Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 55
Filtrar
1.
Lupus ; : 9612033241246642, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594605

RESUMO

BACKGROUND: Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women with pre-existing lupus nephritis (LN) are variable. The impact of different classes of LN on maternal and fetal outcomes during pregnancy is not well defined, as data is very scarce, especially from the developing countries. METHODS: A retrospective analysis was conducted on 52 women with 89 pregnancies. All had biopsy-proven LN. Those women who conceived at least 6 months after the diagnosis were included. The analysis was conducted between July 1998 and June 2018 at Sindh Institute of Urology and Transplantation (SIUT), evaluating the outcomes for both the mother and the fetus with a minimum follow-up of 12 months after child birth. RESULTS: The mean maternal age at SLE diagnosis was 21.45 ± 6 years and at first pregnancy was 26.49 ± 5.63 years. The mean disease duration was 14.02 ± 19.8 months. At conception, 47 (52.8%) women were hypertensive, 9 (10%) had active disease while 38 (42.7%) and 42 (47.2%) were in complete and partial remission, respectively. A total of 17 (19.1%) were on mycophenolate mofetil (MMF), which was switched to azathioprine (AZA). Out of 89 pregnancies, 56 (62.9%) were successful, while 33 (37.07%) had fetal complications like spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation (IUGR). There were more vaginal deliveries (33 [58.92%]) than caesarean sections (23 [41.07%]). Renal flare was observed in 33 (37.1%) women while 15 (16.9%) developed pre-eclampsia. Proliferative LN was found in 56 (62.9%) cases, but no significant differences were found in maternal and fetal outcomes in relation to LN classes (p = .58). However, disease outcomes at 12 months were significantly poor in those with active disease at the time of conception (p < .05). There was only one maternal death. A total of 10 (11.2%) women showed deterioration in renal function and 5 (5.6%) were dialysis-dependent at 12 months. CONCLUSION: The maternal and fetal outcomes in pre-existing LN depend on the disease activity at the time of conception. No correlation was found between International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of LN and adverse disease and pregnancy outcomes.

2.
Dev Cell ; 59(2): 211-227.e5, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38141609

RESUMO

Fetal bone development occurs through the conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Here, we show that the mechanoresponsive transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) spatially couple osteoblast precursor mobilization to angiogenesis, regulate vascular morphogenesis to control cartilage remodeling, and mediate mechanoregulation of embryonic murine osteogenesis. Mechanistically, YAP and TAZ regulate a subset of osteoblast-lineage cells, identified by single-cell RNA sequencing as vessel-associated osteoblast precursors, which regulate transcriptional programs that direct blood vessel invasion through collagen-integrin interactions and Cxcl12. Functionally, in 3D human cell co-culture, CXCL12 treatment rescues angiogenesis impaired by stromal cell YAP/TAZ depletion. Together, these data establish functions of the vessel-associated osteoblast precursors in bone development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Transativadores , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , 60489 , Desenvolvimento Ósseo , Morfogênese , Osteoblastos/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP
3.
Curr Oncol ; 30(12): 10224-10236, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38132378

RESUMO

The development and use of oral anticancer agents (OAAs) continue to grow, and supporting individuals on OAAs is now a priority as they find themselves taking these drugs at home with little professional guidance. This mapping review provides an overview of the current evidence concerning OAA-supportive adherence interventions, identifying potential gaps, and making recommendations to guide future work. Four large databases and the grey literature were searched for publications from 2010 to 2022. Quantitative, qualitative, mixed-method, theses/dissertations, reports, and abstracts were included, whereas protocols and reviews were excluded. Duplicates were removed, and the remaining publications were screened by title and abstract. Full-text publications were assessed and those meeting the inclusion criteria were retained. Data extracted included the year of publication, theoretical underpinnings, study design, targeted patients, sample size, intervention type, and primary outcome(s). 3175 publications were screened, with 435 fully read. Of these, 314 were excluded with 120 retained. Of the 120 publications, 39.2% (n = 47) were observational studies, 38.3% (n = 46) were quasi-experimental, and 16.7% (n = 20) were experimental. Only 17.5% (n = 21) were theory-based. Despite the known efficacy of multi-modal interventions, 63.7% (n = 76) contained one or two modalities, 33.3% (n = 40) included 3, and 3.3% (n = 4) contained four types of modalities. Medication adherence was measured primarily through self-report (n = 31) or chart review/pharmacy refills (n = 28). Given the importance of patient tailored interventions, future work should test whether having four intervention modalities (behavioral, educational, medical, and technological) guided by theory can optimize OAA-related outcomes.


