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2.
Sex Health ; 212024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833542

RESUMO

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/métodos , Ásia , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Piridonas/administração & dosagem , Dicetopiperazinas
3.
Nat Commun ; 15(1): 4577, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830854

RESUMO

Rare-earth elements (REEs) are critical to our modern economy, yet their mining from natural ores bears a profound environmental impact. Traditional separation techniques are chemical and energy-intensive because their chemical similarities make REEs very challenging to purify, requiring multiple extraction steps to achieve high purity products. This emphasizes the need for sustainable and straightforward separation methods. Here we introduce a strategy for the direct separation of europium (Eu) from complex mixtures under ambient conditions, leveraging on the redox non innocence of purely inorganic tungsten tetrathiolate (WS42-) ligands. The recovery of Eu is achieved upon reduction of Eu(III) to a Eu(II) coordination polymer, driven by an induced internal electron transfer from the tetrathiotungstate ligand. Applying this strategy to unconventional feedstock such as spent energy-saving lamps allows selective europium recovery with separation factors over 1000 and recovery efficiency as high as 99% without pre-treatment of the waste.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38873828

RESUMO

OBJECTIVES: To explore the feasibility of linking data from enhanced surveillance patient questionnaires from each enteric fever case in England with genome sequencing data, including antimicrobial resistance (AMR) profiles, from the corresponding isolate of typhoidal salmonellae. METHODS: After linking data we interrogated the merged dataset and assessed the utility of passive surveillance data to match and monitor antimicrobial treatment regimens in enteric fever patients with the AMR profiles of the infectious agent. RESULTS: A high proportion of cases were given antibiotics (n = 1230/1415; 86.9%); half of the cases stated the class of antibiotic they were given (n = 630/1239) and half were prescribed cephalosporins (n = 316/630). Reported treatment with a combination of antibiotics increased with symptom severity. Nearly half of isolates (n = 644/1415; 45.5%) had mutations conferring resistance to ciprofloxacin. Based on genome-derived AMR profiles, typhoidal salmonellae isolates inferred to be susceptible to the recommended first-line antimicrobials were twice as likely to be isolated from individuals residing in the least deprived areas compared with the most deprived (n = 26/169; 15.4% versus n = 32/442; 7.2%). CONCLUSIONS: Due to the high proportion of missing data obtained from patient interviews, we recommend a more transparent and systematic approach to recording the antibiotic prescription details by healthcare professionals in primary and secondary care. A more robust approach to data capture at this point in the care pathway would enable us to audit inconsistencies in the prescribing algorithms across England and ensure equitable treatment across all sections of society. Integrating prescribing data with the genome-derived AMR profiles of the causative agent at the individual patient level provides an opportunity to monitor the impact of treatment on clinical outcomes, and to promote best practice in real time.

5.
bioRxiv ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38826244

RESUMO

Alcohol use disorder (AUD) is a significant global health issue. Despite historically higher rates among men, AUD prevalence and negative alcohol-related outcomes in women are rising. Loneliness in humans has been associated with increased alcohol use, and traditional rodent drinking models involve single housing, presenting challenges for studying social enrichment. We developed LIQ PARTI (Lick Instance Quantifier with Poly-Animal RFID Tracking Integration), an open-source tool to examine home cage continuous access two-bottle choice drinking behavior in a group-housed setting, investigating the influence of sex and social isolation on ethanol consumption and bout microstructure in C57Bl/6J mice. LIQ PARTI, based on our previously developed single-housed LIQ HD system, accurately tracks drinking behavior using capacitive-based sensors and RFID technology. Group-housed female mice exhibited higher ethanol preference than males, while males displayed a unique undulating pattern of ethanol preference linked to cage changes, suggesting a potential stress-related response. Chronic ethanol intake distinctly altered bout microstructure between male and female mice, highlighting sex and social environmental influences on drinking behavior. Social isolation with the LIQ HD system amplified fluid intake and ethanol preference in both sexes, accompanied by sex- and fluid-dependent changes in bout microstructure. However, these effects largely reversed upon resocialization, indicating the plasticity of these behaviors in response to social context. Utilizing a novel group-housed home cage lickometer device, our findings illustrate the critical interplay of sex and housing conditions in voluntary alcohol drinking behaviors in C57Bl/6J mice, facilitating nuanced insights into the potential contributions to AUD etiology.

