuals. We recruited 140 healthy participants 18-85 years old. Facial affect processing was assessed with the Penn Emotion Recognition task (ER40) that contains images of the five basic emotions: Neutral, Happy, Sad, Angry, and Fearful. Structural magnetic resonance imaging (MRI) datasets were acquired on a 4.7T MRI system. Structural equation modeling was used to test the relationship between studied variables. We found that while both sexes demonstrated age-related reduction in recognition of happy emotions and preserved recognition of sadness, male participants showed age-related reduction in recognition of fear, while in female participants, age-related decline was linked to recognition of neutral and angry facial expressions. In both sexes, accurate recognition of sadness negatively correlated with alexithymia traits. On the other hand, better ToM capabilities in male participants were associated with improvement in recognition of positive and neutral emotions. Finally, none of the observed age-related reductions in emotional recognition were related to amygdala and its subnuclei volumes. In contrast, both global volume of amygdala and its cortical and centromedial subnuclei had significant direct effects on recognition of sad images.


Asunto(s)
Síntomas Afectivos , Empatía , Adulto , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Síntomas Afectivos/diagnóstico por imagen , Longevidad , Emociones , Cognición , Amígdala del Cerebelo/diagnóstico por imagen , Expresión Facial , Imagen por Resonancia Magnética
6.
Glob Chang Biol ; 29(1): 41-56, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36251487

RESUMEN

Global climate change has led to more extreme thermal events. Plants and animals harbour diverse microbial communities, which may be vital for their physiological performance and help them survive stressful climatic conditions. The extent to which microbiome communities change in response to warming or cooling may be important for predicting host performance under global change. Using a meta-analysis of 1377 microbiomes from 43 terrestrial and aquatic species, we found a decrease in the amplicon sequence variant-level microbiome phylogenetic diversity and alteration of microbiome composition under both experimental warming and cooling. Microbiome beta dispersion was not affected by temperature changes. We showed that the host habitat and experimental factors affected microbiome diversity and composition more than host biological traits. In particular, aquatic organisms-especially in marine habitats-experienced a greater depletion in microbiome diversity under cold conditions, compared to terrestrial hosts. Exposure involving a sudden long and static temperature shift was associated with microbiome diversity loss, but this reduction was attenuated by prior-experimental lab acclimation or when a ramped regime (i.e., warming) was used. Microbial differential abundance and co-occurrence network analyses revealed several potential indicator bacterial classes for hosts in heated environments and on different biome levels. Overall, our findings improve our understanding on the impact of global temperature changes on animal and plant microbiome structures across a diverse range of habitats. The next step is to link these changes to measures of host fitness, as well as microbial community functions, to determine whether microbiomes can buffer some species against a more thermally variable and extreme world.


Asunto(s)
Biodiversidad , Microbiota , Animales , Temperatura , Filogenia , Bacterias/genética , Plantas
7.
J Am Chem Soc ; 144(43): 19832-19837, 2022 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-36269942

RESUMEN

Automated chemical synthesis has revolutionized synthetic access to biopolymers in terms of simplicity and speed. While automated oligosaccharide synthesis has become faster and more versatile, the parallel synthesis of oligosaccharides is not yet possible. Here, a chemical vapor glycosylation strategy (VaporSPOT) is described that enables the simultaneous synthesis of oligosaccharides on a cellulose membrane solid support. Different linkers allow for flexible and straightforward cleavage, purification, and characterization of the target oligosaccharides. This method is the basis for the development of parallel automated glycan synthesis platforms.


Asunto(s)
Oligosacáridos , Oligosacáridos/química , Glicosilación
8.
Microbiology (Reading) ; 168(4)2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35442184

RESUMEN

Protective symbionts can defend hosts from parasites through several mechanisms, from direct interference to modulating host immunity, with subsequent effects on host and parasite fitness. While research on symbiont-mediated immune priming (SMIP) has focused on ecological impacts and agriculturally important organisms, the evolutionary implications of SMIP are less clear. Here, we review recent advances made in elucidating the ecological and molecular mechanisms by which SMIP occurs. We draw on current works to discuss the potential for this phenomenon to drive host, parasite, and symbiont evolution. We also suggest approaches that can be used to address questions regarding the impact of immune priming on host-microbe dynamics and population structures. Finally, due to the transient nature of some symbionts involved in SMIP, we discuss what it means to be a protective symbiont from ecological and evolutionary perspectives and how such interactions can affect long-term persistence of the symbiosis.


