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The Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in Cuba during 2017, a year after peak transmission in neighboring islands. By sequencing Zika virus, we show that the establishment of the virus was delayed by a year and that the ensuing outbreak was sparked by long-lived lineages of Zika virus from other Caribbean islands. Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective. Our study highlights how Zika virus may still be "silently" spreading and provides a framework for understanding outbreak dynamics. VIDEO ABSTRACT.
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Epidemias , Genômica/métodos , Infecção por Zika virus/epidemiologia , Aedes/virologia , Animais , Cuba/epidemiologia , Humanos , Incidência , Controle de Mosquitos , Filogenia , RNA Viral/química , RNA Viral/metabolismo , Análise de Sequência de RNA , Viagem , Índias Ocidentais/epidemiologia , Zika virus/classificação , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologiaRESUMO
BACKGROUND: Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students. METHODS: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students' empathy using the Jefferson Scale of Empathy- Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students' emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. RESULTS: There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 ("Standing in People's Shoes") following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students' motivation and faculty's perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students' motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation. CONCLUSION: This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients' perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.
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Educação em Farmácia , Medicina Narrativa , Estudantes de Medicina , Humanos , Singapura , Estudantes de Medicina/psicologia , Empatia , Pessoal de SaúdeRESUMO
The pathways through which primates acquire skills are a central focus of cultural evolution studies. The roles of social and genetic inheritance processes in skill acquisition are often confounded by environmental factors. Hybrid macaques from Koram Island (Thailand) provide an opportunity to examine the roles of inheritance and social learning to skill acquisition within a single ecological setting. These hybrids are a cross between tool-using Burmese long-tailed (Macaca fascicularis aurea) and non-tool-using common long-tailed macaques (Macaca fascicularis fascicularis). This population provides an opportunity to explore the roles of social learning and inheritance processes while being able to exclude underlying ecological factors. Here, we investigate the roles of social learning and inheritance in tool use prevalence within this population using social network analysis and simulation. Agent-based modelling (ABM) is used to generate expectations for how social/asocial learning and inheritance structure the patterning in a social network. The results of the simulation show that various transmission mechanisms can be differentiated based on associations between individuals in a social network. The results provide an investigative framework for discussing tool use transmission pathways in the Koram social network. By combining ABM, network analysis, and behavioural data from the field we can investigate the roles social learning and inheritance play in tool acquisition of wild primates.
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Aprendizado Social , Comportamento de Utilização de Ferramentas , Animais , Análise de Rede Social , Macaca fascicularis/genética , TailândiaRESUMO
OBJECTIVE: To evaluate the effectiveness of tranexamic acid (TXA) in reducing blood loss during elective caesarean sections in women with and without risk factors for postpartum haemorrhage (PPH). DESIGN: A double-blind, randomised placebo-controlled trial. SETTING: An academic tertiary referral centre in Singapore. POPULATION: Multiethnic women aged 21 years or older undergoing elective caesarean section. METHODS: Randomisation to intravenous TXA or normal saline (placebo) 10 minutes before skin incision. MAIN OUTCOME MEASURES: Calculated estimated blood loss (cEBL), derived from blood volume and haematocrit levels. RESULTS: Between June 2020 and October 2021, 200 women were randomised to the placebo or TXA groups. Women who received prophylactic TXA had a significantly lower mean cEBL compared with those receiving placebo (adjusted mean difference -126.4 mL, 95% CI -243.7 to -9.1, p = 0.035). The effect was greatest in those at high risk for PPH, with a reduction in cEBL (mean difference -279.6 mL, 95% CI -454.8 to -104.3, p = 0.002) and a lower risk of cEBL ≥500 mL (risk ratio [RR] 0.54, 95% CI 0.36-0.83, p = 0.007) and cEBL ≥1000 mL (RR 0.44, 95% CI 0.20-0.98, p = 0.016). Subgroup analysis showed benefit for women with preoperative haemoglobin <10.5 g/dL (mean difference -281.9 mL, 95% CI -515.0 to -48.8, p = 0.019). There was no significant difference in need for additional medical or surgical interventions. There were no maternal or neonatal adverse outcomes. CONCLUSION: Prophylactic TXA should be considered in women with risk factors for PPH, and those most likely to benefit are those with preoperative haemoglobin <10.5 g/dL.
