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High mitochondrial DNA (mtDNA) amount has been reported to be beneficial for resistance and recovery of metabolic stress, while increased mtDNA synthesis activity can drive aging signs. The intriguing contrast of these two mtDNA boosting outcomes prompted us to jointly elevate mtDNA amount and frequency of replication in mice. We report that high activity of mtDNA synthesis inhibits perinatal metabolic maturation of the heart. The offspring of the asymptomatic parental lines are born healthy but manifest dilated cardiomyopathy and cardiac collapse during the first days of life. The pathogenesis, further enhanced by mtDNA mutagenesis, involves prenatal upregulation of mitochondrial integrated stress response and the ferroptosis-inducer MESH1, leading to cardiac fibrosis and cardiomyocyte death after birth. Our evidence indicates that the tight control of mtDNA replication is critical for early cardiac homeostasis. Importantly, ferroptosis sensitivity is a potential targetable mechanism for infantile-onset cardiomyopathy, a common manifestation of mitochondrial diseases.

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Background: There has been an increase in certain cancers among young adults (YA) aged 20-39, particularly in Latin America. This is the first study to examine cancer incidence and mortality in YA in Costa Rica, focusing on sex-specific patterns. Methods: Invasive cancer cases (excluding non-melanoma skin cancer) in YA from 2006 to 2015 were obtained from the Costa Rican National Registry of Tumors. Utilising SEER∗Stat software, age-standardized incidence rates (IRs) and incidence rate ratios (IRRs) were calculated. Trends and annual percent changes (APCs) in IRs were estimated using the Joinpoint regression analysis program. Cancer deaths from 2000 to 2021 were obtained from the Costa Rican National Institute of Statistics and Census. Age-standardised mortality rates were calculated using STATA®17. Findings: YA comprised 10.7% of all invasive cancer cases diagnosed from 2006 to 2015. The age-standardized incidence rate (ASIR) of invasive cancer in YA was 50.9/100,000 person-years. The ASIR was twofold higher for females compared to males (IRR = 2.03, 95% CI:1.94, 2.13). This difference increased with age, peaking in the 35-39-year age group (IRR = 2.84, 95% CI:2.62, 3.10). Thyroid, breast, and cervical cancer were the most common in females. Testicular cancer was the most common in males. Leading causes of cancer-related deaths included cervical and breast cancer in females and stomach and brain/nervous system cancer in males. Interpretation: The study highlights sex-specific patterns in cancer incidence and mortality among YA in Costa Rica to increase understanding and improve cancer outcomes in this age group. Funding: This study was funded by the Intramural Research Program of the National Cancer Institute.

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Introduction: Lower statin utilization is reported among women compared to men, however large-scale studies evaluating gender disparities in LDL-C management in individuals with ASCVD and its subtypes remain limited, particularly across age and racial/ethnic subgroups. In this study, we address this knowledge gap using data from a large US healthcare system. Methods: All adult patients with established ASCVD in the Houston Methodist Learning Health System Registry during 2016-2022 were included. Statin use and dose were extracted from the database. The association between gender and statin utilization was evaluated using multivariate logistic regression analyses in patients with ASCVD overall, across ASCVD subtypes, and by age, racial/ethnic subgroups, and socioeconomic risk factors. Results: A total of 97,819 patients with prevalent ASCVD were included. Women with ASCVD had lower utilization of any statin (64.3% vs 72.6 %; p < 0.001) and high-intensity statin (29.8% vs 42.5 % p < 0.001) compared with men. In fully adjusted models, women had 40 % lower odds of any (adjusted odds ratio [aOR]:0.58, 95 % CI 0.57-0.60) and high-intensity statin use (aOR:0.59, 0.57-0.61) relative to men. Women were also less likely to have guideline-recommended LDL-C < 70 mg/dL (30.2% vs 42.7 %; p < 0.01). These differences persisted across age, racial/ethnic and socioeconomic subgroups. Conclusion: Significant gender disparities exist in contemporary lipid management among patients with ASCVD, with women being less likely to receive any and high-intensity statin and achieving guideline defined LDL-C goal compared with men across age and racial/ethnic subgroups. These disparities underscore the need to further understand potential socioeconomic drivers of the observed lower statin uptake in women.

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Staphylococcus aureus possesses sar family genes, including sarA, S, R, T, U, V, X, Y, Z, and rot, which are transcription factors involved in biofilm formation and quorum sensing. In contrast, Staphylococcus epidermidis has sarA, R, V, X, Y, Z, and rot genes; specifically, SarA, Z, and X are involved in biofilm formation. The expression of the sar family members in S. epidermidis isolated from clinical and non-clinical environments is unknown. This study aimed to establish if clinical and non-clinical isolates of S. epidermidis express the sar family members. We genotyped isolates from clinical ocular infections (n = 52), or non-clinical healthy conjunctiva (n = 40), and healthy skin (n = 50), using multilocus sequence typing (MLST) and the staphylococcal chromosomal cassette mec (SCCmec). We selected strains with different genotypes and representatives of each source of isolation, and the presence of the sar family genes was detected using PCR and RT-qPCR to determine their expression. The sar family genes were present in all selected strains, with no observed differences. The relative expression of the sar family showed that all selected strains expressed each gene weakly, with no significant differences observed between them or between different sources of isolation. In conclusion, the presence and relative expression of the sar family genes are very similar among strains, with no differences based on their origin of isolation and genotype. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01339-x.

