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1.
Artigo em Inglês | MEDLINE | ID: mdl-38958945

RESUMO

BACKGROUND: The stromal microenvironment (SME) is integral to breast cancer (BC) biology, impacting metastatic proclivity and treatment response. Emerging data indicate that host factors may impact the SME, but the relationship between pre-diagnostic host factors and SME phenotype remains poorly characterized, particularly among women of African ancestry. METHODS: We conducted a case-only analysis involving 792 BC patients (17-84 years) from the Ghana Breast Health Study (GBHS). High-accuracy machine-learning algorithms were applied to standard H&E-stained images to characterize SME phenotypes (including percent tumor-associated connective tissue stroma, Ta-CTS (%), and tumor-associated stromal cellular density, Ta-SCD (%)). Associations between pre-diagnostic host factors and SME phenotypes were assessed in multivariable linear regression models. RESULTS: Decreasing Ta-CTS and increasing Ta-SCD were associated with aggressive, mostly high-grade tumors (p-value<0.001). Several pre-diagnostic host factors were associated with Ta-SCD independently of tumor characteristics. Compared with nulliparous women, parous women had higher levels of Ta-SCD [mean (standard deviation, SD) = 31.3% (7.6%) vs. 28.9% (7.1%); p-value=0.01]. Similarly, women with a positive family history of breast cancer had higher levels of Ta-SCD than those without family history [mean (SD) = 33.0% (7.5%)] vs. 30.9% (7.6%); p-value=0.03]. Conversely, increasing body size was associated with decreasing Ta-SCD [mean (SD) = 32.0% (7.4%), 31.3% (7.3%), and 29.0% (8.0%) for slight, average, and large body sizes, respectively, p-value=0.005]. CONCLUSIONS: Epidemiological risk factors were associated with varying degrees of stromal cellularity in tumors, independently of clinicopathological characteristics. IMPACT: The findings raise the possibility that epidemiological risk factors may partly influence tumor biology via the SME.

2.
BMJ Health Care Inform ; 31(1)2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38909995

RESUMO

BACKGROUND: The learning health system (LHS) concept is a potential solution to the challenges currently faced by primary care. There are few descriptions of the barriers and facilitators to achieving an LHS in general practice, and even fewer that are underpinned by implementation science. This study aimed to describe the barriers and facilitators to achieving an LHS in primary care and provide practical recommendations for general practices on their journey towards an LHS. METHODS: This study is a secondary data analysis from a qualitative investigation of an LHS in a university-based general practice in Sydney, Australia. A framework analysis was conducted using transcripts from semistructured interviews with clinic staff. Data were coded according to the theoretical domains framework, and then to an LHS framework. RESULTS: 91% (n=32) of practice staff were interviewed, comprising general practitioners (n=15), practice nurses (n=3), administrative staff (n=13) and a psychologist. Participants reported that the practice alignment with LHS principles was influenced by many behavioural determinants, some of which were applicable to healthcare in general, for example, some staff lacked knowledge about practice policies and skills in using software. However, many were specific to the general practice environment, for example, the environmental context of general practice meant that administrative staff were an integral part of the LHS, particularly in facilitating partnerships with patients. CONCLUSIONS: The LHS journey in general practice is influenced by several factors. Mapping the LHS domains in relation to the theoretical domains framework can be used to generate a roadmap to hasten the journey towards LHS in primary care settings.


Assuntos
Sistema de Aprendizagem em Saúde , Atenção Primária à Saúde , Pesquisa Qualitativa , Humanos , Entrevistas como Assunto , Austrália , Medicina Geral , Atitude do Pessoal de Saúde
3.
bioRxiv ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38915583

RESUMO

Postnatal genomic regulation significantly influences tissue and organ maturation but is under-studied relative to existing genomic catalogs of adult tissues or prenatal development in mouse. The ENCODE4 consortium generated the first comprehensive single-nucleus resource of postnatal regulatory events across a diverse set of mouse tissues. The collection spans seven postnatal time points, mirroring human development from childhood to adulthood, and encompasses five core tissues. We identified 30 cell types, further subdivided into 69 subtypes and cell states across adrenal gland, left cerebral cortex, hippocampus, heart, and gastrocnemius muscle. Our annotations cover both known and novel cell differentiation dynamics ranging from early hippocampal neurogenesis to a new sex-specific adrenal gland population during puberty. We used an ensemble Latent Dirichlet Allocation strategy with a curated vocabulary of 2,701 regulatory genes to identify regulatory "topics," each of which is a gene vector, linked to cell type differentiation, subtype specialization, and transitions between cell states. We find recurrent regulatory topics in tissue-resident macrophages, neural cell types, endothelial cells across multiple tissues, and cycling cells of the adrenal gland and heart. Cell-type-specific topics are enriched in transcription factors and microRNA host genes, while chromatin regulators dominate mitosis topics. Corresponding chromatin accessibility data reveal dynamic and sex-specific regulatory elements, with enriched motifs matching transcription factors in regulatory topics. Together, these analyses identify both tissue-specific and common regulatory programs in postnatal development across multiple tissues through the lens of the factors regulating transcription.