Assuntos
Antineoplásicos , Adesão à Medicação , Humanos , Antineoplásicos/uso terapêutico
4.
R Soc Open Sci ; 10(10): 231023, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37859832

RESUMO

Mechanical loading is critical for collagen network maintenance and remodelling in adult skeletal tissues, but the role of loading in collagen network formation during development is poorly understood. We test the hypothesis that mechanical loading is necessary for the onset and maturation of spatial localization and structure of collagens in prenatal cartilage and bone, using in vivo and in vitro mouse models of altered loading. The majority of collagens studied was aberrant in structure or localization, or both, when skeletal muscle was absent in vivo. Using in vitro bioreactor culture system, we demonstrate that mechanical loading directly modulates the spatial localization and structure of collagens II and X. Furthermore, we show that mechanical loading in vitro rescues aspects of the development of collagens II and X from the effects of fetal immobility. In conclusion, our findings show that mechanical loading is a critical determinant of collagen network establishment during prenatal skeletal development.

5.
J Pediatr ; : 113774, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37839510

RESUMO

OBJECTIVE: To determine if oral secretions (OS) can be used as a non-invasively collected body fluid, in lieu of tracheal aspirates (TA), to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. STUDY DESIGN: This was a retrospective, single-center cohort study that included data and convenience samples from week-of-life (WoL) 3 from two independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatology Intensive Care Unit (NICU) (Cohort 1; N=23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; N=17 infants including 8 with BPD). RESULTS: In samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (eg, SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. CONCLUSION: OS are a noninvasive, easily accessible alternative to TA and amenable to high-throughput proteomic analysis in preterm newborns. OS samples hold promise to yield actionable biomarkers of BPD development, particularly for prospective categorization of at-risk infants for timely clinical trial enrollment with novel therapies.

6.
Cureus ; 15(9): e44783, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809191

RESUMO

Survivors of out-of-hospital cardiac arrest (OHCA) experience significant mortality rates and neurological impairment, potentially attributed to the hypoxic-ischemic injury sustained amid the cardiac arrest episode. Post-resuscitation care plays a crucial role in determining outcomes for survivors of OHCA. Supportive therapies have proven to be influential in shaping these outcomes. However, targeting higher blood pressure or oxygen levels during the post-resuscitative phase has not been shown to offer any mortality or neurological benefits. In terms of maintaining hemodynamic instability after resuscitation, it is recommended to use norepinephrine rather than epinephrine. While extracorporeal cardiopulmonary resuscitation has shown promising results, targeted temperature management has been found ineffective in improving outcomes despite its previous potential. This review also investigates various challenges and barriers associated with the practical implementation of these supportive therapies in clinical settings. The review also highlights areas ripe for future research and proposes potential directions to further enhance post-resuscitation supportive care for OHCA survivors.

7.
Cureus ; 15(8): e44043, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37746367

RESUMO

Beta-blockers are a class of medications that act on beta-adrenergic receptors and are categorized as cardio-selective and non-selective. They are principally used to treat cardiovascular conditions such as hypertension and arrhythmias. Beta-blockers have also been used to treat non-cardiogenic indications in non-pregnant individuals and the pediatric population. In pregnancy, labetalol is the mainstay treatment for hypertension and other cardiovascular indications. However, contraindications to certain sub-types of beta-blockers include bradycardia, heart failure, obstructive lung diseases, and hemodynamic instability. There is conflicting evidence of the adverse effects on fetal and neonatal health due to a scarce safety and efficacy profile, and further studies are necessary to understand the pharmacokinetics of the different classes of beta-blockers in pregnancy and fetal health. Understanding the hemodynamic changes during the stages of pregnancy is important to target a more beneficial therapy for both mother and fetus as well as better neonatal outcomes. Beta-blocker use in the pediatric population is less documented in studies but does have the potential to treat various cardiogenic and non-cardiogenic conditions. Future comprehensive studies would further benefit the direction of beta-blocker treatment during pregnancy in neonates and pediatrics.