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Superior mesenteric artery syndrome, or Wilkie's syndrome, is one of the rarest gastrointestinal disorders known to medical science. It is characterized by the vascular clamp of the third portion of the duodenum, between the superior mesenteric artery and the aorta. It presents as an uncommon cause of upper intestinal obstruction. Imaging is required, preferably with a contrast-enhanced CT or an MRI; conservative management is preferred, leaving surgery for the most complex cases. We present the case of a 34-year-old man with Duchenne's muscular dystrophy and a history of substantial weight loss after hospital admission for aspiration pneumonia. He underwent an abdominal CT scan that showed enlargement of the stomach, the second and third parts of the duodenum; without observing masses, the patient received conservative management with a nasojejunal feeding tube. At the outpatient reevaluation, 1 month postdischarge, he became asymptomatic and had progressive weight gain.

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This study investigates the synthesis and optimization of nanobots (NBs) loaded with pDNA using the layer-by-layer (LBL) method and explores the impact of their collective motion on the transfection efficiency. NBs consist of biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and are powered by the urease enzyme, enabling autonomous movement and collective swarming behavior. In vitro experiments were conducted to validate the delivery efficiency of fluorescently labeled NBs, using two-dimensional (2D) and three-dimensional (3D) cell models: murine urothelial carcinoma cell line (MB49) and spheroids from human urothelial bladder cancer cells (RT4). Swarms of pDNA-loaded NBs showed enhancements of 2.2- to 2.6-fold in delivery efficiency and 6.8- to 8.1-fold in material delivered compared to inhibited particles (inhibited enzyme) and the absence of fuel in a 2D cell culture. Additionally, efficient intracellular delivery of pDNA was demonstrated in both cell models by quantifying and visualizing the expression of eGFP. Swarms of NBs exhibited a >5-fold enhancement in transfection efficiency compared to the absence of fuel in a 2D culture, even surpassing the Lipofectamine 3000 commercial transfection agent (cationic lipid-mediated transfection). Swarms also demonstrated up to a 3.2-fold enhancement in the amount of material delivered in 3D spheroids compared to the absence of fuel. The successful transfection of 2D and 3D cell cultures using swarms of LBL PLGA NBs holds great potential for nucleic acid delivery in the context of bladder treatments.

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A curious and noticeable structural feature in Schiff bases from 2-aminoaldoses is the fact that imino tautomers arranged equatorially in the most stable ring conformation exhibit a counterintuitive reverse anomeric effect (RAE) in the mutarotational equilibrium, i.e., the most stable and abundant anomer is the equatorial one (ß). As shown by our very recent research, this effect arises from the total or partial inhibition of the exo-anomeric effect due to the presence of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen in the axial anomer (α). When the Schiff base adopts either an enamine structure or the imino group is protonated, the exo-anomeric effect is restored, and the axial α-anomer becomes the most stable species. Although the intramolecular H-bonding should appropriately be interpreted as a genuine stereoelectronic effect, the magnitude of the RAE could be affected by other structural parameters. Herein and through a comprehensive analysis of benzylidene, cinnamylidene, naphthalene, phenanthrene, and anthracene aldehydes, we show the robustness of the RAE effect, which is similar in extent to simple aldehydes screened so far, irrespective of the size and/or hydrophobicity of the substituent at the nitrogen atom.

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BACKGROUND: Postoperative bleeding is associated with significant resource use and an important contributor to other major adverse events in pediatric patients undergoing complex cardiac surgery procedures. Thromboelastography (TEG®6S) can guide perioperative blood product transfusions to reduce the risk of postoperative bleeding. In this study, we validated the use of a previously developed TEG®6S maximum amplitude (TEG-MA) based platelet transfusion calculator utilized during cardiac surgery to minimize the risk of postoperative bleeding. METHODS: In this single-center retrospective study of pediatric patients (≤18yr) undergoing cardiac surgery requiring cardiopulmonary bypass at Boston Children's Hospital (N=1000), volume of platelet transfusion administered based on surgical team discretions were compared to the platelet calculator recommended platelet transfusion volume using linear regression analysis. Associations between adequacy of perioperative platelet transfusion and postoperative bleeding/thrombotic complications within the first 24hr postoperatively (bleeding), and until hospital discharge (thrombosis), were evaluated by logistic regression analysis. RESULTS: Lower TEG-MA (≤45mm) measurements following post transfusion, is associated with higher risk for postoperative bleeding (Odds ratio:4.4;95%CI:2.6,7.4; *p<0.01). The platelet transfusion calculator recommended platelet transfusion volume (based on TEG-MA measured at time of rewarming) demonstrated moderate correlation with the measured TEG-MA value after platelet transfusion (Pearson r: 0.7). Intraoperative volumes of platelet transfusion that failed to increase a postoperative TEG-MA of at least 45mm, significantly increased the risk for postoperative bleeding in the first 24hr post-surgery (Odds ratio:3.2;95%CI:1.9,5.4; *p<0.01). Post transfusion TEG-MA was not independently associated with thrombosis. CONCLUSIONS: Customizing perioperative platelet transfusion therapy using quantitative diagnostic tests can help reduce postoperative bleeding complications.

