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Nutrients Nov 2023Inflammatory bowel disease (IBD) is a chronic and recurrent disease. It has been observed that the incidence and prevalence of IBD are increasing, which consequently...
Inflammatory bowel disease (IBD) is a chronic and recurrent disease. It has been observed that the incidence and prevalence of IBD are increasing, which consequently raises the risk of developing colon cancer. Recently, the regulation of the intestinal barrier by probiotics has become an effective treatment for colitis. -derived extracellular vesicles (Akk EVs) are nano-vesicles that contain multiple bioactive macromolecules with the potential to modulate the intestinal barrier. In this study, we used ultrafiltration in conjunction with high-speed centrifugation to extract Akk EVs. A lipopolysaccharide (LPS)-induced RAW264.7 cell model was established to assess the anti-inflammatory effects of Akk EVs. It was found that Akk EVs were able to be absorbed by RAW264.7 cells and significantly reduce the expression of nitric oxide (NO), TNF-α, and IL-1β ( < 0.05). We explored the preventative effects on colitis and the regulating effects on the intestinal barrier using a mouse colitis model caused by dextran sulfate sodium (DSS). The findings demonstrated that Akk EVs effectively prevented colitis symptoms and reduced colonic tissue injury. Additionally, Akk EVs significantly enhanced the effectiveness of the intestinal barrier by elevating the expression of MUC2 (0.53 ± 0.07), improving mucus integrity, and reducing intestinal permeability ( < 0.05). Moreover, Akk EVs increased the proportion of the beneficial bacteria (33.01 ± 0.09%) and downregulated the proportion of the harmful bacteria (0.32 ± 0.27%). These findings suggest that Akk EVs possess the ability to regulate immune responses, protect intestinal barriers, and modulate the gut microbiota. The research presents a potential intervention approach for Akk EVs to prevent colitis.
Topics: Animals; Mice; Colitis; Intestines; Inflammatory Bowel Diseases; Colon; Disease Models, Animal; Mice, Inbred C57BL; Dextran Sulfate
PubMed: 38004116
DOI: 10.3390/nu15224722 -
International Journal of Stroke :... Jan 2024Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the...
BACKGROUND
Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients.
METHODS
This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0-50 unacceptable; 51-68 poor; 68-80.3 good; >80.3 excellent) were used to determine usability of PreventS-MD.
FINDINGS
Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2; 95% CI [77.0-84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7; 95% CI [79.1-84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations.
INTERPRETATION
The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and individuals at risk of stroke/CVD. Individuals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD.
Topics: Humans; Mobile Applications; Cross-Sectional Studies; Feasibility Studies; Stroke; Surveys and Questionnaires
PubMed: 37485871
DOI: 10.1177/17474930231190745 -
International Journal of Pediatric... Jan 2024To identify and synthesize key research advances from the literature published between 2019 and 2023 on the advances in preventative measures, and medical and surgical... (Review)
Review
OBJECTIVES
To identify and synthesize key research advances from the literature published between 2019 and 2023 on the advances in preventative measures, and medical and surgical treatment of uncomplicated otitis media (OM) including the impact of the COVID-19 pandemic on OM management.
DATA SOURCES
Medline (PubMed), Embase, and the Cochrane Library.
REVIEW METHODS
All relevant original articles published in English between June 2019 and February 2023 were identified. Studies related to guideline adherence, impact of treatment on immune response and/or microbiology, tympanoplasty, Eustachian tube balloon dilatation, mastoidectomy procedures, and those focusing on children with Down's syndrome or cleft palate were excluded.