Asunto(s)
Sistema Inmunológico , Simbiosis , Animales , Ecología , Sistema Inmunológico/fisiología , Parásitos
9.
Arch Biochem Biophys ; 731: 109429, 2022 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-36265649

RESUMEN

Tyrosine-430 of d-ornithine/d-lysine decarboxylase (DOKDC) is located in the active site, and was suggested to be responsible for the D-stereospecificity of the enzyme. We have prepared the Y430F mutant form of Salmonella enterica serovar typhimurium DOKDC and evaluated its catalytic activity with D- and l-lysine and ornithine. The kinetic results show that the Y430F mutant has measurable decarboxylase activity with both D- and l-lysine and ornithine, which wild type DOKDC does not. Spectroscopic experiments show that these amino acids bind to form external aldimine complexes with the pyridoxal-5'-phosphate with λmax = 425 nm. In addition, we have obtained crystal structures of Y430F DOKDC bound to HEPES, putrescine, d-ornithine, d-lysine, and d-arginine. The d-amino acids bind in the crystals to form equilibrium mixtures of gem-diamine and external aldimine complexes. Furthermore, the crystal structures reveal an unexpected allosteric product activator site for putrescine located on the 2-fold axis between the two active sites. Putrescine binds by donating hydrogen bonds from the ammonium groups to Asp-361 and Gln-358 in the specificity helix of both chains. Addition of 0.1-1 mM putrescine eliminates the lag in steady state kinetics and abolishes the sigmoid kinetics. The catalytic loop was modeled with AlphaFold2, and the model shows that Glu-181 can form additional hydrogen bonds with the bound putrescine, likely stabilizing the catalytic closed conformation.


Asunto(s)
Carboxiliasas , Ornitina , Ornitina/química , Ornitina/metabolismo , Putrescina/química , Ornitina Descarboxilasa/genética , Ornitina Descarboxilasa/metabolismo , Lisina/metabolismo , Regulación Alostérica , Mutagénesis Sitio-Dirigida , Carboxiliasas/genética , Carboxiliasas/metabolismo , Fosfato de Piridoxal/química , Fosfato de Piridoxal/metabolismo , Cinética , Salmonella/metabolismo
10.
J Evol Biol ; 35(7): 1002-1011, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35647763

RESUMEN

Many host organisms live in polymicrobial environments and must respond to a diversity of pathogens. The degree to which host defences towards one pathogen species affect susceptibility to others is unclear. We used a panel of Caenorhabditis elegans nematode isolates to test for natural genetic variation in fitness costs of immune upregulation and pathogen damage, as well as for trade-offs in defence against two pathogen species, Staphylococcus aureus and Pseudomonas aeruginosa. We examined the fitness impacts of transient pathogen exposure (pathogen damage and immune upregulation) or exposure to heat-killed culture (immune upregulation only) by measuring host population sizes, which allowed us to simultaneously capture changes in reproductive output, developmental time and survival. We found significant decreases in population sizes for hosts exposed to live versus heat-killed S. aureus and found increased reproductive output after live P. aeruginosa exposure, compared with the corresponding heat-killed challenge. Nematode isolates with relatively higher population sizes after live P. aeruginosa infection produced fewer offspring after live S. aureus challenge. These findings reveal that wild C. elegans genotypes display a trade-off in defences against two distinct pathogen species that are evident in subsequent generations.


Asunto(s)
Caenorhabditis elegans , Staphylococcus aureus , Animales , Caenorhabditis elegans/genética , Genotipo , Pseudomonas aeruginosa/genética , Reproducción , Staphylococcus aureus/genética
11.
J Am Chem Soc ; 143(23): 8893-8901, 2021 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-34060822

RESUMEN

Automated synthesis of DNA, RNA, and peptides provides quickly and reliably important tools for biomedical research. Automated glycan assembly (AGA) is significantly more challenging, as highly branched carbohydrates require strict regio- and stereocontrol during synthesis. A new AGA synthesizer enables rapid temperature adjustment from -40 to +100 °C to control glycosylations at low temperature and accelerates capping, protecting group removal, and glycan modifications using elevated temperatures. Thereby, the temporary protecting group portfolio is extended from two to four orthogonal groups that give rise to oligosaccharides with up to four branches. In addition, sulfated glycans and unprotected glycans can be prepared. The new design reduces the typical coupling cycles from 100 to 60 min while expanding the range of accessible glycans. The instrument drastically shortens and generalizes the synthesis of carbohydrates for use in biomedical and material science.

