Test-retest reliability of the "Home Town Walk" fMRI paradigm for memory activation and lateralization in the pre-surgical evaluation of patients with temporal lobe epilepsy.

Introduction: Functional magnetic resonance imaging (fMRI) can be used to assess language and memory function as part of pre-surgical decision making in refractory epilepsy. Although language paradigms are well established, memory paradigms are not widely used in clinical practice due to a lack of evidence for robust and reliable methods. Here, we aim to investigate the clinical utility of the Home Town Walk (HTW) paradigm for personalized treatment decisions in medial temporal lobe epilepsy. Methods: A cohort of 123 consecutive patients having HTW-fMRI as part of routine MRI scans over a 7.5 year period were included in this retrospective study. Of these, 111 patients underwent repeated HTW-fMRI in two scanning sessions one to three days apart. fMRI analysis was performed at the time of the scans using clinically approved software and retrospectively validated using FSL. We assessed the test-retest within subject reliability of activations within the posterior parahippocampal gyri (pPHG) at the individual subject level. Results and discussion: Activations within the pPHG region were observed for 101 patients (91%) in at least one of the fMRI sessions and for 88 patients (79%) in both fMRI sessions, with 82 patients showing overlapping unilateral or bilateral activations and 8 further patients showing overlapping activations in one of the hemispheres but not the other. Reproducibility was evaluated using metrics based on the concordance ratios for size (Rsize) and location (Roverlap) within the pPHG region, as well as the lateralization index (LI) metric to reflect the asymmetry of hemispheric activations, which is of crucial relevance to inform surgery. Test-retest reliability of visuospatial memory LIs, assessed by an intra-class correlation coefficient (ICC) yielded a value of 0.76, indicating excellent between session stability of memory lateralization. Conclusion: The HTW-fMRI paradigm shows reproducible activations in the medial temporal lobes of individual epilepsy patients sufficient to consistently lateralize visuospatial memory function, demonstrating the clinical utility of HTW memory fMRI and its potential for application in the pre-surgical assessment of people with temporal lobe epilepsy.

Exploring the Relationship Between Instagram Use and Self-Criticism, Self-Compassion, and Body Dissatisfaction in the Spanish Population: Observational Study.

BACKGROUND: The widespread use of online social networks, particularly among the younger demographic, has catalyzed a growing interest in exploring their influence on users' psychological well-being. Instagram (Meta), a visually oriented platform, has garnered significant attention. Prior research has consistently indicated that Instagram usage correlates with heightened levels of perfectionism, body dissatisfaction, and diminished self-esteem. Perfectionism is closely linked to self-criticism, which entails an intense self-scrutiny and is often associated with various psychopathologies. Conversely, self-compassion has been linked to reduced levels of perfectionism and stress, while fostering greater positive affect and overall life satisfaction. OBJECTIVE: This study investigates the relationship between Instagram usage (time of use and content exposure) and users' levels of self-compassion, self-criticism, and body dissatisfaction. METHODS: This study comprised 1051 adult participants aged between 18 and 50 years, either native to Spain or residing in the country for at least a decade. Each participant completed a tailored questionnaire on Instagram usage, along with abbreviated versions of the Self-Compassion Scale, the Body Shape Questionnaire, and the Depressive Experiences Questionnaire, spanning from January 23 to February 25, 2022. RESULTS: A positive correlation was observed between daily Instagram usage and self-criticism scores. Participants of all age groups who spent over 3 hours per day on Instagram exhibited higher self-criticism scores than users who spent less than 1 hour or between 1 and 3 hours per day. Contrary to previous findings, no significant relationship was detected between Instagram usage time and levels of self-compassion or body dissatisfaction. Furthermore, content centered around physical appearance exhibited a positive correlation with self-criticism and body dissatisfaction scores. Among younger participants (aged 18-35 years), those who primarily viewed beauty or fashion content reported higher self-criticism scores than those consuming science-related content. However, this association was not significant for participants aged 35-50 years. Conversely, individuals who predominantly engaged with sports or fitness or family or friends content exhibited higher levels of body dissatisfaction than those focusing on science-related content. No significant associations were observed between self-compassion scores and daily Instagram usage or most-viewed content categories. CONCLUSIONS: The findings of this study underscore the considerable impact of Instagram usage on self-criticism and body dissatisfaction-2 variables known to influence users' psychological well-being and be associated with various symptoms and psychological disorders.

