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1.
Front Psychiatry ; 15: 1380001, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38803674

RESUMEN

Context: Engaging family members in the ongoing care of individuals with mental illness is a practice known to bolster the client's recovery journey and enhance the overall wellbeing of both children and families involved. Despite its potential benefits, there remains a dearth of understanding surrounding the implementation of family-focused practices (FFP) by mental health professionals serving adults, as well as the factors that could either promote or hinder such practices. This knowledge gap is particularly pronounced within North American settings. Goal: The goal of this study was to identify potential hindering and enabling factors of FFP used in adult mental health services. Methods: A sample of 512 professionals working with adult mental health clients, from all regions of Quebec, Canada, with a variety of disciplinary backgrounds and working in different work settings, completed the Family Focused Mental Health Practice Questionnaire (FFMHPQ). Multinominal logistic regression analysis was performed to assess the impact of several factors - organizational, professional, and personal - on the degree of family-based practices of mental health workers. Results and discussion: Findings of this study show that the strongest predictors for the adoption of higher FFP levels among adult mental health professionals in Quebec, are being employed on a full-time basis, perceiving a higher level of skills, knowledge, and confidence toward FFP, and having a supportive workplace environment. Results underscore the need to address both organizational and worker-related aspects to effectively promote better FFP in mental health services.

2.
Nat Biotechnol ; 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383603

RESUMEN

In the era of biodiversity genomics, it is crucial to ensure that annotations of protein-coding gene repertoires are accurate. State-of-the-art tools to assess genome annotations measure the completeness of a gene repertoire but are blind to other errors, such as gene overprediction or contamination. We introduce OMArk, a software package that relies on fast, alignment-free sequence comparisons between a query proteome and precomputed gene families across the tree of life. OMArk assesses not only the completeness but also the consistency of the gene repertoire as a whole relative to closely related species and reports likely contamination events. Analysis of 1,805 UniProt Eukaryotic Reference Proteomes with OMArk demonstrated strong evidence of contamination in 73 proteomes and identified error propagation in avian gene annotation resulting from the use of a fragmented zebra finch proteome as a reference. This study illustrates the importance of comparing and prioritizing proteomes based on their quality measures.

3.
Nucleic Acids Res ; 52(D1): D513-D521, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37962356

RESUMEN

In this update paper, we present the latest developments in the OMA browser knowledgebase, which aims to provide high-quality orthology inferences and facilitate the study of gene families, genomes and their evolution. First, we discuss the addition of new species in the database, particularly an expanded representation of prokaryotic species. The OMA browser now offers Ancestral Genome pages and an Ancestral Gene Order viewer, allowing users to explore the evolutionary history and gene content of ancestral genomes. We also introduce a revamped Local Synteny Viewer to compare genomic neighborhoods across both extant and ancestral genomes. Hierarchical Orthologous Groups (HOGs) are now annotated with Gene Ontology annotations, and users can easily perform extant or ancestral GO enrichments. Finally, we recap new tools in the OMA Ecosystem, including OMAmer for proteome mapping, OMArk for proteome quality assessment, OMAMO for model organism selection and Read2Tree for phylogenetic species tree construction from reads. These new features provide exciting opportunities for orthology analysis and comparative genomics. OMA is accessible at https://omabrowser.org.


Asunto(s)
Bases de Datos Genéticas , Ecosistema , Genoma , Proteoma , Genoma/genética , Filogenia , Sintenía , Internet , Orden Génico/genética
4.
J Child Adolesc Trauma ; 16(4): 959-971, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38045833