8.
J Orthop Res ; 41(10): 2305-2314, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37408453

RESUMO

Externally applied forces, such as those generated through skeletal muscle contraction, are important to embryonic joint formation, and their loss can result in gross morphologic defects including joint fusion. While the absence of muscle contraction in the developing chick embryo leads to dissociation of dense connective tissue structures of the knee and ultimately joint fusion, the central knee joint cavitates whereas the patellofemoral joint does not in murine models lacking skeletal muscle contraction, suggesting a milder phenotype. These differential results suggest that muscle contraction may not have as prominent of a role in the growth and development of dense connective tissues of the knee. To explore this question, we investigated the formation of the menisci, tendon, and ligaments of the developing knee in two murine models that lack muscle contraction. We found that while the knee joint does cavitate, there were multiple abnormalities in the menisci, patellar tendon, and cruciate ligaments. The initial cellular condensation of the menisci was disrupted and dissociation was observed at later embryonic stages. The initial cell condensation of the tendon and ligaments were less affected than the meniscus, but these tissues contained cells with hyper-elongated nuclei and displayed diminished growth. Interestingly, lack of muscle contraction led to the formation of an ectopic ligamentous structure in the anterior region of the joint as well. These results indicate that muscle forces are essential for the continued growth and maturation of these structures during this embryonic period.


Assuntos
Ligamento Cruzado Anterior , Ligamento Patelar , Embrião de Galinha , Animais , Camundongos , Ligamento Cruzado Anterior/fisiologia , Articulação do Joelho/fisiologia , Contração Muscular , Morfogênese , Músculo Esquelético
9.
J Med Internet Res ; 25: e40425, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37307045

RESUMO

BACKGROUND: South Asian individuals experience a higher burden of chronic diseases and limited access to health care services compared with their Caucasian peers. Digital health interventions can enhance the delivery of health care, minimize health inequities, and consequently improve health status among minority ethnic groups. However, it is unclear how South Asian people view and perceive the use of digital health technologies to support their health needs. OBJECTIVE: The aim of the review is to identify South Asian individuals' experiences and attitudes of digital health and explore the barriers and facilitators affecting their use of digital health services. METHODS: The Arksey and O'Malley methodological framework was used to guide this scoping review. Five electronic databases were examined for pertinent papers, which were augmented by searching bibliographies of the retrieved papers and gray literature. A total of 1328 potentially relevant papers were retrieved from the initial search, and the supplemental search added 7 papers to the final list of potentially included papers. Each paper on the initial inclusion list was independently reviewed, leaving 15 papers to be included in the review. RESULTS: Data were analyzed thematically leading to the development of two overarching themes: (1) barriers to uptake of digital health and (2) facilitators of use of digital health services. There was a general consensus that South Asian communities still struggle with inadequate access to digital health technologies. Some studies suggest multiple initiatives to improve accessibility and acceptability of digital health services within South Asian communities in order to mitigate health disparities and develop a more inclusive health care system. These include the development of multiple-language and culturally sensitive interventions and digital skill development sessions. Most studies were conducted in South Asian countries, focusing on measurable outcomes of digital health interventions. Few explored the experiences and views of South Asian community members residing in the West as a minority ethnic group, for example, British South Asians. CONCLUSIONS: Literature mapping proposes that South Asian people frequently struggle with a health care system that may limit their access to digital health services, and sometimes fails to consider social and cultural needs. There is growing evidence that digital health interventions have the potential to facilitate supported self-management, which is part of the plans to adopt person-centered care. These interventions are particularly important for overcoming some of the challenges, for example, time constraints, safety, and gender sensitivity, associated with the delivery of health care interventions in minority ethnic groups such as South Asians in the United Kingdom, and thus to improve minority ethnic groups' access to health care services to support individual health needs, and consequently enhance health status.


Assuntos
Povo Asiático , Tecnologia Biomédica , Etnicidade , Humanos , Grupos Minoritários , População Branca
10.
J Pers Med ; 13(5)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37241021

