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Staphylococcus aureus (S. aureus), a versatile Gram-positive bacterium, is implicated in a spectrum of infections, and its resilience is often attributed to biofilm formation. This study investigates the effect of sub-inhibitory doses of oxacillin on biofilm formation by methicillin-resistant S. aureus (MRSA). Specifically, it examines how these doses influence biofilms' development, maturation, and dispersal. The biofilm's zenith reached 48 h of incubation, followed by a noteworthy decline at 96 h and a distinctive clearance zone around biofilm-positive cells exposed to oxacillin. Scanning electron micrographs unveiled an intriguing active biofilm dispersal mechanism, a rarity in this species. Among 180 isolates, only three carrying the elusive icaD gene exhibited this phenomenon. icaD gene was absent in their counterparts. Notably, the icaD gene emerges as a distinctive marker, crucial in regulating biofilm dispersion and setting these isolates apart. The captivating interplay of oxacillin, biofilm dynamics, and genetic signatures disintegrate novel dimensions in understanding MRSA's adaptive strategies and underscores the importance of the icaD gene in engineering biofilm resilience.
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BACKGROUND: The normative blood pressure values in preterm infants still not well defined during postnatal transition. We aimed to create normative blood pressure (BP) reference values in preterm infants <29 weeks gestational age recorded hourly during the postnatal transition. METHODS: We included only data from hemodynamically stable newborns. Only BP values measured by umbilical arterial catheter (UAC) were included. The regression model showed that only gestational age and postnatal age in hours determine the BP. RESULTS: We included 206 out of 547 admitted preterm infants. The BP increases with increasing gestational ages and overtime during the postnatal transition. We constructed 5 BP centile values for each gestational group. BP histograms show that the BP most of the time fluctuated between the 5th and 75th centile values, particularity during day one of life. CONCLUSIONS: The BP trend values gradually increase in stable preterm infants during the postnatal transition, and preterm infants who do not follow this trend might require hemodynamics assessment. IMPACT: The normative blood pressure is increasing gradually during the first 3 days after birth and is different with gestational ages. This is first normative blood pressure centile values in stable preterm infant and based on invasive blood pressure monitoring. The data enable more accurate monitoring of hemodynamics in preterm infants during postnatal transition.
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Determinação da Pressão Arterial , Recém-Nascido Prematuro , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro/fisiologia , Pressão Sanguínea/fisiologia , Idade Gestacional , Pressão Arterial , Valores de ReferênciaRESUMO
BACKGROUND: Parental involvement in the decision-making processes about medical treatment for children with life-limiting conditions is recognised as good practice. Previous research highlighted factors affecting the decision-making process, but little is known about how parents experience their participation. AIM: To explore how parents experience their participation in the process of decision-making about treatment and future care for their children with life-limiting conditions. DESIGN: A systematically constructed review using narrative synthesis. The PRISMA guidelines were followed to report the findings. Databases Medline, EMBASE, SCOPUS, CINAHL and PsycINFO were searched up to December 2023. The study protocol was registered at PROSPERO (RN CRD42021215863). RESULTS: From the initial 2512 citations identified, 28 papers met the inclusion criteria and were included in the review. A wide range of medical decisions was identified; stopping general or life-sustaining treatment was most frequent. Narrative synthesis revealed six themes: (1) Temporal aspects affecting the experience with decision-making; (2) Losing control of the situation; (3) Transferring the power to decide to doctors; (4) To be a 'good' parent and protect the child; (5) The emotional state of parents and (6) Sources of support to alleviate the parental experience. CONCLUSIONS: Parental experiences with decision-making are complex and multifactorial. Parents' ability to effectively participate in the process is limited, as they are not empowered to do so and the circumstances in which the decisions are taking place are challenging. Healthcare professionals need to support parental involvement in an effective way instead of just formally asking them to participate.