4.
Nat Neurosci ; 27(6): 1064-1074, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38769152

RESUMO

Ancestral differences in genomic variation affect the regulation of gene expression; however, most gene expression studies have been limited to European ancestry samples or adjusted to identify ancestry-independent associations. Here, we instead examined the impact of genetic ancestry on gene expression and DNA methylation in the postmortem brain tissue of admixed Black American neurotypical individuals to identify ancestry-dependent and ancestry-independent contributions. Ancestry-associated differentially expressed genes (DEGs), transcripts and gene networks, while notably not implicating neurons, are enriched for genes related to the immune response and vascular tissue and explain up to 26% of heritability for ischemic stroke, 27% of heritability for Parkinson disease and 30% of heritability for Alzheimer's disease. Ancestry-associated DEGs also show general enrichment for the heritability of diverse immune-related traits but depletion for psychiatric-related traits. We also compared Black and non-Hispanic white Americans, confirming most ancestry-associated DEGs. Our results delineate the extent to which genetic ancestry affects differences in gene expression in the human brain and the implications for brain illness risk.


Assuntos
Negro ou Afro-Americano , Encéfalo , Metilação de DNA , Humanos , Negro ou Afro-Americano/genética , Encéfalo/metabolismo , Feminino , Masculino , População Branca/genética , Autopsia , Expressão Gênica/genética , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/etnologia , Idoso , Pessoa de Meia-Idade
5.
Science ; 384(6698): eadh1938, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38781370

RESUMO

The molecular organization of the human neocortex historically has been studied in the context of its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification of transcriptionally defined spatial domains that move beyond classic cytoarchitecture. We used the Visium spatial gene expression platform to generate a data-driven molecular neuroanatomical atlas across the anterior-posterior axis of the human dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions across spatial domains. Using PsychENCODE and publicly available data, we mapped the enrichment of cell types and genes associated with neuropsychiatric disorders to discrete spatial domains.


Assuntos
Córtex Pré-Frontal Dorsolateral , Análise de Célula Única , Transcriptoma , Adulto , Humanos , Comunicação Celular , Córtex Pré-Frontal Dorsolateral/metabolismo , Perfilação da Expressão Gênica , Neurônios/metabolismo , Neurônios/fisiologia , RNA-Seq , Análise de Sequência de RNA
6.
Ital J Dermatol Venerol ; 159(3): 223-250, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38727633

RESUMO

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.


Assuntos
Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Itália , Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Dermatologia/normas
7.
Ital J Dermatol Venerol ; 159(3): 279-284, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38727635

RESUMO

The evidence- and consensus-based guideline on atopic eczema, published in JEADV on 18 August 2022 (part 1) and 3 September 2022 (part 2) was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. To reflect the most recent evidence on novel systemic medications, an update was published in October 2022. According to the purpose of the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA) to adapt the EuroGuiDerm guideline on the treatment of atopic eczema into the Italian Healthcare setting, the original update has been supplemented by inserting notes, well highlighted by the original text, to emphasize the laws, rules, procedures and suggestions of the Italian Ministry of Health and regional Health authorities.


Assuntos
Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Itália , Dermatologia/normas
8.
Ital J Dermatol Venerol ; 159(3): 251-278, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38727634

RESUMO

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.


