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1.
mSystems ; : e0062724, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012154

ABSTRACT

Clostridia are abundant in the human gut and comprise families associated with host health such as Oscillospiraceae, which has been correlated with leanness. However, culturing bacteria within this family is challenging, leading to their detection primarily through 16S rRNA amplicon sequencing, which has a limited ability to unravel diversity at low taxonomic levels, or by shotgun metagenomics, which is hindered by its high costs and complexity. In this cross-sectional study involving 114 Colombian adults, we used an amplicon-based sequencing strategy with alternative markers-gyrase subunit B (gyrB) and DNA K chaperone heat protein 70 (dnaK)-that evolve faster than the 16S rRNA gene. Comparing the diversity and abundance observed with the three markers in our cohort, we found a reduction in the diversity of Clostridia, particularly within Lachnospiraceae and Oscillospiraceae among obese individuals [as measured by the body mass index (BMI)]. Within Lachnospiraceae, the diversity of Ruminococcus_A negatively correlated with BMI. Within Oscillospiraceae, the genera CAG-170 and Vescimonas also exhibited this negative correlation. In addition, the abundance of Vescimonas was negatively correlated with BMI. Leveraging shotgun metagenomic data, we conducted a phylogenetic and genomic characterization of 120 metagenome-assembled genomes from Vescimonas obtained from a larger sample of the same cohort. We identified 17 of the 72 reported species. The functional annotation of these genomes showed the presence of multiple carbohydrate-active enzymes, particularly glycosyl transferases and glycoside hydrolases, suggesting potential beneficial roles in fiber degradation, carbohydrate metabolism, and butyrate production. IMPORTANCE: The gut microbiota is diverse across various taxonomic levels. At the intra-species level, it comprises multiple strains, some of which may be host-specific. However, our understanding of fine-grained diversity has been hindered by the use of the conserved 16S rRNA gene. While shotgun metagenomics offers higher resolution, it remains costly, may fail to identify specific microbes in complex samples, and requires extensive computational resources and expertise. To address this, we employed a simple and cost-effective analysis of alternative genetic markers to explore diversity within Clostridia, a crucial group within the human gut microbiota whose diversity may be underestimated. We found high intra-species diversity for certain groups and associations with obesity. Notably, we identified Vescimonas, an understudied group. Making use of metagenomic data, we inferred functionality, uncovering potential beneficial roles in dietary fiber and carbohydrate degradation, as well as in short-chain fatty acid production.

2.
Science ; 385(6704): 91-99, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38963839

ABSTRACT

Sickle cell disease (SCD) is a prevalent, life-threatening condition attributable to a heritable mutation in ß-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) can ameliorate disease complications and has been intently pursued. However, safe and effective small-molecule inducers of HbF remain elusive. We report the discovery of dWIZ-1 and dWIZ-2, molecular glue degraders of the WIZ transcription factor that robustly induce HbF in erythroblasts. Phenotypic screening of a cereblon (CRBN)-biased chemical library revealed WIZ as a previously unknown repressor of HbF. WIZ degradation is mediated by recruitment of WIZ(ZF7) to CRBN by dWIZ-1, as resolved by crystallography of the ternary complex. Pharmacological degradation of WIZ was well tolerated and induced HbF in humanized mice and cynomolgus monkeys. These findings establish WIZ degradation as a globally accessible therapeutic strategy for SCD.