RESUMEN

Violence against children and adolescents is a widespread problem. However, most studies conducted in this field has been carried out in Western countries and studies are needed in non-Western countries, especially in Sub-Saharan Africa, where rates of child physical violence are high. The present study aimed firstly to document the different forms of physical violence and attitudes toward corporal punishment (CP) across Cameroon, Switzerland, and Togo. The second objective aimed, on the one hand, to understand the influence of cultural context, childhood physical abuse, and parental attitudes on physically violent parental practices in these three different cultural contexts. On the other, this study aimed to investigate the mediating role of childhood physical abuse and parental attitudes on the effect of cultural contexts on parental practices. Five hundred and forty-seven parents from Togo, Cameroon, and Switzerland filled out questionnaires concerning violent parental practices (ICAST-P), childhood physical abuse (CTQ-SF), and parental attitudes in favor of CP. Firstly, results highlighted some cultural differences regarding parental attitudes and practices. Secondly, the hierarchical regression showed that physical violence could be partially predicted by the cultural context, childhood abuse, and attitudes in favor of CP. Finally, childhood abuse and parental attitudes mediated the link between the cultural context and parental practices. This study underscores the importance of considering the cultural context when examining parental practices. Moreover, these results provide a better understanding of these types of parental practices in less studied contexts.

5.
Sci Rep ; 13(1): 22263, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38097644

RESUMEN

The human sulfatase HSulf-2 is one of only two known endosulfatases that play a decisive role in modulating the binding properties of heparan sulfate proteoglycans on the cell surface and in the extracellular matrix. Recently, HSulf-2 was shown to exhibit an unusual post-translational modification consisting of a sulfated glycosaminoglycan chain. This study describes the structural characterization of this glycosaminoglycan (GAG) and provides new data on its impact on the catalytic properties of HSulf-2. The unrevealed nature of this GAG chain is identified as a chondroitin/dermatan sulfate (CS/DS) mixed chain, as shown by mass spectrometry combined with NMR analysis. It consists primarily of 6-O and 4-O monosulfated disaccharide units, with a slight predominance of the 4-O-sulfation. Using atomic force microscopy, we show that this unique post-translational modification dramatically impacts the enzyme hydrodynamic volume. We identified human hyaluronidase-4 as a secreted hydrolase that can digest HSulf-2 GAG chain. We also showed that HSulf-2 is able to efficiently 6-O-desulfate antithrombin III binding pentasaccharide motif, and that this activity was enhanced upon removal of the GAG chain. Finally, we identified five N-glycosylation sites on the protein and showed that, although required, reduced N-glycosylation profiles were sufficient to sustain HSulf-2 integrity.


Asunto(s)
Glicosaminoglicanos , Sulfatasas , Humanos , Microscopía de Fuerza Atómica , Proteoglicanos de Heparán Sulfato , Sulfatos de Condroitina/metabolismo , Espectrometría de Masas
6.
Front Mol Biosci ; 10: 1298441, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38033386

RESUMEN

In recent years, RNA has gained traction both as a therapeutic molecule and as a therapeutic target in several human pathologies. In this review, we consider the approach of targeting RNA using small molecules for both research and therapeutic purposes. Given the primary challenge presented by the low structural diversity of RNA, we discuss the potential for targeting RNA: protein interactions to enhance the structural and sequence specificity of drug candidates. We review available tools and inherent challenges in this approach, ranging from adapted bioinformatics tools to in vitro and cellular high-throughput screening and functional analysis. We further consider two critical steps in targeting RNA/protein interactions: first, the integration of in silico and structural analyses to improve the efficacy of molecules by identifying scaffolds with high affinity, and second, increasing the likelihood of identifying on-target compounds in cells through a combination of high-throughput approaches and functional assays. We anticipate that the development of a new class of molecules targeting RNA: protein interactions to prevent physio-pathological mechanisms could significantly expand the arsenal of effective therapeutic compounds.