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Hemorragia Pós-Parto , Ácido Tranexâmico , Recém-Nascido , Feminino , Gravidez , Humanos , Ocitocina/uso terapêutico , Hemorragia Pós-Parto/prevenção & controle , Hemorragia Pós-Parto/tratamento farmacológico , Ácido Tranexâmico/uso terapêutico , Cesárea/efeitos adversos , Método Duplo-Cego , HemoglobinasRESUMO
BACKGROUND: Sexual and/or gender minority (SGM) individuals experience higher rates and greater severity of depressive disorders than non-SGM persons. SGM individuals are more likely than non-SGM individuals to seek mental health treatment and to present to treatment with unique characteristics that should be accounted for when considering treatment recommendations. Patients seeking care for treatment-resistant depression (TRD) are offered a variety of evidence-based interventions ranging in modality and invasiveness (eg, psychotherapy and neuromodulation). METHODS: The current study used data from a TRD clinical research program to examine whether SGM (N = 52) and non-SGM (N = 202) patients differed in their clinical presentations and the treatment recommendations offered to them. RESULTS: We found that SGM patients were younger, had a more severe history of childhood trauma, and reported greater current suicidality than non-SGM patients. There were no significant differences in treatment recommendations between groups. CONCLUSIONS: This study adds to nascent literature investigating clinical characteristics of SGM populations seeking mental health care and provides foundational evidence for the unique treatment considerations necessary for SGM individuals seeking treatment for TRD. Research into whether treatment outcomes differ for SGM and non-SGM individuals with TRD is encouraged, given clinical differences in trauma history and suicidality.
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Identidade de Gênero , Minorias Sexuais e de Gênero , Humanos , Masculino , Feminino , Depressão , Comportamento Sexual/psicologia , Ideação SuicidaRESUMO
Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions.
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Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologia , Zika virus/genética , Aedes/virologia , Animais , Região do Caribe/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Feminino , Florida/epidemiologia , Genoma Viral/genética , Humanos , Incidência , Epidemiologia Molecular , Mosquitos Vetores/virologia , Zika virus/isolamento & purificação , Infecção por Zika virus/transmissãoRESUMO
Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests.
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Filogenia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia , Zika virus/genética , Zika virus/isolamento & purificação , Animais , Brasil/epidemiologia , Colômbia/epidemiologia , Culicidae/virologia , Surtos de Doenças/estatística & dados numéricos , Genoma Viral/genética , Mapeamento Geográfico , Honduras/epidemiologia , Humanos , Metagenoma/genética , Epidemiologia Molecular , Mosquitos Vetores/virologia , Mutação , Vigilância em Saúde Pública , Porto Rico/epidemiologia , Estados Unidos/epidemiologia , Zika virus/classificação , Zika virus/patogenicidade , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologiaRESUMO
Acne vulgaris, a common dermatological condition that affects most adolescents and young adults, can indicate an underlying pathology if present prematurely in mid-childhood. Premature acne can be caused by premature adrenarche secondary to non-classical congenital adrenal hyperplasia (NC-CAH), a condition arising from 21-hydroxylase deficiency. This report describes a pair of monozygotic twin brothers with identical premature onset of acne, who were found to have an identical homozygous mutation in the promoter region of the CYP21A2 gene. While it is widely known that NCCAH is associated with genetic changes, the drive behind onset of adrenarche are widely unknown. As such, this report provokes thoughts on whether adrenarche could be influenced by adrenal genetic polymorphisms.
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Acne Vulgar , Hiperplasia Suprarrenal Congênita , Puberdade Precoce , Masculino , Adolescente , Adulto Jovem , Humanos , Criança , Gêmeos Monozigóticos , Hiperplasia Suprarrenal Congênita/genética , Acne Vulgar/genética , Acne Vulgar/complicações , Esteroide 21-Hidroxilase/genéticaRESUMO
BACKGROUND: In July 2020, a COVID-19 outbreak was recognised in the geriatric wards at a subacute campus of the Royal Melbourne Hospital affecting patients and staff. Patients were also admitted to this site after diagnosis in residential care. AIMS: To describe the early symptoms and the outcomes of COVID-19 in older adults. METHODS: Patients diagnosed with COVID-19 at the facility in July or August 2020 were identified and their medical records were examined to identify symptoms present before and after their diagnosis and to determine their outcomes. RESULTS: Overall, 106 patients were identified as having COVID-19, with median age of 84.3 years (range 41-104 years); 64 were diagnosed as hospital inpatients after a median length of stay of 49 days, 31 were transferred from residential aged care facilities with a known diagnosis and 11 were diagnosed after discharge. There were 95 patients included in an analysis of symptom type and timing onset. Overall, 61 (64.2%) were asymptomatic at the time of diagnosis of COVID-19, having been diagnosed through screening initiated on site. Of these, 88.6% developed symptoms of COVID-19 within 14 days. The most common initial symptom type was respiratory, but there was wide variation in presentation, including fever, gastrointestinal and neurological symptoms, many initially not recognised as being due to COVID-19. Of 104 patients, 32 died within 30 days of diagnosis. CONCLUSIONS: COVID-19 diagnosis is challenging due to the variance in symptoms. In the context of an outbreak, asymptomatic screening can identify affected patients early in the disease course.