Subject(s)
Anemia, Sickle Cell , Antisickling Agents , Fetal Hemoglobin , Kruppel-Like Transcription Factors , Nerve Tissue Proteins , Animals , Humans , Mice , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Anemia, Sickle Cell/drug therapy , Anemia, Sickle Cell/metabolism , Antisickling Agents/chemistry , Antisickling Agents/pharmacology , Antisickling Agents/therapeutic use , Crystallography, X-Ray , Drug Discovery , Fetal Hemoglobin/genetics , Fetal Hemoglobin/metabolism , Kruppel-Like Transcription Factors/metabolism , Macaca fascicularis , Nerve Tissue Proteins/metabolism , Proteolysis/drug effects , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Small Molecule Libraries/therapeutic use , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics
3.
Article in English | MEDLINE | ID: mdl-38849115

ABSTRACT

INTRODUCTION: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a serious threat to public health. Globally, carbapenemases-producing CRPA isolates mainly belong to 'high-risk' clones; however, the molecular epidemiology of CRPA isolates circulating in Chile are scarce, where this pathogen is the main aetiological agent of ventilator-associated pneumonia. OBJECTIVES: To characterize the phylogenomics and molecular features of ST654 CRPA isolates collected in Chile between 2016 - 2022. METHODS: 89 CRPA isolates collected in different Chilean hospitals from clinical specimens between 2005 and 2022 were analyzed. Antibiotic susceptibility tests and carbapenemases production were carried out on the CRPA ST654 isolates. Also, they were subjected to whole-genome sequencing (WGS) from which in silico analyses were performed. RESULTS: Thirty-four strains (38.2%) belonged to the ST654 'high risk' clone, being the most predominant lineage of the collection. Most of these isolates belonged to a sub-clade including KPC-producers that also clustered with strains from Argentina and the USA, whereas few VIM and NDM co-producers clustered in two different smaller sub-clades. The isolates exhibited a broad resistome encompassing genes mediating resistance to several other clinically relevant drugs. Additionally, all the 34 ST654 isolates were ExoS+ as a virulence factor and associated to the O4-serotype. CONCLUSIONS: Our report represents the most comprehensive phylogenomic study of CRPA 'high risk' clone ST654 to date. Our analyses suggest that this lineage is undergoing a divergent evolutionary path in Chile, since most of the isolates were KPC-producers and were O4-serotype, differing from previous descriptions, which underline the relevance of performing molecular surveillance on this pathogen.

4.
P R Health Sci J ; 43(2): 84-92, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38860962

ABSTRACT

OBJECTIVE: The Family Adaptability and Cohesion Evaluation Scale III (FACES III) is a self-report instrument that enables the assessment of the dimensions of adaptability and cohesion within a family, establishing whether or not that family is functional and classifying it according to categories within those dimensions. The objective of this research was to determine the psychometric properties of this instrument using a sample of dental students from 5 Latin American countries. MATERIALS AND METHODS: The FACES III was administered to a sample of 2888 university dental students from Colombia (35.3%), Chile (34.6%), the Dominican Republic (19%), Argentina (6%), and El Salvador (5.1%). Confirmatory factor analysis was used to examine the factorial structure of the scale, comparing 3 models proposed in the Latin American literature, establishing a multigroup analysis to examine invariance among countries. RESULTS: The results revealed a structure composed of 2 dimensions: cohesion and adaptability. These dimensions showed adequate structure and internal consistency. The invariance of the measurement model in the participating countries was confirmed. CONCLUSION: In general, this study offers evidence of the adequacy of the psychometric properties of FACES III in Colombian, Chilean, Dominican, Argentine, and Salvadoran dental students.


Subject(s)
Psychometrics , Students, Dental , Humans , Male , Female , Students, Dental/psychology , Young Adult , Adult , Universities , Family Relations/psychology , Factor Analysis, Statistical , Self Report , Latin America , Colombia , Adolescent , Chile
5.
Front Med (Lausanne) ; 11: 1365756, 2024.
Article in English | MEDLINE | ID: mdl-38813384