6.
Am J Ind Med ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856006

RESUMO

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) mitigation measures in workplaces of employed US blood donors by industry and work arrangement. METHODS: During May-December 2021, blood donors responded to a survey; we describe the distribution of reported workplace mitigation measures by industry and work arrangement, organized using the hierarchy of controls. RESULTS: Of 53,433 respondents representing 21 industries, ventilation upgrades were reported by 4%-38% of respondents (overall: 20%); telework access ranged from 14%-80% (53% overall). Requiring masks (overall: 84%; range: 40%-94%), physical distancing (77%; 51%-86%), paid leave for illness (70%; 38%-87%), and encouraging vaccination (61%; 33%-80%) were common. Independent workers reported fewer mitigation measures than those in traditional employment settings. CONCLUSIONS: Mitigation measures varied by industry and work arrangement. Some mitigation measures may be challenging to implement or irrelevant in certain industries, supporting the idea that mitigation is not a one-size-fits-all strategy. POLICY IMPLICATIONS: Tailored strategies to mitigate workplace risks of disease transmission are vital. Strategies should rely on effective methods for identifying workplace controls (e.g., through the hierarchy of controls) and account for industry-specific characteristics and workplace environments.

7.
Cureus ; 16(5): e60054, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38854209

RESUMO

INTRODUCTION: Diversity in healthcare and research is integral to serving our increasingly diverse population. Access to academic enrichment programs, an important pathway to science, technology, engineering, and mathematics (STEM) careers promotes educational attainment through academic preparation and increased interest, useful strategies for improving diverse representation in higher learning. Given this important pathway to STEM fields, attention to equity in enrichment programs admissions is as important as the increasing focus on mitigating racial/ethnic disparities in undergraduate and graduate admissions.  Methods: In a retrospective cohort study at the University of Washington, we used descriptive and Chi-Square statistics to compare a hybrid competitive summer application program with stipend with an asynchronous first-come, first-served enrollment program in injury and violence prevention research. The three main outcomes were: 1) time to application, measured by number of days to apply/enroll after application or enrollment period start date, 2) percentage of application/enrollment period, measured by when application or enrollment occurred in relation to the total application or enrollment period, and 3) differences in Black, Hispanic, and Native American applicants and enrollees.  Results: In a study examining two injury and violence prevention programs, which reached educational institutions including Historically Black Colleges and Universities (HBCU) and Tribal Colleges: 1) Applicants were 9.6% and 6.4% Black (application vs enrollment programs; p<0.0001), 0.4% and 0% Native American to the application and enrollment programs, and 9.1% and 10.3% Hispanic (application vs enrollment programs; p=0.6), 2) Across all racial and ethnic groups, students applied later (last 15% percent of application period) in the competitive application program than to the first-come first-served enrollment program in which students enrolled throughout the enrollment period, and 3) Across both program types, there were racial and ethnic differences in time to application and enrollment start and completion. CONCLUSION: Findings show that free enrollment programs alone do not incentivize educational attainment for all groups and that application rolling admissions processes may not equally promote racial and ethnic diversity for all groups.