MAIN FINDINGS
Of the 9280 unique records screened, 64 were eligible for inclusion; 23 studies related to medical treatment, 20 to vaccines, 13 to surgical treatment, 6 to prevention (excl. vaccines) and 2 to the impact of COVID-19 on OM management. The level of evidence was judged 2 in 11 studies (17.2 %) and 3 or 4 in the remaining 53 studies (82.8 %) mainly due to the observational design, study limitations or low sample sizes. Some important advances in OM management have been made in recent years. Video discharge instructions detailing the identification and management of pain and fever for parents of children with acute otitis media (AOM) was more effective than paper instructions in reducing symptomatology; compared to placebo, levofloxacin solution was more effective for treating chronic suppurative otitis media, whereas AOM recurrences during two years of follow-up did not differ between children with recurrent AOM who received tympanostomy tube (TT) insertion or medical management. Further, novel pneumococcal conjugate vaccines (PCV) schedules for preventing OM in Aboriginal children appeared ineffective, and a protein-based pneumococcal vaccine had no added value over PCV13 for preventing AOM in native American infants. During the COVID-19 pandemic, a decline in OM and TT case volumes and complications was observed.
IMPLICATION FOR PRACTICE AND FUTURE RESEARCH
Whether the observed impact of the COVID-19 pandemic on OM management extends to the post-pandemic era is uncertain. Furthermore, the impact of the pandemic on the conduct of urgently needed prospective methodologically rigorous interventional studies aimed at improving OM prevention and treatment remains to be elucidated since the current report consisted of studies predominantly conducted in the pre-pandemic era.
Topics: Child; Humans; Infant; COVID-19; Otitis Media; Pandemics; Pneumococcal Vaccines; Prospective Studies; Vaccines, Conjugate
PubMed: 38000342
DOI: 10.1016/j.ijporl.2023.111782 -
Metabolism: Clinical and Experimental Mar 2024Dysregulated cholesterol metabolism is the major factor responsible for cholesterol gallstones (CGS). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a...
BACKGROUND & AIMS
Dysregulated cholesterol metabolism is the major factor responsible for cholesterol gallstones (CGS). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in cholesterol homeostasis and its inhibitors secure approval for treating various cholesterol metabolic disorders such as hypercholesterolemia and cardiovascular diseases, but its role in CGS remains unclear. Our study aims to clarify mechanisms by which PCSK9 promotes CGS formation and explore the application of the PCSK9 inhibitor, alirocumab, in preventing and treating CGS.
APPROACH & RESULTS
The expressions of PCSK9 were notably increased in CGS patients' serum, bile, and liver tissues compared to those without gallstones. Moreover, among CGS patients, hepatic PCSK9 was positively correlated with hepatic cholesterol and negatively correlated with hepatic bile acids (BAs), suggesting PCSK9 was involved in disrupted hepatic cholesterol metabolism related to CGS. Mechanistically, in vitro experiments demonstrated that inhibition of PCSK9 enhanced nuclear expression of PPARα by diminishing its lysosomal degradation and subsequently activated CYP7A1 transcription. Finally, inhibition of PCSK9 prevented CGS formation and dissolved the existing stones in CGS mice by elevating the conversion of cholesterol into BAs through PPARα-mediated CYP7A1 activation. Additionally, serum PCSK9 level may function as a prognostic signature to evaluate the therapeutic efficacy of PCSK9 inhibitors.
CONCLUSIONS
Inhibition of PCSK9 exerts preventive and therapeutic effects on CGS by activating PPARα-mediated CYP7A1 expression and facilitating the conversion of cholesterol into BAs, which highlights the potential of PCSK9 inhibition as a promising candidate for preventing and treating CGS in clinical applications.
IMPACT AND IMPLICATIONS
PCSK9 plays a pivotal role in cholesterol metabolism and its inhibitors are approved for clinical use in cardiovascular diseases. Our study observes inhibition of PCSK9 prevents and dissolves CGS by activating PPARα-mediated CYP7A1 expression and facilitating the conversion of cholesterol into BAs. Mechanistically, PCSK9 inhibition enhanced the nuclear expression of PPARα by diminishing its lysosomal degradation and subsequently activated CYP7A1 transcription. Our study sheds light on the new function and mechanism of PCSK9 in CGS, providing a novel preventive and therapeutic target with potential clinical applications.
Topics: Humans; Animals; Mice; Proprotein Convertase 9; PPAR alpha; Cardiovascular Diseases; Gallstones; Cholesterol; Cholesterol 7-alpha-Hydroxylase
PubMed: 38191052
DOI: 10.1016/j.metabol.2023.155774 -
Journal of Prevention & Intervention in... 2023Bullying victimization remains a pressing concern to the health and development of U.S. adolescents. Victims of bullying face threats to their safety and education....
