Search Results (34,778)

Bovine mastitis, particularly that caused by Staphylococcus aureus, presents a major challenge to dairy production worldwide due to its economic impact, animal welfare concerns, and zoonotic potential. This narrative review synthesizes current literature on the epidemiology, pathogenesis, resistance patterns, and control strategies related to S. aureus-associated mastitis in dairy cattle. It highlights the pathogen’s virulence mechanisms, such as biofilm formation, immune evasion, and toxin production, that facilitate persistent infections. The review compiles global prevalence data, revealing significant geographic variation and disparities between clinical and subclinical cases. Antimicrobial resistance, especially the emergence of methicillin-resistant S. aureus (MRSA), is extensively examined alongside resistance gene profiles. Diagnostic approaches, including culture, PCR, MALDI-TOF MS, and AI-based systems, are evaluated for their sensitivity and field applicability. Additionally, the review addresses public health implications, zoonotic risks, and One Health perspectives, culminating in an exploration of prevention strategies, including improved hygiene, vaccination, dry cow therapy, and AI-driven herd management. The findings emphasize the urgent need for integrated surveillance, precision diagnostics, and targeted interventions to mitigate the burden of S. aureus mastitis. Full article

Anxiety and depression are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which can contribute to increased morbidity, reduced quality of life, and worse clinical outcomes. Nevertheless, these psychological conditions remain largely overlooked. This narrative review includes studies published between 1983 and 2025 to synthesise the current evidence on the risk factors, clinical impacts, and therapeutic strategies for these comorbidities. While the exact mechanisms leading to their increased prevalence are not fully understood, growing evidence implicates a combination of biological (e.g., systemic inflammation), social (e.g., isolation and stigma), and behavioural (e.g., smoking and inactivity) factors. Despite current guidelines recommending the identification and management of these comorbidities in COPD, they are not currently included in COPD assessments. Undetected and unmanaged anxiety and depression have serious consequences, including poor self-management, non-adherence to medications, increased risk of exacerbation and hospitalisations, and even mortality; thus, there is a need to incorporate screening as part of COPD assessments. There is robust evidence showing that pulmonary rehabilitation, a core non-pharmacological intervention, can improve mood symptoms, enhance functional capacity, and foster psychosocial resilience. Psychological therapies such as cognitive behavioural therapy (CBT), mindfulness-based approaches, and supportive counselling have also demonstrated value in reducing emotional distress and improving coping mechanisms. Pharmacological therapies, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed in moderate to severe cases or when non-pharmacological approaches prove inadequate. However, the evidence for their efficacy in COPD populations is mixed, with concerns about adverse respiratory outcomes and high discontinuation rates due to side effects. There are also barriers to optimal care, including underdiagnosis, a lack of screening protocols, limited provider training, stigma, and fragmented multidisciplinary coordination. A multidisciplinary, biopsychosocial approach is essential to ensure early identification, integrated care, and improved outcomes for patients with COPD. Full article

(1) Background: The COVID-19 pandemic presented unprecedented challenges for people with multiple sclerosis (PwMS) in Oman, necessitating targeted healthcare planning and patient support. This study aimed to investigate the impact of COVID-19 on MS management and disease course, incidence, and outcomes of COVID-19, psychosocial and mental health effects of the pandemic, and demographic and clinical predictors of the effects related to COVID-19 among Omani PwMS. (2) Methods: This cross-sectional study was conducted from January to April 2021. Adult (18–60 years) Omani PwMS completed a structured interview along with the Expanded Disability Status Scale (EDSS) and World Health Organization Well-being Index (WHO-5). Clinical data on relapses and disease-modifying therapies and adherence were analyzed. The data was statistically analyzed. (3) Results: Of 104 PwMS (73.1% female), 22.1% contracted COVID-19, with fatigue being the most reported symptom (87%). Female sex (p = 0.042), younger age (18–34 vs. 35–45 years; p = 0.014), diagnosis of COVID-19 (p = 0.037), and low current mental well-being scores (p = 0.021) predicted greater COVID-19-related effects. (4) Conclusion: These findings highlight the need to study the mental resilience of this subgroup of PwMS and provide them with targeted support during crises. Full article

