Search Results (955)

Background/Objectives: Solar elastosis, a key histopathological alteration in skin photodamage, results from chronic UV exposure and photoaging. Clinically, it manifests as deep wrinkles, laxity, and a dull complexion. The growing demand for effective treatments has spurred the development of numerous therapeutic strategies. This systematic review aims to synthesize and critically evaluate the scientific evidence regarding interventions for treating the clinical and histological manifestations of solar elastosis, to provide an updated overview and guide future clinical practice. Methods: PubMed, Scopus, ProQuest, and Web of Science databases were searched for articles published in the last ten years. Clinical studies on adults with signs of solar elastosis and photoaging, evaluating therapeutic interventions, were included. Primary outcomes were clinical and histopathological improvements, while secondary outcomes included skin elasticity, safety, and patient satisfaction. This review was registered in the PROSPERO database under registration number CRD420251086680. Results: Twenty-two studies, totaling 608 participants, were included. The analyzed therapies comprised a wide range of strategies, including energy-based devices (laser, radiofrequency), stem cell derivatives, bioactive topical compounds, and growth factor-rich plasma. Device-assisted and biologically augmented interventions consistently improved visible photoaging outcomes and skin elasticity, with selective histologic remodeling, heterogeneous effects on barrier function, and an overall acceptable safety profile, with mild and transient adverse events. Patient satisfaction was consistently high. Conclusions: Therapeutic strategies in solar elastosis and photoaging, particularly those combining energy-based devices with regenerative agents, have proven effective in improving the structural and functional aspects of photodamaged skin. Although the results are promising, the current literature is limited by methodological heterogeneity and small sample sizes. High-quality randomized controlled trials with long-term follow-up are needed to establish standardized, evidence-based protocols. Full article

Biofilm growth on silicone (Si) medical devices is routinely treated with antibiotics or device removal; however, new approaches are needed. The current work evaluates photothermal therapy (PTT) to augment antibiotic efficacy or directly ablate Staphylococcus aureus biofilms. The semiconducting polymer, Poly [4,4-bis(2-ethylhexyl)-cyclopenta [2,1-b;3,4 b’]dithiophene-2,6-diyl-alt22,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe), with a high photothermal conversion efficiency of 53.2%, was formulated into nanoparticles (BSe NPs) and incorporated into Si. Nanocomposites were stimulated with 800 nm light to generate mild hyperthermic conditions of 42 °C, or ablative temperatures above 50 °C. PTT, with or without antibiotics, was deployed against two strains of Staphylococcus aureus biofilms, Xen 29 and Xen 40, followed by an evaluation of bacterial survival, biofilm regrowth, and differential disruption of specific biofilm components. Mild hyperthermia was also used in an in vivo model of silicone implant infection. The results demonstrate a 55–59% reduction in S. aureus when PTT plus antibiotic was used in vitro, and a 51% reduction in vivo. Higher temperatures effectively eradicate both Xen 29 and Xen 40 strains, with a longer exposure time using lower laser power being optimal. Hyperthermia inhibited biofilm regrowth in both strains, resulting in a > 3 log reduction, plus increased dead cells, polysaccharides, and eDNA in treated Xen 40 biofilms. These experiments demonstrate that nanocomposite-based PTT can both reduce viable bacteria and alter individual biofilm components. Full article

Colon cancer (CC) is a common malignancy characterized by poor prognostic outcomes and considerable mortality. Oxaliplatin (OXP) is commonly used in the treatment of CC; however, its efficacy may be limited by side effects and the development of resistance. β-sitosterol (β-Sit), a phytosterol derived from plants, has been documented to be effective in the treatment of tumors. This study aimed to investigate the potential of β-Sit to enhance the antitumor efficacy of OXP in COLO-205 cells, focusing on apoptosis induction and suppression of the vascular endothelial growth factor A (VEGF-A)/survival pathway. Molecular docking studies were performed to assess the binding affinity of β-Sit with the target proteins B-cell lymphoma 2 (Bcl-2), phosphoinositide 3-kinase (PI3K), and VEGF receptor-2 (VEGFR-2). COLO-205 cells were treated with OXP, β-Sit, or a combination of OXP + β-Sit for 48 h. The combination treatment substantially lowered the IC₅₀ achieved with 3.24 µM of OXP and 36.01 µM of β-Sit, compared to 25.64 µM for OXP alone and 275.9 µM for β-Sit alone, demonstrating a pronounced synergistic impact. The combined therapy altered the cell cycle distribution by decreasing the number of cells in the G0/G, S, and G2/M phases, coupled with an increase in the Sub-G1 population. Furthermore, apoptosis was augmented by a shift in cell death from necrosis to late apoptosis, as indicated by an increased BAX/BCL2 ratio relative to each treatment alone. Moreover, the inhibitory effect on angiogenesis was enhanced via the reduction of VEGF-A, and β-catenin and nuclear factor κB (NF-κB-p65) were suppressed, thereby preventing the growth and survival of resistant cancer cells. Additionally, molecular docking supported high binding affinities of β-Sit to Bcl-2, PI3K, and VEGFR-2. This study highlights the potential of β-Sit to enhance the anti-cancer efficacy of OXP in CC. Full article