7.
Cell Rep ; 42(10): 113199, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37804508

RESUMEN

PARP-1 activation at DNA damage sites leads to the synthesis of long poly(ADP-ribose) (PAR) chains, which serve as a signal for DNA repair. Here we show that FUS, an RNA-binding protein, is specifically directed to PAR through its RNA recognition motif (RRM) to increase PAR synthesis by PARP-1 in HeLa cells after genotoxic stress. Using a structural approach, we also identify specific residues located in the FUS RRM, which can be PARylated by PARP-1 to control the level of PAR synthesis. Based on the results of this work, we propose a model in which, following a transcriptional arrest that releases FUS from nascent mRNA, FUS can be recruited by PARP-1 activated by DNA damage to stimulate PAR synthesis. We anticipate that this model offers new perspectives to understand the role of FET proteins in cancers and in certain neurodegenerative diseases such as amyotrophic lateral sclerosis.


Asunto(s)
Daño del ADN , Poli Adenosina Difosfato Ribosa , Poli(ADP-Ribosa) Polimerasas , Proteína FUS de Unión a ARN , Humanos , Reparación del ADN , Células HeLa , Poli(ADP-Ribosa) Polimerasa-1/genética , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli Adenosina Difosfato Ribosa/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Motivo de Reconocimiento de ARN , Proteína FUS de Unión a ARN/genética , Proteína FUS de Unión a ARN/metabolismo
8.
Health Syst Reform ; 9(1): 2267256, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37890079

RESUMEN

A new law was voted in France in 2016 to increase cooperation between public sector hospitals. Hospitals were encouraged to work under the leadership of local referral centers and to share their support functions (e.g., information systems) with newly created hospital groups, called "Regional Hospital Groups." The law made it compulsory for each public sector hospital to become affiliated with one of 136 newly created hospital groups. The policy's aim was to ensure that all patients were sent to the hospital best qualified to treat their unique condition, among the hospitals available at the regional level. Therefore, we aimed to assess whether this regionalization policy was associated with changes in observed patterns of patient mobility between hospitals. This nationwide observational study followed an interrupted time series design. For each stay occurring from 2014 to 2019, we ascertained whether or not the stay was followed by mobility toward another hospital within 90 days, and whether or not the receiving hospital was part of the same Regional Hospital Group as the sender hospital. The proportion of mobility directed toward the same regional hospital group increased from 22.9% in 2014 (95% CI 22.7-23.1) to 24.6% in 2019 (95% CI 24.4-24.8). However, the absence of discontinuity during the policy change year was consistent with the hypothesis of a preexisting trend toward regionalization. Therefore, the policy did not achieve major changes in patterns of mobility between hospitals. Other objectives of the reform, including long-term consequences on the healthcare offer, remain to be assessed.


Asunto(s)
Hospitales , Limitación de la Movilidad , Humanos , Francia , Atención a la Salud , Políticas
9.
Vasc Med ; 28(6): 538-546, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37610880

RESUMEN

BACKGROUND: Medial arterial calcification (MAC) is a vascular disease distinct from atherosclerosis. Recently, several studies have demonstrated that MAC is an important marker of cardiovascular events. We aim to assess the presence of MAC during ultrasound screening of lower-limb vasculature and its association with both cardiovascular (CV) and lower-limb events in patients with type-2 diabetes. METHODS: A retrospective cohort study was conducted on 1119 patients with type-2 diabetes free from CV disease. A CV work-up, including vascular ultrasound, was performed for each patient. The presence of MAC was assessed on posterior tibial arteries and ankle-brachial index (ABI) was measured. Major acute CV events (MACEs) and lower-limb events (MALEs) were recorded as a composite endpoint for a 5-year period. RESULTS: We identified MAC among 212 (18.9%) patients. The independent determinants of MAC were age and diabetic retinopathy. Over a period of 5 years, 125 MACEs and 22 MALEs occurred. MAC was significantly associated with the composite outcome MACE + MALE (HR = 1.94; 95% CI: 1.23, 3.08, p = 0.005) or with MACE (HR = 1.85; 95% CI: 1.16, 2.95, p = 0.010). Adjusted for ABI and diabetic foot wound, MAC remained a determinant of MALE (HR = 5.49; 95% CI: 2.19, 13.76, p < 0.001). Considering each ABI group, MAC was associated with both MACE and MALE in the normal ABI group. CONCLUSIONS: Ultrasound-detected MAC on tibial arteries seems to be a determinant of both CV and lower-limb events, independent from ABI. MAC helps to refine the CV risk in patients with normal ABI.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad Arterial Periférica , Masculino , Humanos , Arterias Tibiales/diagnóstico por imagen , Factores de Riesgo , Estudios Retrospectivos , Extremidad Inferior/irrigación sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Índice Tobillo Braquial , Enfermedad Arterial Periférica/diagnóstico
10.
Redox Biol ; 64: 102757, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37285741