Background/Objectives: Postoperative MRI is crucial for detecting residual tumor, identifying complications, and planning subsequent therapy. This study evaluates accelerated deep learning reconstruction (DLR) versus standard clinical protocols for early postoperative MRI following tumor resection. Methods: This study uses a multidisciplinary approach involving a neuroradiologist, neurosurgeon, neuro-oncologist, and radiotherapist to evaluate qualitative aspects using a 5-point Likert scale, the preferred reconstruction variant and potential residual tumor of DLR and conventional reconstruction (CR) of FLAIR, T1-weighted non-contrast and contrast-enhanced (T1), and coronal T2-weighted (T2) sequences for 1.5 and 3 T MRI. Quantitative analysis included the image quality metrics Structural Similarity Index (SSIM), Multi-Scale SSIM (MS-SSIM), Feature Similarity Index (FSIM), Noise Quality Metric (NQM), signal-to-noise ratio (SNR), and Peak SNR (PSNR) with CR as a reference. Results: All raters strongly preferred DLR over CR. This was most pronounced for FLAIR images at 1.5 and 3 T (91% at 1.5 T and 97% at 3 T) and least pronounced for T1 at 1.5 T (79% for non-contrast-enhanced and 84% for contrast-enhanced sequences) and for T2 at 3 T (69%). DLR demonstrated superior qualitative image quality for all sequences and field strengths (p < 0.001), except for T2 at 3 T, which was observed across all raters (p = 0.670). Diagnostic confidence was similar at 3 T with better but non-significant differences for T2 (p = 0.134) and at 1.5 T with better but non-significant differences for non-contrast-enhanced T1 (p = 0.083) and only marginally significant results for FLAIR (p = 0.033). Both the SSIM and MS-SSIM indicated near-perfect similarity between CR and DLR. FSIM performs worse in terms of consistency between CR and DLR. The image quality metrics NQM, SNR, and PSNR showed better results for DLR. Visual assessment of residual tumor was similar at 3 T but differed at 1.5 T, with more residual tumor detected with DLR, especially by the neurosurgeon (n = 4). Conclusions: An accelerated DLR protocol demonstrates clinical feasibility, enabling high-quality reconstructions in challenging postoperative MRIs. DLR sequences received strong multidisciplinary preference, underscoring their potential to improve neuro-oncologic decision making and suitability for clinical implementation. Full article

Background: Small airway dysfunction (SAD) plays a critical role in the management of severe asthma, particularly in patients at risk of requiring biological therapies (BTs). Short-term studies have shown that switching to single-inhaler triple therapy (SITT) with extrafine beclomethasone–formoterol–glycopyrronium improves outcomes and helps achieve quiet asthma, a state marked by symptom control, no exacerbations or oral steroids, reduced inflammation, and better small airway function. This study investigated whether, over one year, patients could maintain this state as Steady Quiet Asthma (SQA) and whether baseline measures could predict this sustained response. Methods: Twenty-six patients with severe asthma and SAD were transitioned from open triple-inhaler therapy to a closed, single-inhaler triple therapy containing extrafine beclomethasone–formoterol–glycopyrronium. Assessments at baseline (T0) and at one-year follow-up (T12) included clinical evaluations, spirometry, and impulse oscillometry, with a focus on Fres as a predictor for the need for BT. When prescribed, biologic therapies included mepolizumab, benralizumab, and dupilumab. Results: Of the 26 patients, 9 (34.6%) achieved SQA and did not require biologic therapy at the one-year follow-up, while 17 patients (65.4%) initiated biologic treatment. At T0, patients who required biologics had significantly higher median Fres (21 (19.47; 24.58) vs. 17.61 (15.82; 20.63); p = 0.049) compared to those who remained biologic-free. They also exhibited higher residual volume to total lung capacity ratio (%RV/TLC) values and lower forced expiratory volume in one second/forced vital capacity ratios (FEV₁/FVC). At T12, patients spared from BT showed significant reductions in Fres (p = 0.014) and improvements in small airway function (difference in airway resistance between 5 Hz and 20 Hz (R5–20), forced expiratory flow between 25% and 75% of FVC (%FEF25–75), and better asthma control (ACT). In contrast, patients on BT demonstrated less favorable changes in these parameters. Conclusions: Baseline Fres, FEV1/FVC ratio, and %FEV25–75 are valuable predictors of achieving Steady Quiet Asthma (SQA) and sparing biologic therapy. These findings support the use of SITT in severe asthma and highlight the importance of early functional assessments to guide personalized management. Full article

