Search Results (809)

The Mycoplasmataceae are a family of bacteria that typically cause respiratory, arthritic, and genitourinary disease in humans. Mycoplasma spp. of animal origin are also the causative agents of porcine wheezing disease, chronic respiratory disease and arthritis in chickens and other conditions. These diseases have a significant impact on public health and the economic development of livestock breeding. Clinical prevention and treatment of mycoplasma infections is primarily dependent on the use of antibiotics. However, inappropriate and excessive use of antimicrobials has enabled resistance development that has become a significant clinical concern. Mycoplasma are also robust biofilm producers, and this process is a major factor for the persistence of these infections, especially in conjunction with common antibiotic resistance mechanisms, including target gene mutations and the action of efflux pumps. A mycoplasma biofilm refers to a structured and stable microbial community formed by Mycoplasma spp. adhering to biological or non-biological surfaces under suitable conditions and secreting extracellular polymers (EPS) such as polysaccharides. This process allows the microorganisms to adapt to their surrounding environment and survive during the growth process. These biofilms render bacteria more resistant to antimicrobials than planktonic bacteria, resulting in biofilm-associated infections that are more challenging to eradicate and more likely to recur. The current study reviews progress from the fields of biofilm formation, structure and identification, correlations between biofilms and drug resistance and virulence as well as methods of biofilm prevention and control. Our aim was to provide a reference basis for the subsequent in-depth understanding of the research of mycoplasma biofilms. Full article

Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive and invasive. Non-invasive biomarkers like the Fibrosis-4 (FIB-4) index have shown promise in diagnosing liver fibrosis in various chronic liver diseases. This study explores the potential of the FIB-4 index to predict CFLD in an adult CF population and assesses its correlation with transient elastography (TE) as a potential diagnostic tool. The aim of this study is to evaluate the diagnostic performance of the FIB-4 index for CFLD in adults with CF and investigate its relationship with TE-based liver stiffness measurements (LSM). Methods: The study was conducted in a regional cystic fibrosis unit, including 261 adult CF patients. FIB-4 scores were calculated using an online tool (mdcalc.com) based on patient age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. In parallel, 29 patients underwent liver stiffness measurement using TE (Fibroscan^®). Statistical analyses included non-parametric tests for group comparisons and Pearson’s correlation to assess the relationship between FIB-4 scores and TE results. Results: The mean FIB-4 score in patients diagnosed with CFLD was higher (0.99 ± 0.83) compared to those without CFLD (0.64 ± 0.38), although the difference was not statistically significant (p > 0.05). TE results for CFLD patients (5.9 kPa) also did not show a significant difference compared to non-CFLD patients (4.2 ± 1.6 kPa, p > 0.05). However, a positive correlation (r = 0.401, p = 0.031) was found between FIB-4 scores and TE-based LSM, suggesting a potential complementary diagnostic role. Conclusions: The FIB-4 index, while not sufficient as a standalone diagnostic tool for CFLD in adults with CF, demonstrates potential when used in conjunction with other diagnostic methods like TE. This study introduces a novel approach for integrating non-invasive diagnostic markers in CF care, offering a pathway for future clinical practice. The combination of FIB-4 and TE could serve as an accessible, cost-effective alternative to invasive diagnostic techniques, improving early diagnosis and management of CFLD in the CF population. Additionally, future research should explore the integration of these tools with emerging biomarkers and clinical features to refine diagnostic algorithms for CFLD, potentially reducing reliance on liver biopsies and improving patient outcomes. Full article

Background: Polymerase chain reaction (PCR) is highly sensitive and specific for the rapid diagnosis of invasive fungal disease (IFD) but is not yet widely implemented due to concerns regarding limited standardisation between assays, the lack of commercial options and the absence of clear guidance on interpreting results. Objectives and Methods: This review provides an update on technical and clinical aspects of PCR for the diagnosis of the most pertinent fungal pathogens, including Aspergillus, Candida, Pneumocystis jirovecii, Mucorales spp., and endemic mycoses. Summary: Recent meta-analyses have demonstrated that quantitative PCR (qPCR) offers high sensitivity for diagnosing IFD, surpassing conventional microscopy, culture and most serological tests. The reported specificity of qPCR is likely underestimated due to comparison with imperfect reference standards with variable sensitivity. Although the very low limit of detection of qPCR can generate false positive results due to procedural contamination or patient colonisation (particularly in pulmonary specimens), the rates are comparable to those observed for biomarker testing. When interpreting qPCR results, it is essential to consider the pre-test probability, determined by the patient population, host factors, clinical presentation and risk factors. For patients with low to moderate pre-test probability, the use of sensitive molecular tests, often in conjunction with serological testing or biomarkers, can effectively exclude IFD when all tests return negative results, reducing the need for empirical antifungal therapy. Conversely, for patients with high pre-test probability and clinical features of IFD, qPCR testing on invasive specimens from the site of infection (such as tissue or bronchoalveolar lavage fluid) can confidently rule in the disease. The development of next-generation sequencing methods to detect fungal infection has the potential to enhance the diagnosis of IFD, but standardisation and optimisation are essential, with improved accessibility underpinning clinical utility. Full article

