Search Results (44,416)

Background/Objectives: Chronic heart failure (CHF) is a leading cause of global morbidity and mortality, particularly among older adults, significantly impacting their quality of life and imposing a substantial economic burden. While pharmacological and surgical treatments remain essential, non-pharmacological interventions led by nurses are gaining prominence due to their comprehensive approach and biopsychosocial impact. The objective of this study was to synthesise and integrate such interventions for community-dwelling older adults with CHF. Methods: An integrative review was conducted in accordance with the Joanna Briggs Institute protocols and the PRISMA statement, utilising a systematic search across databases including PubMed and Cochrane. Qualitative, quantitative, and mixed-methods studies evaluating non-pharmacological interventions in the home setting were included, whilst those targeting non-specific populations were excluded. Following a rigorous screening process, 12 studies were selected, and their methodological quality was appraised based on study design. Results: The 12 included studies involved a total of 2466 participants and addressed interventions across the domains of education, physical activity, telehealth, and nutrition, with programme durations ranging from 4 weeks to 16 months. Notable improvements were observed in physical capacity, cognitive function, quality of life, and self-care capabilities, alongside potential reductions in hospitalisations reported in some studies. However, considerable methodological variability was identified across the literature. Conclusions: This review synthesises non-pharmacological nursing interventions for older adults with CHF, demonstrating varied benefits across multiple biopsychosocial domains. The findings emphasise the critical need for further research to evaluate the economic viability of these programmes and to adapt interventions to enhance the delivery of community-based care. Full article

Motivational interviewing (MI) is gaining traction in veterinary medicine as an evidence-based approach for engaging clients in conversations that strengthen their intrinsic motivation to change behaviours that affect the welfare of animals in their care. While MI has a substantial and well-established evidence base across human healthcare and related fields, the veterinary evidence base remains small and is currently limited by study design challenges, inconsistent fidelity measurement, and outcome measures that rarely extend beyond short-term changes in communication behaviour. Existing methodological guidance addresses treatment integrity and theoretical mechanisms but does not provide an integrated framework for designing robust studies across the range of questions relevant to veterinary practice. This paper addresses that gap by providing practical methodological guidance for researchers designing MI studies in veterinary clinical settings. A novel conceptual model of the MI implementation pathway, mapping the journey from practitioner awareness through training and delivery to client outcomes, is used to organise key research questions that need to be answered in veterinary contexts. Guidance is then provided on selecting appropriate study designs, measuring fidelity and outcomes, estimating sample size, and managing the practical and ethical challenges specific to veterinary clinical settings, alongside minimum reporting standards to support more rigorous and reproducible MI research. Full article

Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported annually worldwide, 51% of which occur in children. However, currently available topical otic formulations are limited by their inability to achieve predictable therapeutic concentrations at the site of inflammation, resulting in reduced efficacy. In addition, the selection of appropriate active pharmaceutical ingredients (APIs) for drug products remains challenging; as a result, existing therapies do not comprehensively address all stages of pathogenesis. This study aimed to analyze existing locally acting formulations for middle ear drug delivery, evaluate their advantages and limitations, and assess modern approaches to the development of novel drug delivery systems and API combinations. A critical review of 69 publications (2010–2026) was conducted, supplemented by a strengths and limitations analysis of dosage forms and an evaluation of APIs based on clinical data. The findings highlight a lack of targeted drug delivery systems, limited efficacy of existing API combinations against bacterial biofilms, and their risk of ototoxicity. Emerging innovative drug delivery approaches, including microemulsions, vesicular systems, stimuli-responsive systems, and hydrogels, have demonstrated promising results in preclinical studies; however, their efficacy and safety remain to be confirmed in clinical settings before their full therapeutic potential in otitis media treatment can be realized. Full article