ABSTRACT

The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections at the end of the 20th century represents a significant shift in the epidemiology of staphylococcal infections and, consequently, their clinical management. There are diverse CA-MRSA clones that are widely spread worldwide, showing differences in their regional dissemination, which has been dynamically changing over time. Although the first CA-MRSA description occurred about 30 years ago, its epidemiology in certain regions, such as South America, has been poorly explored, resulting in a gap in the understanding of the epidemiology of CA-MRSA in under-represented countries/regions. This report describes the first four clinical cases of invasive infections caused by CA-MRSA in a tertiary hospital in the central-southern region of Chile. It also associates the clinical characteristics of the infections with the microbiological and molecular features of the isolates. The four S. aureus isolates belong to sequence type 8, which has been widely described as a cause of community-acquired infections. All of them presented a wide resistome and virulome. Additionally, in two of them, it was possible to reconstruct the COMER genetic element, present in the USA300-Latin American variant clone. Considering these findings, it is crucial to prepare for a potential increase in invasive CA-MRSA infections in Chile. This would involve enhancing current surveillance systems and maintaining a low threshold of suspicion for these infections among clinicians.

6.
bioRxiv ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38712281

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the world's population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD. CRISPR-based genetic knockout of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of NAFLD-associated liver fibrosis.

7.
Comput Struct Biotechnol J ; 23: 2190-2199, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38817966

ABSTRACT

Spatiotemporal regulation of gene expression is controlled by transcription factor (TF) binding to regulatory elements, resulting in a plethora of cell types and cell states from the same genetic information. Due to the importance of regulatory elements, various sequencing methods have been developed to localise them in genomes, for example using ChIP-seq profiling of the histone mark H3K27ac that marks active regulatory regions. Moreover, multiple tools have been developed to predict TF binding to these regulatory elements based on DNA sequence. As altered gene expression is a hallmark of disease phenotypes, identifying TFs driving such gene expression programs is critical for the identification of novel drug targets. In this study, we curated 84 chromatin profiling experiments (H3K27ac ChIP-seq) where TFs were perturbed through e.g., genetic knockout or overexpression. We ran nine published tools to prioritize TFs using these real-world datasets and evaluated the performance of the methods in identifying the perturbed TFs. This allowed the nomination of three frontrunner tools, namely RcisTarget, MEIRLOP and monaLisa. Our analyses revealed opportunities and commonalities of tools that will help to guide further improvements and developments in the field.

8.
Rev. cienc. salud (Bogotá) ; 22(2): 1-14, 20240531.
Article in Spanish | LILACS | ID: biblio-1555034

ABSTRACT

ntroducción: la empatía es uno de los componentes de la estructura de la humanización en la atención de los pacientes. Los médicos especialistas deben tener mucha empatía. El objetivo del artículo es des-cribir los índices de empatía en médicos que trabajan en un hospital de alta complejidad y explorar si existen diferencias entre las especialidades estudiadas. Métodos: se accedió a una muestra por conve-niencia de 237 médicos que representa el 53.55 % del total poblacional (n = 443). La empatía se midió con la Escala de Empatía para Profesionales de la Salud (hp), junto con análisis factorial confirmatorio y análisis multigrupo (para examinar la invarianza del modelo entre los sexos) y análisis de confia-bilidad (α de Cronbach, coeficiente de correlación intraclase y ω de McDonald). Resultados: la espe-cialidad de pediatría tuvo los mayores índices de empatía general y en las dimensiones "cuidado con compasión" y "caminando en los zapatos del paciente", no así en la dimensión "toma de perspectiva", donde es semejante a las especialidades de anestesiología, medicina crítica y terapia intensiva, y gine-cología. Conclusión: los valores de la empatía y los valores en las subescalas "cuidado con compasión" y "caminando en los zapatos del paciente" fueron (en valores absolutos, pero no estadísticos) mayores en la especialidad de pediatría. En la subescala "toma de perspectiva", las especialidades de pediatría, anestesiología, cirugía y clínica se observaron puntuaciones prácticamente iguales. Se requieren otros estudios que permita arribar a una explicación que permita entender por qué algunas especialidades tienen valores de empatía mayores que otras


