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1.
BMC Health Serv Res ; 24(1): 645, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769571

RESUMO

BACKGROUND: Social prescribing (SP) is a non-clinical approach, most commonly based in healthcare units, that aims to address non-medical health-related social needs by connecting individuals with community-based services. This qualitative study explores the perception of Portuguese older adults regarding the benefits of SP and their willingness to participate in SP initiatives. METHODS: Three face-to-face focus group sessions were conducted with 23 participants in different cities in Portugal. Open and semi-open questions were used to guide the discussions and thematic analysis was used to analyze the data. RESULTS: The participants recognized the potential benefits of SP for older adults, including diversifying leisure activities, improving mental health, and complementing existing support systems. They highlighted the need for external support, usually in the form of link workers, to facilitate personalized referrals and consider individual characteristics and preferences. While some participants expressed reluctance to engage in SP due to their existing busy schedules and a perceived sense of imposition, others showed openness to having new experiences and recognized the potential value of SP in promoting activity. Barriers to participation, including resistance to change, mobility issues, and family responsibilities, were identified. CONCLUSIONS: The study emphasizes the importance of a person-centered and co-designed approach to SP, involving older adults in the planning and implementation of interventions. The findings provide valuable insights for the development of SP programs tailored to the unique needs and aspirations of older adults in Portugal, ultimately promoting active and healthy aging. Future research should consider the perspectives of family doctors and include a broader representation of older adults from diverse geographic areas.


Assuntos
Grupos Focais , Pesquisa Qualitativa , Humanos , Portugal , Masculino , Idoso , Feminino , Idoso de 80 Anos ou mais , Apoio Social , Pessoa de Meia-Idade
2.
iScience ; 27(5): 109806, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38746664

RESUMO

In many social mammals, early social life and social integration in adulthood largely predict individual health, lifespan, and reproductive success. So far, research has mainly focused on chronic stress as the physiological mediator between social environment and fitness. Here, we propose an alternative, non-exclusive mechanism relying on microbially mediated effects: social relationships with conspecifics in early life and adulthood might strongly contribute to diversifying host microbiomes and to the transmission of beneficial microbes. In turn, more diverse and valuable microbiomes would promote pathogen resistance and optimal health and translate into lifelong fitness benefits. This mechanism relies on recent findings showing that microbiomes are largely transmitted via social routes and play a pervasive role in host development, physiology and susceptibility to pathogens. We suggest that the social transmission of microbes could explain the sociality-fitness nexus to a similar or higher extent than chronic social stress and deserves empirical studies in social mammals.

3.
Am J Prev Cardiol ; 18: 100679, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38779187

RESUMO

Background: Multiple cardiovascular outcomes trials (CVOTs) have shown the efficacy of GLP-1RAs in reducing major adverse cardiovascular events (MACEs) for high-risk patients. However, some CVOTs failed to demonstrate cardiovascular benefits. Objectives: We analyzed the impact of GLP-1RA on cardiovascular and renal outcomes in patients with or without T2DM, with subgroup analysis based on sex, estimated glomerular filtration rate (eGFR), body mass index (BMI), and history of cardiovascular disease (CVD). Methods: A comprehensive database search for placebo-controlled RCTs on GLP-1RA treatment was conducted until April 2024. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with log odds ratios and 95 % confidence intervals (CIs). Results: A total of 13 CVOTs comprising 83,258 patients were included. GLP-1RAs significantly reduced MACE (OR 0.86, 95 % CI: 0.80 to 0.94, p < 0.01) all-cause mortality OR 0.87, 95 % CI: 0.82 to 0.93, p < 0.001, CV mortality (OR 0.87, 95 % CI: 0.81 to 0.94, p < 0.001), stroke (fatal: OR 0.74, 95 % CI: 0.56 to 0.96, p = 0.03; non-fatal: OR 0.87, 95 % CI: 0.79 to 0.96, p = 0.005), coronary revascularization (OR 0.86, 95 % CI: 0.74 to 0.99, p = 0.023), and composite kidney outcome (OR 0.76, 95 % CI: 0.67 to 0.85, p < 0.001. GLP-1RA significantly reduced MACE in both sexes. Furthermore, GLP-1RA reduced MACE regardless of CVD history, BMI, and eGFR level. Conclusion: Significant reductions in MACE, overall and CV mortality, stroke, coronary revascularization, and composite kidney outcome with GLP-1RA treatment were noted across all subgroups.