RESUMEN

Using S-phase synchronized RPE1-hTERT cells exposed to the DNA damaging agent, methyl methanesulfonate, we show the existence of a redox state associated with replication stress-induced senescence termed senescence-associated redox state (SA-redox state). SA-redox state is characterized by its reactivity with superoxide-sensing fluorescent probes such as dihydroethidine, lucigenin and mitosox and peroxynitrite or hydroxyl radical sensing probe hydroxyphenyl fluorescein (HPF) but not the hydrogen peroxide (H2O2) reactive fluorescent probe CM-H2DCFDA. Measurement of GSH and GSSH also reveals that SA-redox state mitigates the level of total GSH rather than oxidizes GSH to GSSG. Moreover, supporting the role of superoxide (O2.-) in the SA-redox state, we show that incubation of senescent RPE1-hTERT cells with the O2.- scavenger, Tiron, decreases the reactivity of SA-redox state with the oxidants' reactive probes lucigenin and HPF while the H2O2 antioxidant N-acetyl cysteine has no effect. SA-redox state does not participate in the loss of proliferative capacity, G2/M cell cycle arrest or the increase in SA-ß-Gal activity. However, SA-redox state is associated with the activation of NF-κB, dictates the profile of the Senescence Associated Secretory Phenotype, increases TFEB protein level, promotes geroconversion evidenced by increased phosphorylation of S6K and S6 proteins, and influences senescent cells response to senolysis. Furthermore, we provide evidence for crosstalk between SA redox state, p53 and p21. While p53 mitigates the establishment of SA-redox state, p21 is critical for the sustained reinforcement of the SA-redox state involved in geroconversion and resistance to senolysis.


Asunto(s)
Peróxido de Hidrógeno , Superóxidos , Superóxidos/metabolismo , Peróxido de Hidrógeno/metabolismo , Senescencia Celular , Proteína p53 Supresora de Tumor/metabolismo , Oxidación-Reducción
11.
EBioMedicine ; 93: 104649, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37327675

RESUMEN

BACKGROUND: Expansion of antimicrobial resistance monitoring and epidemiological surveillance are key components of the WHO strategy towards zero leprosy. The inability to grow Mycobacterium leprae in vitro precludes routine phenotypic drug susceptibility testing, and only limited molecular tests are available. We evaluated a culture-free targeted deep sequencing assay, for mycobacterial identification, genotyping based on 18 canonical SNPs and 11 core variable-number tandem-repeat (VNTR) markers, and detection of rifampicin, dapsone and fluoroquinolone resistance-associated mutations in rpoB/ctpC/ctpI, folP1, gyrA/gyrB, respectively, and hypermutation-associated mutations in nth. METHODS: The limit of detection (LOD) was determined using DNA of M. leprae reference strains and from 246 skin biopsies and 74 slit skin smears of leprosy patients, with genome copies quantified by RLEP qPCR. Sequencing results were evaluated versus whole genome sequencing (WGS) data of 14 strains, and versus VNTR-fragment length analysis (FLA) results of 89 clinical specimens. FINDINGS: The LOD for sequencing success ranged between 80 and 3000 genome copies, depending on the sample type. The LOD for minority variants was 10%. All SNPs detected in targets by WGS were identified except in a clinical sample where WGS revealed two dapsone resistance-conferring mutations instead of one by Deeplex Myc-Lep, due to partial duplication of the sulfamide-binding domain in folP1. SNPs detected uniquely by Deeplex Myc-Lep were missed by WGS due to insufficient coverage. Concordance with VNTR-FLA results was 99.4% (926/932 alleles). INTERPRETATION: Deeplex Myc-Lep may help improve the diagnosis and surveillance of leprosy. Gene domain duplication is an original putative drug resistance-related genetic adaptation in M. leprae. FUNDING: EDCTP2 programme supported by the European Union (grant number RIA2017NIM-1847 -PEOPLE). EDCTP, R2Stop: Effect:Hope, The Mission To End Leprosy, the Flemish Fonds Wetenschappelijk Onderzoek.