RESUMO

BACKGROUND: The PREVENTION e-platform was developed to provide accessible and evidence-based health information tailored to different Breast Cancer (BC) risk levels. The demonstration study objectives were to (1) assess the usability and perceived impact of PREVENTION on women with assigned hypothetical BC risk levels (i.e., near population, intermediate or high) and (2) explore perceptions and recommendations for e-platform improvement. METHODS: Thirty women with no history of cancer were recruited through social media, commercial centers, health clinics, and community settings in Montreal, Qc, Canada. Participants accessed e-platform content tailored to their assigned hypothetical BC risk level, and then completed study e-questionnaires including the user Mobile Application Rating Scale (uMARS), an e-platform quality scale (i.e., in terms of engagement, functionality, aesthetics, and information). A subsample (n = 18) was randomly selected for an individual follow-up semi-structured interview. RESULTS: The e-platform overall quality was high, with mean M = 4.01 (out of 5) and SD = 0.50. A total of 87% (n = 26) agreed or strongly agreed that PREVENTION increased their knowledge and awareness of BC risk, and 80% would recommend it to others while reporting likelihood of following lifestyle recommendations to decrease their BC risk. Follow up interviews indicated that participants perceived the e-platform as a trusted source of BC information and a promising means to connect with peers. They also reported that while the e-platform was easy to navigate, improvements were needed for connectivity, visuals, and the organization of scientific resources. CONCLUSION: Preliminary findings support PREVENTION as a promising means to provide personalized BC information and support. Efforts are underway to further refine the platform, assess its impact in larger samples and gather feedback from BC specialists.

11.
Cell Rep Med ; 4(4): 101005, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37075703

RESUMO

To develop therapies for Alzheimer's disease, we need accurate in vivo diagnostics. Multiple proteomic studies mapping biomarker candidates in cerebrospinal fluid (CSF) resulted in little overlap. To overcome this shortcoming, we apply the rarely used concept of proteomics meta-analysis to identify an effective biomarker panel. We combine ten independent datasets for biomarker identification: seven datasets from 150 patients/controls for discovery, one dataset with 20 patients/controls for down-selection, and two datasets with 494 patients/controls for validation. The discovery results in 21 biomarker candidates and down-selection in three, to be validated in the two additional large-scale proteomics datasets with 228 diseased and 266 control samples. This resulting 3-protein biomarker panel differentiates Alzheimer's disease (AD) from controls in the two validation cohorts with areas under the receiver operating characteristic curve (AUROCs) of 0.83 and 0.87, respectively. This study highlights the value of systematically re-analyzing previously published proteomics data and the need for more stringent data deposition.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Proteômica/métodos , Biomarcadores/líquido cefalorraquidiano , Curva ROC
12.
J Pharm Policy Pract ; 16(1): 36, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864489

RESUMO

BACKGROUND: The recent SARS-CoV-2 pandemic has resulted in significant morbidity and mortality worldwide. The healthcare systems, including pharmacies, faced unique challenges, such as managing  an overwhelming patient influx, clinical workforce management, transitioning to remote or online work, medication procurement and several others. The purpose of this study is to describe our hospital pharmacy's experience dealing with the COVID-19 pandemic and to present solutions to the challenges that arose. METHODOLOGY: We retrospectively reviewed and consolidated strategies, interventions, and solutions that were implemented by our pharmaceutical institute in response to the challenges that arose during the COVID-19 pandemic. The study period was from March 1 to September 30, 2020. RESULTS: We reviewed and organized our hospital pharmacy response to the COVID-19 pandemic into different categories. In inpatient and outpatient satisfaction surveys, physicians and patients expressed a high level of satisfaction with pharmacy services. The close collaboration between the pharmacy team and other clinicians was demonstrated through the number of pharmacist interventions, participation in the COVID-19 guidelines reviews, involvement in local and international research, and innovative solutions to inpatient and outpatient pharmacy medication management challenges. CONCLUSIONS: This study highlights the crucial role that our pharmacists and pharmaceutical institute played in ensuring continuity of care during the COVID-19 pandemic. We implemented several key initiatives, innovations, and collaborations with other clinical disciplines to successfully overcome the challenges faced.

13.
Sci Adv ; 9(4): eade2155, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36696489

RESUMO

Biophysical cues are essential for guiding skeletal development, but the mechanisms underlying the mechanical regulation of cartilage and bone formation are unknown. TRPV4 is a mechanically sensitive ion channel involved in cartilage and bone cell mechanosensing, mutations of which lead to skeletal developmental pathologies. We tested the hypothesis that loading-driven prenatal skeletal development is dependent on TRPV4 activity. We first establish that mechanically stimulating mouse embryo hindlimbs cultured ex vivo stimulates knee cartilage growth, morphogenesis, and expression of TRPV4, which localizes to areas of high biophysical stimuli. We then demonstrate that loading-driven joint cartilage growth and shape are dependent on TRPV4 activity, mediated via control of cell proliferation and matrix biosynthesis, indicating a mechanism by which mechanical loading could direct growth and morphogenesis during joint formation. We conclude that mechanoregulatory pathways initiated by TRPV4 guide skeletal development; therefore, TRPV4 is a valuable target for the development of skeletal regenerative and repair strategies.


