Abstract: There has been a growing interest in the use of inertial sensors to explore the temporal aspects of the Timed-Up-and-Go (TUG) test. The current study aimed to analyze the spatiotemporal parameters and the phases of the TUG test in patients with knee osteoarthritis (KOA) using inertial sensors and to compare the results with those of non-arthritic individuals. The study included 20 patients with KOA and 60 non-arthritic individuals aged 65 to 84 years. All volunteers performed the TUG test and 17 spatiotemporal parameters and phase data were collected wirelessly using the BTS G-Walk inertial sensor. Significant differences were observed between KOA patients and non-arthritic controls, with all but 3 parameters not reaching statistical significance. The results of our study align with findings from similar studies involving diverse patient populations. Our study offers valuable insights into specific characteristics of mobility and functional abilities influenced by KOA, enabling healthcare professionals to develop targeted interventions.

Abstract: Intensive Care Unit-Acquired Weakness (ICU-AW) is a common and severe complication in critically ill patients, characterized by profound and often prolonged muscle weakness. The complexity of its diagnosis and management requires a multidimensional approach that integrates clinical, electrophysiological, and imaging tools. This review focuses on the challenges in diagnosing ICU-AW, emphasizing the limitations of traditional methods such as manual muscle testing and electrophysiological studies, and highlights the emerging role of neuromuscular ultrasound (NMUS) as a promising, non-invasive diagnostic aid. Despite its utility, no gold standard exists for NMUS, making it an evolving area of research. The pathophysiological basis of ICU-AW involves multiple mechanisms, including critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and muscle atrophy due to disuse. Understanding these underlying mechanisms is crucial for advancing diagnostic strategies and informing therapeutic interventions. Recent insights into the molecular and cellular pathways involved, such as the role of oxidative stress, mitochondrial dysfunction, and the ubiquitin-proteasome system, have opened new avenues for targeted therapies. Management of ICU-AW remains challenging, as no specific treatment has been proven fully effective. Current strategies focus on early mobilization, minimizing sedation, and optimizing nutritional support. Emerging therapies targeting molecular pathways involved in muscle degradation are under investigation, highlighting the potential to translate pathophysiological understanding into therapeutic innovations. This review underscores the need for ongoing research to establish standardized diagnostic protocols and develop targeted treatments for ICU-AW.

Abstract: Objectives: to evaluate the structural and functional outcomes after the loading phase with Brolucizumab in switched patients with diabetic macular edema (DME), and to identify poten-tial predictive biomarkers of treatment response. Methods: A total of 28 eyes with DME, switched to Brolucizumab, were retrospectively reviewed. Main outcomes during the follow-up period, up to 6 weeks after the fifth injection, included changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), macular volume, subfoveal choroidal thickness, intraretinal and sub-retinal fluid (IRF, SRF), cyst dimension including maximal-horizontal-cyst-diameter (MHCD), maximal-vertical-cyst-diameter (MVCD), width to height ratio (WHR), foveal avascular zone (FAZ) dimension, and vessel density (VD). Results: At the last follow-up, BCVA was significantly improved (p=0.003). Significant reduction of CST was demonstrated after each injection time point (p

Abstract: Chronic kidney disease (CKD) is increasingly common in older cats. The transforming growth factor-beta (TGF-β) pathway is associated with renal fibrosis. This study aimed to quantify the mRNA expression of TGFβ, MAPK, and Bcl2 genes and the protein expression of TGF-β and MAPK in feline kidney cells and tissues. Gene expression analysis was conducted using relative gene expression, while protein expression was assessed through western blot analysis. The immunohistochemistry staining of TGF-β and MAPK was performed on feline kidney tissues. The result reveals the significant upregulation of TGFβ (P = 0.001) and considerable downregulation of Bcl2 (P = 0.010) in doxorubicin-treated feline kidney cells. Protein expression level of TGF-β and MAPK also tended to increase in doxorubicin-induced feline kidney cells. The immunostaining levels of TGF-β and MAPK were higher in the kidney tissues of cats with CKD compared to the no lesions group. A deeper understanding of the TGF-β pathway could enable veterinarians to monitor disease progression and mitigate complications in feline CKD.

Abstract: The first part of this review highlighted the evolving landscape of atherosclerosis, noting emerging cardiometabolic risk factors, the growing impact of exposomes, and social determinants of health. The prominent role of atherosclerosis in the bidirectional relationship between cardiovascular disease and cancer was also discussed. In this second part, we examine the complex interplay between multimorbid cardio-oncologic patients, cardiometabolic risk factors, and the harmful environments that lend a “syndemic” nature to these chronic diseases. We summarize management strategies targeting disordered cardiometabolic factors to mitigate cardiovascular disease and explore molecular mechanisms enabling more tailored therapies. Importantly, we emphasize the early interception of atherosclerosis through multifactorial interventions that detect subclinical signs (via biomarkers and imaging) to treat modifiable risk factors and prevent clinical events. A concerted preventive effort—referred to by some as a “preventome”—is essential to reduce the burden of atherosclerosis-driven chronic diseases, shifting from mere chronic disease management to the proactive promotion of “chronic health.”

Abstract: After more than 30 years since its inception, the utility of brain imaging for understanding and diagnosing mental illnesses is in doubt, receiving well-grounded criticisms from clinical practi-tioners. The symptom-based correlational approach seems unable to provide the field of psychiatry with reliable brain-imaging metrics. However, the emergence of computational psychiatry has paved a new path not only for understanding the psychopathology of mental illness but also to provide practical tools to the clinical practice in terms of computational metrics: computational phenotypes. These phenotypes, however, still lack the necessary test-retest reliability. In this re-view, we describe recent works unveiling that mind and brain-related computational phenotypes show structural (not random) variation over time, longitudinal changes. Furthermore, we show that these findings suggest that understanding the causes of these changes will improve the con-struct validity of the phenotypes with ensued increase in test-retest reliability. Finally, we propose that the active inference framework of brain functioning provides a general-purpose method to causally understand these longitudinal changes by integrating brain images as observations in partially observable Markov decision processes.