Coronary in-stent restenosis (ISR) remains a major contributor to repeat revascularisation despite advances in drug-eluting stent (DES) technology. Its persistence reflects a complex and heterogeneous interplay among mechanical, biological, and procedural factors, and understanding the dominant mechanism in each case is fundamental to effective treatment selection. This narrative review provides a contemporary, mechanism-guided approach to the practical management of coronary ISR. We summarise the definition, incidence, and classification of ISR—including the Mehran, Waksman, and SCAI 2023 time-based frameworks—and outline patient-related, procedural, anatomical, and stent-related risk factors. The pathophysiology of neointimal hyperplasia and neoatherosclerosis is discussed with reference to its clinical implications. Intracoronary imaging with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) is central to ISR characterisation and treatment planning. Current international guidelines support imaging use in ISR management, though it is important to recognise that this recommendation is based largely on observational and surrogate-endpoint data rather than ISR-specific randomised trials demonstrating reductions in hard clinical outcomes, and practical barriers including cost, availability, and operator expertise must be acknowledged. Evidence-based treatment strategies—including drug-coated balloons (DCB), repeat DES implantation, lesion-modifying therapies, vascular brachytherapy, and coronary artery bypass grafting—are reviewed critically with reference to contemporary trial data and their specific clinical applicability. The choice between DCB and repeat DES is addressed with greater nuance, accounting for ISR type (BMS-ISR versus DES-ISR), lesion pattern, stent layering, and bleeding risk. Management considerations in complex subsets—chronic total occlusion ISR, left main ISR, saphenous vein graft ISR, and recurrent ISR—are also addressed. We propose a practical, substrate-driven management framework aligned with the 2024 ESC, 2021 ACC/AHA/SCAI, and 2018 JCS/JSCVS guidelines. Future research priorities include ISR-specific randomised trials with hard clinical endpoints, prospective validation of imaging-guided treatment algorithms, head-to-head comparisons of DCB platforms, and investigation of pharmacological strategies targeting neoatherosclerosis progression. Full article

Background/Objectives: Tirzepatide is a dual GIP and GLP-1 receptor agonist indicated for the treatment of type 2 diabetes and obesity. Oral delivery of tirzepatide is limited by poor gastrointestinal permeability, pH-dependent solubility, and manufacturing challenges associated with high-dose absorption enhancers. Methods: This study developed an immediate-release oral tirzepatide tablet using a Quality by Design (QbD) approach. Sodium caprate (C10) was selected as the absorption enhancer based on acid-neutralizing capacity, Caco-2 permeability enhancement, and preliminary rat pharmacokinetic screening. Quality target product profile, critical quality attributes, preliminary hazard analysis, and failure mode and effects analysis identified binder/disintegrant ratios as critical material attributes and hammer milling conditions as critical process parameters. Face-centered central composite designs and multiple-response optimization (MRO) were applied to optimize dissolution, flowability, and tablet mechanical integrity. Results: The optimized binder/disintegrant composition produced benchmark-comparable dissolution profiles against oral semaglutide tablets in pH 1.2, 4.0, and 6.8 media, with f₂ values exceeding 50 for both C10 300 mg and 500 mg formulations. The optimized process yielded tablets with low friability (0.58%) and acceptable flowability (Carr’s index, 24). In beagle dogs, the C10 300 mg formulation achieved higher systemic exposure than the C10 500 mg formulation, with a C_max of 46.49 ± 23.79 ng/mL and AUC_last of 1261.03 ± 690.44 h·ng/mL. Conclusion: These results support C10-mediated oral tirzepatide delivery and QbD-based optimization for oral peptide tablets. Full article