Injectable biomaterials for vocal fold disorders are being developed to provide not only mechanical reinforcement but also a regenerative microenvironment. Recent hydrogels based on hyaluronic acid (HA) derivatives, calcium hydroxylapatite and decellularized matrix scaffolds are designed to approximate the viscoelastic behavior of native tissue, allow controlled degradation, and modulate local immune responses. Rather than serving merely as space-filling agents, several of these materials deliver extracellular matrix (ECM)-like biochemical signals that help maintain pliability and overcome some limitations of conventional augmentation. Experimental and early clinical studies involving growth factor delivery, stem cell-based injections, and ECM-mimetic hydrogels have demonstrated improved mucosal wave vibration and reduced fibrosis in cases of scarring. In clinical series, benefits from basic fibroblast growth factor can persist for up to 12 months. Further progress will depend on correlating material properties with objective vibratory performance to achieve lasting restoration of phonation and advance true tissue-regenerative therapy. Full article

Prostate cancer is one of the leading causes of cancer-related morbidity and mortality worldwide, and imaging plays a critical role in its detection, localization, staging, treatment, and management. The advent of artificial intelligence (AI) has introduced transformative possibilities in prostate imaging, offering enhanced accuracy, efficiency, and consistency. This review explores the integration of AI in prostate cancer diagnostics across key imaging modalities, including multiparametric MRI (mpMRI), PSMA PET/CT, and transrectal ultrasound (TRUS). Advanced AI technologies, such as machine learning, deep learning, and radiomics, are being applied for lesion detection, risk stratification, segmentation, biopsy targeting, and treatment planning. AI-augmented systems have demonstrated the ability to support PI-RADS scoring, automate prostate and tumor segmentation, guide targeted biopsies, and optimize radiation therapy. Despite promising performance, challenges persist regarding data heterogeneity, algorithm generalizability, ethical considerations, and clinical implementation. Looking ahead, multimodal AI models integrating imaging, genomics, and clinical data hold promise for advancing precision medicine in prostate cancer care and assisting clinicians, particularly in underserved regions with limited access to specialists. Continued multidisciplinary collaboration will be essential to translate these innovations into evidence-based practice. This article explores current AI applications and future directions that are transforming prostate imaging and patient care. Full article

Sepsis-associated acute kidney injury (SA-AKI) often requires renal replacement therapy (RRT), which markedly alters antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations broaden options against multidrug-resistant Gram-negative bacteria, but dosing during RRT remains uncertain. This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane–tazobactam, ceftazidime–avibactam, aztreonam–avibactam, cefiderocol, meropenem–vaborbactam, imipenem–relebactam, and newer agents including sulbactam–durlobactam, cefepime–enmetazobactam, and cefepime–taniborbactam. Pharmacokinetic data, RRT impact, PK/PD targets, pediatric aspects, and clinical outcomes were extracted from experimental models, case reports, and clinical studies. Drug exposure varies with RRT modality, effluent flow, membrane properties, and patient-specific factors such as augmented renal clearance, hypoalbuminemia, and fluid overload. Standard renal-adjusted dosing often yields subtherapeutic concentrations in critically ill patients. Pediatric data remain scarce and largely limited to case reports. Optimal BL/BLI use in septic patients with SA-AKI on RRT requires individualized dosing that accounts for PK/PD variability and dialysis settings. Full-dose initiation during the first 24–48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance. Full article