Introduction: Empathy is one of the components of the structure of humanization in patient care. Medical specialists must have high levels of empathy. Objective: The aim of this paper is to describe the levels of empathy in doctors working in a highly complex hospital and to explore whether there are differ-ences between the specialties studied. Methods: A convenience sample of 237 physicians representing 53.55% of the total population (n = 443) was accessed. Empathy was measured using the Empathy Scale for Health Professionals (hp). Confirmatory factor analysis and multigroup analysis were performed to examine the invariance of the model between the sexes and reliability analyzes (Cronbach's α, intraclass correlation coefficient and McDonald's ω). Results: The specialty of pediatrics had the highest levels in general empathy and in the Compassionate Care and Walking in Patient Shoes subscales, but not in the Perspective Taking subescale where it presents levels similar to the specialties of anesthesiology, critical medicine and intensive care. and gynecology. Conclusions: The empathy values and the values in the compassionate care and "Walking in the patient's shoes" subscales were (in absolute values, but not sta-tistically) higher in the Pediatrics specialty. In the subscale Perspective Taking, Pediatrics, Anesthesiology, Surgery, and Clinic, practically the same scores were observed. Other studies are required to arrive at an explanation that allows us to understand why some specialties have higher empathy values than others.


Introdução: a empatia é um dos componentes da estrutura de humanização no atendimento ao paciente. Os médicos especialistas devem ter altos níveis de empatia. Objetivo: o objetivo deste artigo é descre-ver os níveis de empatia em médicos que trabalham em um hospital de alta complexidade e explorar se há diferenças entre as especialidades estudadas. Materiais e métodos: foi acessada uma amostra de conveniência de 237 médicos, representando 53,55% da população total (n = 443). A empatia foi medida usando a Escala de Empatia para Profissionais de Saúde. A análise fatorial confirmatória e a análise mul-tigrupo foram realizadas (para examinar a invariância do modelo entre os sexos) e a análise de confia-bilidade (α de Cronbach, coeficiente de correlação intraclasse e ω de McDonald). Resultados: a pediatria apresentou os níveis mais altos de empatia geral e nas dimensões "cuidado compassivo" e "estar no lugar do paciente", mas não na dimensão "tomada de perspectiva", em que os níveis foram semelhantes aos da anestesiologia, da medicina crítica e da terapia intensiva, e da ginecologia. Conclusões: os valores de empatia e os valores das subescalas "cuidado compassivo" e "estar no lugar do paciente" foram (em valo-res absolutos, mas não estatisticamente) mais altos na especialidade de pediatria. Na subescala "tomada de perspectiva", as especialidades de pediatria, anestesiologia, cirurgia e clínica tiveram pontuações quase iguais. São necessários mais estudos para explicar por que algumas especialidades têm valores de empatia mais altos do que outras


Subject(s)
Humans , Personnel, Hospital , Ecuador
9.
Curr Issues Mol Biol ; 46(4): 2819-2826, 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38666906

ABSTRACT

DNAM-1 (CD226) is an activating receptor expressed in CD8+ T cells, NK cells, and monocytes. It has been reported that two SNPs in the DNAM-1 gene, rs763361 C>T and rs727088 G>A, have been associated with different autoimmune diseases; however, the role of DNAM-1 in ankylosing spondylitis has been less studied. For this reason, we focused on the study of these two SNPs in association with ankylosing spondylitis. For this, 34 patients and 70 controls were analyzed using endpoint PCR with allele-specific primers. Our results suggest that rs763361 C>T is involved as a possible protective factor under the CT co-dominant model (OR = 0.34, 95% CI = 0.13-0.88, p = 0.022) and the CT + TT dominant model (OR = 0.39, 95% CI = 0.17-0.90, p = 0.025), while rs727088 G>A did not show an association with the disease in any of the inheritance models. When analyzing the relationships of the haplotypes, we found that the T + A haplotype (OR = 0.31, 95% CI = 0.13-0.73, p = 0.0083) is a protective factor for developing the disease. In conclusion, the CT and CT + TT variants of rs763361 C>T and the T + A haplotype were considered as protective factors for developing ankylosing spondylitis.