Assuntos
Cartilagem Articular , Canais de Cátion TRPV , Animais , Camundongos , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Cartilagem Articular/metabolismo , Osteogênese , Morfogênese
14.
Viruses ; 14(12)2022 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-36560759

RESUMO

Herpesviruses have complex mechanisms enabling infection of the human CNS and evasion of the immune system, allowing for indefinite latency in the host. Herpesvirus infections can cause severe complications of the central nervous system (CNS). Here, we provide a novel characterization of cerebrospinal fluid (CSF) proteomes from patients with meningitis or encephalitis caused by human herpes simplex virus 1 (HSV-1), which is the most prevalent human herpesvirus associated with the most severe morbidity. The CSF proteome was compared with those from patients with meningitis or encephalitis due to human herpes simplex virus 2 (HSV-2) or varicella-zoster virus (VZV, also known as human herpesvirus 3) infections. Virus-specific differences in CSF proteomes, most notably elevated 14-3-3 family proteins and calprotectin (i.e., S100-A8 and S100-A9), were observed in HSV-1 compared to HSV-2 and VZV samples, while metabolic pathways related to cellular and small molecule metabolism were downregulated in HSV-1 infection. Our analyses show the feasibility of developing CNS proteomic signatures of the host response in alpha herpes infections, which is paramount for targeted studies investigating the pathophysiology driving virus-associated neurological disorders, developing biomarkers of morbidity, and generating personalized therapeutic strategies.


Assuntos
Encefalite , Infecções por Herpesviridae , Herpesvirus Humano 1 , Meningite , Humanos , Proteoma , Proteômica , Sistema Nervoso Central , Herpesvirus Humano 3 , Herpesvirus Humano 2
15.
Curr Oncol ; 29(10): 7171-7180, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36290841

RESUMO

The SARS-CoV-2 (COVID-19) pandemic has accelerated the development and use of digital health platforms to support individuals with health-related challenges. This is even more frequent in the field of cancer care as the global burden of the disease continues to increase every year. However, optimal implementation of these platforms into the clinical setting requires careful planning and collaboration. An implementation project was launched between the Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Centre-Ouest-de-I'Île-de-Montreal and BELONG-Beating Cancer Together-a person-centred cancer navigation and support digital health platform. The goal of the project was to implement content and features specific to the CIUSSS, to be made available exclusively for individuals with cancer (and their caregivers) treated at the institution. Guided by Structural Model of Interprofessional Collaboration, we report on implementation processes involving diverse stakeholders including clinicians, hospital administrators, researchers and local community/patient representatives. Lessons learned include earlier identification of shared goals and clear expectations, more consistent reliance on virtual means to communicate among all involved, and patient/caregiver involvement in each step to ensure informed and shared decision making.


Assuntos
COVID-19 , Neoplasias , Humanos , SARS-CoV-2 , Participação do Paciente , Cuidadores , Neoplasias/terapia
16.
BMC Public Health ; 22(1): 1802, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138374

RESUMO

BACKGROUND: A sedentary lifestyle increases the risk of adverse health outcomes and frailty,particularly for older adults. To reduce transmission during the COVID-19 pandemic, people were instructed to stay at home, group sports were suspended, and gyms were closed, thereby limiting opportunities for physical activity. Whilst evidence suggests that physical activity levels reduced during the pandemic, it is unclear whether the proportion of older adults realising the recommended minimum level of physical activity changed throughout the various stages of lockdown. METHODS: We used a large sample of 3,660 older adults (aged ≥ 65) who took part in the UK Household Longitudinal Study's annual and COVID-19 studies. We examined changes in the proportion of older adults who were realising the UK Chief Medical Officers' physical activity recommendations for health maintenance at several time points before and after COVID-19 lockdowns were imposed. We stratified these trends by the presence of health conditions, age, neighbourhood deprivation, and pre-pandemic activity levels. RESULTS: There was a marked decline in older adults' physical activity levels during the third national lockdown in January 2021. The proportion realising the Chief Medical Officers' physical activity recommendations decreased from 43% in September 2020 to 33% in January 2021. This decrease in physical activity occurred regardless of health condition, age, neighbourhood deprivation, or pre-pandemic activity levels. Those doing the least activity pre-lockdown increased their activity during lockdowns and those doing the most decreased their activity levels. CONCLUSIONS: Reductions in older adults' physical activity levels during COVID-19 lockdowns have put them at risk of becoming deconditioned and developing adverse health outcomes. Resources should be allocated to promote the uptake of physical activity in older adults to reverse the effects of deconditioning.


