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EClinicalMedicine May 2024The escalating resistance of to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although...
BACKGROUND
The escalating resistance of to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although tetracyclines and quinolones have been proposed as alternative therapeutic options, concerns regarding age-specific safety issues and the lack of consensus in recommendations across various national guidelines prevail. Thus, the primary objective of this study is to ascertain the most efficacious interventions for second-line treatment of . infection while considering the age-specific safety issues associated with these interventions.
METHODS
In this systematic review and network meta-analysis we searched PubMed, Embase, CNKI, and WanFang Data, from inception up to November 11th, 2023. Studies of quinolones or tetracyclines for the treatment of people with infection were collected and screened by reading published reports, with any type of study included, and no individual patient-level data requested. A systematic review and direct meta-analysis compared the efficacy of tetracyclines and quinolones regarding time to defervescence (TTD) and the rates of fever disappearance within 24 h and 48 h of antibiotic administration, for managing . infection. Bayesian network meta-analysis (NMA) was employed to indirectly assess the relative effectiveness of different interventions in people with . infection and the safety profile of medication in paediatric patients. This study is registered with PROSPERO, CRD42023478383.
FINDINGS
The systematic review and direct meta-analysis included a total of 4 articles involving 246 patients, while the NMA encompassed 85 articles involving a substantial cohort of 7095 patients. The NMA measured the effectiveness across all ages and included 7043 patients, with a mean age of 37.80 ± 3.91 years. Of the 85 included studies, 14 (16.5%) were at low risk of bias, 71 (83.5%) were at moderate risk, and no studies were rated as having a high risk of bias. In the direct meta-analysis, no statistically significant differences were found between tetracyclines and quinolones concerning TTD (mean difference: -0.40, 95% CI: -1.43 to 0.63; = 0%), fever disappearance rate within 24 h of antibiotic administration (OR: 0.37, 95% CI: 0.08-1.79; = 58%), and fever disappearance rate within 48 h of antibiotic administration (OR: 1.10, 95% CI: 0.30-3.98; = 59%). However, the comprehensive NMA analysis of clinical response (in 70 studies; n = 6143 patients), shortening of TTD (in 52 studies; n = 4363 patients), shortening length of cough relief or disappearance (in 39 studies; n = 3235 patients), fever disappearance rate at 48 h (in four studies; n = 418 patients) revealed that minocycline exhibited the most favourable outcomes across these various parameters, and the analysis of fever disappearance rate at 24 h (in three studies; n = 145 patients) revealed that levofloxacin may be the most effective, as indicated by the rank probabilities and surface under the cumulative ranking area (SUCRA) value. Moxifloxacin ranked second in clinical response and in shortening the length of cough relief or disappearance, and third in shortening TTD. Notably, when evaluating the occurrence of adverse reactions in paediatric patients (in four studies; n = 239 children), levofloxacin was associated with the highest SUCRA value rankings for the rate of adverse events.
INTERPRETATION
Our findings suggest that tetracyclines and quinolones may be equally effective. Based on the age of participants in the included studies, minocycline may be the most effective intervention for children over eight years of age when all preventive measures are considered, whereas moxifloxacin may benefit people under eight years of age. However, these results should be interpreted with caution, given the limited number of studies and patients included, and the heterogeneity between included studies. Based on a limited number of studies in children, levofloxacin is likely to have one of the highest rates of adverse reactions. The majority of the studies included in the NMA were from the Asian region, and more randomised controlled trials comparing different therapeutic strategies in patients with . are warranted. This comparative study provides clinical pharmacists and clinicians with important information to enable them to make informed decisions about treatment options, considering drug efficacy and safety.
FUNDING
The Natural Science Foundation of Fujian Province, China.