4.
J Acoust Soc Am ; 155(4): 2359-2370, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38563623

RESUMO

Passive acoustic monitoring has been an effective tool to study cetaceans in remote regions of the Arctic. Here, we advance methods to acoustically identify the only two Arctic toothed whales, the beluga (Delphinapterus leucas) and narwhal (Monodon monoceros), using echolocation clicks. Long-term acoustic recordings collected from moorings in Northwest Greenland were analyzed. Beluga and narwhal echolocation signals were distinguishable using spectrograms where beluga clicks had most energy >30 kHz and narwhal clicks had a sharp lower frequency limit near 20 kHz. Changes in one-third octave levels (TOL) between two pairs of one-third octave bands were compared from over one million click spectra. Narwhal clicks had a steep increase between the 16 and 25 kHz TOL bands that was absent in beluga click spectra. Conversely, beluga clicks had a steep increase between the 25 and 40 kHz TOL bands that was absent in narwhal click spectra. Random Forest classification models built using the 16 to 25 kHz and 25 to 40 kHz TOL ratios accurately predicted the species identity of 100% of acoustic events. Our findings support the use of echolocation TOL ratios in future automated click classifiers for acoustic monitoring of Arctic toothed whales and potentially for other odontocete species.


Assuntos
Ecolocação , Animais , Acústica , Baleias
5.
BMJ Open ; 14(4): e082418, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626955

RESUMO

OBJECTIVES: Systematically measuring the work environment of healthcare employees is key to continuously improving the quality of care and addressing staff shortages. In this study, we systematically analyse the responses to the one open-ended question posed in the Dutch version of the Culture of Care Barometer (CoCB-NL) to examine (1) if the responses offered new insights into healthcare employees' perceptions of their work environment and (2) if the original CoCB had any themes missing. DESIGN: Retrospective text analysis using Rigorous and Accelerated Data Reduction technique. SETTING: University hospital in the Netherlands using the CoCB-NL as part of the annual employee survey. PARTICIPANTS: All hospital employees were invited to participate in the study (N=14 671). In total, 2287 employees responded to the open-ended question. RESULTS: 2287 comments were analysed. Comments that contained more than one topic were split according to topic, adding to the total (n=2915). Of this total, 372 comments were excluded because they lacked content or respondents indicated they had nothing to add. Subsequently, 2543 comments were allocated to 33 themes. Most comments (n=2113) addressed the 24 themes related to the close-ended questions in the CoCB-NL. The themes most commented on concerned questions on 'organisational support'. The remaining 430 comments covered nine additional themes that addressed concerns about work environment factors (team connectedness, team effectiveness, corporate vision, administrative burden and performance pressure) and themes (diversity and inclusion, legal frameworks and collective bargaining, resilience and work-life balance, and personal matters). CONCLUSIONS: Analysing responses to the open-ended question in the CoCB-NL led to new insights into relevant elements of the work environment and missing themes in the COCB-NL. Moreover, the analysis revealed important themes that not only require attention from healthcare organisations to ensure adequate improvements in their employees' work environment but should also be considered to further develop the CoCB-NL.


Assuntos
Hospitais , Radar , Humanos , Estudos Retrospectivos , Inquéritos e Questionários , Recursos Humanos em Hospital
6.
Vet J ; 305: 106123, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38642699

RESUMO

Mobility is an essential aspect of a dog's daily life. It is defined as the ability to move freely and easily and deviations from an animals' normal mobility capabilities are often an indicator of disease, injury or pain. When a dog's mobility is compromised, often functionality (ability to perform activities of daily living [ADL]), is also impeded, which can diminish an animal's quality of life. Given this, it is necessary to understand the extent to which conditions impact a dog's physiological ability to move around their environment to carry out ADL, a concept termed functional mobility. In contrast to human medicine, validated measures of canine functional mobility are currently limited. The aim of this review is to summarise the extent to which canine mobility and functionality are associated with various diseases and how mobility and functional mobility are currently assessed within veterinary medicine. Future work should focus on developing a standardised method of assessing functional mobility in dogs, which can contextualise how a wide range of conditions impact a dog's daily life. However, for a true functional mobility assessment to be developed, a greater understanding of what activities dogs do on a daily basis and movements underpinning these activities must first be established.