10.
Psicol Reflex Crit ; 37(1): 5, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38315293

ABSTRACT

BACKGROUND: Psychometric studies of the FACES III scale in Spanish-speaking countries show a lack of agreement on the factorial structure of the scale. In addition, most of the studies have only performed exploratory analyses of its factorial structure. OBJECTIVE: The objective of the present study was to confirm the structure and factorial invariance of the FACES III scale in nursing and obstetric students from Chile, Colombia, Peru, and Mexico. METHODS: A total of 3303 students from the four countries participated in this study (Colombia = 1559, Chile = 1224, Peru = 215, Mexico = 305). RESULTS: The results of the study showed that the Bi-factor model presents the best-fit indexes to the data from Colombia, Chile, and Mexico, but not from Peru. In addition, it was found that this model showed evidence of being strictly invariant among the three countries in the sequence of the invariance models proposed: metric invariance (ΔRMSEA = .000), scalar (ΔRMSEA = .008), and strict (ΔRMSEA = .008). The bi-factor model also showed adequate reliability indexes in the three countries. CONCLUSION: It is concluded that the FACES III scale shows adequate psychometric performance under a bi-factor model in nursing and obstetric students from Colombia, Chile, and Mexico. The lack of fit of the model in Peru could be associated with the small sample size.

11.
BMC Psychol ; 12(1): 23, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38217009

ABSTRACT

BACKGROUND: A psychometric study of the Family Adaptability and Cohesion Scale (FACES III) has been conducted in Spanish-speaking countries from the perspective of the classical test theory. However, this approach has limitations that affect the psychometric understanding of this scale. OBJECTIVE: Accordingly, this study used the item response theory to investigate the psychometric performance of the items. Furthermore, it evaluated the differential performance of the items for Colombia and Chile. METHOD: For this purpose, 518 health science students from both countries participated. Confirmatory Factor Analysis was used. RESULTS: The study results revealed that the cohesion and adaptability items presented adequate discrimination and difficulty indices. In addition, items 5, 8, 13, 17, and 19 of cohesion indicated differential functioning between students from both countries, with Chilean students exhibiting a greater discriminatory power. Further, the Colombian group exhibited a greater discriminatory power for item 18 of adaptability. CONCLUSIONS: The study concluded that the items of FACES III indicated adequate psychometric performance in terms of their discriminative capacity and difficulty in Chile and Colombia.


Subject(s)
Students , Humans , Psychometrics , Chile , Colombia , Factor Analysis, Statistical , Reproducibility of Results , Surveys and Questionnaires
12.
Psicol. reflex. crit ; 37: 5, 2024. tab
Article in English | LILACS-Express | LILACS, Index Psychology - journals | ID: biblio-1558778

ABSTRACT

Abstract Background Psychometric studies of the FACES III scale in Spanish-speaking countries show a lack of agreement on the factorial structure of the scale. In addition, most of the studies have only performed exploratory analyses of its factorial structure. Objective The objective of the present study was to confirm the structure and factorial invariance of the FACES III scale in nursing and obstetric students from Chile, Colombia, Peru, and Mexico. Methods A total of 3303 students from the four countries participated in this study (Colombia = 1559, Chile = 1224, Peru = 215, Mexico = 305). Results The results of the study showed that the Bi-factor model presents the best-fit indexes to the data from Colombia, Chile, and Mexico, but not from Peru. In addition, it was found that this model showed evidence of being strictly invariant among the three countries in the sequence of the invariance models proposed: metric invariance (ΔRMSEA = .000), scalar (ΔRMSEA = .008), and strict (ΔRMSEA = .008). The bi-factor model also showed adequate reliability indexes in the three countries. Conclusion It is concluded that the FACES III scale shows adequate psychometric performance under a bi-factor model in nursing and obstetric students from Colombia, Chile, and Mexico. The lack of fit of the model in Peru could be associated with the small sample size.