Background/Objectives: The aim of this study was to show a standardized four-step technique that can offer individually personalized full-mouth therapy for each complex dental patient with erosive tooth wear resulting from bulimia nervosa, focusing on the individualized vertical dimension of occlusion (VDO), functional and aesthetic stability, and patient-reported outcomes, including dental symptoms, nutrition, self-perception, and quality of life. Methods: The following steps are proposed for structured full-mouth rehabilitation. Step 1: Intraoral diagnosis via a single computer-aided impression. Step 2: Determination of a new adequate vertical dimension of occlusion and soft tissue prediction. Step 3: Removable sample dentures—prototypes. Step 4: Non-prep/minimal-prep crowns as the long-term provisional/definitive treatment. Results: Nine adults (11% male) with dental erosion caused by bulimia nervosa (78%), gastro-esophageal reflux (11%), and soft drinks (11%) were part of this cohort. The novel digital workflow enabled restoration of an individualized vertical dimension of occlusion, stable occlusion, appropriate centric and eccentric contacts, biomimetic dental anatomy, harmonious tooth proportions, and optimized red–white aesthetics. Dental problems (hypersensitivity, dental pain), nutritional behavior, body perception, and quality of life improved after the full-mouth rehabilitation. Conclusions: The presented digital workflow offers a promising approach for full-mouth rehabilitation in patients with severe dental erosion, particularly associated with bulimia nervosa, enabling structured restoration planning and stepwise evaluation of the vertical dimension of occlusion and functional adaptation. Prospective studies with larger cohorts are needed to confirm long-term clinical outcomes and patient-reported benefits. Full article

Introduction: High-Intensity Focused Ultrasound (HIFU) is a widely used non-invasive esthetic treatment for facial/neck rejuvenation, inducing thermal coagulation for neocollagenesis. Despite its general safety, its non-optimal application risks neurological adverse events like tinnitus, trigeminal neuralgia, and headaches. Materials and Methods: Out of a pool of 124 patients treated with HIFU (Dual Hi; Med & Tech, Occhiobello, Italy) by experienced esthetic clinicians, four patients developed neurological or otological disturbances, which are presented as descriptive clinical case reports. These included acute tinnitus, exacerbation of pre-existing tinnitus, trigeminal neuralgia during treatment, and post-procedural headaches. To contextualize the clinical findings, relevant published literature on neurological adverse events associated with esthetic HIFU was reviewed in a non-systematic manner using major scientific databases, and used to support descriptive clinical interpretation rather than formal systematic analysis. Results: Rare transient events include acute tinnitus post-HIFU; exacerbated pre-existing tinnitus; trigeminal neuralgia during a procedure; and post-session headaches. Potential mechanisms might include thermal and mechanical nerve injury adjacent to the superficial musculoaponeurotic system (SMAS); all cases resolved successfully through tailored approaches—spontaneous resolution, corticosteroids plus hyperbaric oxygen therapy, analgesics, or ibuprofen. Conclusions: Neurological adverse effects from esthetic HIFU are uncommon/self-limiting but underscore the need for operator training, anatomical expertise, and patient history screening. Standardized protocols are essential for safety. Full article

Background/Objectives: The use of quantitative neuroimaging to establish objective biomarkers in neurodegenerative diseases (NDD) has attracted increasing interest over the last decade. Advanced magnetic resonance imaging (MRI) such as arterial spin labeling (ASL) and diffusion tensor imaging (DTI), as well as [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET), could provide clinically meaningful biomarkers and may support differential diagnosis. The aim of this investigator-initiated, single-center, retrospective comparative study was to implement a framework for multimodal neuroimaging to evaluate cases with rare NDD, using a methodological approach that integrates metabolic, perfusion, and microstructural parameters from simultaneous FDG-PET/MRI, and to investigate its potential to facilitate diagnosis. Methods: Three patients with pathological motor signs (1f/2m; 63, 73, and 52 years) and 19 control subjects with subjective cognitive deficits (SCDs) underwent combined FDG-PET/MRI with pseudo-continuous ASL and DTI. Standardized uptake values (SUVs), relative cerebral blood flow (rCBF), and fractional anisotropy (FA) were calculated to identify pattern alterations in individual patients based on parameterization mapping. The final diagnosis was corticobasal degeneration (CBD, n = 1) or primary lateral sclerosis (PLS, n = 2). Results: At the individual patient level, disease-specific changes in defined brain regions could be demonstrated and quantified compared to control subjects. All three patients showed significantly decreased FA, primarily along parts of the course of the corticospinal tract (CST). In the patient with CBD, asymmetric SUVR and rCBF decreases were observed, mostly overlapping with motor regions. In the two patients with PLS, SUVR revealed mostly unspecific findings (hypothetically due to a slow progression rate or due to potentially early disease stages), while ASL indicated decreased rCBF primarily overlapping within the motor cortex. Changes at the gray matter level were primarily located adjacent to changes in white matter, as indicated by the multimodal analysis approach using simultaneously acquired FDG-PET/MRI data. Conclusions: According to this proof-of-concept study, multimodal neuroimaging by the combination of quantitative MRI and FDG-PET has the potential to guide differential diagnosis in rare NDDs, especially if clinical diagnosis is not straightforward to achieve. Since particularly early diagnosis remains essential for patient counseling, effective treatment, and clinical management, the present framework appears helpful to be developed further until it aligns and integrates with clinical routine. Full article