Assuntos
COVID-19 , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Exercício Físico , Humanos , Estudos Longitudinais , Pandemias/prevenção & controle , Reino Unido/epidemiologia
17.
Nat Commun ; 13(1): 4234, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918315

RESUMO

Respiratory syncytial virus is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of Th 1 immunity. Here we show application of cationic adjuvant formulation CAF08, a liposomal vaccine formulation tailored to induce Th 1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. We apply quantitative phosphoproteomics to human dendritic cells and reveal a role for Protein Kinase C-δ for enhanced Th1 cytokine production in neonatal dendritic cells and identify signaling events resulting in antigen cross-presentation. In a murine in vivo model a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protects newborn mice from RSV infection by induction of antigen-specific CD8+ T-cells and Th1 cells. Overall, we describe a pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other respiratory viral pathogens.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais , Linfócitos T CD8-Positivos , Humanos , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Virais de Fusão
18.
Pancreas ; 51(5): 435-444, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35881699

RESUMO

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for refractory chronic pancreatitis-related pain. Despite the known clinical implications of TPIAT, the molecular effects remain poorly investigated. We performed the first hypothesis-generating study of the urinary proteome before and after TPIAT. METHODS: Twenty-two patients eligible for TPIAT were prospectively enrolled. Urine samples were collected the week before and 12 to 18 months after TPIAT. The urine samples were prepared for bottom-up label-free quantitative proteomics using the "MStern" protocol. RESULTS: Using 17 paired samples, we identified 2477 urinary proteins, of which 301 were significantly changed post-TPIAT versus pre-TPIAT. Our quantitative analysis revealed that the molecular response to TPIAT was highly sex-specific, with pronounced sex differences pre-TPIAT but minimal differences afterward. Comparing post-TPIAT versus pre-TPIAT, we found changes in cell-cell adhesion, intracellular vacuoles, and immune response proteins. After surgery, immunoglobulins, complement proteins, and cathepsins were increased, findings that may reflect glomerular damage. Finally, we identified both known and novel markers for immunoglobulin A nephropathy after 1 patient developed the disease 2 years after TPIAT. CONCLUSIONS: We found distinct changes in the urinary proteomic profile after TPIAT and the response to TPIAT is highly sex-specific.


Assuntos
Transplante das Ilhotas Pancreáticas , Pancreatite Crônica , Feminino , Humanos , Transplante das Ilhotas Pancreáticas/métodos , Masculino , Pancreatectomia/métodos , Pancreatite Crônica/cirurgia , Proteômica , Transplante Autólogo , Resultado do Tratamento
20.
J Neurovirol ; 28(3): 341-354, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35639337

RESUMO

State-of-the-art liquid chromatography/mass spectrometry (LC/MS)-based proteomic technologies, using microliter amounts of patient plasma, can detect and quantify several hundred plasma proteins in a high throughput fashion, allowing for the discovery of clinically relevant protein biomarkers and insights into the underlying pathobiological processes. Using such an in-house developed high throughput plasma proteomics allowed us to identify and quantify > 400 plasmas proteins in 15 min per sample, i.e., a throughput of 100 samples/day. We demonstrated the clinical applicability of our method in this pilot study by mapping the plasma proteomes from patients infected with human immunodeficiency virus (HIV) or herpes virus, both groups with involvement of the central nervous system (CNS). We found significant disease-specific differences in the plasma proteomes. The most notable difference was a decrease in the levels of several coagulation-associated proteins in HIV vs. herpes virus, among other dysregulated biological pathways providing insight into the differential pathophysiology of HIV compared to herpes virus infection. In a subsequent analysis, we found several plasma proteins associated with immunity and metabolism to differentiate patients with HIV-associated neurocognitive disorders (HAND) compared to cognitively normal people with HIV (PWH), suggesting the presence of plasma-based biomarkers to distinguishing HAND from cognitively normal PWH. Overall, our high-throughput plasma proteomics pipeline enables the identification of distinct proteomic signatures of HIV and herpes virus, which may help illuminate divergent pathophysiology behind virus-associated neurological disorders.


Assuntos
Infecções por HIV , Proteômica , Biomarcadores , Sistema Nervoso Central , Infecções por HIV/complicações , Humanos , Transtornos Neurocognitivos , Projetos Piloto , Proteoma , Proteômica/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...