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1.
J Exp Child Psychol ; 249: 106072, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39316885

RESUMO

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. As these outcomes are related to alterations in developmental processes, growing evidence suggests that deficits in executive functions-inhibitory control in particular-may in part explain this relationship. However, literature examining the development of inhibitory control has been based on children in higher-resource environments, and little is known how low-resource settings might exacerbate the link between inhibitory control and health outcomes. In this context, we collected functional magnetic resonance imaging data during a Go/No-Go inhibitory control task and PA variables for 68 children aged 5 to 7 years living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the children's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyri, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

2.
Heliyon ; 10(18): e37646, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39309815

RESUMO

Introduction: Access to affordable and improved Water, Sanitation, and Hygiene (WASH) facilities is essential for people's daily lives, and it is the primary goal of Sustainable Development Goal 6 (SDG-6). However, achieving this goal is a significant challenge for many countries, including India. The aim of this study is to assess the progress made towards achieving SDG-6 targets in Indian districts, states, and Union Territories (UTs) and to identify clusters by measuring spatial inequality of WASH coverage in India. Aim and objective: The primary objective of this study is to measure the progress made towards achieving the SDG-6 targets for WASH facilities in Indian districts, states, and UTs. To fulfill this objective, the study used the household data of the National Family Health Survey-5 (NFHS-5) conducted from 2019 to 21. Data and methods: The study used the household data of NFHS-5, which is a nationally representative survey that provides information on household and individual-level characteristics related to health and nutrition. The study identified the variables associated with WASH and created a composite index to measure WASH coverage separately and combined. The study used Gini coefficient to show WASH inequality, and Moran's statistics were used to show spatial dependency. Result: The study found that the inequality of improved water coverage sources in Indian districts was high. Western and northeastern districts need to catch up in terms of achieving the SDG-6 targets. The value of the Gini coefficient (0.29) indicates that inequality in sanitation coverage is also high. All states have reached close to SDG-6 achievement in hygiene indicators. Goa, Sikkim, Andaman & Nicobar Islands, and Lakshadweep are close to the overall WASH coverage achievements of SDG-6. However, Jharkhand, Orissa, Tripura, Assam, and Rajasthan are behind in meeting the goal of SDG-6. Conclusion: The study suggests that more government initiatives and investments are needed to increase the availability, accessibility, and affordability of WASH facilities to improve WASH conditions in western and northeastern Indian districts. The localization or bottom-up approach by giving responsibility to rural and urban local bodies can also help enforce the achievement of SDG-6. The findings of this study can be used to guide policymakers in developing targeted interventions to improve WASH conditions and reduce inequality in India.

3.
Nanomedicine (Lond) ; : 1-21, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39143915

RESUMO

Lung cancer is a leading cause of global cancer mortality, often treated with chemotherapeutic agents. However, conventional approaches such as oral or intravenous administration of drugs yield low bioavailability and adverse effects. Nanotechnology has unlocked new gateways for delivering medicine to their target sites. Lipid-polymer hybrid nanoparticles (LPHNPs) are one of the nano-scaled delivery platforms that have been studied to exploit advantages of liposomes and polymers, enhancing stability, drug loading, biocompatibility and controlled release. Pulmonary administration of drug-loaded LPHNPs enables direct lung deposition, rapid onset of action and heightened efficacy at low doses of drugs. In this manuscript, we will review the potential of LPHNPs in management of lung cancer through pulmonary administration.


[Box: see text].