Assuntos
Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/terapia , Itália , Feminino , Gravidez , Criança , Adulto , Masculino , Emolientes/uso terapêutico , Complicações na Gravidez/terapia , Complicações na Gravidez/tratamento farmacológico , Dermatologia/normas
10.
JAMA Dermatol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776110

RESUMO

Importance: Outcome measurement is an essential component of value-based health care and can aid patient care, quality improvement, and clinical effectiveness evidence generation. The Harmonising Outcome Measures for Eczema Clinical Practice initiative aims to identify a list of validated, feasible, outcome measurement instruments recommended to measure atopic dermatitis (AD) in the clinical practice setting. The clinical practice set is a list of instruments that clinicians can pick and choose from to suit their needs in the context of clinical care. Objective: To recommend instruments to measure clinical signs of AD in clinical practice. Evidence Review: Following the predefined roadmap, a mixed methods design was implemented and incorporated systematic reviews and qualitative consensus methods. Previous systematic reviews identified few clinical signs instruments with sufficient validation for recommendation. An updated systematic review evaluating the validity of clinical signs instruments informed an international meeting to reach consensus on recommended instruments to measure AD clinical signs in clinical practice. Consensus was defined as less than 30% disagreement. An in-person consensus exercise was held in Montreal, Canada, on October 16, 2022. The 34 attendees included patient and patient advocate research partners, health care professionals, researchers, methodologists, and industry representatives. Findings: The updated systematic review found that the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis, and objective Scoring Atopic Dermatitis were the only instruments that demonstrated sufficient performance in all assessed measurement properties. The modified EASI and Signs Global Assessment × Body Surface Area instruments were also recommended. The EASI, Validated Investigator Global Assessment, and Investigator's Global Assessment multiplied by or measured concurrently with a body surface area measure achieved consensus in criteria and were adopted. Conclusions and Relevance: This consensus statement by the Harmonising Outcome Measures for Eczema initiative suggests that when assessing and documenting clinical signs of AD, there are several valid and feasible instruments that can best fit a clinician's specific practice needs. These instruments should improve and standardize the documentation of signs severity, help determine the effect of treatment, facilitate the generation of clinical effectiveness evidence, and enhance the implementation of value-based health care.

11.
PLoS One ; 19(5): e0303969, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38814901

RESUMO

BACKGROUND: The left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood. METHODS: Cardiac magnetic resonance (CMR) imaging was performed using a 1.5T scanner in subjects with FRDA who are homozygous for an expansion of an intron 1 GAA repeat in the FXN gene. Standard measurements were performed of LV mass (LVM), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). Native T1 relaxation time and the extracellular volume fraction (ECV) were utilised as markers of left ventricular (LV) diffuse myocardial fibrosis and late gadolinium enhancement (LGE) was utilised as a marker of LV replacement fibrosis. FRDA genetic severity was assessed using the shorter FXN GAA repeat length (GAA1). RESULTS: There were 93 subjects with FRDA (63 adults, 30 children, 54% males), 9 of whom had a reduced LVEF (<55%). A LVEDV below the normal range was present in 39%, a LVM above the normal range in 22%, and an increased LVM/LVEDV ratio in 89% subjects. In adults with a normal LVEF, there was an independent positive correlation of LVM with GAA1, and a negative correlation with age, but no similar relationships were seen in children. GAA1 was positively correlated with native T1 time in both adults and children, and with ECV in adults, all these associations independent of LVM and LVEDV. LGE was present in 21% of subjects, including both adults and children, and subjects with and without a reduced LVEF. None of GAA1, LVM or LVEDV were predictors of LGE. CONCLUSION: An association between diffuse interstitial LV myocardial fibrosis and genetic severity in FRDA was present independently of FRDA-related LV structural changes. Localised replacement fibrosis was found in a minority of subjects with FRDA and was not associated with LV structural change or FRDA genetic severity in subjects with a normal LVEF.


Assuntos
Ataxia de Friedreich , Gadolínio , Ventrículos do Coração , Imageamento por Ressonância Magnética , Humanos , Ataxia de Friedreich/genética , Ataxia de Friedreich/diagnóstico por imagem , Ataxia de Friedreich/patologia , Ataxia de Friedreich/complicações , Masculino , Feminino , Adulto , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/patologia , Criança , Adolescente , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Adulto Jovem , Meios de Contraste , Volume Sistólico , Fibrose , Frataxina
12.
Am J Sports Med ; 52(7): 1845-1854, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38742422