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Tomada de Decisões , Pais , Criança , Humanos , Pais/psicologia , Narração , Pessoal de Saúde/psicologia , Tomada de Decisão ClínicaRESUMO
Alzheimer's disease involves many neurobiological alterations from molecular to macroscopic spatial scales, but we currently lack integrative, mechanistic brain models characterizing how factors across different biological scales interact to cause clinical deterioration in a way that is subject-specific or personalized. As important signalling molecules and mediators of many neurobiological interactions, neurotransmitter receptors are promising candidates for identifying molecular mechanisms and drug targets in Alzheimer's disease. We present a neurotransmitter receptor-enriched multifactorial brain model, which integrates spatial distribution patterns of 15 neurotransmitter receptors from post-mortem autoradiography with multiple in vivo neuroimaging modalities (tau, amyloid-ß and glucose PET, and structural, functional and arterial spin labelling MRI) in a personalized, generative, whole-brain formulation. In a heterogeneous aged population (n = 423, ADNI data), models with personalized receptor-neuroimaging interactions showed a significant improvement over neuroimaging-only models, explaining about 70% (±20%) of the variance in longitudinal changes to the six neuroimaging modalities. In Alzheimer's disease patients (n = 25, ADNI data), receptor-imaging interactions explained up to 39.7% (P < 0.003, family-wise error-rate-corrected) of inter-individual variability in cognitive deterioration, via an axis primarily affecting executive function. Notably, based on their contribution to the clinical severity in Alzheimer's disease, we found significant functional alterations to glutamatergic interactions affecting tau accumulation and neural activity dysfunction and GABAergic interactions concurrently affecting neural activity dysfunction, amyloid and tau distributions, as well as significant cholinergic receptor effects on tau accumulation. Overall, GABAergic alterations had the largest effect on cognitive impairment (particularly executive function) in our Alzheimer's disease cohort (n = 25). Furthermore, we demonstrate the clinical applicability of this approach by characterizing subjects based on individualized 'fingerprints' of receptor alterations. This study introduces the first robust, data-driven framework for integrating several neurotransmitter receptors, multimodal neuroimaging and clinical data in a flexible and interpretable brain model. It enables further understanding of the mechanistic neuropathological basis of neurodegenerative progression and heterogeneity, and constitutes a promising step towards implementing personalized, neurotransmitter-based treatments.
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Doença de Alzheimer , Encéfalo , Disfunção Cognitiva , Idoso , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons/métodos , Receptores de Neurotransmissores , Proteínas tau/metabolismoRESUMO
BACKGROUND: Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo. METHODS: Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects. RESULTS: Controlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO or WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis. CONCLUSIONS: The Padi2/Padi4 DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.
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Citrulina , Infertilidade , Proteína-Arginina Desiminase do Tipo 2/metabolismo , Desiminases de Arginina em Proteínas/metabolismo , Animais , Arginina , Modelos Animais de Doenças , Feminino , Gonadotropinas , Hidrolases/genética , Infertilidade/genética , Masculino , Camundongos , Camundongos Knockout , Proteína-Arginina Desiminase do Tipo 2/genética , Desiminases de Arginina em Proteínas/genética , TestosteronaRESUMO
The purpose of this study was to investigate the safety and effectiveness of the transfemoral transcaval (TFTC) liver biopsy technique in patients with hepatic masses with relative contraindications to percutaneous biopsy and/or mass location abutting the inferior vena cava. The medical records of 16 patients (56% men; age range, 21-88 years) who underwent TFTC biopsy of hepatic masses (ranging in diameter from 2.1 to 13.2 cm) from September 2015 to August 2021 were reviewed. Histopathologic diagnoses were made in 15 of 17 (88%) procedures. Two adverse events were noted: worsened preexisting hemobilia requiring embolization in 1 patient, and a decrease in hematocrit level in another patient, requiring only observation. In conclusion, this report showed that the TFTC technique is a relatively safe and effective method for sampling hepatic masses in select cases.