4.
Sci Rep ; 14(1): 20114, 2024 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-39209872

RESUMO

Ensuring proper menstrual hygiene management remains a significant challenge for young women in India. The term "exclusive use of hygienic period products during menstruation" refers to relying solely on period products like sanitary pads, tampons, or menstrual cups. Poor menstrual hygiene practices not only increase the risk of reproductive tract infections but also lead to various negative health outcomes, including discomfort and potential complications. This study explores factors associated with the exclusive use of period products during menstruation aged 15-24, investigates geographic disparities, examines rural-urban gaps, and assesses inequality in India. Utilizing data from the fifth National Family Health Survey (NFHS-5), responses from 2,41,180 women aged 15 to 24 were analysed using logistic regression and multivariate decomposition analyses to explore socioeconomic predictors. Moran's I statistics also assessed spatial dependency, while Lorenz curves and Gini coefficients measured inequality. Quintile and LISA maps visualized regional disparities. The study found that 76.15% of women in India reported exclusive use of hygienic period products during menstruation. Rural areas reported a lower percentage of exclusive use of hygienic period products (72.32%) during menstruation compared to urban areas (89.37%). Key factors associated with the exclusive use of hygienic period products among 15-24-year-old women in India include age, education, place of residence, wealth, access to media, and healthcare discussions. Geographically, central districts exhibited the lowest coverage (< 65%), while the Southern region reported the highest (> 85). The GINI coefficient of 0.39 highlighted moderate inequality in distribution. Decomposition analysis revealed that household wealth contributed 49.25% to rural-urban differences, followed by education (13.41%), media access (7.97%), and region (4.97%). This study highlights significant regional disparities and low utilization of hygienic period products among young women in India, particularly in central districts. Policymakers should prioritize interventions targeting these regions, addressing socio-economic disparities. Strategies to promote education, improve media access, and enhance household wealth can facilitate menstrual hygiene adoption. Initiatives to reduce sanitary napkin costs and increase accessibility, particularly in rural areas, are crucial to mitigating geographical disparities nationwide.


Assuntos
Menstruação , População Rural , População Urbana , Humanos , Feminino , Índia , Adolescente , Adulto Jovem , Produtos de Higiene Menstrual , Fatores Socioeconômicos , Adulto , Higiene
5.
Pharmaceutics ; 16(8)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39204406

RESUMO

Ivermectin (IVM), a drug originally used for treating parasitic infections, is being explored for its potential applications in cancer therapy. Despite the promising anti-cancer effects of IVM, its low water solubility limits its bioavailability and, consequently, its biological efficacy as an oral formulation. To overcome this challenge, our research focused on developing IVM-loaded lipid polymer hybrid nanoparticles (LPHNPs) designed for potential pulmonary administration. IVM-loaded LPHNPs were developed using the emulsion solvent evaporation method and characterized in terms of particle size, morphology, entrapment efficiency, and release pattern. Solid phase characterization was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated spherical-shaped particles between 302 and 350 nm. Developed formulations showed an entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within 96 h. Carr's index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper flowability of the fabricated LPHNPs. The in vitro aerosolization analysis revealed fine particle fractions (FPFs) ranging from 18.53% to 24.77%. This in vitro study demonstrates the potential of IVM-loaded LPHNPs as a delivery vehicle through the pulmonary route.

6.
BMJ Open ; 14(7): e074902, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38991683

RESUMO

OBJECTIVES: To classify older adults into clusters based on accumulating long-term conditions (LTC) as trajectories, characterise clusters and quantify their associations with all-cause mortality. DESIGN: We conducted a longitudinal study using the English Longitudinal Study of Ageing over 9 years (n=15 091 aged 50 years and older). Group-based trajectory modelling was used to classify people into clusters based on accumulating LTC over time. Derived clusters were used to quantify the associations between trajectory memberships, sociodemographic characteristics and all-cause mortality by conducting regression models. RESULTS: Five distinct clusters of accumulating LTC trajectories were identified and characterised as: 'no LTC' (18.57%), 'single LTC' (31.21%), 'evolving multimorbidity' (25.82%), 'moderate multimorbidity' (17.12%) and 'high multimorbidity' (7.27%). Increasing age was consistently associated with a larger number of LTCs. Ethnic minorities (adjusted OR=2.04; 95% CI 1.40 to 3.00) were associated with the 'high multimorbidity' cluster. Higher education and paid employment were associated with a lower likelihood of progression over time towards an increased number of LTCs. All the clusters had higher all-cause mortality than the 'no LTC' cluster. CONCLUSIONS: The development of multimorbidity in the number of conditions over time follows distinct trajectories. These are determined by non-modifiable (age, ethnicity) and modifiable factors (education and employment). Stratifying risk through clustering will enable practitioners to identify older adults with a higher likelihood of worsening LTC over time to tailor effective interventions to prevent mortality.