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COVID-19 , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste para COVID-19 , Febre , Hospitalização , Humanos , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
INTRODUCTION: Despite palliative care being offered to paediatric cancer patients, it has limited utilisation and often excludes parental support. Therefore, this review aims to consolidate evidence regarding experiences and needs of parents of end-of-life palliative paediatric oncology patients. METHODS: Six electronic databases were searched as follows: CINAHL, The Cochrane Library, Embase, PubMed, Scopus and PsycINFO. Included studies were appraised using the Critical Appraisal Skills Programme Checklist. They were then analysed using a two-step approach comprising firstly meta-summaries followed by meta-synthesis for generating fresh insights to the topic. RESULTS: Thirteen studies were included. Three themes emerged as follows: (1) normalising the pain; (2) failure as a parent; and (3) importance of communication and social support. Parental experiences included moving on despite the pain and harbouring hopes for their children. However, parents felt immense guilt and a sense of failure in carrying out their parental roles. Effective communication with healthcare providers, availability of family support and religion were necessary to help them cope. CONCLUSIONS: Given the emotional challenges faced by parents, healthcare policies and practices should be revised to include parental support in paediatric palliative care services. Future healthcare communication trainings should consider parental need for sensitivity in communication, empathy and kindness from healthcare professionals.
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Necessidades e Demandas de Serviços de Saúde , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Cuidados Paliativos , Criança , Humanos , Neoplasias/terapia , Pais , Pesquisa QualitativaRESUMO
Active fluids, composed of individual self-propelled agents, can generate complex large-scale coherent flows. A particularly important laboratory realization of such an active fluid is a system composed of microtubules, aligned in a quasi-two-dimensional (2D) nematic phase and driven by adenosine-triphosphate-fueled kinesin motor proteins. This system exhibits robust chaotic advection and gives rise to a pronounced fractal structure in the nematic contours. We characterize such experimentally derived fractals using the power spectrum and discover that the power spectrum decays as k-ß for large wavenumbers k. The parameter ß is measured for several experimental realizations. Though ß is effectively constant in time, it does vary with experimental parameters, indicating differences in the scale-free behavior of the microtubule-based active nematic. Though the fractal patterns generated in this active system are reminiscent of passively advected dye in 2D chaotic flows, the underlying mechanism for fractal generation is more subtle. We provide a simple, physically inspired mathematical model of fractal generation in this system that relies on the material being locally compressible, though the total area of the material is conserved globally. The model also requires that large-scale density variations are injected into the material periodically. The model reproduces the power-spectrum decay k-ß seen in experiments. Linearizing the model of fractal generation about the equilibrium density, we derive an analytic relationship between ß and a single dimensionless quantity r, which characterizes the compressibility.
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Hyperphosphorylation of the neuronal tau protein contributes to Alzheimer's disease (AD) by promoting tau pathology and neuronal and cognitive deficits. In contrast, we have previously shown that site-specific tau phosphorylation can inhibit toxic signals induced by amyloid-ß (Aß) in mouse models. The post-synaptic mitogen-activated protein (MAP) kinase p38γ mediates this site-specific phosphorylation on tau at Threonine-205 (T205). Using a gene therapeutic approach, we draw on this neuroprotective mechanism to improve memory in two Aß-dependent mouse models of AD at stages when advanced memory deficits are present. Increasing activity of post-synaptic kinase p38γ that targets T205 in tau reduced memory deficits in symptomatic Aß-induced AD models. Reconstitution experiments with wildtype human tau or phosphorylation-deficient tauT205A showed that T205 modification is critical for downstream effects of p38γ that prevent memory impairment in APP-transgenic mice. Furthermore, genome editing of the T205 codon in the murine Mapt gene showed that this single side chain in endogenous tau critically modulates memory deficits in APP-transgenic Alzheimer's mice. Ablating the protective effect of p38γ activity by genetic p38γ deletion in a tau transgenic mouse model that expresses non-pathogenic tau rendered tau toxic and resulted in impaired memory function in the absence of human Aß. Thus, we propose that modulating neuronal p38γ activity serves as an intrinsic tau-dependent therapeutic approach to augment compromised cognition in advanced dementia.