Predictors of Suicidal Behavior in a Sample of Incarcerated Individuals.

INTRODUCTION: Incarcerated individuals exhibit higher suicide rates compared to the general population. Investigating risk factors aids in developing effective public policies and interventions. The goal of this study was to assess and analyze factors predicting both suicidal thoughts and suicide attempts in a population of male incarcerated individuals who engage in the use of multiple psychoactive substances. METHODS: A cross-sectional observational study was conducted. A total of 174 male individuals deprived of liberty participated in the study, all of whom were serving a closed regime sentence during the data collection steps. Participants were assessed with the following instruments: the "Addiction Severity Index" (ASI-6) and the "Barratt Impulsiveness Scale" (BIS-11). RESULTS: Amongst our sample, prevalences of 36.7% in suicidal ideation and of 16.0% in suicide attempts were found. Impulsivity (OR = 1.098, 95% CI: 1.008 - 1.197), social support (OR = 0.281, 95% CI: 0.085 - 0.925), witnessing someone being killed or beaten (OR = 5.173, 95% CI: 2.143 - 12.486), cigarette use (OR = 3.309, 95% CI: 1.063 - 10.293), and cocaine use (OR = 2.678, 95% CI: 1.040 - 6.897) were also found to be associated with suicidal ideation. No significant associations were found between drug use and suicide attempts. CONCLUSION: A high prevalence of suicidal behaviors was observed in the study's sample, with findings demonstrating that impulsivity moderately differentiates the groups 'with' and 'without' suicidal ideation. Traumatic life events and substance use were also associated with suicide ideation, while social support was established as a protective factor for it.

Design solutions for the hodoscope of the magnetic proton recoil neutron spectrometer of the SPARC tokamak.

A new 14 MeV neutron spectrometer utilizing the magnetic proton recoil (MPR) technique is under development for the SPARC tokamak. This instrument measures neutrons by converting them into protons, whose momenta are subsequently analyzed using a series of magnets before detection by an array of scintillators known as the hodoscope. In this work, we explore various solutions for the hodoscope detectors through laboratory tests with radioactive sources and simulations. We present findings on light collection and pulse shape discrimination based on detector types, as well as optimal solutions for photo-detectors studying the differences between SiPM and PMT. Our results also led to the determination of a better optimized design for the hodoscope detectors, consisting of a 0.7 cm width and a 13 cm length EJ276D scintillation rod.

COSMONAUT: A COmpact spectrometer for measurements of neutrons at the ASDEX upgrade tokamak.

A COmpact Spectrometer for Measurements Of Neutrons at the ASDEX Upgrade Tokamak (COSMONAUT) has been developed for spectroscopy measurements of the 2.45 MeV neutron emission from deuterium plasmas at the ASDEX Upgrade. The instrument is based on a CLYC-7 inorganic scintillator, whereby the detection of fusion neutrons occurs via their interaction with 35Cl nuclei in the detector crystal, leading to a peak in the detector response function and providing excellent neutron/gamma-ray discrimination capabilities. The diagnostics is installed along a radial line of sight and makes use of a digital system to record time resolved data for the whole duration of the discharge. Measurements in ASDEX Upgrade plasmas with neutral beam injection have been carried out and are successfully interpreted using state-of-the-art modeling codes. Next step applications of the diagnostics are in experiments aimed at generating energetic particles by ion cyclotron resonance heating schemes. In these scenarios, COSMONAUT will provide unique information on the acceleration of deuterons beyond the beam injection energy and on their confinement, for comparison with modeling.

Regional insights on tobacco-related tweets: unveiling user opinions and usage patterns.