Assuntos
Multimorbidade , Humanos , Estudos Longitudinais , Idoso , Feminino , Masculino , Pessoa de Meia-Idade , Inglaterra/epidemiologia , Doença Crônica/mortalidade , Doença Crônica/epidemiologia , Idoso de 80 Anos ou mais , Envelhecimento , Mortalidade/tendências , Análise por Conglomerados , Fatores de Risco
8.
Daru ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861247

RESUMO

OBJECTIVES: The efficient delivery of drugs from dry powder inhaler (DPI) formulations is associated with the complex interaction between the device design, drug formulations, and patient's inspiratory forces. Several challenges such as limited emitted dose of drugs from the formulation, low and variable deposition of drugs into the deep lungs, are to be resolved for obtaining the efficiency in drug delivery from DPI formulations. The objective of this study is to review the current challenges of inhaled drug delivery technology and find a way to enhance the efficiency of drug delivery from DPIs. METHODS/EVIDENCE ACQUISITION: Using appropriate keywords and phrases as search terms, evidence was collected from the published articles following SciFinder, Web of Science, PubMed and Google Scholar databases. RESULTS: Successful lung drug delivery from DPIs is very challenging due to the complex anatomy of the lungs and requires an integrated strategy for particle technology, formulation design, device design, and patient inhalation force. New DPIs are still being developed with limited performance and future device design employs computer simulation and engineering technology to overcome the ongoing challenges. Many issues of drug formulation challenges and particle technology are concerning factors associated with drug dispersion from the DPIs into deep lungs. CONCLUSION: This review article addressed the appropriate design of DPI devices and drug formulations aligned with the patient's inhalation maneuver for efficient delivery of drugs from DPI formulations.

9.
Int J Infect Dis ; 146: 107155, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38942167

RESUMO

OBJECTIVE: To identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD). METHODS: Using national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions. RESULTS: Hospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively. INTERPRETATION: Prior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions. FUNDING: NIHR. HDR UK.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Fármacos Cardiovasculares , Doenças Cardiovasculares , Hospitalização , SARS-CoV-2 , Vacinação , Humanos , Hospitalização/estatística & dados numéricos , COVID-19/mortalidade , COVID-19/prevenção & controle , COVID-19/epidemiologia , Idoso , Masculino , Pessoa de Meia-Idade , Feminino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Adulto , Vacinas contra COVID-19/administração & dosagem , Inglaterra/epidemiologia , Idoso de 80 Anos ou mais , Adolescente , Adulto Jovem , Fármacos Cardiovasculares/uso terapêutico , Pré-Escolar , Criança , Lactente , Influenza Humana/mortalidade , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , Recém-Nascido , Vacinas contra Influenza/administração & dosagem , Fatores de Risco
10.
Pharmaceutics ; 16(5)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38794310

RESUMO

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining Pseudomonas phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical P. aeruginosa strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives.

11.
Respir Med ; 227: 107661, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729529

RESUMO

Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus, infections are strongly associated with pulmonary exacerbations and require frequent hospital admissions, usually following failed management in the community. These bacteria are difficult to treat as they demonstrate multiple adaptational mechanisms including biofilm formation to resist antibiotic threats. Currently, many patients with the genetic disease cystic fibrosis (CF), non-CF bronchiectasis (NCFB) and chronic obstructive pulmonary disease (COPD) experience exacerbations of their lung disease and require high doses of systemically administered antibiotics to achieve meaningful clinical effects, but even with high systemic doses penetration of antibiotic into the site of infection within the lung is suboptimal. Pulmonary drug delivery technology that reliably deliver antibacterials directly into the infected cells of the lungs and penetrate bacterial biofilms to provide therapeutic doses with a greatly reduced risk of systemic adverse effects. Inhaled liposomal-packaged antibiotic with biofilm-dissolving drugs offer the opportunity for targeted, and highly effective antibacterial therapeutics in the lungs. Although the challenges with development of some inhaled antibiotics and their clinicals trials have been studied; however, only few inhaled products are available on market. This review addresses the current treatment challenges of antibiotic-resistant bacteria in the lung with some clinical outcomes and provides future directions with innovative ideas on new inhaled formulations and delivery technology that promise enhanced killing of antibiotic-resistant biofilm-dwelling bacteria.


Assuntos
Antibacterianos , Biofilmes , Sistemas de Liberação de Medicamentos , Infecções Respiratórias , Humanos , Biofilmes/efeitos dos fármacos , Administração por Inalação , Antibacterianos/administração & dosagem , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Farmacorresistência Bacteriana , Streptococcus pneumoniae/efeitos dos fármacos , Lipossomos , Bronquiectasia/tratamento farmacológico , Bronquiectasia/microbiologia , Haemophilus influenzae/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Fibrose Cística/microbiologia , Fibrose Cística/tratamento farmacológico , Fibrose Cística/complicações
12.
J Antimicrob Chemother ; 79(6): 1441-1449, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38708643