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Doença de Alzheimer/metabolismo , Transtornos Cognitivos/metabolismo , Transtornos da Memória/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Transtornos Cognitivos/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Memória/fisiologia , Transtornos da Memória/genética , Camundongos , Camundongos TransgênicosRESUMO
Recently, we designed a group of peptides by sequential substitution of the naturally occurring α-amino acid throughout the Ang III peptide sequence with the corresponding ß-amino acid. ß-Amino acid substitution at the proline residue of Ang III (ß-Pro7-Ang III) resulted in a highly selective AT2R ligand, demonstrating remarkable selectivity for the AT2R in both binding and functional studies. To provide additional functional evidence for the suitability of ß-Pro7 Ang III as a novel AT2R agonist, we tested effects of acute systemic administration of ß-Pro7-Ang III on renal hemodynamic and excretory function in anesthetized normotensive male and female rats. We also compared the natriuretic effects of acute intrarenal administration of native Ang III and ß-Pro7-Ang III in the presence of systemic AT1R blockade in anesthetized female rats to allow for the differentiation of systemic versus direct intrarenal natriuretic actions of ß-Pro7-Ang III. In both male and female rats, acute systemic administration of ß-Pro7-Ang III elicited renal vasodilatation and natriuresis. Notably, greater renal vasodilatory effects were observed in female versus male rats at the highest dose of ß-Pro7-Ang III administered. Moreover, intra-renal administration of ß-Pro7-Ang III produced significant natriuretic effects in female rats and, like Ang III, evoked AT2R translocation to the apical plasma membrane in renal proximal tubular cells. Taken together, our findings support the use of ß-Pro7-Ang III as a novel AT2R agonist and experimental tool for exploring AT2R function and its potential as a therapeutic target. Furthermore, our findings provide further evidence of a sex-specific influence of AT2R stimulation on renal function.
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Angiotensina III/análogos & derivados , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Natriurese/efeitos dos fármacos , Receptor Tipo 2 de Angiotensina/agonistas , Circulação Renal/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Angiotensina III/farmacologia , Animais , Feminino , Rim/metabolismo , Masculino , Ratos Sprague-Dawley , Receptor Tipo 2 de Angiotensina/metabolismo , Fatores Sexuais , Transdução de SinaisRESUMO
Examining how animals direct social learning during skill acquisition under natural conditions, generates data for examining hypotheses regarding how transmission biases influence cultural change in animal populations. We studied a population of macaques on Koram Island, Thailand, and examined model-based biases during interactions by unskilled individuals with tool-using group members. We first compared the prevalence of interactions (watching, obtaining food, object exploration) and proximity to tool users during interactions, in developing individuals (infants, juveniles) versus mature non-learners (adolescents, adults), to provide evidence that developing individuals are actively seeking information about tool use from social partners. All infants and juveniles, but only 49% of mature individuals carried out interacted with tool users. Macaques predominantly obtained food by scrounging or stealing, suggesting maximizing scrounging opportunities motivates interactions with tool users. However, while interactions by adults was limited to obtaining food, young macaques and particularly infants also watched tool users and explored objects, indicating additional interest in tool use itself. We then ran matrix correlations to identify interaction biases, and what attributes of tool users influenced these. Biases correlated with social affiliation, but macaques also preferentially targeted tool users that potentially increase scrounging and learning opportunities. Results suggest that social structure may constrain social learning, but the motivation to bias interactions towards tool users to maximize feeding opportunities may also socially modulate learning by facilitating close proximity to better tool users, and further interest in tool-use actions and materials, especially during development.