PubMed: 38596615
DOI: 10.1016/j.eclinm.2024.102589 -
Phytomedicine : International Journal... Dec 2023Sinomenine (SIN) is the main pharmacologically active component of Sinomenii Caulis and protects against rheumatoid arthritis (RA). In recent years, many studies have... (Review)
Review
BACKGROUND
Sinomenine (SIN) is the main pharmacologically active component of Sinomenii Caulis and protects against rheumatoid arthritis (RA). In recent years, many studies have been conducted to elucidate the pharmacological mechanisms of SIN in the treatment of RA. However, the molecular mechanism of SIN in RA has not been fully elucidated.
PURPOSE
To summarize the pharmacological effects and molecular mechanisms of SIN in RA and clarify the most valuable regulatory mechanisms of SIN to provide clues and a basis for basic research and clinical applications.
METHODS
We systematically searched SciFinder, Web of Science, PubMed, China National Knowledge Internet (CNKI), the Wanfang Databases, and the Chinese Scientific Journal Database (VIP). We organized our work based on the PRISMA statement and selected studies for review based on predefined selection criteria.
OUTCOME
After screening, we identified 201 relevant studies, including 88 clinical trials and 113 in vivo and in vitro studies on molecular mechanisms. Among these studies, we selected key results for reporting and analysis.
CONCLUSIONS
We found that most of the known pharmacological mechanisms of SIN are indirect effects on certain signaling pathways or proteins. SIN was manifested to reduce the release of inflammatory cytokines such as Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and IL-1β, thereby reducing the inflammatory response, and apparently blocking the destruction of bone and cartilage. The regulatory effects on inflammation and bone destruction make SIN a promising drug to treat RA. More notably, we believe that the modulation of α7nAChR and the regulation of methylation levels at specific GCG sites in the mPGES-1 promoter by SIN, and its mechanism of directly targeting GBP5, certainly enriches the possibilities and the underlying rationale for SIN in the treatment of inflammatory immune-related diseases.
Topics: Humans; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Morphinans; Signal Transduction
PubMed: 37816287
DOI: 10.1016/j.phymed.2023.155114 -
Ecotoxicology and Environmental Safety Nov 2023Human activities have been exerting widespread stress and environmental risks in aquatic ecosystems. Environmental stress, including temperature rise, acidification,... (Review)
Review
Human activities have been exerting widespread stress and environmental risks in aquatic ecosystems. Environmental stress, including temperature rise, acidification, hypoxia, light pollution, and crowding, had a considerable negative impact on the life histology of aquatic animals, especially on sex differentiation (SDi) and the resulting sex ratios. Understanding how the sex of fish responds to stressful environments is of great importance for understanding the origin and maintenance of sex, the dynamics of the natural population in the changing world, and the precise application of sex control in aquaculture. This review conducted an exhaustive search of the available literature on the influence of environmental stress (ES) on SDi. Evidence has shown that all types of ES can affect SDi and universally result in an increase in males or masculinization, which has been reported in 100 fish species and 121 cases. Then, this comprehensive review aimed to summarize the molecular biology, physiology, cytology, and epigenetic mechanisms through which ES contributes to male development or masculinization. The relationship between ES and fish SDi from multiple aspects was analyzed, and it was found that environmental sex differentiation (ESDi) is the result of the combined effects of genetic and epigenetic factors, self-physiological regulation, and response to environmental signals, which involves a sophisticated network of various hormones and numerous genes at multiple levels and multiple gradations in bipotential gonads. In both normal male differentiation and ES-induced masculinization, the stress pathway and epigenetic regulation play important roles; however, how they co-regulate SDi is unclear. Evidence suggests that the universal emergence or increase in males in aquatic animals is an adaptation to moderate ES. ES-induced sex reversal should be fully investigated in more fish species and extensively in the wild. The potential aquaculture applications and difficulties associated with ESDi have also been addressed. Finally, the knowledge gaps in the ESDi are presented, which will guide the priorities of future research.