8.
Lancet Oncol ; 25(6): 779-789, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701815

RESUMO

BACKGROUND: Numerous studies have shown that older women with endometrial cancer have a higher risk of recurrence and cancer-related death. However, it remains unclear whether older age is a causal prognostic factor, or whether other risk factors become increasingly common with age. We aimed to address this question with a unique multimethod study design using state-of-the-art statistical and causal inference techniques on datasets of three large, randomised trials. METHODS: In this multimethod analysis, data from 1801 women participating in the randomised PORTEC-1, PORTEC-2, and PORTEC-3 trials were used for statistical analyses and causal inference. The cohort included 714 patients with intermediate-risk endometrial cancer, 427 patients with high-intermediate risk endometrial cancer, and 660 patients with high-risk endometrial cancer. Associations of age with clinicopathological and molecular features were analysed using non-parametric tests. Multivariable competing risk analyses were performed to determine the independent prognostic value of age. To analyse age as a causal prognostic variable, a deep learning causal inference model called AutoCI was used. FINDINGS: Median follow-up as estimated using the reversed Kaplan-Meier method was 12·3 years (95% CI 11·9-12·6) for PORTEC-1, 10·5 years (10·2-10·7) for PORTEC-2, and 6·1 years (5·9-6·3) for PORTEC-3. Both overall recurrence and endometrial cancer-specific death significantly increased with age. Moreover, older women had a higher frequency of deep myometrial invasion, serous tumour histology, and p53-abnormal tumours. Age was an independent risk factor for both overall recurrence (hazard ratio [HR] 1·02 per year, 95% CI 1·01-1·04; p=0·0012) and endometrial cancer-specific death (HR 1·03 per year, 1·01-1·05; p=0·0012) and was identified as a significant causal variable. INTERPRETATION: This study showed that advanced age was associated with more aggressive tumour features in women with endometrial cancer, and was independently and causally related to worse oncological outcomes. Therefore, our findings suggest that older women with endometrial cancer should not be excluded from diagnostic assessments, molecular testing, and adjuvant therapy based on their age alone. FUNDING: None.


Assuntos
Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/mortalidade , Fatores Etários , Idoso , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Idoso de 80 Anos ou mais
9.
Transl Vis Sci Technol ; 13(5): 19, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38776107

RESUMO

Purpose: We sought to introduce the materials, design, and biocompatibility of a flexible and suturable artificial corneal device. Methods: Single-piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall surfaces were lined with a porous tissue ingrowth material using expanded polytetrafluoroethylene. Full-thickness macroapertures around the skirt perimeter were placed to facilitate nutrition of the recipient cornea. Material properties including the skirt's modulus of elasticity and bending stiffness, optic light transmission, wetting behavior, topical drug penetrance, and degradation profile were evaluated. Results: The final prototype suitable for human use has a transparent optic with a diameter of 4.60 mm anteriorly, 4.28 mm posteriorly, and a skirt outer diameter of 6.8 mm. The biomechanical and optical properties of the device closely align with the native human cornea with an average normalized device skirt-bending stiffness of 4.7 kPa·mm4 and light transmission in the visible spectrum ranging between 92% and 96%. No optical damage was seen in the 36 devices tested in fouling experiments. No significant difference was observed in topical drug penetrance into the anterior chamber of the device implanted eye compared with the naïve rabbit eye. Conclusions: The flexibility and biocompatibility of our artificial cornea device may offer enhanced tissue integration and decreased inflammation, leading to improved retention compared with rigid keratoprosthesis designs. Translational Relevance: We have developed a fully synthetic, flexible, suturable, optic-skirt design prototype artificial cornea that is ready to be tested in early human feasibility studies.


Assuntos
Materiais Biocompatíveis , Córnea , Teste de Materiais , Desenho de Prótese , Animais , Coelhos , Materiais Biocompatíveis/química , Teste de Materiais/métodos , Humanos
10.
BMC Palliat Care ; 23(1): 128, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778297