Introduction: Tobacco consumption and its impact on health remain high worldwide. Additionally, it is a contentious issue generating significant controversy. Twitter has proven to be a useful platform for evaluating public health topics related to population health behaviors, and tobacco consumption. Objective: The objective of this study is to analyze the content of tweets related to tobacco. Moreover, geolocation data will be considered to understand regional differences. Methods: Tweets published between 2018 and 2022, in both English and Spanish, containing the keyword "tobacco," were analyzed. A total of 56,926 tweets were obtained. The tweets were classified into different categories. 550 tweets were manually analyzed, and an automated and computerized classification was performed for the remaining and largest subset of tweets. Results: The analysis yielded 30,812 classifiable tweets. Healthcare professionals were the most frequent contributors to the topic (50.2%), with the most common theme being general information about the toxic effects of tobacco. 57.9% of the tweets discussed the harmful effects of tobacco on health, with fear being the predominant emotion. The largest number of tweets were located in America. Conclusions: Our study revealed a substantial number of tweets highlighting the health risks and negative perceptions of tobacco consumption. Africa showed the lowest percentage of tweets discussing the health risks associated with tobacco, coinciding with the continent having the least developed anti-tobacco policies. Healthcare professionals emerged as the most prominent users discussing the topic, which is encouraging as they play a crucial role in disseminating accurate and scientific health information.

Enterolignans: from natural origins to cardiometabolic significance, including chemistry, dietary sources, bioavailability, and activity.

The enterolignans, enterolactone and enterodiol, the main metabolites produced from plant lignans by the gut microbiota, have enhanced bioavailability and activity compared to their precursors, with beneficial effects on metabolic and cardiovascular health. Although extensively studied, the biosynthesis, cardiometabolic effects, and other therapeutic implications of mammalian lignans are still incompletely understood. The aim of this review is to provide a comprehensive overview of these phytoestrogen metabolites based on up-to-date information reported in studies from a wide range of disciplines. Established and novel synthetic strategies are described, as are the various lignan precursors, their dietary sources, and a proposed metabolic pathway for their conversion to enterolignans. The methodologies used for enterolignan analysis and the available data on pharmacokinetics and bioavailability are summarized and their cardiometabolic bioactivity is explored in detail. The special focus given to research on the health benefits of microbial-derived lignan metabolites underscores the critical role of lignan-rich diets in promoting cardiovascular health.

Epidemiology of Q fever in humans in four selected regions, Spain, 2016 to 2022.

BackgroundQ fever is a bacterial zoonosis caused by Coxiella burnetii. Spain has the highest number of notified human cases in Europe. Small ruminants are a key reservoir for the pathogen, transmission from animals to humans is usually airborne.AimWe aimed at exploring temporal and spatial epidemiological patterns of sporadic and outbreak cases of Q fever in four Spanish regions with the highest number of notified cases.MethodsWe extracted data on Q fever cases in the Canary Islands, Basque Country, La Rioja and Navarre between 2016 and 2022 from the Spanish National Epidemiological Surveillance Network. We calculated standardised incidence ratios (SIR), spatial relative risks (sRR) and posterior probabilities (PP) utilising Besag-York-Mollié models.ResultsThere were 1,059 notifications, with a predominance of males aged 30-60 years. In Basque Country, La Rioja and Navarre area, 11 outbreaks were reported, while no in the Canary Islands. A seasonal increase in incidence rates was observed between March and June. In the Canary Islands, elevated sRR was seen in La Palma, Gran Canaria, Lanzarote and Fuerteventura. In Basque Country, La Rioja and Navarre area, the highest sRR was identified in the south of Biscay province.ConclusionGoats were the main source for humans in outbreaks reported in the literature. Seasonal increase may be related to the parturition season of small ruminants and specific environmental conditions. Local variations in sRR within these regions likely result from diverse environmental factors. Future One Health-oriented studies are essential to deepen our understanding of Q fever epidemiology.

The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy.

Muscle weakness is a common symptom in CKD patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by PTH and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 ± 12 yr; 18 women), before and 6 mo after parathyroidectomy (PTx). We examined the relationships among CKD-mineral and bone disorder parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, BMD, and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-ß), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, p=.01) and TGF-ß (21 vs 7%, p=.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35 pg/mg, p=.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1ß, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggest that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx.

Introducing Cationic Selenium-Containing Triazapentadiene Ligand Framework: Synthesis, Coordination Chemistry, and Antifungal Activity.