RESUMO

BACKGROUND: Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes. HYPOTHESIS: New or worsened neck pain is common after a concussion (>30%), negatively influences recovery, and is associated with patient sex and level of contact in sport. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Varsity-level athletes from 29 National Collegiate Athletic Association member institutions as well as nonvarsity sport athletes at military service academies were eligible for enrollment. Participants completed a preseason baseline assessment and follow-up assessments at 6 and 24 to 48 hours after a concussion, when they were symptom-free, and when they returned to unrestricted play. Data collection occurred between January 2014 and September 2018. RESULTS: A total of 2163 injuries were studied. New or worsened neck pain was reported with 47.0% of injuries. New or worsened neck pain was associated with patient sex (higher in female athletes), an altered mental status after the injury, the mechanism of injury, and what the athlete collided with. The presence of new/worsened neck pain was associated with delayed recovery. Those with new or worsened neck pain had 11.1 days of symptoms versus 8.8 days in those without (P < .001). They were also less likely to have a resolution of self-reported symptoms in ≤7 days (P < .001). However, the mean duration of the return-to-play protocol was not significantly different for those with new or worsened neck pain (7.5 ± 7.7 days) than those without (7.4 ± 8.3 days) (P = .592). CONCLUSION: This novel study shows that neck pain was common in collegiate athletes sustaining a concussion, was influenced by many factors, and negatively affected recovery.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Cervicalgia , Humanos , Masculino , Feminino , Cervicalgia/etiologia , Cervicalgia/epidemiologia , Concussão Encefálica/complicações , Concussão Encefálica/epidemiologia , Traumatismos em Atletas/epidemiologia , Adulto Jovem , Prevalência , Atletas/estatística & dados numéricos , Universidades , Adolescente , Volta ao Esporte , Estudos de Coortes , Fatores Sexuais
13.
Audiol Res ; 14(3): 412-431, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38804459

RESUMO

BACKGROUND: Cognitive behavioural therapy (CBT) for tinnitus management is effective and widely recommended by national and international practice guidelines. However, all the evidence for CBT so far has come from Psychologist-led programs, and the potential role of Audiologists in providing CBT for tinnitus remains an important consideration. OBJECTIVES: This study sets out to systematically map the body of literature relating to Audiologist-provided CBT for tinnitus, in order to summarise the current state of evidence and determine directions for future research. ELIGIBILITY CRITERIA: Sources were eligible for inclusion if they addressed the concept of Audiologist-provided CBT. No restrictions were imposed on the date of publication. Only sources published in English were included. SOURCES OF EVIDENCE: A wide range of primary and secondary literature sources were sought. CHARTING METHODS: Data from included sources were charted systematically using a pre-designed data charting form. RESULTS: Of the 267 identified sources, 30 were included in this review. This included both primary and secondary literature sources. Primary sources were compared and showed variation across Audiologist-provided CBT programs both in terms of procedural details and from a research standpoint. CONCLUSIONS: A growing body of evidence has addressed the concept of Audiologist-provided CBT. Directions for future research include further primary research with an increased focus on face-to-face Audiologist-provided CBT, and a comparison of the outcomes of Audiologist-provided vs. Psychologist-provided CBT.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38780711

RESUMO

PURPOSE: Exercise imaging using current modalities can be challenging. This was patient focused study to establish the feasibility and reproducibility of exercise-cardiovascular magnetic resonance imaging (EX-CMR) acquired during continuous in-scanner exercise in asymptomatic patients with primary mitral regurgitation (MR). METHODS: This was a prospective, feasibility study. Biventricular volumes/function, aortic flow volume, MR volume (MR-Rvol) and regurgitant fraction (MR-RF) were assessed at rest and during low- (Low-EX) and moderate-intensity exercise (Mod-EX) in asymptomatic patients with primary MR. RESULTS: Twenty-five patients completed EX-CMR without complications. Whilst there were no significant changes in the left ventricular (LV) volumes, there was a significant increase in the LVEF (rest 63 ± 5% vs. Mod-EX 68 ± 6%;p = 0.01). There was a significant reduction in the right ventricular (RV) end-systolic volume (rest 68 ml(60-75) vs. Mod-EX 46 ml(39-59);p < 0.001) and a significant increase in the RV ejection fraction (rest 55 ± 5% vs. Mod-EX 65 ± 8%;p < 0.001). Whilst overall, there were no significant group changes in the MR-Rvol and MR-RF, individual responses were variable, with MR-Rvol increasing by ≥ 15 ml in 4(16%) patients and decreasing by ≥ 15 ml in 9(36%) of patients. The intra- and inter-observer reproducibility of LV volumes and aortic flow measurements were excellent, including at Mod-EX. CONCLUSION: EX-CMR is feasible and reproducible in patients with primary MR. During exercise, there is an increase in the LV and RV ejection fraction, reduction in the RV end-systolic volume and a variable response of MR-Rvol and MR-RF. Understanding the individual variability in MR-Rvol and MR-RF during physiological exercise may be clinically important.