RESUMO

BACKGROUND: Values are broadly understood to have implications for how individuals make decisions and cope with serious illness stressors, yet it remains uncertain how patients and their family and friend caregivers discuss, reflect upon, and act on their values in the post-left ventricular assist device (LVAD) implantation context. This study aimed to explore the values elicitation experiences of patients with an LVAD in the post-implantation period. METHODS: Qualitative descriptive study of LVAD recipients. Socio-demographics and patient resource use were analyzed using descriptive statistics and semi-structured interview data using thematic analysis. Adult (> 18 years) patients with an LVAD receiving care at an outpatient clinic in the Southeastern United States. RESULTS: Interviewed patients (n = 27) were 30-76 years, 59% male, 67% non-Hispanic Black, 70% married/living with a partner, and 70% urban-dwelling. Three broad themes of patient values elicitation experiences emerged: 1) LVAD implantation prompts deep reflection about life and what is important, 2) patient values are communicated in various circumstances to convey personal goals and priorities to caregivers and clinicians, and 3) patients leverage their values for strength and guidance in navigating life post-LVAD implantation. LVAD implantation was an impactful experience often leading to reevaluation of patients' values; these values became instrumental to making health decisions and coping with stressors during the post-LVAD implantation period. Patient values arose within broad, informal exchanges and focused, decision-making conversations with their caregiver and the healthcare team. CONCLUSIONS: Clinicians should consider assessing the values of patients post-implantation to facilitate shared understanding of their goals/priorities and identify potential changes in their coping.


Assuntos
Coração Auxiliar , Pesquisa Qualitativa , Humanos , Coração Auxiliar/psicologia , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Idoso , Adaptação Psicológica
11.
Adv Sci (Weinh) ; : e2400921, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696611

RESUMO

Endothelial programmed death-ligand 1 (PD-L1) expression is higher in tumors than in normal tissues. Also, tumoral vasculatures tend to be leakier than normal vessels leading to a higher trans-endothelial or transmural fluid flow. However, it is not clear whether such elevated transmural flow can control endothelial PD-L1 expression. Here, a new microfluidic device is developed to investigate the relationship between transmural flow and PD-L1 expression in microvascular networks (MVNs). After treating the MVNs with transmural flow for 24 h, the expression of PD-L1 in endothelial cells is upregulated. Additionally, CD8 T cell activation by phytohemagglutinin (PHA) is suppressed when cultured in the MVNs pre-conditioned with transmural flow. Moreover, transmural flow is able to further increase PD-L1 expression in the vessels formed in the tumor microenvironment. Finally, by utilizing blocking antibodies and knock-out assays, it is found that transmural flow-driven PD-L1 upregulation is controlled by integrin αVß3. Overall, this study provides a new biophysical explanation for high PD-L1 expression in tumoral vasculatures.

14.
Lancet Neurol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38782015

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis. METHODS: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed. FINDINGS: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI -0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]). INTERPRETATION: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated. FUNDING: Orphazyme.

15.
Public Health Rep ; : 333549241245655, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38785340

RESUMO

OBJECTIVES: The risk for mpox virus (MPXV) transmission in most workplaces has not been thoroughly assessed in the context of the 2022 global mpox outbreak. Our objectives were to describe mpox case patients who worked while infectious and the subsequent workplace contact tracing efforts, risk assessments, and outcomes. METHODS: The Centers for Disease Control and Prevention requested information from health departments in the United States in September 2022 to identify people with confirmed or probable mpox who worked outside the home while infectious, either before or after diagnosis, from June 1 through August 31, 2022. We collected and summarized data on demographic, clinical, and workplace characteristics of case patients and workplace contact investigations. We stratified data by industry and occupation categories. RESULTS: In total, 102 case patients were reported by 6 jurisdictions. The most common industries were accommodation and food services (19.8%) and professional business, management, and technical services (17.0%). Contact investigations identified 178 total contacts; 54 cases (52.9%) had no contacts identified. Of 178 contacts, 54 (30.3%) were recommended to receive postexposure prophylaxis (PEP) and 18 (10.1%) received PEP. None of the contacts developed a rash or were tested for orthopox or mpox, and none were reported to have confirmed or probable mpox. CONCLUSION: Data from 6 jurisdictions suggest that the risk of MPXV transmission from workers to others in workplace settings in many industries is low. These findings might support future updates to exposure risk classifications and work activity recommendations for patients. These findings also demonstrate the importance of collecting and analyzing occupation and industry data in case reports to better understand risks in workplaces.