Positively charged ligands are scarce. Here, we report the synthesis of unprecedented cationic selenium-containing triazapentadiene ligand framework. The reaction between 2-pyridylselenyl reagents and NaN(CN)2 in a 2:1 ratio produces the sodium complexes featuring the cationic selenium-containing triazapentadiene (SeTAP) ligand. The sodium-to-metal transmetalation allows facile preparation of SeTAP metal complexes, as exemplified by the reactions with CuCl2, AgNO3, NaAuCl4, and FeCl3. Density functional theory calculations have been used to analyze and characterize the chalcogen bonding interactions observed in the solid state for these compounds. Moreover, antifungal properties of the SeTAP ligand and its metal complexes were screened for in vitro activity against several phytopathogenic fungi. Phoma eupyrena exhibited prominent sensitivity against the action of most of the tested compounds.

Unlocking the power of polyphenols: A promising biomarker of improved metabolic health and anti-inflammatory diet in adolescents.

BACKGROUND: Metabolic syndrome (MetS) in adolescence is a risk factor for future cardiovascular disease. The chronic inflammation associated with MetS can be attenuated by the anti-inflammatory effect of polyphenols. We aimed to evaluate total urinary polyphenols as a biomarker of anti-inflammatory diets and their effect on MetS in adolescents. METHODS: In this retrospective analysis of a longitudinal cohort study, the relationship between total polyphenol excretion (TPE) in urine, the inflammatory potential of the diet measured through the Children's Dietary Inflammatory Index (C-DII), and the presence of metabolic syndrome was evaluated. The study population consisted of adolescents enrolled in the SI! Program for Secondary Schools trial, who had completed all the study forms and provided urine samples at baseline and at the two-year follow-up. Multivariate linear regression and multinominal logistic regression models were generated to evaluate the relationship of changes in TPE with changes in the C-DII score and changes in MetS status, respectively. An analysis of the ROC curve was performed to assess the potential of TPE as a biomarker of an anti-inflammatory diet. RESULTS: This study included 662 adolescents, 51.2% were males, and 48.8% were females, with a mean age of 12 (0.38) years at baseline. The relationship between changes in TPE and changes in the C-DII score was stratified by sex with a p-value <0.001 for the interaction. TPE and C-DII were inversely associated in males (-0.13 mg GAE/g creatinine [-0.26; -0.01] per 1-SD increase, p-value = 0.037). In addition, an increase in changes in TPE levels were associated with a reversal in MetS status in all adolescents (1.30 [1.27; 1.34] per 1-SD increase, p-value<0.001). The ROC curve showed that urinary TPE levels can predict dietary inflammatory potential with an AUC = 0.793 (0.725; 0.863) in males. CONCLUSION: Polyphenols excreted in urine are a potential biomarker of anti-inflammatory diets in males and are associated with a reversal of MetS status in adolescents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03504059, https://clinicaltrials.gov/study/NCT03504059.

Associations between mental health & substance use treatment and alcohol use progression and recovery among US women drinkers.

BACKGROUND: Alcohol use has profound public health impact on women; however, modifiable factors that may influence alcohol use progression/recovery, including health service utilization, are understudied in women. OBJECTIVE: To investigate the association between mental health (MH) and substance use (SU) treatment with alcohol use progression and recovery among women who currently use alcohol or have in the past. METHODS: This study is a secondary data analysis of prospective data from waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; a US-nationally representative sample of adults). The analytic sample was limited to women who reported past or current alcohol use at wave 1 (N = 15,515). Latent transition analysis (LTA) examined whether receiving SU/MH treatment in the year prior to wave 1 was associated with transitioning between three empirically-derived stages of alcohol involvement (no, moderate, and severe problems classes), between Waves 1 and 2 adjusting for possible confounders using propensity score weight. RESULTS: Compared to White female drinkers, female drinkers who were from Black, Hispanic, or other races were less likely to receive SU/MH treatment (p-values ≤. 001). SU/MH treatment in the year prior to wave 1 was associated with transitioning from the moderate problems class to the no problems class between Waves 1 and 2 (p-value = .04). CONCLUSION: Receipt of SU or MH treatment among women, was associated with a higher likelihood of remission from moderate alcohol use problems to no problems over time. Future research, including investigation into treatment characteristics (e.g., frequency, duration, type) should further explore why women initially experiencing severe alcohol use problems did not experience similar remission.