13.
Rev. latinoam. enferm. (Online) ; 31: e3968, ene.-dic. 2023. tab, graf
Article in Spanish | LILACS, BDENF - Nursing | ID: biblio-1450110

ABSTRACT

Objetivo: determinar los niveles de empatía en profesionales de enfermería de un hospital de alta complejidad, relacionar la edad con la empatía (y cada una de sus dimensiones), y establecer si existen diferencias entre estos niveles según el tipo de jornada laboral. Método: diseño comparativo, correlacional y transversal. La muestra utilizada (n=271) constituyó el 40,9% del total de profesionales de enfermería. Se estudiaron las propiedades psicométricas de la Escala de Empatía de Jefferson para Profesionales de la Salud. Se calcularon estadísticos descriptivos: media y desviación estándar. La asociación entre empatía y edad se estimó mediante ecuaciones de regresión y significancia estadística de los coeficientes de regresión, luego de evaluar el tipo de curva mediante análisis de varianza. Resultados: se identificó el modelo subyacente de las tres dimensiones de la empatía. Los valores de los estadísticos descriptivos observados fueron relativamente bajos en empatía y sus dimensiones. Los niveles de empatía no se asociaron con el rango de edad. No se encontraron diferencias en la empatía entre los tipos de horarios de trabajo. Se encontró variabilidad en las dimensiones: "cuidado compasivo" y "ponerse en los zapatos del paciente". Conclusión: estos resultados muestran que los niveles de empatía observados pueden implicar un desempeño deficiente en el cuidado empático de los pacientes.


Objective: to determine the levels of empathy in professional nurses of a high-complexity hospital, to relate age to empathy (and each one of its dimensions), and to establish if there are differences between these levels according to the type of working schedules. Method: comparative, correlational and cross-sectional design. The sample used (n=271) constituted 40.9% of the total number of nursing professionals. Psychometric properties of the Jefferson Scale of Empathy for Health Professionals were studied. Descriptive statistics were calculated: mean and standard deviation. The association between empathy and age was estimated using regression equations and statistical significance of the regression coefficients, after evaluating the type of curve using variance analysis. Results: the underlying model of three dimensions of empathy was identified. The values of the descriptive statistics observed were relatively low in empathy and its dimensions. Empathy levels were not associated with the age range. No differences in empathy were found between the types of work schedules. Variability was found in the dimensions: "compassionate care" and "Walking on the patient's shoes". Conclusion: these results show that the levels of empathy observed may imply a deficient performance in empathetic care for patients.


Objetivo: determinar os níveis de empatia em enfermeiros profissionais de um hospital de alta complexidade, relacionar a idade com a empatia (e cada uma das suas dimensões) e verificar se existem diferenças entre esses níveis, de acordo com o tipo de horário de trabalho. Método: delineamento comparativo, correlacional e transversal. A amostra utilizada (n=271) constituiu 40,9% do total de profissionais de enfermagem. Foram estudadas as propriedades psicométricas da Escala de Empatia de Jefferson para Profissionais da Saúde. Foram calculadas estatísticas descritivas: média e desvio padrão. A associação entre empatia e idade foi estimada por meio de equações de regressão e significância estatística dos coeficientes de regressão, após avaliação do tipo de curva por meio de análise de variância. Resultados: o modelo subjacente de três dimensões de empatia foi identificado. Os valores das estatísticas descritivas observados foram relativamente baixos em empatia e suas dimensões. Níveis de empatia não foram associados com a faixa etária. Não foram encontradas diferenças de empatia entre os tipos de horários de trabalho. Foi encontrada variabilidade nas dimensões: "cuidado compassivo" e "colocar-se no lugar do paciente". Conclusão: esses resultados mostram que os níveis de empatia observados podem implicar em um desempenho deficiente no atendimento empático aos pacientes.