Abstract:

Background: Global health organizations recommend breastfeeding, but maternal pharmacotherapy can disrupt this due to safety concerns. Physiologically-based pharmacokinetic (PBPK) models predict medication transfer through breastfeeding, relying on validated milk intake volume data. However, literature mainly focused on different measurement methods, or such intake data were collected without systematic review. This systematic review therefore aims to gather data on human milk intake volume derived using the (dose-to-the-mother) deuterium oxide dilution method, allowing comparison with literature. Additionally, it aims to explore effects of maternal conditions on milk intake volume. Methods: PubMed, Embase, Web of science, Cochrane library, Scopus and CINAHL were searched for studies on the dilution method and breastfeeding in healthy infants. Risk of Bias was assessed using the Newcastle-Ottawa Scale (NOS) and the Risk of Bias 2 (RoB2) tool. Data on mean human milk intake volume were extracted and synthesized (mL/day and mL/kg/day) throughout infancy. Results: Sixty studies (34 countries) reported on milk intake volume of 5502 infants. This intake was best described by logarithmic regression y(mL/kg/day) = 149.4002 -0.2268*x -0.1365*log(x) (x=postnatal age, days). Maternal conditions showed no significant influence on human milk intake, except for maternal smoking (reduction). Conclusion: This function corresponds with previous literature, particularly between 1.5 to 12 months. Limited availability of early infancy data underscores the need for additional data in future PBPK modelling to enhance informed healthcare decisions and improved outcomes for mother and infant.

Abstract: In light of the current interest in the bidirectional relationship between epilepsy and dementia, primary attention is currently focused on the role of hyperphosphorylated tau (pTau) in cognition in epilepsy. Synthesizing available data from studies investigating pTau burden in surgical biopsy specimens from patients with temporal lobe epilepsy, the prevalence of pTau across five studies with a total number of 142 patients ranges from 3.5% to 95%. Findings also varied with regard to the location of pTau in the hippocampus and/or temporal cortex. Two of five studies (40%) demonstrated an inverse relationship between pTau burden and cognitive performance, one study with regard to executive functions and the other with regard to naming and verbal short-term memory. This is partly unexpected since executive functions and verbal short-term memory depend less on temporal than extratemporal fronto-parietal networks. The only longitudinal study found a significant link between pTau and cognitive decline in verbal learning and memory and in part also in naming from pre- to postoperative and from three to 12 months postoperative. Given the heterogeneity of the study cohorts, the neuropsychological and neuropathological methods and findings, no clear picture emerges regarding the association between pTau and cognition in temporal lobe epilepsy. This could in part be expected due to the multifactorial etiology of cognitive impairment in epilepsy, including the active epilepsy, the underlying and sometimes dynamic pathology, and anti-seizure medication. Some of these factors may affect pTau expression. Further research should investigate pTau longitudinally and noninvasively on a whole-brain level, using standardized, targeted neuropsychological outcome measures, while controlling for age and other factors that may influence cognitive trajectories in epilepsy.

Abstract:

Heart Failure (HF) is a prevalent condition which places a substantial burden on healthcare systems worldwide. Pharmacological therapy structures the cornerstone of management in HF reduced ejection fraction (HFrEF), including angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor-neprilysin inhibitors (ARNI), beta blockers (BB), mineralocorticoid receptor antagonists (MRA) and sodium/glucose co-transporter 2 (SGLT2) inhibitors, which all improve survival rates. Mortality reduction with pharmacological treatments in HF preserved ejection fraction (HFpEF) are yet to be established. Cardiac rehabilitation and exercise training can play an important role in both HFrEF and HFpEF. Cardiac rehabilitation significantly improves functional capacity, exercise duration and quality of life. Exercise training has shown beneficial effects on peak oxygen consumption (pVO2) and 6-minute walk test distance in HFrEF and HFpEF patients as well as a reduction in hospitalisation and mortality rates. ET also has been shown to have beneficial effects on depression and anxiety levels. High intensity training and moderate continuous training have both shown benefit, while resistance exercise training and ventilatory assistance may also be beneficial. ET adherence rates are higher when enrolled to a supervised programme but prescription rates remain low worldwide. Further research is required to establish the most efficacious exercise prescriptions in patients with HFrEF and HFpEF, but personalised exercise regimens should be considered as part of HF management.

Abstract:

The study focused on developing transungual patches for the targeted treatment of onychomycosis, a common fungal infection of the nail. By incorporating Sertaconazole nitrate into patches using the Self-Microemulsifying Drug Delivery System (SMEDDS) technique, the aim was to overcome challenges related to drug penetration across the nail plate while enhancing solubility and permeability. Various patch formulations were prepared and extensively evaluated for key parameters such as thickness, weight variation, drug content, folding endurance, moisture content, moisture uptake, and in vitro drug release. The release data were analyzed using different kinetic models to understand the drug release mechanism. Selected formulations underwent accelerated stability testing per ICH guidelines, demonstrating stability under accelerated conditions. The study successfully addressed the challenges of transungual drug delivery, with the developed patches showing promising characteristics and stable release profiles. The application of kinetic models provided valuable insights, and the formulations passed stability testing, indicating their potential as effective and stable transungual drug delivery systems for the treatment of onychomycosis.