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Embolização Terapêutica , Fígado , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/efeitos adversos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Veia Cava Inferior , Adulto JovemRESUMO
Transcriptional activation by p53 provides powerful, organism-wide tumor suppression. We hypothesized that the local chromatin environment, including differential enhancer activities, contributes to various p53-dependent transcriptional activities in different cell types during stress-induced signaling. In this work, using ChIP-sequencing, immunoblotting, quantitative PCR, and computational analyses across various mammalian cell lines, we demonstrate that the p53-induced transcriptome varies by cell type, reflects cell type-specific activities, and is considerably broader than previously anticipated. We found that these molecular events are strongly influenced by p53's engagement with differentially active cell type-specific enhancers and promoters. We also observed that p53 activity depends on the p53 family member tumor protein p63 in epithelial cell types. Notably, we demonstrate that p63 is required for epithelial enhancer identity, including enhancers used by p53 during stress-dependent signaling. Loss of p63, but not p53, caused site-specific depletion of enhancer-associated chromatin modifications, suggesting that p63 functions as an enhancer maintenance factor in epithelial cells. Additionally, a subset of epithelial-specific enhancers depends on the activity of p63 providing a direct link between lineage determination and enhancer structure. These results suggest that a broad, cell-intrinsic mechanism controls p53-dependent cellular stress response through differential regulation of cis-regulatory elements.
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Elementos Facilitadores Genéticos , Fatores de Transcrição/metabolismo , Ativação Transcricional , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Cromatina/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Histonas/metabolismo , Humanos , Camundongos , Mutagênese , Regiões Promotoras Genéticas , Ligação Proteica , Fatores de Transcrição/química , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/química , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: Research is important internationally, impacting on health service provision and patient benefit. Journals play an important dissemination role, but there may be geographical bias, potentially affecting access to evidence. AIM: To understand if there is a relationship between the continent of journals and that of contributing authors. DESIGN: Bibliometric analysis of journal citation report data (June 2018). Odds ratio of association of an author being from region, region of journal publication, publication model and the number of papers. SETTING: Journals specialising in palliative care research, with an impact factor above the median impact factor for their most common indexing category. RESULTS: Five journals: three published in Europe (Palliative Medicine, BMJ Supportive and Palliative Care, and BMC Palliative Care) and two in North America (Journal of Pain and Symptom Management and Journal of Palliative Medicine). Authors were from 30+ countries, but mostly North America (54.18%) or Europe (27.94%). Preliminary sensitivity tests show that the odds of an author being from a North American institution increase 16.4 times (p < 0.01; 95% confidence interval: 12.9, 20.8) if the region of journal publication is North America. The odds of an author being from a European institution is 14.0 times (p < 0.01; 95% confidence interval: 10.9, 17.9) higher if the region of journal publication is Europe. CONCLUSION: Publishers, editors and authors are concentrated in North America or Europe. North American authors are more present in North American journals and European authors in European journals. This polarised approach, if replicated across readerships, may lead to research waste, duplication, and be sub-optimal for healthcare development.
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Bibliometria , Cuidados Paliativos , Publicações Periódicas como Assunto , Europa (Continente) , América do NorteRESUMO
BACKGROUND: Core outcome sets (COS) prioritise outcomes based on their importance to key stakeholders, reduce reporting bias and increase comparability across studies. The first phase of a COS study is to form a 'long-list' of outcomes. Key stakeholders then decide on their importance. COS reporting is described as suboptimal and this first phase is often under-reported. Our objective was to develop a 'long-list' of outcome items for non-pharmacological interventions for people with dementia living at home. METHODS: Three iterative phases were conducted. First, people living with dementia, care partners, health and social care professionals, policymakers and researchers (n = 55) took part in interviews or focus groups and were asked which outcomes were important. Second, existing dementia trials were identified from the ALOIS database. 248 of 1009 pharmacological studies met the inclusion criteria. Primary and secondary outcomes were extracted from a 50% random sample (n = 124) along with eight key reviews/qualitative papers and 38 policy documents. Third, extracted outcome items were translated onto an existing qualitative framework and mapped into domains. The research team removed areas of duplication and refined the 'long-list' in eight workshops. RESULTS: One hundred seventy outcome items were extracted from the qualitative data and literature. The 170 outcome items were consolidated to 54 in four domains (Self-Managing Dementia Symptoms, Quality of Life, Friendly Neighbourhood & Home, Independence). CONCLUSIONS: This paper presents a transparent blueprint for 'long-list' development. Though a useful resource in their own right, the 54 outcome items will be distilled further in a modified Delphi survey and consensus meeting to identify core outcomes.