Influence of the COVID-19 pandemic on the defined daily dose of antimicrobials in patients requiring elective and emergency surgical procedures.

BACKGROUND: The COVID-19 pandemic has resulted in great incertitude and overwhelming changes in healthcare that have had a direct impact on antibiotic prescription. However, the influence of this pandemic on antibiotic consumption in patients undergoing surgery has not yet been analysed. The goal of this study was to analyse antimicrobial consumption and prescription in the same period of 2019 (pre-COVID-19), 2020 (beginning of the COVID-19 pandemic) and 2021 (established COVID-19) according to the DDD system in surgical patients at a tertiary-level hospital. METHODS: A prospectively maintained database was analysed. All patients who underwent elective or emergency gastrointestinal surgery during the same period (2019, 2020 and 2021) were included. Those who received at least 1 of the 10 most frequently prescribed antimicrobials during those periods were analysed. RESULTS: A total of 2975 patients were included in this study. In 2020, the number of procedures performed decreased significantly (653 versus 1154 and 1168 in 2020 versus 2019 and 2021, respectively; P = 0.005). Of all patients who underwent surgery during these periods, 45.08% received at least one of the antimicrobials studied (45.8% in 2020 versus 22.9% and 22.97% in 2019 and 2021, respectively; P = 0.005). Of these, 22.97% of the patients received a combination of these antimicrobials, with ceftriaxone/metronidazole being the most frequent. Hepato-Pancreato-Biliary and Liver Transplant, Emergency Surgery and Colorectal Surgery units had higher antibiotic consumption. CONCLUSIONS: The COVID-19 pandemic has resulted in a significant decrease in surgical activity and higher post-operative antimicrobial prescription compared with previous and subsequent years.

Pyric herbivory decreases soil denitrification despite increased nitrate availability in a temperate grassland.

Pyric herbivory, the combination of controlled burning and targeted grazing, is an effective strategy for restoring abandoned, shrub-encroached rangelands to open ecosystems. This practice may impact soil nitrogen pools by altering soil nitrification and denitrification rates, and may lead to an increase of nitrogen losses through nitrate leaching and N-gas emissions. This research, located in the south-western Pyrenees, investigated the effects of pyric herbivory on soil nitrification and denitrification potentials and mineral nitrogen content in a gorse-encroached temperate rangeland six months after the burning was implemented. The study included three treatments: high-severity burning plus grazing, low-severity burning plus grazing, and unburned and ungrazed areas (control). We measured soil nitrification and denitrification potentials (net and gross), the limitation of denitrifiers by nitrogen or organic carbon, and the abundance of nitrite- and nitrous oxide-reducing bacteria. Additional soil and vegetation data complemented these measurements. Results showed that pyric herbivory did not significantly affect nitrification potential, which was low and highly variable. However, it decreased gross denitrification potential and nitrous oxide reduction to dinitrogen in high-severely burned areas compared to the control. Denitrification rates directly correlated with microbial biomass nitrogen, soil organic carbon, soil water content and abundance of nirS-harbouring bacteria. Contrary to the expected, soil nitrate availability did not directly influence denitrification despite being highest in burned areas. Overall, the study suggests that pyric herbivory does not significantly affect mid-term nitrification rates in temperate open ecosystems, but may decrease denitrification rates in intensely burned areas. These findings highlight the importance of assessing the potential impacts of land management practices, such as pyric herbivory, on soil nutrient cycling and ecosystem functioning.

Clinical exome analysis and targeted gene repair of the c.1354dupT variant in iPSC lines from patients with PROM1-related retinopathies exhibiting diverse phenotypes.