7.
BMJ Open ; 14(4): e080551, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589260

RESUMO

INTRODUCTION: Dementia is a complex medical condition that poses significant challenges to healthcare systems and support services. People living with dementia (PLWD) and their carers experience complex needs often exacerbated by social isolation and challenges in accessing support. Social prescribing (SP) seeks to enable PLWD and their carers to access community and voluntary sector resources to support them address such needs. Existing research, however, does not describe what SP interventions are currently in place in dementia care. Little is known about the needs these interventions are designed to address, the reasons that lead PLWD and their carers to participate in them, their effectiveness and the extent to which they could increase positive health outcomes if adopted and how. METHODS AND ANALYSIS: A complex intervention systematic review of SP for PLWD and/or their carers will be conducted using an iterative logic model approach. Six electronic (MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus and Cochrane/CENTRAL) and two grey literature databases (EThOS and CORE) were searched for publications between 1 January 2003 and June 2023, supplemented by handsearching of reference lists of included studies. Study selection, data extraction and risk of bias assessment, using Gough's Weight of Evidence Framework, will be independently performed by two reviewers. A narrative approach will be employed to synthesise and report quantitative and qualitative data. Reporting will be informed by the Preferred Reporting Items for Systematic Review and Meta-Analysis Complex Interventions extension statement and checklist. ETHICS AND DISSEMINATION: No ethical approval is required due to this systematic review operating only with secondary sources. Findings will be disseminated through peer-reviewed publications, conference presentations and meetings with key stakeholders including healthcare professionals, patient and carer groups, community organisations (eg, the Social Prescribing Network and the Evidence Collaborative at the National Academy for Social Prescribing), policymakers and funding bodies. PROSPERO REGISTRATION NUMBER: CRD42023428625.


Assuntos
Cuidadores , Demência , Humanos , Atenção à Saúde , Pessoal de Saúde , Metanálise como Assunto , Revisões Sistemáticas como Assunto
8.
Cell Rep ; 43(3): 113849, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38427560

RESUMO

CRISPR-Cas immune systems provide bacteria with adaptive immunity against bacteriophages, but they are often transcriptionally repressed to mitigate auto-immunity. In some cases, CRISPR-Cas expression increases in response to a phage infection, but the mechanisms of induction are largely unknown, and it is unclear whether induction occurs strongly and quickly enough to benefit the bacterial host. In S. pyogenes, Cas9 is both an immune effector and auto-repressor of CRISPR-Cas expression. Here, we show that phage-encoded anti-CRISPR proteins relieve Cas9 auto-repression and trigger a rapid increase in CRISPR-Cas levels during a single phage infective cycle. As a result, fewer cells succumb to lysis, leading to a striking survival benefit after multiple rounds of infection. CRISPR-Cas induction also reduces lysogeny, thereby limiting a route for horizontal gene transfer. Altogether, we show that Cas9 is not only a CRISPR-Cas effector and repressor but also a phage sensor that can mount an anti-anti-CRISPR transcriptional response.


Assuntos
Bacteriófagos , Bacteriófagos/fisiologia , Sistemas CRISPR-Cas/genética , Bactérias/metabolismo , Lisogenia , Proteínas Virais/genética , Proteínas Virais/metabolismo
9.
J Allergy Clin Immunol Pract ; 12(3): 670-680, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38182097

