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.

Abstract: Objective: Navigated Transcranial Magnetic Stimulation (nTMS) has been little used to study Visuo-spatial (VS) circuits so far. Our work studies: I) VS functions in neurosurgical oncological patients by using repetitive nTMS (rnTMS); II) the possible subcortical circuits underneath. III) the correspondence between nTMS and Direct Cortical Stimulation (DCS) during awake procedures. Methods: We designed a monocentric prospective study, adopting a protocol to use rnTMS for preoperative planning, including VS functions for lesions potentially involving the VS network, including neurosurgical awake and asleep procedures. nTMS-based-DTI tractography allowed visualization of subcortical circuits. Statistical analyses on n TMS/DCS points were performed. Clinical results were collected pre- and postoperatively. Results: Finally, 27 patients with primitive intra-axial brain lesions were enrolled between April 2023-March 2024. Specific tests and an experimental integrated VS test (VISA) were used. The clinical evaluation (at 5±7, 30±10, 90±10 days after surgery) documented 33% of patients with ne-glect in the left hemisphere four days after surgery, and during 3-months-follow-up preservation of visuospatial function/clinical recovery [90.62% in MMSE, 98.86% in Bell Test, 80% in Clock test, 98% in OCS test]. The surgical strategy was modulated according to nTMS map. Subcortical bun-dles were traced to identify those most involved in these functions: SFLII>SLFII>SLFI. Comparison of nTMS and DCS points in awake surgery (n=10 patients) documented: Sensitivity (Se)=12%, Specificity (Sp)=91.21%, Positive Predictive Value (PPV)=42%, Negative Predictive Value (NPV)=66%. Accuracy ~63.7%. Conclusions: Based on our preliminary results, nTMS is advantageous to study cognitive func-tions, minimising neurological impairment. Further analyses are needed to validate our data.

Abstract: Background: Disease-related malnutrition and sarcopenia are prevalent conditions in gastrointestinal cancer patients, whose early diagnosis is essential to establish a nutritional intervention that contributes to preventing adverse outcomes and improving the disease prognosis. Phase angle (PhA), rectus femoris cross-sectional area (RFCSA) and rectus femoris thickness (RF-Y-axis) are considered effort-independent markers of muscle mass, strength and functionality. These markers are influenced by the metabolic changes in cancer patients but have not been fully validated in this population. Objective: This study aimed to evaluate the potential utility of PhA, RFCSA and RF-Y-axis in predicting malnutrition and sarcopenia in patients with esophagogastric cancer (EGC). Methods: This was a cross-sectional study of patients diagnosed with EGC. PhA was obtained using bioelectrical impedance vector analysis (BIVA), along with ASMMI. RFCSA and RF-Y-axis were measured via nutritional ultrasound (NU®). Muscle capacity was assessed using handgrip strength (HGS), and functionality by applying the Short-Physical-Performance-Battery (SPPB). Malnutrition and sarcopenia were determined according to GLIM and EWGSOP2 criteria, respectively. Results: Out of the 35 patients evaluated, 82.8% had malnutrition and 51.4% sarcopenia. RFCSA(r=0.582) and RF-Y-axis(r=0.602) showed significant, moderate correlations with ASMMI, unlike PhA(r=0.439), which displayed a weak correlation with this parameter. However, PhA (OR=0.167,CI 95%:0.047-0.591,p=0.006), RFCSA (OR=0.212, CI 95%:0.074-0.605,p=0.004), and RF-Y-axis (OR=0.002,CI 95%:0.000-0.143,p=0.004) all showed good predicting ability for sarcopenia in the crude models, but only RF-Y-axis was able to explain malnutrition in the regression model (OR=0.002, CI 95%:0.000-0.418,p=0.023). Conclusion: RF-Y-axis emerged as the only independent predictor of both malnutrition and sarcopenia in this study, likely due to its stronger correlation with ASMMI compared to PhA and RFCSA.

Abstract: Pulsed light (PL) is a non-thermal technology which leads to different applications (food, pharmaceutical and cosmetic packaging, medical devices) by inactivating microorganisms, knowing that the properties of PL technology are cumulative treatment, especially for bacteria. PL uses intense flashes of white light (200 nm–1100 nm wavelengths), rich in UV (200 nm–400 nm) and produced by xenon flash lamps. Localized photothermal and photophysical effects, but also the capability of its UV light component to modify the structure of biomolecules (photochemical effect), such as DNA and proteins, are the main mechanisms involved to explain the inactivation of microorganisms by PL. As compared to other sterilization methods, such as heat or chemical disinfectant treatment, PL treatment has several advantages; it is faster, induces low operational cost and leaves no residues. Nevertheless, no exhaustive data on exposure conditions are available, which would make it possible to repeat, interpret and evaluate the data needed for large-scale industrial deployment of PL in pharmaceutical and cosmetic packaging and medical devices. Research should also focus on understanding the inactivation mechanisms of different bacterial strains, states, and morphologies when exposed to PL.