12.
Clin Mol Allergy ; 19(1): 11, 2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34256766

RESUMEN

BACKGROUND: It is apparent that the interaction between platelets and eosinophils plays a critical role in the activation of allergic inflammation. We investigated whether blocking of the glycoprotein (GP) IIb/IIIa receptor can attenuate allergic inflammation and airway hyperresponsiveness through inhibition of platelet-eosinophil aggregation (PEA) in asthma. METHODS: BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by 3 nebulized OVA challenges on days 28-30. On each challenge day, 5 mg/kg tirofiban was administered intraperitoneally 30 min before the challenge. Mice were assessed for airway hyperresponsiveness (AHR), airway inflammation, and the degree of PEA. Finally, the activation levels of platelets and eosinophils were evaluated. RESULTS: Tirofiban treatment decreased AHR and eosinophilic inflammation in Bronchoalveolar Lavage (BAL) fluid. This treatment also reduced the levels of interleukin (IL)-4, IL-5, and IL-13 in BAL fluid and airway inflammatory cell infiltration in histological evaluation. Interestingly, the blocking of the GP IIb/IIIa receptor more reduced PEA in both blood and lung tissue of tirofiban-treated mice than in those of the positive control mice, and both eosinophilic and platelet activations were attenuated in tirofiban-treated mice. CONCLUSIONS: The blocking of GP IIb/IIIa receptor with tirofiban can attenuate AHR and airway inflammation through the inhibition of PEA and activation.

13.
BMC Med Inform Decis Mak ; 21(1): 323, 2021 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-34809626

RESUMEN

BACKGROUND: MyDiabetesPlan is a web-based, interactive patient decision aid that facilitates patient-centred, diabetes-specific, goal-setting and shared decision-making (SDM) with interprofessional health care teams. OBJECTIVE: Assess the feasibility of (1) conducting a cluster randomized controlled trial (RCT) and (2) integrating MyDiabetesPlan into interprofessional primary care clinics. METHODS: We conducted a cluster RCT in 10 interprofessional primary care clinics with patients living with diabetes and at least two other comorbidities; half of the clinics were assigned to MyDiabetesPlan and half were assigned to usual care. To assess recruitment, retention, and resource use, we used RCT conduct logs and financial account summaries. To assess intervention fidelity, we used RCT conduct logs and website usage logs. To identify barriers and facilitators to integration of MyDiabetesPlan into clinical care across the IP team, we used audiotapes of clinical encounters in the intervention groups. RESULTS: One thousand five hundred and ninety-seven potentially eligible patients were identified through searches of electronic medical records, of which 1113 patients met the eligibility criteria upon detailed chart review. A total of 425 patients were randomly selected; of these, 213 were able to participate and were allocated (intervention: n = 102; control: n = 111), for a recruitment rate of 50.1%. One hundred and fifty-one patients completed the study, for a retention rate of 70.9%. A total of 5745 personnel-hours and $6104 CAD were attributed to recruitment and retention activities. A total of 179 appointments occurred (out of 204 expected appointments-two per participant over the 12-month study period; 87.7%). Forty (36%), 25 (23%), and 32 (29%) patients completed MyDiabetesPlan at least twice, once, and zero times, respectively. Mean time for completion of MyDiabetesPlan by the clinician and the patient during initial appointments was 37 min. From the clinical encounter transcripts, we identified diverse strategies used by clinicians and patients to integrate MyDiabetesPlan into the appointment, characterized by rapport building and individualization. Barriers to use included clinician-related, patient-related, and technical factors. CONCLUSION: An interprofessional approach to SDM using a decision aid was feasible. Lower than expected numbers of diabetes-specific appointments and use of MyDiabetesPlan were observed. Addressing facilitators and barriers identified in this study will promote more seamless integration into clinical care. Trial registration Clinicaltrials.gov Identifier: NCT02379078. Date of Registration: February 11, 2015. Protocol version: Version 1; February 26, 2015.