RESUMO

BACKGROUND: Evidence suggests that children who had received an initial priming dose of whole-cell pertussis (wP) vaccine, rather than acellular pertussis (aP) vaccine, had a lower risk of developing IgE-mediated food allergy, the most common cause of anaphylaxis-related hospital presentations of childhood. OBJECTIVE: To assess the association between wP versus aP vaccination in infancy and subsequent hospital presentations for anaphylaxis. METHODS: This study was preregistered under PMID 34874968. Perinatal records for a cohort of New South Wales-born children (1997-1999) receiving their first dose of pertussis-containing vaccine before age 4 months were probabilistically linked to hospital and immunization records. We used adjusted Cox models to estimate hazard ratios (aHRs) and 95% CIs for anaphylaxis-coded hospitalizations. RESULTS: There were 218,093 New South Wales-born children who received a first dose of wP or aP before age 4 months. Among these children, 86 experienced at least one hospitalization for food-induced anaphylaxis at age 5-15 years (range of events per patient, one to three). The person-time of follow-up was 1,476,969 years, and 665,519 years for children vaccinated with wP as a first dose (wP-1 children) and aP as a first dose (aP-1 children), respectively. The incidence rates for first hospitalization for food anaphylaxis were 3.5 (95% CI, 2.6-4.6) and 5.1 (95% CI, 3.5-7.1) per 100,000 child-years among wP-1 children and aP-1 children, respectively (aHR for wP vs aP = 0.47; 95% CI, 0.26-0.83). For first admission for venom anaphylaxis, the incidence rate was 4.9 (95% CI, 3.9-6.2) per 100,000 child-years among wP-1 children and 5.1 (95% CI, 3.5-7.1) per 100,000 child-years among aP-1 children (aHR for wP vs aP = 0.92; 95% CI, 0.53-1.60), and for all-cause anaphylaxis, the incidence rate was 10.6 (95% CI, 9.0-12.4) per 100,000 child-years among wP-1 children and 12.8 (95% CI, 10.2-15.8) per 100,000 child-years among aP-1 children (aHR for wP vs aP = 0.92; 95% CI, 0.53-1.60). CONCLUSION: Vaccination with wP in infancy was associated with a lower risk of hospitalizations for food-induced anaphylaxis (and therefore severe IgE-mediated food allergy) occurring in childhood.


Assuntos
Acetazolamida/análogos & derivados , Anafilaxia , Hipersensibilidade Alimentar , Tetraciclinas , Coqueluche , Lactente , Humanos , Pré-Escolar , Coqueluche/prevenção & controle , Anafilaxia/epidemiologia , Estudos de Coortes , Fator de Transcrição AP-1 , Imunização Secundária , Vacina contra Coqueluche , Vacinação , Hipersensibilidade Alimentar/epidemiologia , Hospitalização , Imunoglobulina E
10.
Animals (Basel) ; 14(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38254375

RESUMO

The commercial greyhound racing industry in New Zealand is struggling with an eroding social license and 'on-notice' status. Multiple independent reviews of the industry have identified ongoing issues of animal welfare during and between races, euthanasia decisions, poor data tracking, a lack of transparency and problems with rehoming dogs, resulting in New Zealand animal advocacy agencies and the general public questioning the continuation of greyhound racing. The current paper assessed the New Zealand public's awareness and familiarity with commercial greyhound racing, identified current levels of public support or opposition for racing, and provided context in terms of engagement with greyhound racing using a comprehensive survey of a robust sample of New Zealanders. The results confirm that the social license of the greyhound industry is under challenge with most respondents expressing disagreement with or lack of knowledge of current industry practices and indicating they would vote in support of a ban. There is scope for increasing public acceptability by addressing welfare issues, increasing awareness of positive industry practices, and encouraging transparency of the greyhound racing agency. However, as greyhound racing is on the decline worldwide, calls are likely to continue for a phase-out of commercial greyhound racing.

11.
BMJ Open Qual ; 13(1)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296605

RESUMO

INTRODUCTION: Measure Yourself Concerns and Wellbeing is a validated person-centred outcome measure, piloted as a core monitoring tool to understand what matters to people living with frailty in Gloucestershire. This paper describes the acceptability of MYCaW used in this setting, and the development of a framework for analysing personalised concerns from people living with frailty. METHODS: MYCaW was implemented in the Complex Care at Home service and South Cotswold Frailty Service from November 2020 onwards. MYCaW was completed at the person's first meeting with a community matron and then 3 months later. Nineteen staff completed an anonymous survey to provide feedback on the acceptability of the tool. A framework of concerns bespoke to people living with frailty was created via iterative rounds of independent coding of 989 concerns from 526 people. The inter-rater reliability of the framework was determined by using the Cronbach alpha test. RESULTS: MYCaW was simple to use and helped health professionals' discussions to be patient focused. A pictorial scale accompanying the Numerical Rating Scale was developed and tested to help people engage with scoring their concerns and well-being more easily. A framework of concerns from people living with frailty was produced with five main supercategories: Mental and Emotional Concerns; Physical Concerns; Healthcare and Service Provision Concerns, Concerns with General Health and Well-being and Practical Concerns. Inter-rater reliability was kappa=0.905. CONCLUSIONS: MYCaW was acceptable as a core monitoring tool for people living with frailty and enabled a systematic approach to opening 'What Matters to Me' conversations. The personalised data generated valuable insights into how the frailty services positively impacted the outcomes for people living with frailty. The coding framework demonstrated a wide range of concerns-many linked to inequalities and not identified on existing outcome measures recommended for people living with frailty.