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Serviços de Saúde Comunitária/métodos , Técnica Delphi , Demência/psicologia , Grupos Focais/métodos , Qualidade de Vida/psicologia , Seguridade Social/psicologia , Demência/diagnóstico , Demência/epidemiologia , Humanos , Características de Residência , Resultado do TratamentoRESUMO
BACKGROUND: Ethnic minorities report poorer evaluations of primary health care compared to White British patients. Emerging evidence suggests that when a doctor and patient share ethnicity and/or language this is associated with more positive reports of patient experience. Whether this is true for adults in English general practices remains to be explored. METHODS: We analysed data from the 2010/2011 English General Practice Patient Survey, which were linked to data from the NHS Choices website to identify languages which were available at the practice. Our analysis was restricted to single-handed practices and included 190,582 patients across 1,068 practices. Including only single-handed practices enabled us to attribute, more accurately, reported patient experience to the languages that were listed as being available. We also carried out sensitivity analyses in multi-doctor practices. We created a composite score on a 0-100 scale from seven survey items assessing doctor-patient communication. Mixed-effect linear regression models were used to examine how differences in reported experience of doctor communication between patients of different self-reported ethnicities varied according to whether a South Asian language concordant with their ethnicity was available in their practice. Models were adjusted for patient characteristics and a random effect for practice. RESULTS: Availability of a concordant language had the largest effect on communication ratings for Bangladeshis and the least for Indian respondents (p < 0.01). Bangladeshi, Pakistani and Indian respondents on average reported poorer communication than White British respondents [-2.9 (95%CI -4.2, -1.6), -1.9 (95%CI -2.6, -1.2) and -1.9 (95%CI -2.5, -1.4), respectively]. However, in practices where a concordant language was offered, the experience reported by Pakistani patients was not substantially worse than that reported by White British patients (-0.2, 95%CI -1.5,+1.0), and in the case of Bangladeshi patients was potentially much better (+4.5, 95%CI -1.0,+10.1). This contrasts with a worse experience reported among Bangladeshi (-3.3, 95%CI -4.6, -2.0) and Pakistani (-2.7, 95%CI -3.6, -1.9) respondents when a concordant language was not offered. CONCLUSIONS: Substantial differences in reported patient experience exist between ethnic groups. Our results suggest that patient experience among Bangladeshis and Pakistanis is improved where the practice offers a language that is concordant with the patient's ethnicity.
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Barreiras de Comunicação , Idioma , Prontuários Médicos/normas , Relações Médico-Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sudeste Asiático , Bangladesh , Etnicidade , Medicina de Família e Comunidade/normas , Feminino , Disparidades em Assistência à Saúde/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão , Atenção Primária à Saúde/normas , Reino Unido/etnologiaRESUMO
People with serious mental illness have higher morbidity and mortality rates compared with the general population. Mental health nurses are in an optimal position to address physical healthcare needs and inequalities experienced by this group. Research evidence suggests that mental health nurses may lack appropriate skills and confidence. The training needs of mental health nurses in physical health care of patients with serious mental illness and the perceived effectiveness of training that is provided to mental health nurses are explored in this review. A narrative synthesis approach (PROSPERO protocol registration ID=CRD42021230923) involved searching five electronic databases (PsycInfo, Cinahl, Embase, Medline and Web of Science) from 1990 to 2021. Study quality was assessed, and analysis and synthesis were initially deductively guided by a theoretical framework of training effectiveness prior to inductive data analysis. Eleven studies met the inclusion criteria. For studies examining perceived effectiveness of training, four themes were derived from the theoretical framework (individual trainee characteristics, work environment, learning outcomes, transfer of training to job) and further theme (service user factor) generated inductively. For studies examining training needs, three themes were derived inductively (knowledge and skills requirements, modality of training, service and healthcare factors). The study highlights the need for ongoing learning to improve practice. It also provides another perspective in terms of understanding the influence of service user factors (motivation and mental state) in designing and implementing of future training in mental health settings.