Topics: Animals; Humans; Male; Ecosystem; Epigenesis, Genetic; Sex Differentiation; Aquaculture; Gonads
PubMed: 37918334
DOI: 10.1016/j.ecoenv.2023.115654 -
Frontiers in Nutrition 2023The gastrointestinal (GI) microbiota is a complex and dynamic ecosystem whose composition and function are influenced by many internal and external factors. Overall, the... (Review)
Review
PURPOSE
The gastrointestinal (GI) microbiota is a complex and dynamic ecosystem whose composition and function are influenced by many internal and external factors. Overall, the individual GI microbiota composition appears to be rather stable but can be influenced by extreme shifts in environmental exposures. To date, there is no systematic literature review that examines the effects of extreme environmental conditions, such as strict isolation and confinement, on the GI microbiota.
METHODS
We conducted a systematic review to examine the effects of isolated and confined environments on the human GI microbiota. The literature search was conducted according to PRISMA criteria using PubMed, Web of Science and Cochrane Library. Relevant studies were identified based on exposure to isolated and confined environments, generally being also antigen-limited, for a minimum of 28 days and classified according to the microbiota analysis method (cultivation- or molecular based approaches) and the isolation habitat (space, space- or microgravity simulation such as MARS-500 or natural isolation such as Antarctica). Microbial shifts in abundance, alpha diversity and community structure in response to isolation were assessed.
RESULTS
Regardless of the study habitat, inconsistent shifts in abundance of 40 different genera, mainly in the phylum Bacillota (formerly Firmicutes) were reported. Overall, the heterogeneity of studies was high. Reducing heterogeneity was neither possible by differentiating the microbiota analysis methods nor by subgrouping according to the isolation habitat. Alpha diversity evolved non-specifically, whereas the microbial community structure remained dissimilar despite partial convergence. The GI ecosystem returned to baseline levels following exposure, showing resilience irrespective of the experiment length.
CONCLUSION
An isolated and confined environment has a considerable impact on the GI microbiota composition in terms of diversity and relative abundances of dominant taxa. However, due to a limited number of studies with rather small sample sizes, it is important to approach an in-depth conclusion with caution, and results should be considered as a preliminary trend. The risk of dysbiosis and associated diseases should be considered when planning future projects in extreme environments.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022357589.
PubMed: 37492598
DOI: 10.3389/fnut.2023.1214016 -
International Journal of Molecular... Apr 2024Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body... (Review)
Review
Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body temperature, and immune response. In this review, we highlight the relevance of the different mediators that control adipose tissue activity through a systematic review of the main players present in white and brown adipose tissues. Among them, inflammatory mediators secreted by the adipose tissue, such as classical adipokines and more recent ones, elements of the immune system infiltrated into the adipose tissue (certain cell types and interleukins), as well as the role of intestinal microbiota and derived metabolites, have been reviewed. Furthermore, anti-obesity mediators that promote the activation of beige adipose tissue, e.g., myokines, thyroid hormones, amino acids, and both long and micro RNAs, are exhaustively examined. Finally, we also analyze therapeutic strategies based on those mediators that have been described to date. In conclusion, novel regulators of obesity, such as microRNAs or microbiota, are being characterized and are promising tools to treat obesity in the future.
Topics: Humans; Animals; Obesity; Adipose Tissue; Adipokines; MicroRNAs; Gastrointestinal Microbiome; Adipose Tissue, Brown; Adipose Tissue, White; Inflammation Mediators; Energy Metabolism
PubMed: 38731880
DOI: 10.3390/ijms25094659 -
Military Medical Research Oct 2023Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,...
BACKGROUND
Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.
METHODS
To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics modalities.
RESULTS
Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.
CONCLUSION
This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.
Topics: Humans; Multiomics; Exercise; Cytokines
PubMed: 37853489
DOI: 10.1186/s40779-023-00477-5 -
Current Oncology (Toronto, Ont.) Sep 2023Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation.... (Review)
Review
Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.