Assuntos
Fragilidade , Serviços de Assistência Domiciliar , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Avaliação de Resultados em Cuidados de Saúde
14.
Am J Biol Anthropol ; 183(3): e24755, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37171151

RESUMO

OBJECTIVES: In this study, we investigated the shape differences of the distal ulna in a phylogenetic context among a broad range of primate taxa. Furthermore, we evaluated covariation between ulnar and triquetrum shape and a possible association between ulnar shape and locomotor behavior. MATERIALS AND METHODS: We applied 3D geometric morphometrics on a large dataset comprising the distal ulna of 124 anthropoid primate specimens belonging to 12 different genera. For each species, a mean shape was calculated using 11 Procrustes-aligned surface landmarks on the distal ulna. These mean shapes are used in a bgPCA, pPCA, and PACA and 3D morphs were used to visualize more subtle differences between taxa. A p2B-PLS analysis was performed to test the covariance between distal ulnar and triquetrum shape. RESULTS: The results show that more closely related species exhibit a similar distal ulnar shape. Overall, extant hominid ulnae show a shape shift compared to those of extant monkeys and hylobatids. This includes a shortening of the ulnar styloid process and dorspalmarly widening of the ulnar head, shape characteristics that are independent of phylogeny. Within the hominids, Pongo pygmaeus seem to possess the most plesiomorphic distal ulnar shape, while Gorilla and Homo sapiens display the most derived distal ulna. Cercopithecoids, hylobatids, and P. pygmaeus are characterized by a relatively deep ECU groove, which is a shape trait dependent of phylogeny. Although there was no significant covariation between distal ulnar shape and triquetrum shape, the shape differences of the distal ulna between the different primate taxa reveal a possible link with locomotor behavior. CONCLUSIONS: The comparative analyses of this study reveal different shape trends in a phylogenetic context. Highly arboreal primates, such as hylobatids and Ateles fusciceps, show a distal ulnar morphology that appears to be adapted to tensile and torsional forces. In primates that use their wrist under more compressive conditions, such as quadrupedal cercopithecoids and great apes, the distal ulnar morphology seems to reflect increased compressive forces. In modern humans, the distal ulnar shape can be associated to enhanced manipulative skills and power grips. There was no significant covariation between distal ulnar shape and triquetrum shape, probably due to the variation in the amount of contact between the triquetrum and ulna. In combination with future research on wrist mobility in diverse primate taxa, the results of this study will allow us to establish form-function relationships of the primate wrist and contribute towards an evidence-based interpretation of fossil remains.


Assuntos
Hominidae , Primatas , Animais , Humanos , Filogenia , Hominidae/anatomia & histologia , Ulna/anatomia & histologia , Punho/anatomia & histologia , Gorilla gorilla , Haplorrinos , Pongo pygmaeus
15.
Angew Chem Int Ed Engl ; 63(5): e202312823, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38010646

RESUMO

Concerns over the sustainability and end-of-life properties of fossil-derived surfactants have driven interest in bio-based alternatives. Lignocellulosic biomass with its polar functional groups is an obvious feedstock for surfactant production but its use is limited by process complexity and low yield. Here, we present a simple two-step approach to prepare bio-based amphiphiles directly from hemicellulose and lignin at high yields (29 % w/w based on the total raw biomass and >80 % w/w of these two fractions). Acetal functionalization of xylan and lignin with fatty aldehydes during fractionation introduced hydrophobic segments and subsequent defunctionalization by hydrogenolysis of the xylose derivatives or acidic hydrolysis of the lignin derivatives produced amphiphiles. The resulting biodegradable xylose acetals and/or ethers, and lignin-based amphiphilic polymers both largely retained their original natural structures, but exhibited competitive or superior surface activity in water/oil systems compared to common bio-based surfactants.