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Atenção , Macaca fascicularis , Aprendizado Social , Animais , Viés , Feminino , Aprendizagem , MasculinoRESUMO
Hair is a useful source of biological information. For example, the bulb can be a source of high-quality genetic material, whereas the shaft can be useful for measuring heavy metals and some hormones, such as cortisol. The stable isotope composition of hair is another valuable source of biological information. Consequently, noninvasive methods of hair sampling have become important research tools. Several hair-trapping methods have been developed for use on mammals, but these are rarely deployed on primates in part because their travel patterns can be difficult to predict and because many species are averse to novel objects in their environments. Yet if a species has a natural propensity to envision, manipulate, and withdraw extractable food resources, then a baited receptacle lined with double-sided tape may prove successful as a hair trap. Recently, researchers demonstrated the success of such a contraption with tufted capuchins, a Neotropical monkey species with a high degree of somatosensory intelligence and a proclivity for extractive foraging. Here, we replicate this method in a population of tool-using long-tailed macaques (Macaca fascicularis). Our trials validate the effectiveness of the method, suggesting that it is suitable for long-tailed macaques and other extractive-foraging primates.
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Cabelo , Macaca fascicularis , Manejo de Espécimes/métodos , Animais , Ecologia/instrumentação , Ecologia/métodos , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Feminino , Masculino , Manejo de Espécimes/instrumentação , TailândiaRESUMO
OBJECTIVES: To evaluate the reliability of using the thenar eminence to determine steak doneness. DESIGN: Double-blinded, cross-sectional study. SETTING: Various home kitchens in Melbourne, Australia. PARTICIPANTS: Amateur/home cooks. MAIN OUTCOME MEASURES: The accuracy of the finger test (the tenseness of the thenar eminence in different hand positions) for determining how well a random beef steak has been cooked (rare v medium-rare v medium v well-done). We also examined whether participants improved with practice and whether the accuracy of the finger test was correlated with age, sex, cooking experience or self-rated steak-cooking ability. RESULTS: Twenty-six participants completed the study, and showed that they could accurately determine the doneness of a steak with the finger test better than chance (χ2[1, n = 156] = 9.88; P < 0.01). Their overall accuracy, however, was low (36%). There was no correlation between accuracy in application of the finger test with the other collected participant and steak variables. CONCLUSIONS: The finger test can be used by amateur cooks to determine beef steak doneness. However, the low overall accuracy of the test suggests that more invasive tests are to be recommended for determining steak doneness for its health benefits.
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Comportamento do Consumidor , Culinária/métodos , Produtos da Carne/normas , Inquéritos e Questionários , Adulto , Idoso , Animais , Austrália , Bovinos , Estudos Transversais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Paladar , Adulto JovemRESUMO
In 2013, the Singapore General Hospital (SGH) Campus initiated a shared electronic system where patient records and documentations were standardized and shared across institutions within the Campus. The project was initiated to enhance quality of health care, improve accessibility, and ensure integrated (as opposed to fragmented) care for best outcomes in our patients. In mitigating the risks of ICT, it was found that familiarity with guiding ethical principles, and ensuring adherence to regulatory and technical competencies in medical social work were important. The need to negotiate and maneuver in a large environment within the Campus to ensure proactive integrative process helped.