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Saúde Mental , Enfermagem Psiquiátrica , Humanos , Atenção à Saúde , Aprendizagem , Competência ClínicaRESUMO
Context: Non-alcoholic fatty liver disease (NAFLD) is an escalating global health issue. Early detection and precise diagnosis are imperative for effective management. Aim: To evaluate the sociodemographic and clinical attributes of study participants concerning their ultrasound grading with FibroScan and FLI values. Settings and Design: A cross-sectional study was carried out among patients visiting gastroenterology clinics at a tertiary care hospital situated in Karachi, Pakistan. Methods and Material: We included participants after written informed consent underwent an extensive array of laboratory assessments, encompassing liver function tests, lipid profile, fasting blood sugar analysis, hepatitis B and C screening, and abdominal ultrasound, while those with positive hepatitis B or C markers, documented alcohol use, or those who declined to offer informed consent were excluded from the study. Statistical Analysis: Data were analyzed using SPSS version 26. Results: Around 225 patients were studied with a median age of 42 years (IQR = 34-50 years). Metabolic syndrome (MetS) was present in 61.8%. Steatosis was not found among 4.9% of patients, whereas severe steatosis was seen among 51.1% of patients. Significant variations in BMI, WC, GGT, and TG levels were identified when comparing FLI scores. The same was observed for the frequency of MetS as FLI scores increased. The agreement between FLI and ultrasound observations was found to be slight (k = 0.077, P = 0.027). On the multivariable regression model, having diabetes, elevated serum glutamate pyruvate transaminase levels and mild disease on ultrasound were associated with increased odds of severe steatosis. Conclusion: FLI is a good predictor of frequency of MetS and NAFLD and correlates well with increasing steatosis score (CAP) on FibroScan which can be utilized for early detection of NAFLD in primary care.
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Background In applied sciences, statistical models are pivotal for uncovering relationships in complex datasets. The applied linear model establishes associative links between variables. While qualitative predictors are essential, their integration into linear models poses challenges. The dummy variable approach transforms qualitative variables into binary ones for regression analysis. Multilayer Feedforward Neural Networks (MLFFNN) offer validation of regression models, and fuzzy regression offers alternative methods to address the ambiguity of qualitative predictors. This study aims to enhance the integration of qualitative predictors in applied linear models through statistical methodologies. Material and methods This study design involves the transformation of qualitative predictors into dummy variables, the bootstrapping technique to improve the parameter estimates, the Multilayer Feedforward Neural Network, and fuzzy regression. This study uses the programming language R as an analysis tool. Results The multiple linear regression model demonstrates precision and a significant fit (p<0.05), with an R-squared value of 0.95 and mean square error (MSE) of 9.97. Comparing actual and predicted values, fuzzy regression exhibits superior predictability over linear regression. The MLFFNN yields a reduced MSE net of 0.362, indicating enhanced prediction precision for derived models. Conclusion This study presents a precise methodology for integrating qualitative variables into linear regression, supported by the combination of specific statistical methodologies to enhance predictive modeling. By integrating fuzzy linear regression, MLFF neural networks, and bootstrapping, the proposed technique emerges as the most effective approach for modeling and prediction. These findings underscore the efficacy of this method in seamlessly integrating qualitative variables into linear models, ultimately enhancing accuracy and prediction capabilities.
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Antimicrobial Stewardship Programs (ASP) were introduced in healthcare as a public health priority to promote appropriate prescribing of antimicrobials, to reduce adverse events related to antimicrobials, as well as to control the escalating challenges of antimicrobial resistance. To deliver aimed outcome objectives, ASPs involve multiple connected implementation process measures. A systematic review was conducted to evaluate both concepts of ASPs. Guided by PRISMA frames, published systematic reviews (SR) focusing on ASPs restricted to secondary and tertiary healthcare were evaluated over the past 10 years involving all age groups. Out of 265 identified SR studies, 63 met the inclusion criteria. The majority were conducted in Europe and North America, with limited studies from other regions. In the reviewed studies, all age groups were examined, although they were conducted mainly on adults when compared to children and infants. Both process and outcomes measures of ASPs were examined equally and simultaneously through 25 different concepts, dominated by efficacy, antimicrobial resistance, and economic impact, while information technology as well as role of pharmacy and behavioral factors were equally examined. The main broad conclusions from the review were that, across the globe, ASPs demonstrated effectiveness, proved efficacy, and confirmed efficiency, while focused evaluation advocated that developed countries should target medium- and small-sized hospitals while developing countries should continue rolling ASPs across healthcare facilities. Additionally, the future of ASPs should focus on embracing evolving information technology to bridge the gaps in knowledge, skills, and attitude, as well as to enhance appropriate decision making.