BACKGROUND: Inherited retinal dystrophies (IRD) are one of the main causes of incurable blindness worldwide. IRD are caused by mutations in genes that encode essential proteins for the retina, leading to photoreceptor degeneration and loss of visual function. IRD generates an enormous global financial burden due to the lack of understanding of a significant part of its pathophysiology, molecular diagnosis, and the near absence of non-palliative treatment options. Patient-derived induced pluripotent stem cells (iPSC) for IRD seem to be an excellent option for addressing these questions, serving as exceptional tools for in-depth studies of IRD pathophysiology and testing new therapeutic approaches. METHODS: From a cohort of 8 patients with PROM1-related IRD, we identified 3 patients carrying the same variant (c.1354dupT) but expressing three different IRD phenotypes: Cone and rod dystrophy (CORD), Retinitis pigmentosa (RP), and Stargardt disease type 4 (STGD4). These three target patients, along with one healthy relative from each, underwent comprehensive ophthalmic examinations and their genetic panel study was expanded through clinical exome sequencing (CES). Subsequently, non-integrative patient-derived iPSC were generated and fully characterized. Correction of the c.1354dupT mutation was performed using CRISPR/Cas9, and the genetic restoration of the PROM1 gene was confirmed through flow cytometry and western blotting in the patient-derived iPSC lines. RESULTS: CES revealed that 2 target patients with the c.1354dupT mutation presented monoallelic variants in genes associated with the complement system or photoreceptor differentiation and peroxisome biogenesis disorders, respectively. The pluripotency and functionality of the patient-derived iPSC lines were confirmed, and the correction of the target mutation fully restored the capability of encoding Prominin-1 (CD133) in the genetically repaired patient-derived iPSC lines. CONCLUSIONS: The c.1354dupT mutation in the PROM1 gene is associated to three distinct AR phenotypes of IRD. This pleotropic effect might be related to the influence of monoallelic variants in other genes associated with retinal dystrophies. However, further evidence needs to be provided. Future experiments should include gene-edited patient-derived iPSC due to its potential as disease modelling tools to elucidate this matter in question.

A single-blinded, randomized, parallel intervention to evaluate genetics and omics-based personalized nutrition in general population via an e-commerce tool: The PREVENTOMICS e-commerce study.

BACKGROUND: Personalized nutrition (PN) has been proposed as a strategy to increase the effectiveness of dietary recommendations and ultimately improve health status. OBJECTIVES: We aimed to assess whether including omics-based PN in an e-commerce tool improves dietary behavior and metabolic profile in general population. METHODS: A 21-wk parallel, single-blinded, randomized intervention involved 193 adults assigned to a control group following Mediterranean diet recommendations (n = 57, completers = 36), PN (n = 70, completers = 45), or personalized plan (PP, n = 68, completers = 53) integrating a behavioral change program with PN recommendations. The intervention used metabolomics, proteomics, and genetic data to assist participants in creating personalized shopping lists in a simulated e-commerce retailer portal. The primary outcome was the Mediterranean diet adherence screener (MEDAS) score; secondary outcomes included biometric and metabolic markers and dietary habits. RESULTS: Volunteers were categorized with a scoring system based on biomarkers of lipid, carbohydrate metabolism, inflammation, oxidative stress, and microbiota, and dietary recommendations delivered accordingly in the PN and PP groups. The intervention significantly increased MEDAS scores in all volunteers (control-3 points; 95% confidence interval [CI]: 2.2, 3.8; PN-2.7 points; 95% CI: 2.0, 3.3; and PP-2.8 points; 95% CI: 2.1, 3.4; q < 0.001). No significant differences were observed in dietary habits or health parameters between PN and control groups after adjustment for multiple comparisons. Nevertheless, personalized recommendations significantly (false discovery rate < 0.05) and selectively enhanced the scores calculated with biomarkers of carbohydrate metabolism (ß: -0.37; 95% CI: -0.56, -0.18), oxidative stress (ß: -0.37; 95% CI: -0.60, -0.15), microbiota (ß: -0.38; 95% CI: -0.63, -0.15), and inflammation (ß: -0.78; 95% CI: -1.24, -0.31) compared with control diet. CONCLUSIONS: Integration of personalized strategies within an e-commerce-like tool did not enhance adherence to Mediterranean diet or improved health markers compared with general recommendations. The metabotyping approach showed promising results and more research is guaranteed to further promote its application in PN. This trial was registered at clinicaltrials.gov as NCT04641559 (https://clinicaltrials.gov/study/NCT04641559?cond=NCT04641559&rank=1).

Shift of the reduction potential of nickel(II) Schiff base complexes in the presence of redox innocent metal ions.