Asunto(s)
Toma de Decisiones Conjunta , Diabetes Mellitus , Diabetes Mellitus/terapia , Estudios de Factibilidad , Humanos , Grupo de Atención al Paciente , Atención Primaria de Salud
14.
BMC Cardiovasc Disord ; 20(1): 223, 2020 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-32408892

RESUMEN

BACKGROUND: Although hospital readmission for heart failure (HF) is an issue for both men and women, little is known about differences in readmission rates by sex. Consequently, strategies to optimize readmission reduction programs and care strategies for women and men remain unclear. Our study aims were: (1) to identify studies examining readmission rates according to sex, and (2) to provide a qualitative overview of possible considerations for the impact of sex or gender. METHODS: We conducted a scoping review using the Arksey and O'Malley framework to include full text articles published between 2002 and 2017 drawn from multiple databases (MEDLINE, EMBASE), grey literature (i.e. National Technical information, Duck Duck Go), and expert consultation. Eligible articles included an index heart failure episode, readmission rates, and sex/gender-based analysis. RESULTS: The search generated 5887 articles, of which 746 underwent full abstract text consideration for eligibility. Of 164 eligible articles, 34 studies addressed the primary outcome, 103 studies considered sex differences as a secondary outcome and 25 studies stratified data for sex. Good inter-rater agreement was reached: 83% title/abstract; 88% full text; kappa: 0.69 (95%CI: 0.53-0.85). Twelve of 34 studies reported higher heart failure readmission rates for men and six studies reported higher heart failure readmission rates for women. Using non composite endpoints, five studies reported higher HF readmission rates for men compared to three studies reporting higher HF readmission rates for women. Overall, there was heterogeneity between studies when examined by sex, but one observation emerged that was related to the timing of readmissions. Readmission rates for men were higher when follow-up duration was longer than 1 year. Women were more likely to experience higher readmission rates than men when time to event was less than 1 year. CONCLUSIONS: Future studies should consider different time horizons in their designs and avoid the use of composite measures, such as readmission rates combined with mortality, which are highly skewed by sex. Co-interventions and targeted post-discharge approaches with attention to sex would be of benefit to the HF patient population.


Asunto(s)
Disparidades en el Estado de Salud , Disparidades en Atención de Salud/tendencias , Insuficiencia Cardíaca/terapia , Readmisión del Paciente/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Factores de Riesgo , Caracteres Sexuales , Factores Sexuales
15.
Curr Osteoporos Rep ; 18(3): 180-188, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32242305

RESUMEN

PURPOSE OF REVIEW: The aim of the review is to conduct a literature search on cost-effectiveness or cost savings of osteoporosis fracture liaison services. RECENT FINDINGS: We identified four types of FLS. A total of 11 cost-effectiveness studies examining 15 models of secondary fracture prevention models were identified. Nine models were found to be cost-saving, and five were found to be cost-effective. It is possible to adopt a cost-effective model for fracture liaison services and expand across geographical regions. Adopting registries can have the added benefit of monitoring quality improvement practices and treatment outcomes. Challenges exist in implementing registries where centralized data collections across different chronic conditions are politically driving agendas. In order to align political and organizational strategic plans, a core set of outcome evaluations that are both focused on patient and provider experience in addition to treatment outcomes can be a step toward achieving better health and services.


Asunto(s)
Atención a la Salud/organización & administración , Fracturas de Cadera/terapia , Fracturas Osteoporóticas/terapia , Derivación y Consulta/organización & administración , Sistema de Registros , Análisis Costo-Beneficio , Atención a la Salud/economía , Fracturas de Cadera/economía , Humanos , Ortopedia , Fracturas Osteoporóticas/economía , Política , Atención Primaria de Salud/organización & administración , Prevención Secundaria/organización & administración
16.
J Med Internet Res ; 22(9): e16984, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32996893