Bullying victimization remains a pressing concern to the health and development of U.S. adolescents. Victims of bullying face threats to their safety and education. Hence, interventions are needed to prevent bullying and equip others to intervene in bullying situations. Prior research has examined preventive interventions with little consideration of promotion-tailored, peace-encouraging, interventions. Further, there is a need to test whether people's motives toward preventive and promotive actions may fit with certain intervention tracks. Here, we tested an upstander approach consisting of a universal assembly presentation with promotion-oriented education () and prevention-oriented education (), as well as a tailored 150-minute workshop (. High school students ( = 388; 53.9% girls) participated in the study with a control group ( = 335) and intervention group who self-selected to experience upstanding for peace promotion ( = 15) or upstanding for bullying prevention ( = 35). Students in the prevention-tailored track reported stronger safety beliefs (violence prevention beliefs and care promotion beliefs) than students in the control group and endorsed using more defending actions than control-group students. Students' gain, non-gain, and loss motivations moderated ties between upstanding track involvement and post-test safety beliefs, barriers to upstanding, and defending behaviors.
Topics: Adolescent; Female; Humans; Male; Crime Victims; Violence; Students; Bullying; Adolescent Behavior
PubMed: 38440847
DOI: 10.1080/10852352.2024.2313383 -
Clinical and Translational Medicine Jan 2024Radiotherapy is the main treatment modality for thoracic tumours, but it may induce pulmonary fibrosis. Currently, the pathogenesis of radiation-induced pulmonary...
BACKGROUND
Radiotherapy is the main treatment modality for thoracic tumours, but it may induce pulmonary fibrosis. Currently, the pathogenesis of radiation-induced pulmonary fibrosis (RIPF) is unclear, and effective treatments are lacking. Transforming growth factor beta 1 (TGFβ1) plays a central role in RIPF. We found that activated TGFβ1 had better performance for radiation pneumonitis (RP) risk prediction by detecting activated and total TGFβ1 levels in patient serum. αv integrin plays key roles in TGFβ1 activation, but the role of αv integrin-mediated TGFβ1 activation in RIPF is unclear. Here, we investigated the role of αv integrin-mediated TGFβ1 activation in RIPF and the application of the integrin antagonist cilengitide to prevent RIPF.
METHODS
Itgav ;Pdgfrb-Cre mice were generated by conditionally knocking out Itgav in myofibroblasts, and wild-type mice were treated with cilengitide or placebo. All mice received 16 Gy of radiation or underwent a sham radiation procedure. Lung fibrosis was measured by a modified Ashcroft score and microcomputed tomography (CT). An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum TGFβ1 concentration, and total Smad2/3 and p-Smad2/3 levels were determined via Western blotting.
RESULTS
Conditional Itgav knockout significantly attenuated RIPF (p < .01). Hounsfield units (HUs) in the lungs were reduced in the knockout mice compared with the control mice (p < .001). Conditional Itgav knockout decreased active TGFβ1 secretion and inhibited fibroblast p-Smad2/3 expression. Exogenous active TGFβ1, but not latent TGFβ1, reversed these reductions. Furthermore, cilengitide treatment elicited similar results and prevented RIPF.
CONCLUSIONS
The present study revealed that conditional Itgav knockout and cilengitide treatment both significantly attenuated RIPF in mice by inhibiting αv integrin-mediated TGFβ1 activation.
HIGHLIGHTS
Activated TGFβ1 has a superior capacity in predicting radiation pneumonitis (RP) risk and plays a vital role in the development of radiation-induced pulmonary fibrosis (RIPF). Conditional knock out Itgav in myofibroblasts prevented mice from developing RIPF. Cilengitide alleviated the development of RIPF by inhibiting αv integrin-mediated TGFβ1 activation and may be used in targeted approaches for preventing RIPF.