Topics: Humans; Female; Bevacizumab; Prospective Studies; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Peritoneal Neoplasms; Ovarian Neoplasms
PubMed: 37754507
DOI: 10.3390/curroncol30090592 -
Clinical Nutrition ESPEN Dec 2023Hypertension is a serious complication linked to a higher risk for organs. Caffeine is a natural component that affects the cardiovascular system, while the mechanisms... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Hypertension is a serious complication linked to a higher risk for organs. Caffeine is a natural component that affects the cardiovascular system, while the mechanisms of its effects are not fully established. Therefore, we aimed to examine the impact of caffeine supplementation on blood pressure (BP) by conducting a systematic review and dose-response meta-analysis of randomized controlled clinical trials (RCTs).
METHODS AND RESULTS
We searched online databases using relevant keywords up to July 2022 to identify RCTs using caffeine on systolic (SBP) and diastolic BP (DBP) in adults. Inclusion criteria were adult participants ≥18 years old for subjects, examining the effect of caffeine supplementation on BP, and RCTs studies. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (CI). The pooled of 11 effect sizes analysis of 8 studies demonstrated significant increases in SBP (WMD:1.94 mmHg; 95%CI:0.52, 3.35; p = 0.007) and DBP (WMD:1.66 mmHg; 95% CI:0.75, 2.57; p = 0.000) after caffeine supplementation. The subgroup analysis showed that caffeine supplementation more effectively increased SBP and DBP in males than females. Moreover, meta-regression analysis demonstrated a significant relationship between the dose of caffeine intake and changes in SBP (p = 0.000), DBP (p = 0.000), and duration of the trial in SBP (p = 0.005), and DBP (p = 0.001). The non-linear dose-response analysis detected the dosage of supplementation >400 mg/day is effective for increasing DBP (p = 0.034), and the duration of supplementation of more than nine weeks makes increasing in both SBP and DBP.
CONCLUSION
This meta-analysis shows that caffeine supplementation significantly increased SBP and DBP in adults.
Topics: Adult; Female; Humans; Male; Blood Pressure; Caffeine; Dietary Supplements; Hypertension
PubMed: 38057002
DOI: 10.1016/j.clnesp.2023.09.923 -
Advances in Nutrition (Bethesda, Md.) Jan 2024Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with >300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.
Topics: Animals; Humans; Cognitive Dysfunction; Dairy Products; Dementia; Diet; Milk; Prospective Studies; Risk Factors
PubMed: 38043604
DOI: 10.1016/j.advnut.2023.100160 -
Nutrition Journal Oct 2023The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines,... (Meta-Analysis)
Meta-Analysis Review
The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose-response meta-analysis.
BACKGROUND
The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines, cytokines, malondialdehyde (MDA) and liver function enzymes in patients at risk of cardiovascular disease.
METHODS
Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods.
RESULTS
A pooled analysis of 13 randomized controlled trials (RCTs) revealed that CLA supplementation led to a significant increment in fasting blood glucose (FBG) (WMD: 4.49 mg/dL; 95%CI: 2.39 to 6.59; P < 0.001), and aspartate aminotransferase (AST) (WMD: 2.54 IU/L; 95%CI: 0.06 to 5.01; P = 0.044). Moreover, CLA supplementation decreased leptin (WMD: -1.69 ng/ml; 95% CI: -1.80 to -1.58; P < 0.001), and interleukin 6 (IL-6) (WMD: -0.44 pg/ml; 95%CI: -0.86 to -0.02; P = 0.037). However, there was no effect on hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and alanine aminotransferase (ALT) adiponectin compared to the control group.
CONCLUSION
Our findings showed the overall favorable effect of CLA supplementation on the adipokines and cytokines including serum IL-6, and leptin, while increasing FBG and AST. It should be noted that the mentioned metabolic effects of CLA consumption were small and may not reach clinical importance.
PROSPERO REGISTERATION COD
CRD42023426374.
Topics: Humans; Dietary Supplements; Leptin; Cytokines; Linoleic Acids, Conjugated; Interleukin-6; Adipokines; Cardiovascular Diseases; Glycemic Control; Malondialdehyde; Liver; Blood Glucose
PubMed: 37794481
DOI: 10.1186/s12937-023-00876-3