RESUMEN

BACKGROUND: Person-centered care is critical for delivering high-quality diabetes care. Shared decision making (SDM) is central to person-centered care, and in diabetes care, it can improve decision quality, patient knowledge, and patient risk perception. Delivery of person-centered care can be facilitated with the use of patient decision aids (PtDAs). We developed MyDiabetesPlan, an interactive SDM and goal-setting PtDA designed to help individualize care priorities and support an interprofessional approach to SDM. OBJECTIVE: This study aims to assess the impact of MyDiabetesPlan on decisional conflict, diabetes distress, health-related quality of life, and patient assessment of chronic illness care at the individual patient level. METHODS: A two-step, parallel, 10-site cluster randomized controlled trial (first step: provider-directed implementation only; second step: both provider- and patient-directed implementation 6 months later) was conducted. Participants were adults 18 years and older with diabetes and 2 other comorbidities at 10 family health teams (FHTs) in Southwestern Ontario. FHTs were randomly assigned to MyDiabetesPlan (n=5) or control (n=5) through a computer-generated algorithm. MyDiabetesPlan was integrated into intervention practices, and clinicians (first step) followed by patients (second step) were trained on its use. Control participants received static generic Diabetes Canada resources. Patients were not blinded. Participants completed validated questionnaires at baseline, 6 months, and 12 months. The primary outcome at the individual patient level was decisional conflict; secondary outcomes were diabetes distress, health-related quality of life, chronic illness care, and clinician intention to practice interprofessional SDM. Multilevel hierarchical regression models were used. RESULTS: At the end of the study, the intervention group (5 clusters, n=111) had a modest reduction in total decisional conflicts compared with the control group (5 clusters, n=102; -3.5, 95% CI -7.4 to 0.42). Although there was no difference in diabetes distress or health-related quality of life, there was an increase in patient assessment of chronic illness care (0.7, 95% CI 0.4 to 1.0). CONCLUSIONS: Use of goal-setting decision aids modestly improved decision quality and chronic illness care but not quality of life. Our findings may be due to a gap between goal setting and attainment, suggesting a role for optimizing patient engagement and behavioral support. The next steps include clarifying the mechanisms by which decision aids impact outcomes and revising MyDiabetesPlan and its delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02379078; https://clinicaltrials.gov/ct2/show/NCT02379078.


Asunto(s)
Enfermedad Crónica/psicología , Toma de Decisiones/fisiología , Diabetes Mellitus/terapia , Atención Dirigida al Paciente/métodos , Calidad de la Atención de Salud/normas , Calidad de Vida/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Internet , Conocimiento , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
17.
J Cell Mol Med ; 23(5): 3441-3450, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30905080

RESUMEN

Platelets modulate asthma pathogenesis by forming the platelet-eosinophil aggregation (PEA), which facilitates the activation of eosinophils. Platelets exhibit the purinergic receptor (P2Y12R), which responds to cysteinyl leukotriene E4 (LTE4 ). We have suggested that the combination of an antiplatelet drug (clopidogrel, [Clo]) and montelukast (Mon) would synergistically suppress asthma. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) on days 0 and 14 and subsequently challenged on days 28-30 and 42-44. Mice were administered with Clo (10 mg/kg), Mon (10 mg/kg) or both drugs (Clo/Mon) orally 30 minutes before the OVA (1%) challenge on days 42-44. Mice were assayed for airway hyper-responsiveness (AHR) to methacholine and airway inflammation. Clopidogrel and montelukast attenuated the increased AHR; the combined treatment was more effective than a single treatment for total and eosinophil counts (all P < 0.05). Levels of interleukin (IL)-4, IL-5, IL-13, platelet factor 4, eosinophil peroxidase and LTE4 increased in the bronchoalveolar lavage fluid of asthmatic mice, but these levels decreased in mice treated with Clo/Mon (all P < 0.05). Goblet cell hyperplasia decreased in response to Clo/Mon. Mouse platelets and eosinophils were isolated and co-cultured for an in vitro assay with 10 µmol/L adenosine diphosphate (ADP), LTE4 (200 nmol/L), Mon (1 µmol/L), Clo (1 µmol/L) and Clo/Mon (1 µmol/L). Flow cytometry revealed that the increased formation of the PEA (%) was fully mediated by ADP and partly mediated by LTE4 . Clo/Mon reduced ADP-induced PEA formation and P-selectin expression (P < 0.05). In conclusion, Clo/Mon synergistically relieved asthma by inhibiting ADP-mediated PEA formation.