In the last two decades, there has been a considerable surge in the development of artificial intelligence. Imaging is most frequently employed for the diagnostic evaluation of patients, as it is regarded as one of the most precise methods for identifying the presence of a disease. However, a study indicates that approximately 800,000 individuals in the USA die or incur permanent disability because of misdiagnosis. The present study is based on the use of computer-aided diagnosis of colorectal cancer. The objective of this study is to develop a practical, low-cost, AI-based decision-support tool that integrates clinical test data (blood/stool) and, if needed, colonoscopy images to help reduce misdiagnosis and improve early detection of colorectal cancer for clinicians. Convolutional neural networks (CNNs) and artificial neural networks (ANNs) are utilized in conjunction with a graphical user interface (GUI), which caters to individuals lacking programming expertise. The performance of the artificial neural network (ANN) is measured using the mean squared error (MSE) metric, and the obtained performance is 7.38. For CNN, two distinct cases are under consideration: one with two outputs and one with three outputs. The precision of the models is 97.2% for RGB and 96.7% for grayscale, respectively, in the first instance, and 83% for RGB and 82% for grayscale in the second instance. However, using a pretrained network yielded superior performance with 99.5% for 2-output models and 93% for 3-output models. The GUI is composed of two panels, with the best ANN model and the best CNN model being utilized in each. The primary function of the tool is to assist medical personnel in reducing the time required to make decisions and the probability of misdiagnosis. Full article

Objective: Gut dysbiosis has been implicated in the pathology of inflammatory bowel disease (IBD). There is some evidence to suggest that the use of antibiotic treatment can incite an early clinical response or remission when used in conjunction with standard-of-care (SOC) therapy to treat IBD-related flares. Furthermore, antibiotics have been historically investigated for use as a bridge when initiating biologic therapy while waiting for peak biologic treatment effect to occur. This study investigated and compared the time to clinical response when treated with combination antibiotics, metronidazole monotherapy, or SOC therapy in pediatric patients with an active IBD flare. Methods: This study was a retrospective, Institution Review Board-approved, single-centered cohort study which included patients who were less than 18 years of age with a confirmed diagnosis of IBD who received conventional treatment alone or with either combination antibiotic therapy or metronidazole monotherapy to treat an active IBD flare between March 2013 and January 2024. Patients were excluded if they received antibiotic therapy to treat an active infection, had positive stool cultures or enteric pathogen polymerase chain reaction panel, or had colonic disease limited to the rectum. Results: Fifty-nine patients were included and divided into metronidazole monotherapy (n = 18), SOC therapy (n = 20), and combination antibiotics (n = 21). The primary outcome of days to clinical response was not significantly different across all groups; however, patients who received combination antibiotics achieved the fastest time to clinical response (median (IRQ))—4 days (1, 65), compared to 7.5 days (1, 119) for the SOC group and 9 days (2, 217) for the metronidazole group. Secondary outcomes of achievement of clinical response, remission, or failure were determined to be non-significant between all groups. Conclusions: There is no significant difference in time to clinical response, attaining clinical response or remission, or treatment failure rate for patients treated with combination antibiotics, metronidazole monotherapy, or SOC. However, results of this study suggest that the use of combination antibiotics plus SOC may lead to a faster time to clinical response and remission compared to SOC therapy alone. Further studies are warranted to elucidate the role of antimicrobial therapy in management of pediatric IBD. Full article