RESUMO

INTRODUCTION: FebriDx® is a CE-marked, single-use point-of-care test with markers for bacterial [C-reactive protein (CRP)] and viral [myxovirus resistance protein A (MxA)] infection, using finger-prick blood samples. Results are available after 10-12 min. We explored the usability and potential impact of FebriDx® in reducing antibiotic prescriptions for lower respiratory tract infection (LRTI) in primary care, and the feasibility of conducting a randomized controlled trial (RCT). METHODS: Patients (aged ≥1 year) with LRTI deemed likely to receive antibiotic prescription were recruited at nine general practices and underwent FebriDx® testing. Data collection included FebriDx® results, antibiotic prescribing plan (before and after testing) and re-consultation rates. Staff completed System Usability Scale questionnaires. RESULTS: From 31 January 2023 to 9 June 2023, 162 participants participated (median age 57 years), with a median symptom duration of 7 days (IQR 5-14). A valid FebriDx® result was obtained in 97% (157/162). Of 155 patients with available results, 103 (66%) had no detectable CRP or MxA, 28 (18%) had CRP only, 5 (3%) had MxA only, and 19 (12%) had both CRP and MxA. The clinicians' stated management plan was to prescribe antibiotics for 86% (134/155) before testing and 45% (69/155) after testing, meaning a 41% (95% CI: 31%, 51%) difference after testing, without evidence of increased re-consultation rates. Ease-of-use questionnaires showed 'good' user-friendliness. CONCLUSIONS: Use of FebriDx® to guide antibiotic prescribing for LRTI in primary care was associated with a substantial reduction in prescribing intentions. These results support a fully powered RCT to confirm its impact and safety.


Assuntos
Antibacterianos , Estudos de Viabilidade , Testes Imediatos , Atenção Primária à Saúde , Infecções Respiratórias , Humanos , Infecções Respiratórias/tratamento farmacológico , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Idoso , Adulto Jovem , Proteína C-Reativa/análise , Adolescente , Criança , Biomarcadores/sangue
13.
Sci Rep ; 14(1): 10289, 2024 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704437

RESUMO

Myocarditis is considered a fatal form of foot-and-mouth disease (FMD) in suckling calves. In the present study, a total of 17 calves under 4 months of age and suspected clinically for FMD were examined for clinical lesions, respiratory rate, heart rate, and heart rhythm. Lesion samples, saliva, nasal swabs, and whole blood were collected from suspected calves and subjected to Sandwich ELISA and reverse transcription multiplex polymerase chain reaction (RT-mPCR) for detection and serotyping of FMD virus (FMDV). The samples were found to be positive for FMDV serotype "O". Myocarditis was suspected in 6 calves based on tachypnoea, tachycardia, and gallop rhythm. Serum aspartate aminotransferase (AST), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH), and cardiac troponins (cTnI) were measured. Mean serum AST, cTn-I and LDH were significantly higher (P < 0.001) in < 2 months old FMD-infected calves showing clinical signs suggestive of myocarditis (264.833 ± 4.16; 11.650 ± 0.34 and 1213.33 ± 29.06) than those without myocarditis (< 2 months old: 110.00 ± 0.00, 0.06 ± 0.00, 1050.00 ± 0.00; > 2 months < 4 months: 83.00 ± 3.00, 0.05 ± 0.02, 1159.00 ± 27.63) and healthy control groups (< 2 months old: 67.50 ± 3.10, 0.047 ± 0.01, 1120.00 ± 31.62; > 2 months < 4 months: 72.83 ± 2.09, 0.47 ± 0.00, 1160.00 ± 18.44). However, mean serum CK-MB did not differ significantly amongst the groups. Four calves under 2 months old died and a necropsy revealed the presence of a pathognomic gross lesion of the myocardial form of FMD known as "tigroid heart". Histopathology confirmed myocarditis. This study also reports the relevance of clinical and histopathological findings and biochemical markers in diagnosing FMD-related myocarditis in suckling calves.