Assuntos
Lignina , Xilose , Lignina/química , Biomassa , Água , Tensoativos , Hidrólise
16.
Eur Ann Otorhinolaryngol Head Neck Dis ; 141(2): 81-85, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38135563

RESUMO

Evaluation of the results of laryngeal transplantation (LT) in humans. Analysis of 3 bibliographic databases with the keywords "larynx, transplantation, autograft". In total, 626 abstracts were read and 25 articles selected. The main objective was to analyze the characteristics of laryngeal transplant patients. The accessory objectives comprised analysis of operative technique, immunosuppressive treatment and results. Four articles were selected for analysis. Two patients were transplanted after total laryngectomy for laryngeal carcinoma and 2 after laryngeal trauma. Three of the 4 patients had true transplantation with arterial, venous and neural microanastomosis. Two patients were decannulated and the tracheostomy tube was maintained in the other 2. Three of the 4 patients had good-quality phonation and could feed without a gastric tube. One patient died of carcinoma progression and 1 patient had to be explanted 14 years after transplantation. The number of LTs reported is too small for scientific determination of the place of this intervention in laryngology. The published results could, at first sight, suggest that the future of LT is uncertain. However, several elements, also suggest that otolaryngologists should continue to take an interest in this technique.


Assuntos
Carcinoma , Neoplasias Laríngeas , Laringe , Humanos , Laringectomia/métodos , Laringe/cirurgia , Laringe/patologia , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Fonação , Carcinoma/patologia
17.
Biosci Rep ; 44(1)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38131452

RESUMO

Upon SARS-CoV-2 infection, patients with severe forms of COVID-19 often suffer from a dysregulated immune response and hyperinflammation. Aberrant expression of cytokines and chemokines is associated with strong activation of the immunoregulatory transcription factor NF-κB, which can be directly induced by the SARS-CoV-2 protein NSP14. Here, we use NSP14 mutants and generated cells with host factor knockouts (KOs) in the NF-κB signaling pathways to characterize the molecular mechanism of NSP14-induced NF-κB activation. We demonstrate that full-length NSP14 requires methyltransferase (MTase) activity to drive NF-κB induction. NSP14 WT, but not an MTase-defective mutant, is poorly expressed and inherent post-translational instability is mediated by proteasomal degradation. Binding of SARS-CoV-2 NSP10 or addition of the co-factor S-adenosylmethionine (SAM) stabilizes NSP14 and augments its potential to activate NF-κB. Using CRISPR/Cas9-engineered KO cells, we demonstrate that NSP14 stimulation of canonical NF-κB activation relies on NF-κB factor p65/RELA downstream of the NEMO/IKK complex, while c-Rel or non-canonical RelB are not required to induce NF-κB transcriptional activity. However, NSP14 overexpression is unable to induce canonical IκB kinase ß (IKKß)/NF-κB signaling and in co-immunoprecipitation assays we do not detect stable associations between NSP14 and NEMO or p65, suggesting that NSP14 activates NF-κB indirectly through its methyltransferase activity. Taken together, our data provide a framework how NSP14 can augment basal NF-κB activation, which may enhance cytokine expression in SARS-CoV-2 infected cells.


Assuntos
COVID-19 , NF-kappa B , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , COVID-19/genética , Transdução de Sinais , Metiltransferases/genética , Metiltransferases/metabolismo
18.
Mol Genet Metab ; 141(1): 108097, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113552