Subject(s)
Humans , Cross-Sectional Studies , Surveys and Questionnaires , Empathy , Hospitals, Public , Nurses
14.
bioRxiv ; 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37961113

ABSTRACT

Replication of the complex retrovirus mouse mammary tumor virus (MMTV) is antagonized by murine Apobec3 (mA3), a member of the Apobec family of cytidine deaminases. We have shown that MMTV-encoded Rem protein inhibits proviral mutagenesis by the Apobec enzyme, activation-induced cytidine deaminase (AID) during viral replication in BALB/c mice. To further study the role of Rem in vivo , we have infected C57BL/6 (B6) mice with a superantigen-independent lymphomagenic strain of MMTV (TBLV-WT) or a mutant strain (TBLV-SD) that is defective in Rem and its cleavage product Rem-CT. Unlike MMTV, TBLV induced T-cell tumors in µMT mice, indicating that mature B cells, which express the highest AID levels, are not required for TBLV replication. Compared to BALB/c, B6 mice were more susceptible to TBLV infection and tumorigenesis. The lack of Rem expression accelerated B6 tumorigenesis at limiting doses compared to TBLV-WT in either wild-type B6 or AID-deficient mice. However, unlike proviruses from BALB/c mice, high-throughput sequencing indicated that proviral G-to-A or C-to-T changes did not significantly differ in the presence and absence of Rem expression. Ex vivo stimulation showed higher levels of mA3 relative to AID in B6 compared to BALB/c splenocytes, but effects of agonists differed in the two strains. RNA-Seq revealed increased transcripts related to growth factor and cytokine signaling in TBLV-SD-induced tumors relative to those from TBLV-WT, consistent with a third Rem function. Thus, Rem-mediated effects on tumorigenesis in B6 mice are independent of Apobec-mediated proviral hypermutation.

15.
BMJ Open ; 13(11): e073307, 2023 11 23.
Article in English | MEDLINE | ID: mdl-37996232

ABSTRACT

OBJECTIVES: Health and care resources are under increasing pressure, partly due to the ageing population. Physical activity supports healthy ageing, but motivating exercise is challenging. We aimed to explore staff perceptions towards a virtual reality (VR) omnidirectional treadmill (MOTUS), aimed at increasing physical activity for older adult care home residents. DESIGN: Interactive workshops and qualitative evaluation. SETTINGS: Eight interactive workshops were held at six care homes and two university sites across Cornwall, England, from September to November 2021. PARTICIPANTS: Forty-four staff participated, including care home, supported living, clinical care and compliance managers, carers, activity coordinators, occupational therapists and physiotherapists. INTERVENTIONS: Participants tried the VR treadmill system, followed by focus groups exploring device design, potential usefulness or barriers for care home residents. Focus groups were audio-recorded, transcribed verbatim and thematically analysed. We subsequently conducted a follow-up interview with the technology developer (September 2022) to explore the feedback impact. RESULTS: The analysis produced seven key themes: anticipated benefits, acceptability, concerns of use, concerns of negative effects, suitability/unsuitability, improvements and current design. Participants were generally positive towards VR to motivate care home residents' physical activity and noted several potential benefits (increased exercise, stimulation, social interaction and rehabilitation). Despite the reported potential, staff had safety concerns for frail older residents due to their standing position. Participants suggested design improvements to enhance safety, usability and accessibility. Feedback to the designers resulted in the development of a new seated VR treadmill to address concerns about falls while maintaining motivation to exercise. The follow-up developer interview identified significant value in academia-industry collaboration. CONCLUSION: The use of VR-motivated exercise holds the potential to increase exercise, encourage reminiscence and promote meaningful activity for care home residents. Staff concerns resulted in a redesigned seated treadmill for those too frail to use the standing version. This novel study demonstrates the importance of stakeholder feedback in product design.