Background: Mutations in the KRAS oncogene occur in approximately 40% of colorectal cancers, predominantly within exon 2. Non-exon 2 mutations are less common and remain poorly characterized in terms of their clinical and biological significance. Systemic inflammatory markers are well-established prognostic indicators in colorectal cancer, yet whether their prognostic value differs across KRAS mutation subtypes has yet to be defined. We aimed to characterize and compare the clinicopathological and inflammatory profiles of patients with exon 2 versus non-exon 2 KRAS-mutated colorectal cancer and evaluate their prognostic implications. Methods: This retrospective cohort study analyzed 272 patients with microsatellite stable metastatic colorectal cancer with KRAS mutations, comprising 236 exon 2 and 36 non-exon 2 cases. Clinical, molecular, and laboratory data, including baseline systemic inflammatory markers, were extracted from electronic medical records. Survival outcomes and the prognostic impact of these variables were evaluated with Kaplan-Meier curves and univariable and multivariable Cox proportional hazards regression analyses. Results: Non-exon 2 mutations were significantly more frequent in female patients (64% vs. 45%, p = 0.048) and in left-sided primary tumors (83% vs. 64%, p = 0.035). Median overall survival was 45.7 months for the non-exon 2 group compared to 32.4 months for the exon 2 cohort; KRAS mutation subtype was not significantly associated with overall survival on univariable or multivariable analysis (univariable HR 1.36, 95% CI 0.85–2.16, p = 0.2; multivariable HR 1.376, 95% CI 0.794–2.383, p = 0.255). Systemic inflammation demonstrated distinct prognostic value, with elevated white blood cells, absolute neutrophil count, platelets, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and low albumin levels demonstrating association with worse overall survival in the exon 2 cohort. Conversely, only an elevated neutrophil-to-lymphocyte ratio predicted worse survival in the non-exon 2 group. Conclusions: KRAS exon 2 and non-exon 2 mutated metastatic colorectal cancers exhibit distinct clinical and inflammatory characteristics. Systemic inflammation exerts a significantly greater prognostic impact in exon 2 disease. As the therapeutic landscape for KRAS-mutated CRC continues to evolve, these findings hold promise for informing KRAS mutation-specific approaches to patient stratification and treatment planning. Full article