Despite recent advances in the treatment of obesity, lifestyle medicine remains foundational to the treatment of individuals with obesity, regardless of the modality chosen by the patient with the guidance of the clinician they are working with, including in conjunction with, as appropriate, anti-obesity medications and metabolic surgery. Lifestyle medicine involves the use of diet, exercise, sleep, stress, and other lifestyle modalities in the treatment of disease. Clinicians and health systems should, after a patient-centered discussion with the patient, do their best to ensure access to lifestyle treatments. Gold standard guidelines recommend intensive, multicomponent lifestyle change programs for obesity treatments with evidence-based diet and exercise counseling and established, theoretically driven behavior change components. Clinicians treating obesity should be aware of their own biases, make efforts to reduce stigmatizing experiences in their practice, and address weight stigma in their treatment plans as needed. A variety of dietary patterns can be used to support patients with obesity, and clinicians should make evidence-based but patient-centered recommendations that aim to maximize adherence. Diet and exercise can play an important role in reducing the side effects of treatment and optimizing outcomes in weight loss, attenuating the effects of metabolic adaptation, and weight maintenance. Exercise should be increased gradually to reduce injury with a goal of 200–300 min (approximately 3.3–5 h) of moderate to vigorous intensity exercise per week to maximize weight maintenance effects with exercise prescriptions customized to patients risks. A variety of practice models can be leveraged along with the use of an interdisciplinary team to provide lifestyle medicine care for those with obesity. Full article

Background/Objectives: Gouty arthritis (GA) is a chronic inflammatory disorder frequently linked to systemic inflammation and impaired kidney function. Growth differentiation factor-15 (GDF-15) has been suggested as a potential biomarker involved in both inflammatory responses and renal dysfunction. Studies on GDF-15 serum levels and renal function decline in GA patients are limited. This study aimed to investigate serum GDF-15 levels in patients with GA and to evaluate the relationship between GDF-15 and renal function parameters. Methods: This prospective case–control study included 60 (intercritical group: 30; acute attack group: 30) patients with gout arthritis and 60 healthy controls, matched for body mass index and sex. The enzyme-linked immunosorbent assay measured serum GDF-15, and renal function and inflammatory markers were also assessed. Group comparisons used non-parametric tests, Spearman’s analysis evaluated correlations, and receiver operating characteristic (ROC) analysis assessed diagnostic performance. Results: Serum GDF-15 levels were significantly higher in GA patients than controls (p < 0.001), especially during acute attacks. GDF-15 correlated moderately with renal function markers. ROC analysis showed high diagnostic accuracy for both acute (area under the curve (AUC) = 0.98) and intercritical gout phases (AUC = 0.96). Conclusions: Serum GDF-15 levels are increased in patients with gouty arthritis and are associated with impaired renal function. GDF-15 may serve as a helpful biomarker for disease activity and renal involvement in GA, but its interpretation should be considered in conjunction with other clinical and laboratory parameters. Full article

Background: Development Assistance for Health (DAH) plays a vital role in health financing across Sub-Saharan Africa, particularly in tackling communicable diseases such as HIV/AIDS, malaria, and tuberculosis. Despite its importance, the efficiency and equity of DAH allocation remain contested. Objectives: The study aims to evaluate the cost-effectiveness of DAH in Sub-Saharan Africa from 1995 to 2018, as well as to explore differences in efficiency across diseases and country contexts. Methods: Data were drawn from the Institute for Health Metrics and Evaluation and applied Generalized Cost-Effectiveness Analysis in conjunction with the Gross Domestic Product-based thresholds. Averted Disability-Adjusted Life Years were analyzed across countries and diseases, and countries were categorized by the Human Development Index (HDI) level to assess differential DAH performance. Results: DAH cost-effectiveness showed similar patterns across HDI groups, with roughly equal proportions of cost-effective and dominated outcomes in both low- and middle-HDI countries. Thirteen countries were identified as very cost-effective, nine as cost-effective, and two as non-cost-effective. Twenty-one countries were dominated, reflecting persistent inefficiencies in aid impact that transcends the various levels of development. Conclusions: Tailoring DAH allocation to specific disease burdens and development levels enhances its impact. The study underscores the need for targeted investment and a strategic shift toward integrated health system strengthening. Additionally, microinsurance is highlighted as a key mechanism for improving healthcare access and financial protection in low-income settings. Full article

CKD is a leading cause of illness in older cats, but early detection is challenging due to the limitations of conventional biomarkers. This study evaluated the clinical utility of the UAC for identifying early-stage renal dysfunction in cats and proposed a diagnostic matrix incorporating the UAC with other biomarkers. Blood and urine samples from 59 healthy cats and 190 cats with CKD were analyzed, and UAC levels were compared with symmetric dimethylarginine (SDMA), creatinine, and blood urea nitrogen (BUN). UAC values were significantly elevated in cats with CKD, including those in stage 1. Receiver operating characteristic analysis identified a UAC cut-off of 16.3 mg/g, yielding 100% specificity and 43.7% sensitivity for early-stage CKD classification. The UAC showed significant correlations with other renal biomarkers and was incorporated into a multi-parameter matrix to support disease staging. These findings suggest that the UAC may be a promising supplementary biomarker for evaluating renal function in cats and could aid clinical decision-making when interpreted in conjunction with established diagnostic parameters. Full article