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Background: This systematic review evaluates the efficacy of rehabilitation-focused exercise interventions for lumbar degenerative disc disease (DDD), a leading cause of chronic low back pain. Methods: Following PRISMA guidelines, a comprehensive search was conducted across international and regional databases (PubMed, Scopus, Web of Science, Magiran, SID, and Noormags) covering the period from January 2010 to January 2025. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251088811. Using keywords such as “lumbar DDD,” “exercise therapy,” and “rehabilitation,” a total of 2495 records were identified. After screening, 20 studies—including clinical trials, quasi-experimental, and experimental designs—met the inclusion criteria and were assessed using the McMaster Critical Review Form for Quantitative Studies. Results: Interventions such as hydrotherapy, core stability training, Pilates, and suspension exercises were found to significantly reduce pain and improve functional outcomes. While multimodal approaches (e.g., aquatic exercise combined with acupuncture) showed positive effects, the comparative studies revealed no significant differences between modalities. Suspension training demonstrated superior efficacy in pain reduction compared to isolated core stability exercises. The methodological quality of included studies ranged from good to excellent, with the majority rated as very good or excellent (McMaster scores: 8 “excellent,” 7 “very good,” and 5 “good”). Common limitations among the studies included methodological heterogeneity, small sample sizes (n = 14–30), and insufficient long-term follow-up. Conclusions: Exercise-based rehabilitation is an effective strategy for managing lumbar DDD. Evidence particularly supports the use of suspension training and aquatic therapy for superior improvements in pain and functional outcomes. Future research should aim to adopt standardized protocols, recruit larger sample sizes, and include extended follow-up periods to produce more robust and generalizable findings. Full article

Background/Objectives: Acute severe ulcerative colitis (ASUC) is often managed by tacrolimus induction therapy followed by maintenance therapy. We compared the effectiveness of ustekinumab versus vedolizumab as maintenance therapies after tacrolimus induced improvement in patients with ASUC. Methods: This single-center retrospective cohort study included patients with ASUC who received tacrolimus induction therapy followed by ustekinumab or vedolizumab between January 2018 and November 2024. The primary outcome was clinical remission at week 16. Secondary and exploratory outcomes included clinical remission at week 8, biologic persistence, and relapse risk. An inverse probability of treatment weighting (IPTW) analysis was performed using the following covariates: male sex, prior biologics or JAK inhibitors, partial Mayo score, CRP, and albumin. Results: Among 235 tacrolimus-treated patients, 29 received ustekinumab and 22 received vedolizumab. After IPTW adjustment, the clinical remission rates were significantly higher in the ustekinumab group at both week 8 (82.1% vs. 51.8%, p = 0.02) and week 16 (85.4% vs. 36.8%, p = 0.02). Biologic persistence was significantly higher in the ustekinumab group (p = 0.004), and ustekinumab significantly reduced the hazard of relapse in multivariable analyses (HR 0.42 [95% CI: 0.20–0.88], p = 0.02). Conclusions: Ustekinumab showed greater effectiveness than vedolizumab in terms of achieving remission at 16 weeks after tacrolimus induction therapy in patients with ASUC. Full article