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Tuberculosis (TB) is the second leading cause of mortality after COVID-19, with a global death toll of 1.6 million in 2021. The escalating situation of drug-resistant forms of TB has threatened the current TB management strategies. New therapeutics with novel mechanisms of action are urgently required to address the current global TB crisis. The essential mycobacterial primase DnaG with no structural homology to homo sapiens presents itself as a good candidate for drug targeting. In the present study, Mitoxantrone and Vapreotide, two FDA-approved drugs, were identified as potential anti-mycobacterial agents. Both Mitoxantrone and Vapreotide exhibit a strong Minimum Inhibitory Concentration (MIC) of ≤25µg/ml against both the virulent (M.tb-H37Rv) and avirulent (M.tb-H37Ra) strains of M.tb. Extending the validations further revealed the inhibitory potential drugs in exâ vivo conditions. Leveraging the computational high-throughput multi-level docking procedures from the pool of ~2700 FDA-approved compounds, Mitoxantrone and Vapreotide were screened out as potential inhibitors of DnaG. Extensive 200â ns long all-atoms molecular dynamic simulation of DnaGDrugs complexes revealed that both drugs bind strongly and stabilize the DnaG during simulations. Reduced solvent exposure and confined motions of the active centre of DnaG upon complexation with drugs indicated that both drugs led to the closure of the active site of DnaG. From this study's findings, we propose Mitoxantrone and Vapreotide as potential anti-mycobacterial agents, with their novel mechanism of action against mycobacterial DnaG.
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Mycobacterium tuberculosis , Somatostatina/análogos & derivados , Humanos , Antituberculosos/farmacologia , DNA Primase/química , DNA Primase/metabolismo , Mitoxantrona/farmacologiaRESUMO
Background and Aims: Music-based interventions have been found to benefit people living with dementia and have positive impacts on cognition and well-being. Most people with dementia live in the community and compared to people with dementia in residential care often have less access to music-based interventions. There are many forms of music interventions and singing has shown particular promise; in the realm of music interventions. It is important to determine what aspects of music interventions yield the most benefits for people with dementia. This review aimed to synthesise evidence on the impacts of singing interventions on quality of life, mood and neuropsychiatric symptoms for community-dwelling people with dementia. Methods: We systematically searched three electronic databases (PsycINFO, MEDLINE and Web of Science) for studies reporting on singing interventions with community-dwelling people with dementia. Studies were eligible for inclusion if they reported on a singing intervention with people living with dementia that included an outcome measure of quality of life, mood or agitation. Fourteen publications were identified and included in this review, with a total of n = 361 people with dementia. Results: Despite some inconsistencies across the literature, evidence suggests that singing interventions led to an improvement in mood and a reduction in agitation levels in people living with dementia. There was no strong evidence to suggest that singing interventions led to significant improvements in quality of life. Conclusions: This review highlights the potential of singing interventions as an effective psychosocial intervention for community-dwelling people with dementia. For key developments in this area, we urge that future studies include a control group where possible which will allow for more robust examinations of singing interventions and allow intervention effects to be distinguished from general deterioration in dementia symptoms over time.