Cardiogenic shock (CS) is a complex, life-threatening syndrome characterized by inadequate tissue perfusion due to impaired cardiac function. Acute myocardial infarction (AMI) and acute decompensated heart failure are the leading causes, with mortality remaining high despite advances in revascularization and supportive care. The Society for Cardiovascular Angiography and Interventions (SCAI) classification allows risk stratification and guides clinical decision making by capturing the spectrum of shock severity. Percutaneous mechanical circulatory support (pMCS) devices, such as the intra-aortic balloon pump (IABP) and Impella, aim to stabilize hemodynamics by augmenting cardiac output and unloading the left ventricle. However, randomized trials and meta-analyses have not demonstrated a consistent survival advantage of Impella over IABP, while reporting higher rates of bleeding and vascular complications. Landmark trials, including ECLS-SHOCK and DanGer, have provided conflicting results, likely reflecting differences in baseline severity and timing of device implantation. Veno-arterial extracorporeal membrane oxygenator (VA-ECMO) offers full cardiopulmonary support but increases left ventricular afterload, potentially worsening myocardial injury. Combined strategies such as ECPELLA (Impella + VA-ECMO) or ECMO + IABP may mitigate left ventricle (LV) overload and improve bridging to recovery or advanced therapies, although evidence remains largely observational and complication rates are considerable. In right-sided or biventricular failure, tailored options (e.g., Impella RP, Bi-Pella) guided by invasive hemodynamics may be required. Current evidence suggests that pMCS benefits are limited to carefully selected subgroups, underscoring the importance of early diagnosis, prompt referral, and individualized intervention. Robust randomized data are still needed to define the optimal role of pMCS in AMI-related CS. Full article

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous spectrum of disorders that lead to progressive and irreversible vision loss. Gene therapy is the most promising emerging treatment for IRDs. While gene augmentation strategies have demonstrated clinical benefit and results within the first approved ocular gene therapy, their application is restricted by adeno-associated virus (AAV) packaging capacity and limited efficacy for dominant mutations. Recent breakthroughs in precision genome editing, particularly base editing (BE) and prime editing (PE), have provided alternatives capable of directly correcting pathogenic variants. BE enables targeted single-nucleotide conversions, whereas PE further allows for precise insertions and deletions, both circumventing the double-strand DNA cleavage or repair processes typically induced by conventional CRISPR–Cas editing systems, thereby offering advantages in post-mitotic retinal cells. Preclinical investigations across murine and non-human primate models have demonstrated the feasibility, molecular accuracy, and preliminary safety profiles of these platforms in targeting IRD-associated mutations. However, critical challenges remain before clinical application can be realized, including limited editing efficiency in photoreceptors, interspecies variability in therapeutic response, potential risks of off-target effects, and barriers in large-scale vector manufacturing. Moreover, the delivery of genome editors to the outer retina remains suboptimal, prompting intensive efforts in capsid engineering and the development of non-viral delivery systems. This review synthesizes the current progress in BE and PE optimization, highlights innovations in delivery platforms that encompass viral and emerging non-viral systems and summarizes the major barriers to clinical translation. We further discuss AI-driven strategies for the rational design of BE/PE systems, thereby outlining their future potential and perspectives in the treatment of IRDs. Full article

Background/Objectives: The implementation of adaptive radiation therapy (ART) is increasingly becoming widely available in the clinical practice of radiotherapy (RT). For patients with pharyngeal cancer receiving RT, this study aimed to develop a deep learning (DL) model by merging baseline and ART simulation computed tomography (CT) images to predict treatment outcomes. Methods: Clinical and imaging data from 162 patients of newly diagnosed oropharyngeal or hypopharyngeal cancer were analyzed. All completed definitive treatment and their baseline and ART non-contrast simulation CTs were utilized for training. After augmentation of the CT images, a deep contrastive learning model was employed to predict the occurrence of local recurrence (LR), neck lymph node relapse (NR), and distant metastases (DM). Receiver operating characteristic curve analysis was conducted to evaluate the model’s performance. Results: Over a median follow-up period of 34 months, 53 (32.7%), 36 (22.2%), and 23 (14.0%) patients developed LR, NR, and DM, respectively. Following the integration of prediction results from baseline and ART simulation CTs, the area under the curve for predicting the occurrence of LR, NR, and DM reached 0.773, 0.747, and 0.793. At the same time, the accuracy for the three endpoints was 72.4%, 74.7%, and 75.7%, respectively. Conclusions: For patients with pharyngeal cancer ready to receive RT-based treatment, our proposed models can predict the development of LR, NR, or DM through baseline and ART simulation CTs. External validation needs to be conducted to confirm the model’s performance. Full article