Topics: Animals; Humans; Mice; Integrin alphaV; Lung; Pulmonary Fibrosis; Radiation Pneumonitis; X-Ray Microtomography
PubMed: 38239077
DOI: 10.1002/ctm2.1546 -
Heliyon Oct 2023Tuberculosis is a leading cause of death, despite being a largely curable and preventable disease. The goals of TB control are to reduce infection transmission,...
INTRODUCTION
Tuberculosis is a leading cause of death, despite being a largely curable and preventable disease. The goals of TB control are to reduce infection transmission, morbidity, and mortality until TB cannot be a threat to public health any longer while preventing drug resistance. Assessing KAP on TB control and prevention among family members is more essential, and taking action based on the result can break the transmission of TB infection.
METHODS
From August to September 2022, a community-based cross-sectional study method was used. A total of 422 participants were selected from a list of sample frames who were family members of PTB patients who had used anti-TB medication in the previous 12 months prior to the study period using a systematic random sampling method. SPSS version 25 software was used to analyze the data. Bivariate and multivariate analyses were used to determine variables related to KAP on TB prevention and control. A variable with p-values less than 0.25 was included in the multivariable logistic regression model to find independent determinant factors. In the multivariate logistic regression, variables with p-values ≤0.05 were identified as statistically significant.
RESULT
A total of 414 family members responded to the survey questionnaire. The average knowledge score on TB was 17.11 ± 6.34. The majority (51.9%) of respondents had a good knowledge of TB cases. One-third of those polled had an unfavorable attitude towards PTB prevention, with a mean score of 3.16 ± 1.78 and 55.1% had good practice in preventing tuberculosis. Marital status (AOR = 1.7, 95% CI: 1.5-2.5) was an independent predictor of knowledge. Practice level is independently affected by occupation (AOR = 3.9; 95% CI = (1.7-8.7)) and health education on PTB (AOR = 2.4; 95% CI = (1.6-3.9).
CONCLUSION
Knowledge, attitudes, and preventive practices about tuberculosis were not satisfactory when compared to several national and international studies. It is necessary to strengthen the program for health education and awareness-building on PTB.
PubMed: 37818014
DOI: 10.1016/j.heliyon.2023.e20565 -
International Journal of Medical... Nov 2023The Q-GAPS (Q fever GermAn interdisciplinary Program for reSearch) consortium was launched in 2017 as a German consortium of more than 20 scientists with exceptional... (Review)
Review
The Q-GAPS (Q fever GermAn interdisciplinary Program for reSearch) consortium was launched in 2017 as a German consortium of more than 20 scientists with exceptional expertise, competence, and substantial knowledge in the field of the Q fever pathogen Coxiella (C.) burnetii. C. burnetii exemplifies as a zoonotic pathogen the challenges of zoonotic disease control and prophylaxis in human, animal, and environmental settings in a One Health approach. An interdisciplinary approach to studying the pathogen is essential to address unresolved questions about the epidemiology, immunology, pathogenesis, surveillance, and control of C. burnetii. In more than five years, Q-GAPS has provided new insights into pathogenicity and interaction with host defense mechanisms. The consortium has also investigated vaccine efficacy and application in animal reservoirs and identified expanded phenotypic and genotypic characteristics of C. burnetii and their epidemiological significance. In addition, conceptual principles for controlling, surveilling, and preventing zoonotic Q fever infections were developed and prepared for specific target groups. All findings have been continuously integrated into a Web-based, interactive, freely accessible knowledge and information platform (www.q-gaps.de), which also contains Q fever guidelines to support public health institutions in controlling and preventing Q fever. In this review, we will summarize our results and show an example of how an interdisciplinary consortium provides knowledge and better tools to control a zoonotic pathogen at the national level.