Asunto(s)
Lepra , Mycobacterium tuberculosis , Humanos , Mycobacterium leprae/genética , Pruebas de Sensibilidad Microbiana , Genotipo , Farmacorresistencia Bacteriana/genética , Lepra/diagnóstico , Lepra/tratamiento farmacológico , Lepra/epidemiología , Dapsona , Biopsia , Resistencia a Múltiples Medicamentos
12.
Child Abuse Negl ; 143: 106284, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37352648

RESUMEN

BACKGROUND: Since the beginning of the COVID-19 pandemic, there has been a worldwide increase in the incidence of child abuse. Studies show that the pandemic context contributes to exacerbate several risk factors usually associated with the use of violent disciplinary practices. OBJECTIVE: This study aims to better understand the role of parental burnout and child perceived as difficult as a parental stressor in the link between fear of COVID-19 and the use of parental violence (minor and severe physical violence and repeated psychological aggression). PARTICIPANTS: The sample includes 467 mothers living in Québec (Canada) with a child aged 5 or less. METHOD: An online questionnaire, administered one year after the beginning of the COVID-19 pandemic in Québec (March to May 2021), was used to measure parental violence, parental burnout, parental stress related to the perception of the child as difficult and fear of COVID-19. Serial mediation analyses were performed. RESULTS: The main analyses confirmed the indirect association between fear of COVID-19 and the three forms of parental violence studied, through parental burnout and the child perceived as difficult. Unlike physical violence (minor and severe), the association between fear of COVID-19 and repeated psychological aggression is explained only by parental burnout. CONCLUSIONS: This study has identified new mechanisms that allow a better understanding of processes underlying parental violence during the pandemic. It also shows that parental violence can also occur in low-risk families. It is crucial to develop strategies to prevent the use of violent disciplinary practices in future socio-health crises such as the COVID-19 pandemic.


Asunto(s)
COVID-19 , Pandemias , Femenino , Niño , Humanos , COVID-19/epidemiología , Violencia/psicología , Padres/psicología , Miedo , Agotamiento Psicológico/epidemiología
13.
Biology (Basel) ; 12(5)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37237461

RESUMEN

Graft-versus-host disease (GVHD) is a life-threatening systemic complication of allogeneic hematopoietic stem cell transplantation (HSCT) characterized by dysregulation of T and B cell activation and function, scleroderma-like features, and multi-organ pathology. The treatment of cGVHD is limited to the management of symptoms and long-term use of immunosuppressive therapy, which underscores the need for developing novel treatment approaches. Notably, there is a striking similarity between cytokines/chemokines responsible for multi-organ damage in cGVHD and pro-inflammatory factors, immune modulators, and growth factors secreted by senescent cells upon the acquisition of senescence-associated secretory phenotype (SASP). In this pilot study, we questioned the involvement of senescent cell-derived factors in the pathogenesis of cGVHD triggered upon allogeneic transplantation in an irradiated host. Using a murine model that recapitulates sclerodermatous cGVHD, we investigated the therapeutic efficacy of a senolytic combination of dasatinib and quercetin (DQ) administered after 10 days of allogeneic transplantation and given every 7 days for 35 days. Treatment with DQ resulted in a significant improvement in several physical and tissue-specific features, such as alopecia and earlobe thickness, associated with cGVHD pathogenesis in allograft recipients. DQ also mitigated cGVHD-associated changes in the peripheral T cell pool and serum levels of SASP-like cytokines, such as IL-4, IL-6 and IL-8Rα. Our results support the involvement of senescent cells in the pathogenesis of cGVHD and provide a rationale for the use of DQ, a clinically approved senolytic approach, as a potential therapeutic strategy.