16.
J Cardiovasc Nurs ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38786984

RESUMO

BACKGROUND: Intentional exploration, or elicitation, of patient and family values-who/what matters most-is critical to the delivery of person-centered care, yet the values elicitation experiences of family caregivers have been understudied. Understanding caregiver experiences discussing, reflecting upon, and acting on their values is critical to optimizing health decisions after left ventricular assist device (LVAD) implantation. OBJECTIVE: The aim of this study was to explore the values elicitation experiences of family caregivers of individuals with an LVAD in the postimplantation period. METHODS: This was a qualitative descriptive study of LVAD caregivers recruited from an outpatient clinic in the southeast United States. After completing one-on-one semistructured interviews, participants' transcripts were analyzed using thematic analysis. RESULTS: Interviewed caregivers (n = 21) were 27 to 76 years old, with 67% African American, 76% female, 76% urban-dwelling, and 62% a spouse/partner. LVAD implantation was an impactful experience prompting caregiver reevaluation of their values; these values became instrumental to navigating decisions and managing stressors from their caregiving role. Three broad themes of caregiver values elicitation experiences emerged: (1) caregivers leverage their values for strength and guidance in navigating their caregiving role, (2) LVAD implantation prompts (re)evaluation of relationships and priorities, and (3) caregivers convey their goals and priorities when deemed relevant to patient care. CONCLUSIONS: Having a care recipient undergo LVAD implantation prompted caregivers to reevaluate their values, which were used to navigate caregiving decisions and stressors. Findings highlight the need for healthcare professionals to engage and support caregivers after LVAD implantation.

17.
Sci Rep ; 14(1): 11590, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773178

RESUMO

Human interaction is immersed in laughter; though genuine and posed laughter are acoustically distinct, they are both crucial socio-emotional signals. In this novel study, autistic and non-autistic adults explicitly rated the affective properties of genuine and posed laughter. Additionally, we explored whether their self-reported everyday experiences with laughter differ. Both groups could differentiate between these two types of laughter. However, autistic adults rated posed laughter as more authentic and emotionally arousing than non-autistic adults, perceiving it to be similar to genuine laughter. Autistic adults reported laughing less, deriving less enjoyment from laughter, and experiencing difficulty in understanding the social meaning of other people's laughter compared to non-autistic people. Despite these differences, autistic adults reported using laughter socially as often as non-autistic adults, leveraging it to mediate social contexts. Our findings suggest that autistic adults show subtle differences in their perception of laughter, which may be associated with their struggles in comprehending the social meaning of laughter, as well as their diminished frequency and enjoyment of laughter in everyday scenarios. By combining experimental evidence with first-person experiences, this study suggests that autistic adults likely employ different strategies to understand laughter in everyday contexts, potentially leaving them socially vulnerable in communication.


Assuntos
Transtorno Autístico , Riso , Humanos , Riso/psicologia , Masculino , Adulto , Feminino , Transtorno Autístico/psicologia , Transtorno Autístico/fisiopatologia , Adulto Jovem , Emoções/fisiologia , Pessoa de Meia-Idade
18.
Can J Cardiol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38705272

RESUMO

BACKGROUND: Patients with congenital heart disease (CHD) and their parents face challenges throughout their lives that can lead to anxiety lasting into adulthood. We aim to assess the association between perceived parenting practices and anxiety beyond pediatric medical-surgical histories in adults with CHD. METHODS: A cross-sectional study of adults with CHD was conducted at the Montreal Heart Institute (MHI). Perception of parental practices during childhood was retrospectively assessed using validated self-report questionnaires, while anxiety in adulthood was assessed with the Hospital Anxiety and Depression Scale (HADS). Sociodemographic and medical information were collected from a questionnaire and medical records. Hierarchical multiple linear regression was conducted. RESULTS: Of the 223 participants, 59% were female, and the mean age was 46 ± 14 years. Perceived parenting practices explained more variance (11%) in the anxiety score than pediatric medical-surgical history (2%). In our final model, anxiety was significantly associated with age, parental history of anxiety, and positive parenting practices, but not with overprotection. CONCLUSIONS: Parenting practices are associated with anxiety in adults with CHD beyond pediatric medical-surgical history and sociodemographic. Positive parenting practices may be protective against anxiety in adulthood. Longitudinal studies are needed to determine causality.