With the objective of gaining insight into the modulation of the reduction potential of the Ni(II/I) couple, we have synthesized two mononuclear nickel(II) complexes, NiLen (H2Len = N,N'-bis(3-methoxysalicylidene)-1,2-diamino-2-methylpropane) and NiLpn (H2Lpn = N,N'-bis(3-methoxysalicylidene)-1,3-diamino-2,2-dimethylpropane) of two N2O4 donor ligands and recorded their cyclic voltammograms. Both the nickel complexes show reversible reduction processes for the Ni(II/I) couple in acetonitrile solution but the reduction potential of NiLpn (E1/2 = -1.883 V) is 188 mV more positive than that of NiLen (E1/2 = -2.071 V). In the presence of redox inactive metal ions (Li+, Na+, K+, Mg2+, Ca2+ and Ba2+), the reduction potentials are shifted by 49-331 mV and 99-435 mV towards positive values compared to NiLen and NiLpn, respectively. The shift increases with the decrease of the pKa of the respective aqua-complexes of the metal ion but is poorly co-linear; however, better linearity is found when the shift of the mono- and bi-positive metal ion aqua complexes is plotted separately. Spectrophotometric titrations of these two nickel complexes with the guest metal ions in acetonitrile showed a well-anchored isosbestic point in all cases, confirming the adduct formation of NiLen and NiLpn with the metal ions. Structural analysis of single crystals, [(NiLen)Li(H2O)2]·ClO4 (1), [(NiLpn)Li(H2O)]·ClO4 (2), [(NiLpn)2Na]·BF4 (3) and [(NiLpn)2Ba(H2O)(ClO4)]·ClO4 (4), also corroborates the heterometallic adduct formation. The orbital energies of the optimised heterometallic adducts from which electron transfers originated were calculated in order to explain the observed reduction process. A strong linear connection between the calculated orbital energies and the experimental E1/2 values was observed. According to MEP and 2D vector field plots, the largest shift for divalent metal ions is most likely caused by the local electric field that they impose in addition to Lewis acidity.

Occult residual ovarian tissue at the time of minimally invasive risk reducing surgery in women with BRCA mutations.

OBJECTIVE: To describe extension of ovarian tissue beyond visible and National Comprehensive Cancer Network recommended margins among patients with BRCA mutations undergoing minimally invasive risk-reducing salpingo-oophorectomy. METHODS: A prospective study of patients with BRCA mutations who underwent minimally invasive risk-reducing bilateral salpingo-oophorectomy was conducted. Patient enrollment occurred between October 2021 and 2023. Tissue specimens were analyzed according to the Sectioning and Extensively Examining the Fimbriated End protocol. RESULTS: Twenty women with BRCA mutations were prospectively enrolled. All patients underwent minimally invasive surgery with 70% undergoing concurrent hysterectomy (n = 14). Approximately half of these procedures were performed with robotic assistance (n = 9, 45%). One patient was admitted overnight (5%); the other nineteen were discharged on the day of surgery (95%). One patient experienced a major complication and required readmission (5%). Extension of ovarian tissue beyond the visible ovary was noted on pathologic examination of six specimens (30%). In one patient this was observed on the left (17%), in three on the right (50%), and in two bilateral extension (33%) was noted. The distance ovarian stroma extended microscopically beyond the visible ovary was between 2 and 14 mm, with a median of 5 mm. Among patients with microscopic extension of ovarian tissue, the majority (n = 5, 83%) had a BRCA2 mutation. CONCLUSION: In women with BRCA mutations undergoing risk-reducing minimally invasive surgery, approximately one third had microscopic extension of ovarian stroma beyond the visible ovary. Current guidelines which recommend resection of at least 20 mm of tissue beyond the visible ovary are likely adequate in this population.

Fatty Acid Synthase Promotes Hepatocellular Carcinoma Growth via S-Phase Kinase-Associated Protein 2/p27KIP1 Regulation.