Topics: Animals; Humans; Coxiella burnetii; Q Fever; One Health; Zoonoses; Interdisciplinary Studies
PubMed: 38056089
DOI: 10.1016/j.ijmm.2023.151590 -
American Journal of Infection Control Sep 2023Extended-spectrum β-lactamases-producing Enterobacteriaceae (ESBL-E) is a critical antimicrobial resistance pathogen, to which we need to pay the greatest attention.... (Review)
Review
INTRODUCTION
Extended-spectrum β-lactamases-producing Enterobacteriaceae (ESBL-E) is a critical antimicrobial resistance pathogen, to which we need to pay the greatest attention. This study was aimed at uncovering the present evidence for the preventive effectiveness of contact precautions for patients colonized or infected with ESBL-E.
METHODS
According to the Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) Extension for Scoping Reviews, we searched MEDLINE for articles with relevant keywords from the beginning of 2010 to October 18, 2022.
RESULTS
Of the 355 articles found, 9, including 8 observational studies and 1 randomized controlled trial, were selected. Safety of discontinuing contact precautions was evaluated mainly in acute-care and long-term care hospitals. Consistently, all authors concluded that contact precautions can be safely discontinued in patients colonized or infected with ESBL-E.
CONCLUSION
The clinical impact of discontinuing contact precautions for patients with ESBL-E is minimal and can be safely withdrawn at acute, noncritical, adult care wards. Relevant data from pediatric and geriatric wards, as well as intensive care units, were insufficient and should be investigated in future research.
Topics: Adult; Humans; Child; Aged; Enterobacteriaceae; Enterobacteriaceae Infections; Cross Infection; beta-Lactamases; Infection Control
PubMed: 36736903
DOI: 10.1016/j.ajic.2023.01.018 -
Frontiers in Public Health 2023Cost-effectiveness analyses (CEAs) on prevention of non-communicable diseases (NCDs) are necessary to guide decision makers to allocate scarce healthcare resource,...
BACKGROUND
Cost-effectiveness analyses (CEAs) on prevention of non-communicable diseases (NCDs) are necessary to guide decision makers to allocate scarce healthcare resource, especially in Southeast Asia (SEA), where many low- and middle-income countries (LMICs) are in the process of scaling-up preventive interventions. This scoping review aims to summarize the cost-effectiveness evidence of primary, secondary, or tertiary prevention of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) as well as of major NCDs risk factors in SEA.
METHODS
A scoping review was done following the PRISMA checklist for Scoping Reviews. Systematic searches were performed on Cochrane Library, EconLit, PubMed, and Web of Science to identify CEAs which focused on primary, secondary, or tertiary prevention of T2DM, CVDs and major NCDs risk factors with the focus on primary health-care facilities and clinics and conducted in SEA LMICs. Risks of bias of included studies was assessed using the Consensus of Health Economic Criteria list.
RESULTS
This study included 42 CEAs. The interventions ranged from screening and targeting specific groups for T2DM and CVDs to smoking cessation programs, discouragement of smoking or unhealthy diet through taxation, or health education. Most CEAs were model-based and compared to a do-nothing scenario. In CEAs related to tobacco use prevention, the cost-effectiveness of tax increase was confirmed in all related CEAs. Unhealthy diet prevention, mass media campaigns, salt-reduction strategies, and tax increases on sugar-sweetened beverages were shown to be cost-effective in several settings. CVD prevention and treatment of hypertension were found to be the most cost-effective interventions. Regarding T2DM prevention, all assessed screening strategies were cost-effective or even cost-saving, and a few strategies to prevent T2DM complications were found to be cost-effective in certain settings.
CONCLUSION
This review shows that the cost-effectiveness of preventive strategies in SEA against T2DM, CVDs, and their major NCDs risk factors are heterogenous in both methodology as well as outcome. This review combined with the WHO "best buys" could guide LMICs in SEA in possible interventions to be considered for implementation and upscaling. However, updated and country-specific information is needed to further assess the prioritization of the different healthcare interventions.
SYSTEMATIC REVIEW REGISTRATION
https://osf.io, identifier: 10.17605/OSF.IO/NPEHT.
Topics: Humans; Diabetes Mellitus, Type 2; Cost-Benefit Analysis; Noncommunicable Diseases; Risk Factors; Cardiovascular Diseases; Asia, Southeastern
PubMed: 38026322
DOI: 10.3389/fpubh.2023.1206213