Background/Objectives: Eating disorders (EDs) frequently emerge during critical stages of childhood and adolescence, when identity development and emotional regulation are still maturing. Disturbances in self-concept clarity and identity integration may transform the body into a symbolic battlefield for autonomy, belonging, and self-worth. This review synthesizes developmental, psychosocial, neurocognitive, and therapeutic perspectives on the role of identity disturbance in EDs. Methods: A narrative review was conducted (2010–2025) using combinations of terms related to identity, self-concept clarity, self-discrepancy, objectification, interoception, and eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder). Results: Findings indicate that identity vulnerability (expressed as low self-concept clarity, heightened self-discrepancies, and self-objectification) mediates the association between early adversity, sociocultural pressures, and ED symptoms. Neurocognitive studies reveal altered self-referential processing, default mode network connectivity, and interoceptive signaling. Clinically, comorbid borderline personality features further exacerbate identity disturbance and complicate recovery. Evidence-based treatments such as enhanced cognitive-behavioral therapy (CBT-E) effectively target core maintaining mechanisms, while adjunctive interventions (mentalization-based therapy, schema therapy, narrative approaches, and compassion- or acceptance-based methods) show promise in addressing identity-related processes and improving outcomes. Conclusions: Identity disturbance provides a unifying framework for understanding why ED symptoms become entrenched despite adverse consequences. Integrating identity-focused approaches with nutritional and medical care may enhance recovery and reduce chronicity in youth. Future research should adopt longitudinal and mechanistic designs to clarify pathways linking identity change to clinical improvement and test identity-specific augmentations to standard ED treatments. Full article

Background: Patient-reported outcomes are integral to chronic coronary syndrome (CCS) care. The Seattle Angina Questionnaire (SAQ) is validated and prognostic, yet its clinical integration in Bulgaria is undefined. Aim: The aim of this study was to provide a structured, clinically oriented framework for integrating the SAQ into the full CCS care pathway—from screening and phenotyping (obstructive vs. ANOCA/INOCA endotypes) to diagnostics, mechanism-tailored therapy, and follow-up—while outlining a pragmatic roadmap for Bulgarian implementation. Methods: We conducted a semi-structured narrative review (1995–2024) of SAQ’s validation, prognostic utility, and implementation in the literature, augmented with guideline-based frameworks for CCS/ANOCA care. Results: The SAQ (and SAQ-7) shows strong reliability and responsiveness and independently predicts health status and clinical outcomes. Embedding the SAQ at baseline, at 4–12 weeks after therapy changes, and after 6–12 months enables symptom-guided decision-making. A phenotype-guided pathway is proposed that couples the SAQ with CAD burden assessment and—where indicated—ANOCA diagnostics (CFR/IMR, vasoreactivity testing). Mechanism-tailored therapy maps to endotypes (e.g., VSA → CCB ± nitrates; MVA → beta-blocker/ACEi/statin ± ranolazine; obstructive CADGDMT ± PCI/CABG). A minimum dataset, metrics, and registry fields are specified for Bulgarian deployment. Conclusions: A clinically structured framework clarifies how the SAQ adds value beyond description—by informing triage, treatment selection, and follow-up across CCS phenotypes. This approach provides educational guidance and a practical blueprint for pilot implementation in Bulgaria. Full article

Candida spp. are common components of normal microbiota in the oral cavity. However, Candida albicans can be a primary cause of superficial infections in the oral cavity and esophagus, especially in immunocompromised individuals. While these infections are rarely life-threatening, they can significantly impair quality of life and, in severe cases, progress to hematogenous dissemination. Oral candidiasis often exhibits as pseudomembranous, erythematous (atrophic), chronic hyperplastic, denture stomatitis, or angular cheilitis. Esophageal candidiasis is typically diagnosed by upper endoscopy, which involves histological examination and brushing. Clinical guidelines recommend topical antifungal agents for mild oral candidiasis, and systemic agents for moderate-to-severe disease or when topical therapy fails. However, azole antifungals pose a substantial risk of drug–drug interactions, primarily due to the inhibition of cytochrome P450 enzymes and drug transporters, which dramatically alters the pharmacokinetics of co-administered drugs. Additionally, amphotericin B, a polyene macrolide antibiotic, may cause nephrotoxicity and electrolyte disturbances (e.g., hypokalemia and hypomagnesemia). Moreover, the co-administration of nephrotoxic drugs may augment the toxicity associated with amphotericin B. Therefore, this review aimed to provide a comprehensive overview of the management of oral and esophageal candidiasis from the viewpoint of clinical pharmacology, with a particular focus on drug–drug interactions and adverse effect profiles. Full article