14.
Child Abuse Negl ; 141: 106204, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37119691

RESUMEN

BACKGROUND: The Triple P - Positive Parenting Program was rolled-out in two communities in Quebec, Canada, in order to prevent child maltreatment. OBJECTIVES: (1) Evaluate the effects of Triple P versus care as usual on positive parenting practices, dysfunctional disciplinary practices, and family violence towards the child; (2) verify whether the observed changes persisted over time. PARTICIPANTS AND SETTING: A quasi-experimental protocol with an active comparison group was used. Participants were 384 parents or parental figures of at least one 0-12-year-old child, assigned to one of two groups: Triple P (n = 291) and Care as usual (n = 93). We conducted a follow-up study with 164 parents from the Triple P group. METHODS: We administered questionnaires at pretest, post-test, and follow-up. Standardized instruments measured positive parenting practices, dysfunctional disciplinary practices (overreactivity, laxness, hostility), and family violence towards the child (repeated psychological aggression, minor physical violence). The intervention dose received by each parent was calculated from data provided by practitioners. RESULTS: Belonging to the Triple P group was associated with increased positive practices and decreased overreactive and hostile discipline. A higher dose of intervention was associated with a decrease in laxness. All observed changes were maintained at follow-up, with medium (η2p = 0.073, hostility) to large (η2p = 0.271, overreactivity) effect sizes. Also, Triple P was more effective in reducing minor physical violence, this effect persisting over time (from 36 % to 21 %). CONCLUSIONS: This study supports the sustainable efficacy of the Triple P parenting program, except for repeated psychological aggression towards children.


Asunto(s)
Maltrato a los Niños , Violencia Doméstica , Niño , Humanos , Responsabilidad Parental/psicología , Estudios de Seguimiento , Violencia Doméstica/prevención & control , Padres/psicología , Maltrato a los Niños/prevención & control
15.
Evolution ; 77(1): 186-198, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36622671

RESUMEN

Epigenetic modifications are thought to be one of the molecular mechanisms involved in plastic adaptive responses to environmental variation. However, studies reporting associations between genome-wide epigenetic changes and habitat-specific variations in life history traits (e.g., lifespan, reproduction) are still scarce, likely due to the recent application of methylome resequencing methods to non-model species. In this study, we examined associations between whole genome DNA methylation and environmentally driven life history variation in 2 lineages of a marine fish, the capelin (Mallotus villosus), from North America and Europe. In both lineages, capelin harbor 2 contrasting life history tactics (demersal vs. beach-spawning). Performing whole genome and methylome sequencing, we showed that life history tactics are associated with epigenetic changes in both lineages, though the effect was stronger in European capelin. Genetic differentiation between the capelin harboring different life history tactics was negligible, but we found genome-wide methylation changes in both lineages. We identified 9,125 European and 199 North American differentially methylated regions (DMRs) due to life history. Gene ontology (GO) enrichment analysis for both lineages revealed an excess of terms related to neural function. Our results suggest that environmental variation causes important epigenetic changes that are associated with contrasting life history tactics in lineages with divergent genetic backgrounds, with variable importance of genetic variation in driving epigenetic variation. Our study emphasizes the potential role of genome-wide epigenetic variation in adaptation to environmental variation.