15.
Health Expect ; 27(3): e14082, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38783770

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) affects a significant and growing proportion of pregnant women each year. The condition entails additional monitoring, self-management and healthcare use during pregnancy, and some women also join GDM support groups on Facebook. Little is known about the practices inside these groups, but examining them may elucidate support needs, women's experience of healthcare and improve overall outcomes. The aims of this study were to explore motivations for joining GDM Facebook groups and the perceived value and benefits of such spaces. DESIGN: A cross-sectional design using a web-based survey collected data from two peer-led GDM Facebook groups; relevant quantitative and qualitative data were extracted from open and closed questions, and analysed using descriptive statistics and content analysis. RESULTS: A total of 340 women responded to the survey, with 306 (90%) tendering their motivations to join a GDM Facebook group. Their answers were classified into six categories: peer support; information and practical advice; lived experiences; community; a safe place to ask questions and being recommended. The most commonly reported benefits of membership were 'reading about food ideas' and 'finding helpful information and tips'. Respondents reported finding their group strongly sympathetic, sincere, compassionate, heart-felt, tolerant, sensitive, warm and supportive. DISCUSSION AND CONCLUSIONS: GDM Facebook groups are valuable for informational and emotional support, and the sharing and perusal of lived experiences; another key benefit for women is feeling belonging to a community. GDM Facebook groups provide women with access to more tailored and readily available support, filling gaps not addressed by healthcare providers. PATIENT CONTRIBUTION: This study was led by a person with lived experience of GDM, and the survey was pilot tested with women who had also experienced GDM, which contributed to its development.


Assuntos
Diabetes Gestacional , Autogestão , Mídias Sociais , Humanos , Feminino , Diabetes Gestacional/terapia , Diabetes Gestacional/psicologia , Gravidez , Adulto , Estudos Transversais , Inquéritos e Questionários , Apoio Social , Motivação , Grupos de Autoajuda
16.
Mol Ecol ; : e17371, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38721849

RESUMO

Large lipid-storing copepods dominate mesozooplankton biomass in the polar oceans and form a critical link between primary production and higher trophic levels. The ecological success of these species depends on their ability to survive periods of food deprivation in a highly seasonal environment, but the molecular changes that mediate starvation tolerance in these taxa are unknown. We conducted starvation experiments for two dominant Southern Ocean copepods, Calanoides acutus and Calanus propinquus, allowing us to compare the molecular starvation response between species. These species differ in life history, diet and metabolic traits, and expressed overlapping but distinct transcriptomic responses to starvation. Most starvation-response genes were species-specific, but we identified a conserved core set of starvation-response genes related to RNA and protein metabolism. We used phylotranscriptomics to place these results in the context of copepod evolution and found that starvation-response genes are under strong purifying selection at the sequence level and stabilizing selection at the expression level, consistent with their role in mediating essential biological functions. Selection on starvation-response genes was especially strong in our focal lipid-storing lineage relative to other copepod taxa, underscoring the significance of starvation tolerance for these species. We also found that certain key lipid enzymes (elongases and desaturases) have experienced diversification and positive selection in lipid-storing lineages, reflecting the unique lipid storage needs of these animals. Our results shed light on the molecular adaptations of high-latitude zooplankton to variable food conditions and suggest that starvation-response genes are under particularly strong sequence and expression constraints.