Abstract: Background/Objectives: The incidence of acute kidney injury (AKI) following advanced epithelial ovarian cancer (EOC) surgery has not been extensively studied. This study aimed to investigate the incidence of AKI and identify preoperative and intraoperative predictors in patients undergoing advanced EOC cytoreduction using both traditional statistics and Artificial Intelligence (AI) modelling. Methods: Retrospective data was collected for 134 patients with a suspected or confirmed diagnosis of advanced EOC (FIGO Stage III-IV) who underwent surgical cytoreduction between January 2021 and December 2022 at a UK tertiary referral centre. AKI was diagnosed according to the KDIGO criteria. Data on 22 patient variables were extracted, including age, Charlson Comorbidity Index (CCI), procedure length, surgical complexity, and length of hospital stay. Logistic regression analysis was used for feature selection to identify AKI predictors, and an extreme gradient boost (XGBoost) model was applied to all variables related to AKI events. Results: The incidence of postoperative AKI was 6.72% (n=9). Predictive factors for AKI included younger age (OR = 0.942, p=0.037), lower CCI (OR = 0.415, p=0.015), longer procedure duration (OR = 1.006, p=0.019), and greater surgical effort (OR = 1.427, p=0.007). Patients with perioperative AKI experienced a doubling in the length of hospital stay (p=0.008). Mortality rates were similar between patients with and without AKI. AI-driven algorithms highlighted the complexity of AKI prediction and provided individual risk profiles, enabling future stratification and prompting different frequencies of AKI monitoring following cytoreduction. Conclusions: Predicting AKI is a complex task. This study found a lower-than-expected incidence of AKI following advanced EOC cytoreductive surgery. AKI is linked to heightened surgical risk-taking, underscoring the need for improved guidelines focusing on postoperative monitoring for targeted patients. Artificial Intelligence offers the potential for personalized AKI prediction.

Abstract:

Background/Objectives: Artificial intelligence is transforming neuroimaging by enhancing di-agnostic precision and treatment planning. However, its applications in pediatric cancer neu-roimaging remain limited. This review assesses the current state, potential applications, and challenges of AI in pediatric neuroimaging for cancer, emphasizing the unique needs of the pe-diatric population. Methods: A comprehensive literature review was conducted, focusing on artificial intelligence impact on pediatric neuroimaging through accelerated image acquisition, reduced radiation, and improved tumor detection. Key methods include convolutional neural networks for tumor segmentation, radiomics for tumor characterization, and several tools for functional imaging. We analyzed challenges such as limited pediatric datasets, developmental variability, ethical concerns, and the need for explainable models. Results: Artificial intelligence has shown significant potential to improve imaging quality, reduce scan times, and enhance diagnostic accuracy in pediatric neuroimaging. Artificial intelligence algorithms demonstrated improved accuracy in tumor segmentation and outcome prediction for tumor treatments. Conclusions: Artificial intelligence offers significant potential for enhancing pediatric neuroim-aging in cancer care, aiding in precise diagnoses and personalized treatments. To overcome current limitations, future research should focus on building robust pediatric datasets and developing interpretable models suited for clinical practice.

Abstract:

Background: Since the gut microbiota is important for athlete health and performance, its optimization is increasingly gaining attention in sports nutrition, for example with whole fermented foods. Sauerkraut is a traditional fermented food rich in pro-, pre- and postbiotics, which has not yet been investigated in the field of sports nutrition. Methods: To determine whether sauerkraut could be used for gut microbiota optimization in sports nutrition a proof-of-concept study was conducted. The microbiota composition of organic pasteurized sauerkraut was analyzed, and then healthy active athletes were provided with the same sauerkraut for 10 days as an intervention. The effects of sauerkraut on the athlete’s gut microbiota, laboratory parameters and bowel function were assessed. Objectives: Significant changes in the gut microbiota composition were seen on taxonomic and functional level, independent of baseline microbiota composition, even after short-term supplementation. Most notably an increase of several health-promoting genera of family Lachnospiraceae, as well as significant alterations in metabolic pathways regarding cell wall synthesis and the metabolism of nucleotide bases. An increase in the proportion of lymphocytes and decrease in B12 vitamin levels was observed as well as a risk of indigestion in certain athletes, which significantly resolved after seven days of supplementation in all athletes. It is unclear whether the observed effects are attributable to the sauerkraut's own microbiome, or its pre- and postbiotics since it is a whole food. Our study has demonstrated that the concept of whole fermented foods, such as sauerkraut, could potentially be feasible and effective in sports nutrition for gut microbiota optimization.