Cytoreductive surgery remains one of the key treatment modalities in advanced ovarian cancer. Complete cytoreduction is the main surgical goal. PARP inhibitors are currently established mainly as maintenance therapy after response to platinum-based chemotherapy, particularly in patients with BRCA-mutated or homologous recombination-deficient tumors. Their use before cytoreductive surgery remains investigational. This review evaluates preoperative PARP inhibition from a surgical perspective. This narrative review summarizes current evidence, ongoing clinical trials, and perioperative considerations related to preoperative or neoadjuvant PARP inhibitor strategies in advanced ovarian cancer. Particular attention was given to the review of current clinical trials’ strategies, resectability, complete cytoreduction, patient selection, perioperative safety, treatment timing, and surgery-specific endpoints. Current studies explore several preoperative approaches, including short window-of-opportunity treatment before primary debulking surgery, PARP inhibitor monotherapy as potential conversion therapy in homologous recombination-deficient disease, PARP inhibitor-based strategies before interval debulking surgery, combination regimens with immunotherapy or antiangiogenic therapy, and preoperative PARP inhibitor use before secondary cytoreduction in recurrent disease. These studies suggest that preoperative PARP inhibition may provide biological and surgical insights, but available evidence remains preliminary. Key concerns include hematologic toxicity, surgical postponement, perioperative complications, wound healing, postoperative recovery, and the risk of delaying standard chemotherapy or surgery. Preoperative PARP inhibitor therapy is theoretically promising but an unproven strategy in ovarian cancer. Its future value will depend on prospective trials showing that it can safely improve resectability and complete cytoreduction without compromising treatment timing. Future studies should include surgery-specific endpoints in addition to conventional oncologic outcomes. Full article

Human endogenous retroviruses (HERVs) originate from ancient retroviral integration into the primate germline. Although most are defective proviruses, the most recently endogenized groups, like the HERV-K family, retain intact ORFs encoding retroviral proteins. HERVs usually remain transcriptionally silent, yet this status is reversible. Multiple HIV-HERV interactions, mainly mediated by the HIV Tat protein, lead to HERV transcription and protein production. The present study investigates HERV-K transcription in particular of Human MMTV-like (HML) group-2 and 6 in peripheral blood of people with HIV (PWH). Using different experimental approaches—such as single-cell and plasma transcriptomics-, we found that HERV-K transcripts may be detected during both acute and chronic phases of the infection, with HML-6 showing higher expression compared to HML-2, predominantly within myeloid cells. Effective combined antiretroviral therapy (cART) was able to significantly reduce HML-6 transcription, regardless of whether the treatment was initiated in the acute or late chronic phases of HIV infection. Notably, chronic infections showed higher HML-6 transcript levels compared to acute infections in both naïve and successfully cART-treated subjects, potentially associated with persistent immune dysregulation observed in chronic HIV infection, although a direct causal role of HML-6 expression remains to be established. Full article

Introduction: Nicotine dependence is a chronic disorder with both psychological and somatic components which, in the intensive care unit (ICU) setting, may affect the course of treatment through mechanisms related both to long-term nicotine exposure and to the consequences of its abrupt cessation. The aim was to collect and map the current knowledge on smoking-related complications, the prevalence of nicotine withdrawal symptoms in this group, and to identify and describe interventions used to prevent or alleviate nicotine withdrawal symptoms in patients hospitalised in the ICU. Methods: The review included sources retrieved from databases such as PubMed, CINAHL, Scopus, Web of Science, and the Cochrane Library, published in English, that met the PCC criteria, with no time restrictions. Results: Forty-four sources were included. Twenty-nine contributed evidence on smoking-related status as an exposure or associated factor, five explicitly focused on abrupt nicotine cessation or nicotine withdrawal syndrome, and fifteen addressed interventions; categories overlapped. Delirium was the most frequently investigated outcome in smoking-related exposure studies. Withdrawal-focused sources reported or discussed nonspecific manifestations, including agitation, restlessness, anxiety, craving, and delirium-like presentations, but no validated ICU-specific diagnostic approach or robust prevalence estimate was identified. NRT was the only intervention evaluated. Conclusions: Smoking-related status was associated with agitation and delirium in several observational studies; however, heterogeneous exposure definitions and inconsistent evidence syntheses preclude causal or general prognostic conclusions. Evidence specific to nicotine withdrawal syndrome was limited, and the effectiveness and safety of NRT remain uncertain. Implications for clinical practice included routine identification of nicotine dependence at ICU admission, early monitoring of withdrawal symptoms, individualisation of sedation management, careful and selective consideration of nicotine replacement therapy (NRT), education of the therapeutic team, planning of further care, and smoking cessation interventions. Full article