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Prestação Integrada de Cuidados de Saúde/normas , Registros Eletrônicos de Saúde/normas , Registro Médico Coordenado/normas , Assistência Centrada no Paciente/normas , Serviço Social/normas , Prestação Integrada de Cuidados de Saúde/métodos , Prestação Integrada de Cuidados de Saúde/organização & administração , Hospitais Gerais/métodos , Hospitais Gerais/organização & administração , Hospitais Gerais/normas , Humanos , Disseminação de Informação/métodos , Registro Médico Coordenado/métodos , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/organização & administração , Competência Profissional/normas , Gestão de Riscos , Singapura , Serviço Social/métodos , Serviço Social/organização & administraçãoRESUMO
Bile acids (BA) are synthesized in the human liver and undergo metabolism by host gut bacteria. In diseased states, gut microbial dysbiosis may lead to high primary unconjugated BA concentrations and significant perturbations to secondary BA. Hence, it is important to understand the microbial-mediated formation kinetics of secondary bile acids using physiologically relevant ex vivo human faecal microbiota models. Here, we optimized an ex vivo human faecal microbiota model to recapitulate the metabolic kinetics of primary unconjugated BA and applied it to investigate the formation kinetics of novel secondary BA metabolites and their sequential pathways. We demonstrated (1) first-order depletion of primary BA, cholic acid (CA) and chenodeoxycholic acid (CDCA), under non-saturable conditions and (2) saturable Michaelis-Menten kinetics for secondary BA metabolite formation with increasing substrate concentration. Notably, relatively lower Michaelis constants (Km) were associated with the formation of deoxycholic acid (DCA, 14.3 µM) and lithocholic acid (LCA, 140 µM) versus 3-oxo CA (>1000 µM), 7-keto DCA (443 µM) and 7-keto LCA (>1000 µM), thereby recapitulating clinically observed saturation of 7α-dehydroxylation relative to oxidation of primary BA. Congruently, metagenomics revealed higher relative abundance of functional genes related to the oxidation pathway as compared to the 7α-dehydroxylation pathway. In addition, we demonstrated gut microbial-mediated hyocholic acid (HCA) and hyodeoxycholic acid (HDCA) formation from CDCA. In conclusion, we optimized a physiologically relevant ex vivo human faecal microbiota model to investigate gut microbial-mediated metabolism of primary BA and present a novel gut microbial-catalysed two-step pathway from CDCA to HCA and, subsequently, HDCA.
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Ácidos e Sais Biliares , Fezes , Humanos , Fezes/microbiologia , Cinética , Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal , Ácido Quenodesoxicólico/metabolismo , Modelos Biológicos , MicrobiotaRESUMO
OBJECTIVE: To systematically evaluate the risk factors of depression and anxiety in older adults with cancer. METHOD: This PRISMA-adherent systematic review (PROSPERO CRD42022372747) involved a systematic database search for prospective and retrospective cohort studies. RESULTS: We included 33 cohort studies with 31 evaluating depression and seven evaluating anxiety. Systematic synthesis yielded various protective and exacerbating factors for depression and anxiety amongst older adults with cancer. These factors span a range of domains: (1) Cancer and associated treatment-related factors; (2) Medical, physical and functional factors; (3) Demographic factors and; (4) Social and lifestyle factors. At the individual-level, the most significant factors were the presence of chronic medical comorbidities, having pre-existing psychological symptoms, and poor baseline physical and functional status. Within the social unit, the degree of social support and presence of a partner were most significant. CONCLUSION: The deleterious impact comorbid psychological symptoms can have on older adults with cancer can be profound. In this review, we highlight a range of protective and exacerbating factors identified from cohort studies that may enable policymakers to tailor and individualise interventions to manage depression, anxiety and associated burden in this vulnerable population. The relative paucity of studies evaluating anxiety highlights an important research gap.
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Depressão , Neoplasias , Idoso , Humanos , Ansiedade/epidemiologia , Ansiedade/etiologia , Depressão/epidemiologia , Neoplasias/epidemiologia , Neoplasias/psicologia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Past research has established that adverse childhood experiences (ACE) are correlated with depression severity. The purpose of the present study was to examine how the number and nature of ACE exposure is associated with symptomatology and treatment outcomes in adult patients with treatment resistant depression (TRD). METHODS: Participants include 454 patients with a diagnosis of major depression or persistent depressive disorder. A one-way analysis of variance (ANOVA) was used to assess whether number of ACEs was associated with certain outcomes. Linear regression analyses were performed to model the associations between the five ACE subtypes (e.g., sexual abuse, physical violence, injury/illness, childhood grief, and parental upheaval) and symptom severity. Logistic regression analyses were then used to model the association between ACE subtypes and history of lifetime suicide attempt(s) and inpatient admission(s). RESULTS: Greater ACE exposure was associated with more severe symptomatology and treatment outcomes, but these differences were only seen between patients reporting no ACEs versus 3+ ACEs. Only the subtypes of violence and illness/injury were significant predictors of more severe symptomatology. The ACE subtypes of sexual trauma and violence uniquely predicted a lifetime suicide attempt(s), and only the subtype of sexual trauma predicted lifetime inpatient admission(s). LIMITATIONS: Limitations of the present study include retrospective adult assessments of childhood trauma, lack of data on ACE severity and timing, and the cross-sectional reporting of multiple study measures. CONCLUSIONS: Exposure to multiple ACE subtypes, particularly sexual and physical trauma, is associated with depression symptom severity, and history of suicidality, and inpatient admission(s).