Asunto(s)
Acetatos/uso terapéutico , Asma/tratamiento farmacológico , Clopidogrel/uso terapéutico , Quinolinas/uso terapéutico , Adenosina Difosfato/farmacología , Animales , Asma/sangre , Asma/fisiopatología , Biomarcadores/metabolismo , Líquido del Lavado Bronquioalveolar , Agregación Celular/efectos de los fármacos , Quimiocinas/metabolismo , Ciclopropanos , Citocinas/metabolismo , Sinergismo Farmacológico , Eosinófilos/metabolismo , Eosinófilos/patología , Femenino , Inflamación/patología , Mediadores de Inflamación/metabolismo , Recuento de Leucocitos , Leucotrieno E4/sangre , Leucotrieno E4/metabolismo , Pulmón/patología , Ratones Endogámicos BALB C , Moco/metabolismo , Activación Plaquetaria/efectos de los fármacos , Hipersensibilidad Respiratoria/complicaciones , Hipersensibilidad Respiratoria/fisiopatología , Sulfuros , Células Th2/metabolismo
18.
J Am Chem Soc ; 141(22): 9079-9086, 2019 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-31091089

RESUMEN

Automated glycan assembly (AGA) aims at accelerating access to synthetic oligosaccharides to meet the demand for defined glycans as tools for molecular glycobiology. The linkers used to connect the growing glycan chain to the solid support play a pivotal role in the synthesis strategy as they determine all chemical conditions used during the synthesis and the form of the glycan obtained at the end of it. Here, we describe a traceless photolabile linker used to prepare carbohydrates with a free reducing end. Modification of the o-nitrobenzyl scaffold of the linker is key to high yields and compatibility with the AGA workflow. The assembly of an asymmetrical biantennary N-glycan from oligosaccharide fragments prepared by AGA and linear as well as branched ß-oligoglucans is described to illustrate the power of the method. These substrates will serve as standards and biomarkers to examine the unique specificity of glycosyl hydrolases.


Asunto(s)
Oligosacáridos/síntesis química , Polisacáridos/síntesis química , Nitrobencenos/síntesis química , Nitrobencenos/química , Nitrobencenos/efectos de la radiación , Rayos Ultravioleta
19.
J Urol ; 201(5): 1012-1016, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30688774

RESUMEN

PURPOSE: We assessed the impact of a 2-phase Plan-Do-Study-Act cycle to decrease opioid prescriptions following pediatric urological surgery. MATERIALS AND METHODS: Parents of children undergoing outpatient urological procedures were given questionnaires to assess opioid dosing and pain scores using the Parents' Postoperative Pain Measure scale. Age, procedure and opioid prescription data were recorded, as well as volume of medication administered. During the first phase of data collection children received an opioid prescription for 10 doses. In the second phase opioid prescriptions were reduced by 50%. Nonparametric tests and Fisher exact test were used for analysis. RESULTS: Of 250 eligible children 98 (39%) with a median age of 3.0 years (IQR 7.0) participated. In the 81 patients prescribed opioids a median of 2 doses (IQR 3.6) were used in the preintervention and postintervention groups (p = 0.68). Using nonparametric statistical testing, no significant differences were found between pain scores in the 5-dose group (31 patients) and the 10-dose group (24 patients; p = 0.05 for day 1, p = 0.07 for day 2, p = 0.06 for day 3). There was no association between age and percent opioid used (p = 0.83). There were no significant differences in median pain scores or median doses among procedure types. CONCLUSIONS: In outpatient pediatric surgical practice opioid prescriptions can be decreased without increasing pain scores. Physician prescribing practices may contribute more to opioid consumption than actual pain patterns.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios/métodos , Analgésicos Opioides/administración & dosificación , Utilización de Medicamentos/estadística & datos numéricos , Dolor Postoperatorio/tratamiento farmacológico , Procedimientos Quirúrgicos Urológicos/efectos adversos , Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pacientes Ambulatorios/estadística & datos numéricos , Manejo del Dolor/métodos , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Pediatría , Medición de Riesgo , Resultado del Tratamiento , Procedimientos Quirúrgicos Urológicos/métodos
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