19.
Immun Ageing ; 21(1): 27, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698438

RESUMO

BACKGROUND: Atherosclerosis, the main underlying pathology of cardiovascular disease, is a chronic inflammatory disease characterized by lipid accumulation and immune cell responses in the vascular wall, resulting in plaque formation. It is well-known that atherosclerosis prevalence and manifestation vary by sex. However, sexual dimorphism in the immune landscape of atherosclerotic plaques has up to date not been studied at high-resolution. In this study, we investigated sex-specific differences in atherosclerosis development and the immunological landscape of aortas at single-cell level in aged Ldlr-/- mice. METHODS: We compared plaque morphology between aged male and female chow diet-fed Ldlr-/- mice (22 months old) with histological analysis. Using single-cell RNA-sequencing and flow cytometry on CD45+ immune cells from aortas of aged Ldlr-/- mice, we explored the immune landscape in the atherosclerotic environment in males and females. RESULTS: We show that plaque volume is comparable in aged male and female mice, and that plaques in aged female mice contain more collagen and cholesterol crystals, but less necrotic core and macrophage content compared to males. We reveal increased immune cell infiltration in female aortas and found that expression of pro-atherogenic markers and inflammatory signaling pathways was enriched in plaque immune cells of female mice. Particularly, female aortas show enhanced activation of B cells (Egr1, Cd83, Cd180), including age-associated B cells, in addition to an increased M1/M2 macrophage ratio, where Il1b+ M1-like macrophages display a more pro-inflammatory phenotype (Nlrp3, Cxcl2, Mmp9) compared to males. In contrast, increased numbers of age-associated Gzmk+CD8+ T cells, dendritic cells, and Trem2+ macrophages were observed in male aortas. CONCLUSIONS: Altogether, our findings highlight that sex is a variable that contributes to immunological differences in the atherosclerotic plaque environment in mice and provide valuable insights for further preclinical studies into the impact of sex on the pathophysiology of atherosclerosis.

20.
J Vet Intern Med ; 38(3): 1639-1650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38700383

RESUMO

BACKGROUND: It is not known how much information clients retrieve from discharge instructions. OBJECTIVE: To investigate client's understanding of discharge instructions and influencing factors. ANIMALS: Dogs and cats being hospitalized for neurological diseases. METHODS: Clients were presented questionnaires regarding their pet's disease, diagnostics, treatments, prognosis and discharge instructions at time of discharge and 2 weeks later. The same questions were answered by discharging veterinarians at time of discharge. Clients answered additional questions regarding the subjective feelings during discharge conversation. Data collected included: data describing discharging veterinarian (age, gender, years of clinical experience, specialist status), data describing the client (age, gender, educational status). Raw percentage of agreement (RPA) between answers of clinicians and clients as well as factors potentially influencing the RPA were evaluated. RESULTS: Of 230 clients being approached 151 (65.7%) and 70 (30.4%) clients responded to the first and second questionnaire, respectively (130 dog and 30 cat owners). The general RPA between clinician's and client's responses over all questions together was 68.9% and 66.8% at the 2 time points. Questions regarding adverse effects of medication (29.0%), residual clinical signs (35.8%), and confinement instructions (36.8%) had the lowest RPAs at the first time point. The age of clients (P = .008) negatively influenced RPAs, with clients older than 50 years having lower RPA. CONCLUSIONS AND CLINICAL IMPORTANCE: Clients can only partially reproduce information provided at discharge. Only clients' increasing age influenced recall of information. Instructions deemed to be important should be specifically stressed during discharge.


Assuntos
Doenças do Gato , Doenças do Cão , Doenças do Sistema Nervoso , Gatos , Cães , Animais , Doenças do Gato/terapia , Doenças do Cão/terapia , Inquéritos e Questionários , Masculino , Feminino , Humanos , Doenças do Sistema Nervoso/veterinária , Hospitais Veterinários , Adulto , Pessoa de Meia-Idade , Alta do Paciente , Médicos Veterinários/psicologia
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