18.
J Am Acad Dermatol ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38653344

RESUMO

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

19.
PLoS Negl Trop Dis ; 18(4): e0012119, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38635840

RESUMO

BACKGROUND: Mozambique has one of the highest burdens of neglected tropical diseases in Africa. Lymphatic filariasis, schistosomiasis and soil-transmitted helminths are being targeted for elimination as part of integrated mass drug administration campaigns. The progress made towards interruption of transmission has been affected by recent conflict in Cabo Delgado province. The aim of this paper was to determine the potential impact of this crisis on the neglected tropical diseases programme and the challenges in reaching the elimination goals of 2030. METHODOLOGY: A desk-based secondary data analysis was conducted on publicly available sources of neglected tropical diseases, conflict incidents, internally displaced persons and geographical access between 2020 and 2022. Data were summarised and mapped using GIS software. A combined risk stratified assessment at district level was developed with five classifications i) Very high-risk; ii) High-risk; iii) Medium to high-risk; iv) Medium risk; and v) Not at risk due to conflict absence but co-endemic. RESULTS: Lymphatic filariasis, schistosomiasis and soil-transmitted helminths were co-endemic in 115 out of 156 (74%) districts. Between 2020 and 2022 a total of 1,653 conflict-related incidents were reported, most of them in Cabo Delgado province (n = 1,397, 85%). A five-fold increase of internally displaced persons was recorded from April 2020 (n = 172,186) to November 2022 (n = 935,130). Geographical accessibility also deteriorated across the province with an increase from five (29%) in 2021 to seven (41%) districts in 2022 classified as hard-to-reach. The combined risk stratification identified that most districts in Cabo Delgado province had medium to high-risk (n = 7; 41%); very high-risk (n = 5, 29%); medium risk (n = 3, 18%); high-risk (n = 2, 12%). CONCLUSION: Most of the districts of Cabo Delgado were considered to be at risk of not meeting the neglected tropical diseases road map 2030 targets due to the humanitarian crisis ongoing. There is the need for practical strategies and funding to overcome these hostile challenges.


Assuntos
Filariose Linfática , Helmintíase , Doenças Negligenciadas , Esquistossomose , Solo , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Filariose Linfática/transmissão , Humanos , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Esquistossomose/transmissão , Moçambique/epidemiologia , Solo/parasitologia , Doenças Negligenciadas/prevenção & controle , Doenças Negligenciadas/epidemiologia , Helmintíase/epidemiologia , Helmintíase/prevenção & controle , Helmintíase/transmissão , Erradicação de Doenças , Animais , Administração Massiva de Medicamentos
20.
Am J Sports Med ; 52(6): 1585-1595, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38656160

RESUMO

BACKGROUND: Few previous studies have investigated how different injury mechanisms leading to sport-related concussion (SRC) in soccer may affect outcomes. PURPOSE: To describe injury mechanisms and evaluate injury mechanisms as predictors of symptom severity, return to play (RTP) initiation, and unrestricted RTP (URTP) in a cohort of collegiate soccer players. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The Concussion Assessment, Research and Education (CARE) Consortium database was used. The mechanism of injury was categorized into head-to-ball, head-to-head, head-to-body, and head-to-ground/equipment. Baseline/acute injury characteristics-including Sports Concussion Assessment Tool-3 total symptom severity (TSS), loss of consciousness (LOC), and altered mental status (AMS); descriptive data; and recovery (RTP and URTP)-were compared. Multivariable regression and Weibull models were used to assess the predictive value of the mechanism of injury on TSS and RTP/URTP, respectively. RESULTS: Among 391 soccer SRCs, 32.7% were attributed to a head-to-ball mechanism, 27.9% to a head-to-body mechanism, 21.7% to a head-to-head mechanism, and 17.6% to a head-to-ground/equipment mechanism. Event type was significantly associated with injury mechanism [χ2(3) = 63; P < .001), such that more head-to-ball concussions occurred in practice sessions (n = 92 [51.1%] vs n = 36 [17.1%]) and more head-to-head (n = 65 [30.8%] vs n = 20 [11.1]) and head-to-body (n = 76 [36%] vs n = 33 [18.3%]) concussions occurred in competition. The primary position was significantly associated with injury mechanism [χ2(3) = 24; P < .004], with goalkeepers having no SRCs from the head-to-head mechanism (n = 0 [0%]) and forward players having the least head-to-body mechanism (n = 15 [19.2%]). LOC was also associated with injury mechanism (P = .034), with LOC being most prevalent in head-to-ground/equipment. Finally, AMS was most prevalent in head-to-ball (n = 54 [34.2%]) and head-to-body (n = 48 [30.4%]) mechanisms [χ2(3) = 9; P = .029]. In our multivariable models, the mechanism was not a predictor of TSS or RTP; however, it was associated with URTP (P = .044), with head-to-equipment/ground injuries resulting in the shortest mean number of days (14 ± 9.1 days) to URTP and the head-to-ball mechanism the longest (18.6 ± 21.6 days). CONCLUSION: The mechanism of injury differed by event type and primary position, and LOC and AMS were different across mechanisms. Even though the mechanism of injury was not a significant predictor of acute symptom burden or time until RTP initiation, those with head-to-equipment/ground injuries spent the shortest time until URTP, and those with head-to-ball injuries had the longest time until URTP.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Volta ao Esporte , Futebol , Humanos , Futebol/lesões , Masculino , Adulto Jovem , Traumatismos em Atletas/epidemiologia , Adolescente , Feminino , Estudos de Coortes , Universidades
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