Narrative psychotherapy focuses on jointly discussing life stories with patients to promote shifts in sense of self and narrative identity. Narrative approaches have roots in constructivism which requires various elements or cognitive processes necessary for meaning making, such as the discussion of thoughts and feelings, how thoughts and feeling change over time, and how the patient’s construction of meaning contributes to their sense of self and place in the world. Narrative psychotherapy may have unique elements that promote recovery for people with psychosis. For instance, narrative approaches may help to integrate narratives that are fragmented or focused on illness identity, though the research is limited. The current study is a narrative review that aims to (1) discuss current theoretical and research findings related to narratives and narrative identity in people with psychosis; (2) identify and describe psychotherapy approaches that focus on narratives. We summarize recent findings that highlight positive outcomes for people experiencing psychosis, and how people move towards more integrated and complex narratives. We found a range of therapeutic approaches that focus on narratives including metacognitive therapy (i.e., metacognitive reflection and insight therapy), trauma-based psychotherapy (i.e., trauma-focused cognitive-behavioral therapy for psychosis and narrative enhancement therapy), treatment focused on self-stigma or illness identity (i.e., narrative enhancement and cognitive therapy and self-concept and engagement and life), and art and creative therapies. We discuss interpretation of findings and their implication for mechanisms of change. Full article

Aronia melanocarpa puree is rich in anthocyanins and proanthocyanidins, but its pronounced tannin-derived astringency limits product acceptance. This study developed a non-removal astringency-modulation strategy using food-grade L-proline and evaluated its molecular basis, processing window, and quality effects. Ultraviolet–visible (UV–Vis) and Fourier-transform infrared (FT-IR) spectroscopic analyses suggested that L-proline altered the local microenvironment of procyanidin B2 (PC-B2) through hydrogen bonding, hydrophobic association, and molecular packing rearrangement, without evident disruption of the PC-B2 aromatic skeleton. In a PC-B2–bovine serum albumin model, an appropriate L-proline level reduced the protein precipitation rate from 45.3% to 31.2% and increased soluble phenolic retention, suggesting weakened polyphenol–protein precipitation. The strategy was then optimized in puree using machine learning-assisted multi-response analysis and Box–Behnken validation. The recommended condition was 150 mg/100 mL L-proline at 40 °C for 60 min, yielding a deastringency rate of 36.13%, with anthocyanin and vitamin C retention rates of 88.80% and 55.56%, respectively. The optimized treatment maintained red color, colloidal dispersion, and shear-thinning behavior; increased the anthocyanin digestion retention index from 50.0% to 87.4%; and improved overall sensory acceptance from 4.17 to 8.17. These findings support L-proline-mediated microenvironmental modulation as a mild processing approach for high-tannin cloudy berry products. Full article

The increasing contamination of municipal wastewater by a broad spectrum of pharmaceuticals necessitates effective quaternary treatment stages. This pilot study evaluates an innovative combined technology: physical electrostatic pretreatment (conducted using experimental equipment based on a patented design (EP 2388068)) followed by biodegradation in real secondary effluent samples (COD_(Cr) 22.0 mg·L⁻¹ to 32.0 mg·L⁻¹). A total of 17 selected micropollutants were subjected to an 8-h exposure in a high-intensity electrostatic field (20 kV) and a subsequent 20-day microbial degradation using a mixed culture of erythropolis, R. rhodochrous, and R. degradans. Results demonstrate high substance-specific efficiency. The most significant synergistic effect was observed for moderately biodegradable compounds, particularly venlafaxine (improvement up to ~44%), trimethoprim (25–36%), and tramadol (31–58%), representing a ~30–37% efficiency increase over standalone biodegradation. For readily biodegradable (e.g., metoprolol) or highly persistent substances, the impact was inconsistent. Physical pretreatment alone at 20 kV exhibited low to moderate efficiency (up to ~30%) without the biological stage. This combined approach represents a promising synergistic solution for wastewater treatment plant intensification. The primary mechanism involves enhancement of target compound bioavailability induced by the electrostatic field, which subsequently accelerates microbial metabolism. Full article