Background and Objectives: Aberrant upregulation of fatty acid synthase (FASN), catalyzing de novo synthesis of fatty acids, occurs in various tumor types, including human hepatocellular carcinoma (HCC). Although FASN oncogenic activity seems to reside in its pro-lipogenic function, cumulating evidence suggests that FASN's tumor-supporting role might also be metabolic-independent. Materials and Methods: In the present study, we show that FASN inactivation by specific small interfering RNA (siRNA) promoted the downregulation of the S-phase kinase associated-protein kinase 2 (SKP2) and the consequent induction of p27KIP1 in HCC cell lines. Results: Expression levels of FASN and SKP2 directly correlated in human HCC specimens and predicted a dismal outcome. In addition, forced overexpression of SKP2 rendered HCC cells resistant to the treatment with the FASN inhibitor C75. Furthermore, FASN deletion was paralleled by SKP2 downregulation and p27KIP1 induction in the AKT-driven HCC preclinical mouse model. Moreover, forced overexpression of an SKP2 dominant negative form or a p27KIP1 non-phosphorylatable (p27KIP1-T187A) construct completely abolished AKT-dependent hepatocarcinogenesis in vitro and in vivo. Conclusions: In conclusion, the present data indicate that SKP2 is a critical downstream effector of FASN and AKT-dependent hepatocarcinogenesis in liver cancer, envisaging the possibility of effectively targeting FASN-positive liver tumors with SKP2 inhibitors or p27KIP1 activators.

Barriers and Facilitators Along the PrEP Continuum of Care Among Latinx Sexual Minoritized Men and Transgender Women: A Systematic Review.

Latinx cisgender sexually minoritized men (SMM) and transgender women (TW) in the U.S. are disproportionately affected by HIV. Although pre-exposure prophylaxis (PrEP) is a highly effective strategy for HIV prevention, rates of PrEP use among Latinx SMM and TW remain suboptimal. The main purpose of this systematic review was to (1) describe engagement in the various stages of the PrEP care continuum among Latinx SMM and TW, and (2) identify multilevel determinants that function as barriers or facilitators to engagement in the PrEP continuum of care for Latinx SMM and TW. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement (PRISMA). Five databases (MEDLINE, CINAHL, PsycINFO, Embase, Scopus) were searched to examine the available qualitative, quantitative, and mixed method studies relevant to the research question. A total of 56 studies were included, with the majority focusing on SMM and being cross-sectional in design. Barriers included PrEP knowledge, risk perception, intersecting stigma, and structural conditions. Community resources, social support, and PrEP navigation services facilitated engagement in the PrEP continuum of care. This review highlights the complex factors that influence PrEP care engagement among Latinx SMM and TW. These findings call for comprehensive, multilevel approaches to address inequities disparities in PrEP care engagement among these groups.

RESUMEN: Los hombres cisgénero sexualmente minorizados (SMM) y las mujeres transgénero (TW) latinx en EE. UU. son desproporcionadamente afectados por el VIH. Aunque la profilaxis previa a la exposición (PrEP) es una estrategia efectiva para la prevención del VIH, el uso de la PrEP entre SMM y TW latinx siguen siendo deficiente. El propósito principal de esta revisión sistemática fue describir la participación en las etapas del continuo de atención de la PrEP entre SMM y TW latinx, e identificar factores de multinivel que funcionan como barreras o facilitadores para la participación en el continuo de atención de la PrEP en estos grupos. Esta revisión se realizó de acuerdo con la Declaración de los Elementos de Informes Preferidos para Revisiones Sistemáticas y Metaanálisis (PRISMA). Cinco bases de datos (MEDLINE, CINAHL, PsycINFO, Embase, Scopus) se utilizaron para examinar los estudios cualitativos, cuantitativos y de métodos mixtos relevantes para la pregunta de esta investigación. Se incluyeron un total de 56 estudios, la mayoría se enforcaron en SMM y usaron diseño transversal. Las barreras incluyeron falta de conocimiento sobre PrEP, percepción de riesgo, estigma interseccional y condiciones estructurales. Los recursos comunitarios, el apoyo social y los servicios de navegación de PrEP facilitaron la participación en el continuo de atención de PrEP. Esta revisión resplandece los factores complejos que influyen en la participación del continuo de atención de PrEP entre SMM y TW latinx. Estos descubrimientos exigen enfoques holistas y de multinivel para abordar las disparidades en uso y acceso a de la PrEP entre estos grupos.