Asunto(s)
Rasgos de la Historia de Vida , Osmeriformes , Animales , Metilación de ADN , ADN , Epigénesis Genética , Genoma , Osmeriformes/fisiología
16.
Elife ; 122023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36651723

RESUMEN

RNA-protein interactions (RPIs) are promising targets for developing new molecules of therapeutic interest. Nevertheless, challenges arise from the lack of methods and feedback between computational and experimental techniques during the drug discovery process. Here, we tackle these challenges by developing a drug screening approach that integrates chemical, structural and cellular data from both advanced computational techniques and a method to score RPIs in cells for the development of small RPI inhibitors; and we demonstrate its robustness by targeting Y-box binding protein 1 (YB-1), a messenger RNA-binding protein involved in cancer progression and resistance to chemotherapy. This approach led to the identification of 22 hits validated by molecular dynamics (MD) simulations and nuclear magnetic resonance (NMR) spectroscopy of which 11 were found to significantly interfere with the binding of messenger RNA (mRNA) to YB-1 in cells. One of our leads is an FDA-approved poly(ADP-ribose) polymerase 1 (PARP-1) inhibitor. This work shows the potential of our integrative approach and paves the way for the rational development of RPI inhibitors.


Asunto(s)
Neoplasias , ARN , Humanos , Simulación de Dinámica Molecular , Descubrimiento de Drogas , ARN Mensajero/genética , Proteína 1 de Unión a la Caja Y/genética , Proteína 1 de Unión a la Caja Y/metabolismo
17.
Health Serv Manage Res ; 36(1): 75-81, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35331042

RESUMEN

The place of hospitals in health systems is undergoing rapid change worldwide due to the high cost of hospital care and the changing health needs of the population. The Covid-19 pandemic has recently drawn public attention towards hospital capacity and has added new urgency to discussions on the future role of hospitals. In this context, recent experience in Germany provides valuable information for health systems seeking to manage hospital capacity. Despite reform efforts to reduce hospital capacity, Germany has the highest rates of intensive care beds among high-income countries and the highest overall hospital capacity in Europe. The capacity of the German hospital system can be explained in large part by the high number of elderly in-patients. This, in turn, is driven by (1) a fragmented ambulatory care system; (2) physicians admitting and maintaining elderly patients in hospital at a high rate; (3) a hospital market adding incentives to admit patients; and (4) a political commitment to egalitarian access and universal care. Additionally, recent policies to reduce hospital capacity have had limited impact because hospitals have not responded to financial incentives in the expected manner. Countries looking to learn from Germany's hospital capacity must therefore consider systemic features, political commitments, and unintended policy consequences.


Asunto(s)
COVID-19 , Humanos , Anciano , Pandemias , Alemania , Europa (Continente) , Hospitales
18.
Sante Ment Que ; 48(2): 121-150, 2023.
Artículo en Francés | MEDLINE | ID: mdl-38578187

RESUMEN

Context Children living with a mentally ill parent are a vulnerable population, at higher risk of various psychosocial and mental health problems. They are overrepresented in youth mental health and child protection services. Adult mental health services that treat parents have the opportunity to identify and support children in these families. However, to date, there is still little knowledge on the extent of family-centered practices offered by professionals from different disciplinary fields in Quebec. Objective This study aims to document the family-focused practices of adult mental health professionals according to different disciplines (social work, nursing, psychoeducation, psychology, and special education). Method A total of 524 participants, from all regions of Quebec and working with adult mental health clients, responded to an online provincial survey. A subsample of 380 participants, members of a professional order or association, was retained for the present study. These come from five discipline: social work (n=127), nursing (n=99), psychoeducation (n=57), psychology (n=56) and special education (n=41) A MANCOVA analysis was performed to compare groups on the five subscales of the French version of the Family Focused Mental Health Practice (FFMHPQ-FR, Piché et al., in press), controlling for gender, years of experience working in mental health services and estimated proportion of clients with a parental role. Results Significant differences were found between social workers and psychologists in reported family-focused practices. Participants also reported very different levels of facilitating factors such as workplace support, openness to training, perceived knowledge and skills, and attitudes towards these practices. Discussion This study helps to increase knowledge on the use of family-focused practices by professionals from different disciplinary fields, in the context of adult mental health services in Quebec. The results allow to better support the adoption of such practices in mental health services.