Lippia multiflora Moldenke is widely used in Angola, on the African continent, and beyond for the treatment of many health conditions such as hypertension, enteritis, colds, gastrointestinal disturbances, stomachaches, jaundice, coughs, fevers, nausea, bronchial inflammation, conjunctivitis, malaria, and venereal diseases. However, there is limited literature about the active compounds linked with the reported biological activities. This study aims to assess the chemical profiles, antioxidant properties, and the cytotoxicity effects of the roots, stem bark, and leaves of L. multiflora. Chemical characterization of the crude extracts was assessed through quantification of total phenolic and flavonoid contents followed by Q exactive plus orbitrap™ ultra-high-performance liquid chromatography-mass spectrometer (UHPLC-MS) screening. The correlation between the extracts and the correlation between the compounds were studied using the multivariate analysis. Principal component analysis (PCA) loading scores and principal component analysis (PCA) biplots and correlation plots were used to connect specific compounds with observed biological activities. The antioxidant activities of the crude extracts were carried out in vitro using DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging and reducing power assays, while the in vitro toxicology of the crude extracts was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A total of twenty constituents were characterized and identified using the UHPLC–Q/Orbitrap/MS. The methanol leaf extract showed the highest antioxidant activity in the DPPH free radical scavenging activity (IC₅₀ = 0.559 ± 0.269 μg/mL); however, the stem bark extract had the highest reducing power (IC_0.5 = 0.029 ± 0.026 μg/mL). High phenolic and flavonoid content was found in the dichloromethane leaf extract (32.100 ± 1.780 mg GAE/g) and stem bark extract (624.153 ± 29.442 mg QE/g), respectively. The results show the stem bark, methanol leaf, and dichloromethane leaf extracts were well-tolerated by the Vero cell line at concentrations up to 50 µg/mL. However, at 100 µg/mL onward, some toxicity was observed in the root, methanol leaf, and dichloromethane leaf extracts. The UHPLC–Q/Orbitrap/MS profiles showed the presence of terpenoids (n = 5), flavonoids (n = 5), phenols (n = 4), alkaloids (n = 3), coumarins (n = 1), fatty acids (n = 1), and organic acids (n = 1). According to several studies, these secondary metabolites have been reported and proven to be the most abundant for antioxidant potential. The identified flavonoids (catechin, quercitrin, and (−)-epigallocatechin) and phenolic compound (6-gingerol) can significantly contribute to the antioxidant properties of different plant parts of L. multiflora. The research findings obtained in this study provide a complete phytochemical profile of various parts of L. multiflora that are responsible for the antioxidant activity using UHPLC–Q/Orbitrap/MS analysis. Furthermore, the results obtained in this study contribute to the scientific information or data on the therapeutic properties of Lippia multiflora and provide a basis for further assessment of its potential as a natural remedy. Full article

Background and Aims: Gastroesophageal reflux disease (GERD) is the most common esophageal disorder worldwide and a progressive condition leading to Barrett’s esophagus and adenocarcinoma. Continuous medical therapy with proton pump inhibitors fails to restore the antireflux barrier and is unable to relieve symptoms in up to 40% of patients. A tailored and standardized antireflux surgical procedure may increase cure rates and meet patient expectations. Methods and Results: Antireflux surgery aims to reestablish the natural antireflux barrier, which includes the diaphragmatic crura, the lower esophageal sphincter (LES), and the angle of His along with the gastroesophageal flap valve. For decades, the Nissen total fundoplication has been the primary procedure and remains the gold standard for surgical treatment. Alternatives such as Toupet partial fundoplication, Dor partial fundoplication, and the magnetic sphincter augmentation (LINX™) procedure have been developed to mitigate side effects like dysphagia, gas-bloat syndrome, and the inability to belch or vomit. Recent clinical findings regarding a novel procedure, RefluxStop™, indicate that restoring the gastroesophageal flap valve, in conjunction with anterior fundoplication and a silicone device for stabilizing the LES beneath the diaphragm, can achieve lasting reflux control and enhance patient-reported outcomes. Conclusions: The planning of healthcare services and actionable strategies to improve equity and quality of treatment is critical to address the global burden of GERD. Modern laparoscopic surgery for GERD is safe and effective and should be performed in centers offering a complete diagnostic pathway and specific surgical techniques tailored to the individual GERD phenotype. Shared decision-making between the surgeon and the patient is essential for the choice of operation. A personalized approach can offer clinical benefits over total fundoplication and improve patient-reported outcomes. Full article