Assuntos
Febre Aftosa , Miocardite , Animais , Bovinos , Miocardite/veterinária , Miocardite/virologia , Miocardite/patologia , Febre Aftosa/virologia , Febre Aftosa/patologia , Doenças dos Bovinos/virologia , Doenças dos Bovinos/sangue , Doenças dos Bovinos/patologia , Vírus da Febre Aftosa/patogenicidade , Vírus da Febre Aftosa/isolamento & purificação , Animais Lactentes , Fatores Etários , Aspartato Aminotransferases/sangue , Masculino , L-Lactato Desidrogenase/sangue
15.
BMJ Open ; 14(3): e081932, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38508652

RESUMO

INTRODUCTION: Effective communication can help optimise healthcare interactions and patient outcomes. However, few interventions have been tested clinically, subjected to cost-effectiveness analysis or are sufficiently brief and well-described for implementation in primary care. This paper presents the protocol for determining the effectiveness and cost-effectiveness of a rigorously developed brief eLearning tool, EMPathicO, among patients with and without musculoskeletal pain. METHODS AND ANALYSIS: A cluster randomised controlled trial in general practitioner (GP) surgeries in England and Wales serving patients from diverse geographic, socioeconomic and ethnic backgrounds. GP surgeries are randomised (1:1) to receive EMPathicO e-learning immediately, or at trial end. Eligible practitioners (eg, GPs, physiotherapists and nurse practitioners) are involved in managing primary care patients with musculoskeletal pain. Patient recruitment is managed by practice staff and researchers. Target recruitment is 840 adults with and 840 without musculoskeletal pain consulting face-to-face, by telephone or video. Patients complete web-based questionnaires at preconsultation baseline, 1 week and 1, 3 and 6 months later. There are two patient-reported primary outcomes: pain intensity and patient enablement. Cost-effectiveness is considered from the National Health Service and societal perspectives. Secondary and process measures include practitioner patterns of use of EMPathicO, practitioner-reported self-efficacy and intentions, patient-reported symptom severity, quality of life, satisfaction, perceptions of practitioner empathy and optimism, treatment expectancies, anxiety, depression and continuity of care. Purposive subsamples of patients, practitioners and practice staff take part in up to two qualitative, semistructured interviews. ETHICS APPROVAL AND DISSEMINATION: Approved by the South Central Hampshire B Research Ethics Committee on 1 July 2022 and the Health Research Authority and Health and Care Research Wales on 6 July 2022 (REC reference 22/SC/0145; IRAS project ID 312208). Results will be disseminated via peer-reviewed academic publications, conference presentations and patient and practitioner outlets. If successful, EMPathicO could quickly be made available at a low cost to primary care practices across the country. TRIAL REGISTRATION NUMBER: ISRCTN18010240.


Assuntos
Instrução por Computador , Dor Musculoesquelética , Adulto , Humanos , Análise de Custo-Efetividade , Dor Musculoesquelética/terapia , Análise Custo-Benefício , Medicina Estatal , Qualidade de Vida , Inglaterra , Atenção Primária à Saúde , Comunicação , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Int J Pharm ; 655: 124046, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38554739

RESUMO

Typical antibiotic treatments are often ineffectual against biofilm-related infections since bacteria residing within biofilms have developed various mechanisms to resist antibiotics. To overcome these limitations, antimicrobial-loaded liposomal nanoparticles are a promising anti-biofilm strategy as they have demonstrated improved antibiotic delivery and eradication of bacteria residing in biofilms. Antibiotic-loaded liposomal nanoparticles revealed remarkably higher antibacterial and anti-biofilm activities than free drugs in experimental settings. Moreover, liposomal nanoparticles can be used efficaciously for the combinational delivery of antibiotics and other antimicrobial compounds/peptide which facilitate, for instance, significant breakdown of the biofilm matrix, increased bacterial elimination from biofilms and depletion of metabolic activity of various pathogens. Drug-loaded liposomes have mitigated recurrent infections and are considered a promising tool to address challenges associated to antibiotic resistance. Furthermore, it has been demonstrated that surface charge and polyethylene glycol modification of liposomes have a notable impact on their antibacterial biofilm activity. Future investigations should tackle the persistent hurdles associated with development of safe and effective liposomes for clinical application and investigate novel antibacterial treatments, including CRISPR-Cas gene editing, natural compounds, phages, and nano-mediated approaches. Herein, we emphasize the significance of liposomes in inhibition and eradication of various bacterial biofilms, their challenges, recent advances, and future perspectives.