Substance-induced psychosis is a recognized clinical entity, commonly linked to cannabinoids, stimulants, hallucinogens, alcohol, and polysubstance use. These agents may provoke transient or persistent psychotic symptoms during intoxication or withdrawal. Opioids, however, constitute a noteworthy exception: psychosis is rarely observed during opioid intoxication, and emerging data suggest that opioid agonists might even exert antipsychotic-like effects. This article examines the paradoxical interaction between opioids and psychosis, with attention to clinical reports of psychotic symptoms arising following abrupt discontinuation of methadone or buprenorphine. In numerous cases, symptoms resolved swiftly after reintroduction of the opioid agonist, implying a neuromodulatory role. Opioids, unlike other substances of abuse, seem to lack intrinsic psychotogenic effects and may influence dopaminergic activity via kappa-opioid receptor antagonism and endorphinergic mechanisms. This challenges standard models of substance-induced psychosis and calls for a refined understanding of opioid pharmacodynamics in psychiatric contexts. In psychotic presentations among polysubstance users who also use opioids, restoring opioid agonist therapy should be prioritized, with antipsychotics reserved as second-line options—preferably agents with favorable receptor profiles. Where opioids are not involved, antipsychotics remain first-line, but should be applied judiciously, with efforts to taper when clinically appropriate. Full article

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

Cell-based therapies emerge as potential treatment options for various debilitating diseases. Preclinical research and clinical studies involving cells increased exponentially in the past decade. In addition to cell-based approaches, the use of extracellular vesicles (EVs), which are released by nearly all cell types, emerged as a promising cell-free alternative. Those approaches are also being explored in the field of ophthalmology. Several clinical trials involving EVs are underway to develop potential treatments for advanced ocular surface diseases, including corneal disorders, injuries, and dry eye disease. The cargo carried by EVs has been shown to include a diverse array of functional molecules such as transcription factors, cytokines, growth factors, mRNA, tRNA, rRNA, miRNA, and fragments of dsDNA. While the molecular composition of EVs is already well characterised, the specific activity of these molecules upon delivery to recipient cells remains poorly understood. In this review, we summarise recent studies investigating the bioactive molecules within EVs shown to influence or modulate cellular activity on the ocular surface. Among these, various miRNAs have most commonly been identified as therapeutic agents targeting distinct molecular pathways. The EVs studied were predominantly derived from various mesenchymal stem cells. Full article

Background and Objectives: Breast reconstruction after mastectomy has been shown to significantly improve psychosocial wellbeing and quality of life. Enhanced Recovery After Surgery (ERAS) protocols, especially those tailored to breast reconstruction, have revolutionized recovery by reducing complications, pain, opioid use, and hospital stay while improving patient satisfaction. The purpose of this narrative review was to present existing practices and supporting evidence within current ERAS protocols, as well as propose a modern ERAS framework centered around enhancing the patient experience following breast reconstruction. Methods: A focused literature search was conducted to identify studies investigating emerging approaches to patient care and surgical techniques adopted as part of a broader ERAS workflow Results: Some recent innovations include digital ERAS tracking, robot-assisted techniques, neurotization, and closed incision negative pressure therapy (ciNPT). These innovations show promise in reducing morbidity following reconstruction and may greatly improve sensory and functional outcomes. These advancements also reflect a shift toward more holistic, patient-centered care, extending beyond immediate clinical needs to address long-term wellbeing through psychosocial support and patient-reported outcome measures. Incorporating tools that validate patient perspectives helps guide interventions to optimize satisfaction and recovery. Conclusions: Future research should aim to standardize ERAS protocols by incorporating evidence-based practices, reinforcing breast reconstruction as a patient-centered, evidence-driven process that is focused on comprehensive recovery and improved quality of life. Full article