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. Full article

In the United States, the Food and Drug Administration (FDA) is the regulatory authority with the responsibility to evaluate scientific data included in each vaccine’s prescribing information (e.g., safety, indication(s) for use, and dosing schedule) based on several factors, including safety, quality, potency, and effectiveness in preventing disease to assess benefit/risk prior to approval. After approval, the FDA continues to work with sponsors to ensure safety and effectiveness data in the prescribing information remain current. In conjunction with FDA approval or authorization, the Advisory Committee on Immunization Practices (ACIP) recommends immunization dosing schedules and target populations for use. ACIP recommendations that are adopted by the Centers for Disease Control and Prevention (CDC) Director inform national immunization schedules, which influence immunization access, coverage, and provider behavior. This targeted review aims to explore historical instances when vaccine dosing regimens approved by the FDA differ from those recommended by the ACIP, focusing on the frequency and factors behind these differences to inform future ACIP recommendations. Out of n = 78 vaccines assessed, the analysis identified n = 5 vaccines with deviations and only one that reduced dosing. Deviations from the FDA label were determined to be a rare occurrence and are most frequently observed to be additive, not reductive. Full article

The ocular surface is susceptible to a wide spectrum of inflammatory, degenerative, and neurotrophic diseases that can impair vision. The complex pathophysiology and limited therapeutic options associated with these conditions continue to pose significant clinical challenges. Nerve Growth Factor (NGF), a neurotrophin initially recognized for its role in neuronal survival and differentiation, has emerged as a key regulator of ocular surface homeostasis and repair. Beyond its neurotrophic functions, NGF is suggested to influence epithelial proliferation, immune responses, tear secretion, and angiogenesis. Experimental and clinical studies have implicated NGF in both the pathogenesis and potential treatment of various ocular surface diseases, including allergic conjunctivitis, neurotrophic keratopathy (NK), immune-mediated and herpetic keratitis, and dry eye disease (DED), as well as post-surgical corneal wound healing. Notably, recombinant human NGF (rhNGF, cenegermin) has been approved as the first topical biologic therapy for NK. Despite encouraging clinical outcomes, challenges such as high treatment costs, limited long-term data, and potential proangiogenic effects remain. This review consolidates current evidence on the role of NGF in ocular surface health and disease, highlighting its biological mechanisms, clinical applications, and future therapeutic potential. Full article

Background: Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is a severe complication associated with bisphosphonate therapy, commonly used in the treatment of osteoporosis and metastatic bone diseases. Low-Level Laser Therapy (LLLT) has been proposed as a potential treatment modality for BRONJ, with its anti-inflammatory, analgesic, and regenerative effects being of particular interest. This systematic review aims to critically assess the current evidence regarding the efficacy of LLLT in the management of BRONJ. Methods: This review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of electronic databases, including PubMed, Scopus, and Web of Science, was performed to identify relevant studies published up to September 2024. The systematic review protocol has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) with the number 423003. All studies considered are observational. Studies were included if they investigated the application of LLLT in BRONJ treatment, reporting clinical outcomes such as pain reduction, lesion healing, and quality of life. The quality of the studies was assessed using the Cochrane Risk of Bias tool, and the data were synthesized descriptively. Results: A total of four studies met the inclusion criteria. The findings indicate that LLLT, particularly when used in conjunction with surgical debridement and pharmacological therapy, significantly may reduce pain and promote soft tissue healing in patients with BRONJ. However, the heterogeneity of study designs, laser parameters, and outcome measures limits the generalizability of these results. Furthermore, most studies were small-scale, with moderate to high risk of bias. Conclusions: The current evidence suggests that LLLT may be a beneficial adjunctive therapy in the treatment of BRONJ. However, conclusions are limited by the lack of randomized controlled trials and methodological heterogeneity, particularly for pain management and soft tissue regeneration. However, further high-quality randomized controlled trials with standardized laser protocols are necessary to establish its efficacy and optimize clinical application. Therefore, one of the limitations of this literature review with meta-analysis is that only four studies were considered and, moreover, they were observational. The results of the meta-analysis showed that there is not enough evidence to declare a statistical correlation; this result will surely be due to the small number of studies and heterogeneity. Full article