RESUMO

Citrullinemia type 1 (CTLN1) is a rare autosomal recessive urea cycle disorder caused by deficiency of the cytosolic enzyme argininosuccinate synthetase 1 (ASS1) due to pathogenic variants in the ASS1 gene located on chromosome 9q34.11. Even though hyperammenomia is considered the major pathomechanistic factor for neurological impairment and cognitive dysfunction, a relevant subset of individuals presents with a neurodegenerative course in the absence of hyperammonemic decompensations. Here we show, that ASS1 deficiency induced by antisense-mediated knockdown of the zebrafish ASS1 homologue is associated with defective neuronal differentiation ultimately causing neuronal cell loss and consecutively decreased brain size in zebrafish larvae in vivo. Whereas ASS1-deficient zebrafish larvae are characterized by markedly elevated concentrations of citrulline - the biochemical hallmark of CTLN1, accumulation of L-citrulline, hyperammonemia or therewith associated secondary metabolic alterations did not account for the observed phenotype. Intriguingly, coinjection of the human ASS1 mRNA not only normalized citrulline concentration but also reversed the morphological cerebral phenotype and restored brain size, confirming conserved functional properties of ASS1 across species. The results of the present study imply a novel, potentially non-enzymatic (moonlighting) function of the ASS1 protein in neurodevelopment.


Assuntos
Citrulinemia , Hiperamonemia , Animais , Humanos , Citrulinemia/patologia , Peixe-Zebra/genética , Citrulina , Argininossuccinato Sintase/genética , Argininossuccinato Sintase/metabolismo , Fenótipo , Hiperamonemia/genética
19.
Primates ; 65(2): 75-80, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38133716

RESUMO

Birth is a fundamental event in the life of animals, including our own species. More reports of wild non-human primate births and stillbirths are thus needed to better understand the evolutionary pressures shaping parturition behaviors in our lineage. In diurnal non-human primates, births generally occur at night, when individuals are resting. Consequently, they are difficult to observe in the wild and most of the current knowledge regarding perinatal behaviors comes from rare daytime births. Information about stillbirths is even rarer and their proximate causes are generally unknown. Here, we present detailed observations of a daytime birth of a stillborn wild mandrill (Mandrillus sphinx). During this event, which lasted an entire day, we recorded the behaviors of the parturient female ad libitum, using video recordings and photos. The 5-year-old female was primiparous and of low dominance rank. The length of her pregnancy was shorter than usual and the partum phase was extremely long compared to other birth reports in non-human primates. The female disappeared shortly after this event and was assumed to have died. We discuss the possible causes of this stillbirth including the infant's presentation at birth and maternal inexperience.


Assuntos
Mandrillus , Humanos , Gravidez , Animais , Feminino , Natimorto/epidemiologia , Natimorto/veterinária , Parto , Evolução Biológica
20.
Am J Vet Res ; 84(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041947

RESUMO

OBJECTIVE: To determine the effects of using either a linear or curvilinear oscillating, battery-powered saw blade on the extent of bone resection, bone fissure or fragmentation, soft tissue trauma, and surgical time for femoral head and neck excision (FHNE) in feline cadavers. ANIMALS: 18 feline cadavers. METHODS: Paired feline cadaveric femora were randomly assigned to either a 10 mm linear or 12 mm curvilinear blade for FHNE by 2 surgical residents. CT of each femur pre- and postoperatively were used to create 3D reconstructions of each femur. The residual remaining or excessively resected bone volume at the ostectomy site was compared to an "ideal" ostectomy line made by a board-certified surgeon on preoperative CTs. RESULTS: There were no significant differences in residual or excessive bone resection by a saw blade (P = .84), between surgeons (P = .65), or in surgery time (P = .39). When compared to the "ideal" ostectomy, the linear saw blade removed slightly less bone compared to the curvilinear blade, but was not statistically significant (P = .82). No fissures or fractures were noted; however, the curvilinear blade removed the entire lesser trochanter in 1 cadaver and the linear blade partially removed the greater trochanter in 1 femur and 2 lesser trochanters in 2 femora. CLINICAL RELEVANCE: The use of a curvilinear blade may be a viable option for performing FHNE in cats. In vivo studies are warranted to determine its efficacy in clinical cases where FHNE is performed and the incidence of complications postoperatively.


Assuntos
Doenças do Gato , Procedimentos de Cirurgia Plástica , Animais , Gatos/cirurgia , Cadáver , Doenças do Gato/cirurgia , Fêmur/cirurgia , Cabeça do Fêmur/cirurgia , Procedimentos de Cirurgia Plástica/veterinária , Instrumentos Cirúrgicos/veterinária , Distribuição Aleatória
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