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The increasing prevalence of drug-resistant Tuberculosis (TB) is imposing extreme difficulties in controlling the TB infection rate globally, making treatment critically challenging. To combat the prevailing situation, it is crucial to explore new anti-TB drugs with a novel mechanism of action and high efficacy. The Mycobacterium tuberculosis (M.tb)DciA is an essential protein involved in bacterial replication and regulates its growth. DciA interacts with DNA and provides critical help in binding other replication machinery proteins to the DNA. Moreover, the lack of any structural homology of M.tb DciA with human proteins makes it an appropriate target for drug development. In this study, FDA-approved drugs were virtually screened against M.tb DciA to identify potential inhibitors. Four drugs namely Lanreotide, Risedronate, Triflusal, and Zoledronic acid showed higher molecular docking scores. Further, molecular dynamics simulations analysis of DciA-drugs complexes reported stable interaction, more compactness, and reduced atomic motion. The anti-TB activity of drugs was further evaluated under in vitro and ex vivo conditions where Triflusal was observed to have the best possible activity with the MIC of 25 µg/ml. Our findings present novel DciA inhibitors and anti-TB activity of Triflusal. Further investigations on the use of Triflusal may lead to the discovery of a new anti-TB drug.
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Mycobacterium tuberculosis , Salicilatos , Tuberculose , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Simulação de Acoplamento Molecular , Tuberculose/microbiologia , DNA/uso terapêuticoRESUMO
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.
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Síndrome de Fadiga Crônica , Humanos , Síndrome de Fadiga Crônica/genética , Síndrome de Fadiga Crônica/diagnóstico , Exercício Físico/fisiologia , Perfilação da Expressão Gênica , Transcriptoma , MonócitosRESUMO
The devastating impact of Tuberculosis (TB) has been a menace to mankind for decades. The World Health Organization (WHO) End TB Strategy aims to reduce TB mortality up to 95% and 90% of overall TB cases worldwide, by 2035. This incessant urge will be achieved with a breakthrough in either a new TB vaccine or novel drugs with higher efficacy. However, the development of novel drugs is a laborious process involving a timeline of almost 20-30 years with huge expenditure; on the other hand, repurposing previously approved drugs is a viable technique for overcoming current bottlenecks in the identification of new anti-TB agents. The present comprehensive review discusses the progress of almost all the repurposed drugs that have been identified to the present day (â¼100) and are in the development or clinical testing phase against TB. We have also emphasized the efficacy of repurposed drugs in combination with already available frontline anti-TB medications along with the scope of future investigations. This study would provide the researchers a detailed overview of nearly all identified anti-TB repurposed drugs and may assist them in selecting the lead compounds for further in vivo/clinical research.
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The reconstruction of craniomaxillofacial deformities, especially zygomatic bone repair, can be exigent due to the complex anatomical structure and the sensitivity of the crucial organs involved. The need to reconstruct the zygomatic bone in the most precise way is of crucial importance for enhancing the patient outcomes and health care-related quality of life (HRQL). Autogenous bone grafts, despite being the gold standard, do not match bone forms, have limited donor sites and bone volume, and can induce substantial surgical site morbidity, which may lead to adverse outcomes. The goal of this study is to provide an integrated approach that includes various processes, from patient scanning to implant manufacture, for the restoration of zygomatic bone abnormalities utilizing Polyetheretherketone (PEEK) material, while retaining adequate aesthetic and facial symmetry. This study takes an integrated approach, including computer-aided implant design using the mirror reconstruction technique, investigating the biomechanical behavior of the implant under loading conditions, and carrying out a fitting accuracy analysis of the PEEK implant fabricated using state-of-the-art additive manufacturing technology. The findings of the biomechanical analysis results reveal the largest stress of approximately 0.89 MPa, which is relatively low in contrast to the material's yield strength and tensile strength. A high degree of sturdiness in the implant design is provided by the maximum value of strain and deformation, which is also relatively low at roughly 2.2 × 10-4 and 14 µm. This emphasizes the implant's capability for load resistance and safety under heavy loading. The 3D-printed PEEK implant observed a maximum deviation of 0.4810 mm in the outside direction, suggesting that the aesthetic result or the fitting precision is adequate. The 3D-printed PEEK implant has the potential to supplant the zygoma bone in cases of severe zygomatic reconstructive deformities, while improving the fit, stability, and strength of the implant.