Assuntos
Anti-Infecciosos , Lipossomos , Lipossomos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Biofilmes , Bactérias , Testes de Sensibilidade Microbiana
17.
Avian Pathol ; 53(4): 247-256, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38420684

RESUMO

UvrC is a subunit of excinuclease ABC, which mediates nucleotide excision repair (NER) in bacteria. Our previous studies showed that transposon Tn4531 insertion in the UvrC encoding gene Riean_1413 results in reduced biofilm formation by Riemerella anatipestifer strain CH3 and attenuates virulence of strain YZb1. In this study, whether R. anatipestifer UvrC has some biological functions other than NER was investigated. Firstly, the uvrC of R. anatipestifer strain Yb2 was in-frame deleted by homologous recombination, generating deletion mutant ΔuvrC, and its complemented strain cΔuvrC was constructed based on Escherichia coli - R. anatipestifer shuttle plasmid pRES. Compared to the wild-type (WT) R. anatipestifer strain Yb2, uvrC deleted mutant ΔuvrC significantly reduced biofilm formation, tolerance to H2O2- and HOCl-induced oxidative stress, iron utilization, and adhesion to and invasion of duck embryonic hepatocytes, but not its growth curve and proteolytic activity. In addition, animal experiments showed that the LD50 value of ΔuvrC in ducklings was about 13-fold higher than that of the WT, and the bacterial loads in ΔuvrC infected ducklings were significantly lower than those in Yb2-infected ducklings, indicating uvrC deletion in R. anatipestifer attenuated virulence. Taken together, the results of this study indicate that R. anatipestifer UvrC is required for iron utilization, biofilm formation, oxidative stress tolerance and virulence of strain Yb2, demonstrating multiple functions of UvrC.RESEARCH HIGHLIGHTSDeletion of uvrC in R. anatipestfer Yb2 significantly reduced its biofilm formation.uvrC deletion led to reduced tolerance to H2O2- and HOCl-induced oxidative stress.The iron utilization of uvrC deleted mutant was significantly reduced.The uvrC deletion in R. anatipestifer Yb2 attenuated its virulence.


Assuntos
Biofilmes , Patos , Ferro , Doenças das Aves Domésticas , Riemerella , Biofilmes/crescimento & desenvolvimento , Animais , Riemerella/genética , Riemerella/patogenicidade , Virulência , Patos/microbiologia , Ferro/metabolismo , Doenças das Aves Domésticas/microbiologia , Infecções por Flavobacteriaceae/veterinária , Infecções por Flavobacteriaceae/microbiologia , Estresse Oxidativo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Hepatócitos/microbiologia , Peróxido de Hidrogênio
18.
bioRxiv ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38370839

RESUMO

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. As these outcomes are related to alterations in developmental processes, growing evidence suggests that deficits in executive functions-inhibitory control in particular-may, in part, explain this relationship. However, literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how low resource settings might exacerbate the link between inhibitory control and health outcomes. In this context, we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the child's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyri, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

19.
Antibiotics (Basel) ; 13(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38247621

RESUMO

Recent research has shown that antibiotic-resistant microorganisms are becoming more prevalent in intensive care units (ICUs) at an exponential rate. Patients in the ICU can get infected by pathogens due to invasive operation procedures and critical health conditions. This study primarily emphasized tracheal samples from ICU patients due to their reliance on ventilators, increasing their susceptibility to Ventilator-Associated Pneumonia (VAP). Moreover, the rise of multidrug-resistant (MDR) pathogens makes treatment strategies more challenging for these patients. In this study, we tested 200 tracheal specimens to determine the prevalence of microorganisms and analyzed the antibiotic susceptibility of these isolates against regular antibiotics, including 4th generation drugs. Among the 273 isolates, 81% were gram-negative bacteria, 10% were gram-positive bacteria, and 9% were fungi. The most prevalent gram-negative bacteria were Acinetobacter spp. (34%), Klebsiella spp. (22%), Pseudomonas spp. (14%), and Escherichia coli (9.2%). The most prevalent gram-positive bacteria were Staphylococcus aureus (5.9%), and the fungi were Candida spp. (7.3%). Among the most prevalent bacteria, except Staphylococcus aureus isolates, around 90% were resistant to multiple drugs, whereas 60% of Acinetobacter spp. and Pseudomonas spp. were extensively drug resistant. Sensitivity analysis against the gram-negative and gram-positive drug panel using a one-way ANOVA test followed by Tukey's post hoc test showed that in the in vitro assay, colistin was the most effective antibiotic against all gram-negative bacteria. In contrast, linezolid, vancomycin, and fusidic acid were most effective against all gram-positive bacteria. Regular monitoring of nosocomial infections and safe management of highly resistant bacteria can help prevent future pandemics.

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