Subject(s)
Homes for the Aged , Virtual Reality , Humans , Aged , Follow-Up Studies , Feedback , Exercise
16.
mSphere ; 8(6): e0013923, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37855643

ABSTRACT

IMPORTANCE: Social bees are an important model for the ecology and evolution of gut microbiomes. These bees harbor ancient, specific, and beneficial gut microbiomes and are crucial pollinators. However, most of the research has concentrated on managed honeybees and bumblebees in the temperate zone. Here we used 16S rRNA gene sequencing to characterize gut microbiomes in wild neotropical bumblebee communities from Colombia. We also analyzed drivers of microbiome structure across our data and previously published data from temperate bumblebees. Our results show that lineages of neotropical bumblebees not only retained their ancient gut bacterial symbionts during dispersal from North America but also are prone to major disruption, a shift that is strongly associated with parasite infection. Finally, we also found that microbiomes are much more strongly structured by host phylogeny than by geography, despite the very different environmental conditions and plant communities in the two regions.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Bees , Animals , Gastrointestinal Microbiome/genetics , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Ecology
17.
Rev Lat Am Enfermagem ; 31: e3968, 2023.
Article in Spanish, English, Portuguese | MEDLINE | ID: mdl-37556616

ABSTRACT

OBJECTIVE: to determine the levels of empathy in professional nurses of a high-complexity hospital, to relate age to empathy (and each one of its dimensions), and to establish if there are differences between these levels according to the type of working schedules. METHOD: comparative, correlational and cross-sectional design. The sample used (n=271) constituted 40.9% of the total number of nursing professionals. Psychometric properties of the Jefferson Scale of Empathy for Health Professionals were studied. Descriptive statistics were calculated: mean and standard deviation. The association between empathy and age was estimated using regression equations and statistical significance of the regression coefficients, after evaluating the type of curve using variance analysis. RESULTS: the underlying model of three dimensions of empathy was identified. The values of the descriptive statistics observed were relatively low in empathy and its dimensions. Empathy levels were not associated with the age range. No differences in empathy were found between the types of work schedules. Variability was found in the dimensions: "compassionate care" and "Walking on the patient's shoes". CONCLUSION: these results show that the levels of empathy observed may imply a deficient performance in empathetic care for patients. (1) The levels of empathy are low in the nursing professionals studied. (2) These levels are not associated with age and type of work performed. (3) Low levels of empathy could imply a negative alteration of humanized attention.


Subject(s)
Empathy , Nurses , Humans , Cross-Sectional Studies , Hospitals, Public , Health Personnel , Surveys and Questionnaires
19.
G3 (Bethesda) ; 13(10)2023 09 30.
Article in English | MEDLINE | ID: mdl-37431950

ABSTRACT

Subtelomeric gene silencing is the negative transcriptional regulation of genes located close to telomeres. This phenomenon occurs in a variety of eukaryotes with salient physiological implications, such as cell adherence, virulence, immune-system escape, and ageing. The process has been widely studied in the budding yeast Saccharomyces cerevisiae, where genes involved in this process have been identified mostly on a gene-by-gene basis. Here, we introduce a quantitative approach to study gene silencing, that couples the classical URA3 reporter with GFP monitoring, amenable to high-throughput flow cytometry analysis. This dual silencing reporter was integrated into several subtelomeric loci in the genome, where it showed a gradual range of silencing effects. By crossing strains with this dual reporter at the COS12 and YFR057W subtelomeric query loci with gene-deletion mutants, we carried out a large-scale forward screen for potential silencing factors. The approach was replicable and allowed accurate detection of expression changes. Results of our comprehensive screen suggest that the main players influencing subtelomeric silencing were previously known, but additional potential factors underlying chromatin conformation are involved. We validate and report the novel silencing factor LGE1, a protein with unknown molecular function required for histone H2B ubiquitination. Our strategy can be readily combined with other reporters and gene perturbation collections, making it a versatile tool to study gene silencing at a genome-wide scale.


Subject(s)
Saccharomyces cerevisiae Proteins , Saccharomycetales , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics , Silent Information Regulator Proteins, Saccharomyces cerevisiae/metabolism , Saccharomycetales/genetics , Saccharomycetales/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Telomere/genetics , Telomere/metabolism , Heterochromatin/metabolism , Gene Expression Regulation, Fungal
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