Background and Aim: Long-term treatment with biologic therapy alongside immunomAfodulators in patients with inflammatory bowel disease (IBD) can be associated with severe side effects. The objective of this study was to determine whether discontinuing anti-TNF treatment after two years in patients who have achieved mucosal healing is associated with lower relapse rates. Materials and Methods: A total of 67 patients with IBD from a single tertiary IBD Center who had achieved mucosal healing were enrolled in this retrospective study. In this single-center retrospective study (January 2014–December 2022), we screened 67 IBD patients in deep remission (endoscopic mucosal healing after ≥2 years of anti-TNF therapy). After excluding three patients without histologic data, 64 patients (25 ulcerative colitis, 39 Crohn’s disease) were analyzed. Mayo endoscopic sub-score and SES-CD were used to evaluate endoscopic activity after two years of anti-TNF therapy. Histological activity was assessed using the GHAS (for CD) and Nancy index (for UC). Results: A total of 67 patients were screened, of whom 3 were excluded due to a lack of biopsies. Of the 64 included patients, 39.06% (25/64) had UC and 60.9% (39/64) had CD, with a mean disease duration of 11.6 ± 8.0 years. All patients were in endoscopic remission at the time of therapy de-escalation, and 60.9% (39/64) also achieved histological remission (“deep remission”). In the follow-up of 38.6 months (IQR 30–48) after biologic therapy was stopped, 57.8% (37/64) relapsed with a median time to relapse of 13.5 months (IQR 8–24) off anti-TNF—a total of 34 patients required a restarting of biologic therapy. Using Spearman’s correlation, a moderate connection was observed between histological activity at withdrawal and subsequent relapse (rho = 0.467, p < 0.001). The probability of relapsing within 4 years after anti-TNF cessation was significantly higher (OR 2.72) in patients with histologically active disease at the time of de-escalation. Conclusions: Achieving ‘deep remission’ (clinical, endoscopic, and histological healing) may be a suitable parameter for making decisions on when to de-escalate therapy; however, given that over half of patients in endoscopic remission relapse after discontinuation, any de-escalation should be approached with caution and individualized patient assessment. Full article

Background: Exposure-based cognitive behavioral therapy (Ex-CBT) is widely seen as the gold-standard treatment for anxiety and obsessive-compulsive disorder (OCD). Yet, minoritized youth are underrepresented in efficacy studies, raising questions about the applicability of Ex-CBT to minoritized youth. Effectiveness data suggest systematic adaptation of Ex-CBT to address youth culture and context is likely needed, and many clinicians make adaptations and augmentations in practice. However, research on the specific strategies clinicians use to address their youth clients’ culture and context within anxiety and OCD treatment is lacking. In the current study, we assess practice-based adaptations, augmentations, and process-based approaches utilized when delivering treatment to youth for OCD and anxiety in public mental health clinics. Methods: We conducted qualitative interviews with 16 clinicians from both specialty anxiety and general mental health clinics serving youth with anxiety or OCD in the public mental health system. Participating clinicians had a mean age of 32.19 (SD = 5.87) and 69% of therapists identified as female; 69% identified as White, 25% identified as Asian, and 6% as Black or African American. In qualitative interviews, clinicians shared how they addressed clients’ culture and context (e.g., social identities, stressors and strengths related to social identities and lived environment). Thematic analysis identified the strategies clinicians employed to address culture and context. Results: Clinicians reported incorporating culture and context through process-based approaches (e.g., building trust gradually, considering clients’ social identity stressors, engaging in self-awareness to facilitate cultural responsiveness) and through culturally adapting and augmenting treatment to promote person-centered care. Core strategies included proactive and ongoing assessment of clients’ cultural and contextual factors, adapting exposures and augmenting Ex-CBT with strategies such as case management and discussion of cultural context, and taking a systems-informed approach to care. Conclusions: Examining practice-based adaptations, augmentations, and process-based approaches to treatment for minoritized youth with OCD or anxiety can inform efforts to understand what comprises person-centered culturally responsive Ex-CBT. Empirical testing of identified strategies is a needed area of future research. Full article

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine. Full article