For drug-susceptible TB, the WHO-endorsed first-line regimen (isoniazid, rifampicin, ethambutol, pyrazinamide) remains the global reference. Therapy must always be tailored to drug susceptibility, especially in MDR- and XDR-TB. HIV-associated mycobacterial infections—including Mycobacterium tuberculosis (TB), disseminated Mycobacterium avium complex (MAC), and Mycobacterium leprae (M. leprae)—remain leading causes of morbidity and mortality in people living with HIV (PLWH). TB continues to account for the highest burden of AIDS-related deaths worldwide, while MAC and leprosy complicate care in advanced immunosuppression. This review synthesizes current evidence on epidemiology, clinical features, and management challenges of HIV–mycobacterial co-infections. We discuss drug-susceptible and drug-resistant TB therapies, drug–drug interactions with antiretroviral therapy (ART), and the clinical impact of immune reconstitution inflammatory syndrome (IRIS). Beyond established regimens, we highlight host-directed strategies such as metformin, glutathione augmentation, mTOR modulation, and vitamin D; immunotherapies including interferon-γ, GM-CSF, and IL-7; and therapeutic vaccines (M72/AS01E, MTBVAC, VPM1002) as promising adjuncts. Distinct from guideline-focused overviews, this review emphasizes non-tuberculous mycobacterial disease (NTM, including MAC) and leprosy in PLWH and synthesizes host-directed and adjunctive strategies with their translational prospects, including ART compatibility and IRIS. By integrating TB, NTM, and leprosy across the HIV care continuum, we highlight opportunities not treated in detail elsewhere—particularly HDT-enabled approaches and implementation considerations in PLWH. Full article

Outward remodelling of arteries is a feature of cardiovascular pathologies such as atherosclerosis and aneurysm, so a greater understanding of the processes involved in remodelling may aid the development of improved therapies for patients. As ageing increases the risk of atherosclerosis and aneurysmal disease, it was therefore hypothesised that ageing affects arterial remodelling and thereby contributes to these diseases. To test this hypothesis, we compared right carotid artery remodelling in young (2 months, n = 13) and old (18–20 months, n = 13) mice resulting from increased blood flow after ligation of the left carotid artery. The media area, thickness, collagen content and α-SM-actin content per cell of control right carotid arteries from old mice were significantly greater than observed in young mice. Positive remodelling was observed in the carotid arteries of both old and young mice 21 days after ligation of the left carotid artery. However, arteries from old mice had a significantly larger increase in lumen size and reduction in media area, thickness and α-SM-actin content per cell compared to young arteries, indicative of augmented positive remodelling in arteries from old mice. Remodelling was associated with significantly increased MMP-2 protein in arteries from young mice, but this was not observed in arteries from old mice. This study demonstrates that the extent of positive remodelling of carotid arteries is greater in old mice than in young mice and results in a potentially less resilient medial layer with decreased α-SM-actin content per cell, elastin and collagen that may promote atherosclerosis and aneurysm formation. Full article

In left ventricular hypertrophy (LVH), the combined external administration of hydrogen sulfide (H₂S) and nitric oxide (NO) has been shown to reverse LVH by activating the endothelial nitric oxide synthase pathway (eNOS/NO), independent of the cystathionine γ-lyase (CSE/H₂S) pathway. Individually, both H₂S and NO have also been reported to significantly improve RCBP, restore renal excretory performance, and enhance α-adrenergic receptor responsiveness in rats. The induction of LVH was performed over a period of two weeks using drinking water with caffeine and isoprenaline. Five weeks later, the rats were fed with L-arginine (1.25 g/L) as a nitrogen oxide donor. Vascular reactions to methoxamine, phenylephrine, and noradrenaline were assessed in presences and absence of 5-methylurapidil (5-MeU), BMY7378, and chloroethylclonidine (CeC) and α1-adrenoceptor antagonists. In both the Control WKY and LVH-WKY groups, combined H₂S+NO therapy significantly (p < 0.05) upregulated the renal mRNA of CSE and eNOS when compared with untreated LVH rats. The treatment also markedly increased RCBP in LVH-H₂S+NO rats relative to LVH controls. Furthermore, H₂S+NO administration enhanced the activity of α_1A, α_1B, and α_1D adrenergic receptors in mediating renal vasoconstriction. Even under receptor blockade with high doses (HDs) of 5-MeU, CeC, and BMY 7378, renal vasoconstriction responses to adrenergic agonists like NA, PE, and ME in the LVH-H₂S+NO group remained comparable to those observed in the counterpart Control-H₂S+NO group. The findings of current study suggest that simultaneous exogenous administration of H₂S and NO donors improve renal cortical blood flow, support renal function, and augment α_1A, α_1B, and α_1D adrenergic receptor responsiveness to adrenergic agonists like NA, PE, and ME in LVH rats. This effect appears to rely primarily on the eNOS/NO pathway, with partial contribution from the CSE/H₂S pathway. Full article