Asunto(s)
Servicios de Salud Mental , Salud Mental , Adulto , Niño , Adolescente , Humanos , Quebec , Padres/psicología , Medicina Familiar y Comunitaria
19.
Emerg Infect Dis ; 28(13): S49-S58, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36502426

RESUMEN

Since 2003, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported implementation and maintenance of health information systems for HIV/AIDS and related diseases, such as tuberculosis, in numerous countries. As the COVID-19 pandemic emerged, several countries conducted rapid assessments and enhanced existing PEPFAR-funded HIV and national health information systems to support COVID-19 surveillance data collection, analysis, visualization, and reporting needs. We describe efforts at the US Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia, USA, and CDC country offices that enhanced existing health information systems in support COVID-19 pandemic response. We describe CDC activities in Haiti as an illustration of efforts in PEPFAR countries. We also describe how investments used to establish and maintain standards-based health information systems in resource-constrained settings can have positive effects on health systems beyond their original scope.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , COVID-19 , Infecciones por VIH , Sistemas de Información en Salud , Humanos , Cooperación Internacional , COVID-19/epidemiología , COVID-19/prevención & control , Infecciones por VIH/epidemiología , Pandemias/prevención & control , Síndrome de Inmunodeficiencia Adquirida/epidemiología
20.
PLoS One ; 17(9): e0274760, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36129879

RESUMEN

BACKGROUND: Haiti's first COVID-19 cases were confirmed on March 18, 2020, and subsequently spread throughout the country. The objective of this study was to describe clinical manifestations of COVID-19 in Haitian outpatients and to identify risk factors for severity of clinical manifestations. METHODS: We conducted a retrospective study of COVID-19 outpatients diagnosed from March 18-August 4, 2020, using demographic, epidemiological, and clinical data reported to the Ministry of Health (MoH). We used univariate and multivariate analysis, including multivariable logistic regression, to explore the risk factors and specific symptoms related to persons with symptomatic COVID-19 and the severity of symptomatic COVID-19 disease. RESULTS: Of 5,389 cases reported to MOH during the study period, 1,754 (32.5%) were asymptomatic. Amongst symptomatic persons 2,747 (75.6%) had mild COVID-19 and 888 (24.4%) had moderate-to-severe disease; the most common symptoms were fever (69.6%), cough (51.9%), and myalgia (45.8%). The odds of having moderate-to-severe disease were highest among persons with hypertension (aOR = 1.72, 95% Confidence Interval [CI] (1.34, 2.20), chronic pulmonary disease (aOR = 3.93, 95% CI (1.93, 8.17)) and tuberculosis (aOR = 3.44, 95% CI (1.35, 9.14)) compared to persons without those conditions. The odds of having moderate-to-severe disease increased with age but was also seen among children aged 0-4 years (OR: 1.73, 95% CI (0.93, 3.08)), when using 30-39 years old as the reference group. All of the older age groups, 50-64 years, 65-74 years, 75-84 years, and 85+ years, had significantly higher odds of having moderate-to-severe COVID-19 compared with ages 30-39 years. Diabetes was associated with elevated odds of moderate-to-severe disease in bivariate analysis (OR = 2.17, 95% CI (1.58,2.98) but, this association did not hold in multivariable analyses (aOR = 1.22,95%CI (0.86,1.72)). CONCLUSION: These findings from a resource-constrained country highlight the importance of surveillance systems to track emerging infections and their risk factors. In addition to co-morbidities described elsewhere, tuberculosis was a risk factor for moderate-to-severe COVID-19 disease.


Asunto(s)
COVID-19 , Adulto , Anciano , COVID-19/epidemiología , Niño , Haití/epidemiología , Humanos , Pacientes Ambulatorios , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2
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