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INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is the 2nd most common primary liver malignancy. For nonsurgical candidates, the primary treatment option is systemic chemotherapy, which can be combined with locoregional therapies to enhance local control. Common intra-arterial locoregional therapies include transarterial hepatic embolization, conventional transarterial chemoembolization, drug-eluting bead transarterial chemoembolization, transarterial radioembolization with Yttrium-90 microspheres, and hepatic artery infusion. This article aims to review the latest literature on intra-arterial locoregional therapies for treating ICC. AREAS COVERED: A literature search was conducted on PubMed using keywords: intrahepatic cholangiocarcinoma, intra-arterial locoregional therapy, embolization, chemoembolization, radioembolization, hepatic artery infusion, and immunotherapy. Articles from 2008 to 2024 were reviewed. Survival data from retrospective and prospective studies, meta-analyses, and clinical trials were evaluated. EXPERT OPINION: Although no level I evidence supports the superiority of any specific intra-arterial therapy, there has been a shift toward favoring radioembolization. In our expert opinion, radioembolization may offer superior outcomes when performed by skilled operators with meticulous planning and personalized dosimetry, particularly for radiation segmentectomy or treating lobar/bilobar disease in appropriate candidates.

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Nanometer-scale control over surface functionalization of soft gels is important for a variety of applications including controlling interactions with cells for in vitro cell culture and for regenerative medicine. Recently, we have shown that it is possible to transfer a nanometer-thick precision functional polymer layer to the surface of relatively stiff polyacrylamide gels. Here, we develop a fundamental understanding of the way in which the precision polymer backbone participates in the polyacrylamide radical polymerization and cross-linking process, which enables us to generate high-efficiency transfer to much softer hydrogels (down to 5 kPa) with stiffness similar to that of soft tissue. This approach creates hydrogel surfaces with exposed nanostructured functional arrays that open the door to controlled ligand presentation on soft hydrogel surfaces.

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Background: Critical illness, or acute organ failure requiring life support, threatens over five million American lives annually. Electronic health record (EHR) data are a source of granular information that could generate crucial insights into the nature and optimal treatment of critical illness. However, data management, security, and standardization are barriers to large-scale critical illness EHR studies. Methods: A consortium of critical care physicians and data scientists from eight US healthcare systems developed the Common Longitudinal Intensive Care Unit (ICU) data Format (CLIF), an open-source database format that harmonizes a minimum set of ICU Data Elements for use in critical illness research. We created a pipeline to process adult ICU EHR data at each site. After development and iteration, we conducted two proof-of-concept studies with a federated research architecture: 1) an external validation of an in-hospital mortality prediction model for critically ill patients and 2) an assessment of 72-hour temperature trajectories and their association with mechanical ventilation and in-hospital mortality using group-based trajectory models. Results: We converted longitudinal data from 94,356 critically ill patients treated in 2020-2021 (mean age 60.6 years [standard deviation 17.2], 30% Black, 7% Hispanic, 45% female) across 8 health systems and 33 hospitals into the CLIF format, The in-hospital mortality prediction model performed well in the health system where it was derived (0.81 AUC, 0.06 Brier score). Performance across CLIF consortium sites varied (AUCs: 0.74-0.83, Brier scores: 0.06-0.01), and demonstrated some degradation in predictive capability. Temperature trajectories were similar across health systems. Hypothermic and hyperthermic-slow-resolver patients consistently had the highest mortality. Conclusions: CLIF facilitates efficient, rigorous, and reproducible critical care research. Our federated case studies showcase CLIF's potential for disease sub-phenotyping and clinical decision-support evaluation. Future applications include pragmatic EHR-based trials, target trial emulations, foundational multi-modal AI models of critical illness, and real-time critical care quality dashboards.

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The aim was to estimate the vaccination timeliness defined as the proportion of children under 6 years of age who received their immunization in the time range established by the Colombian Expanded Immunization Program (EIP). A retrospective cohort study that collected reports of vaccination opportunities between 2014 and 2019 provided by the Ministry of Health. Age, sex, city, ethnicity, health system affiliation regimen, vaccine applied, and timing of vaccination were considered for the time range under study. A total of 3,370,853 immunized children were included from all regions of the country. More than 80% of children had a timeliness to get most vaccines. The exceptions were yellow fever (17%) and seasonal influenza (42%). No differences in timeliness were found according to geographic region or by health system affiliation regime, but the average timeliness for all vaccines of children of the indigenous population (65.8% ±18.4%) was lower than that of the rest of the population (78·6% ± 19·3%) (p = 0·021). The timeliness for vaccination under the EIP of Colombia is high, with proportions of 72-96%, but intergroup differences were identified, mainly lower timeliness among indigenous people. These findings warrant improvement strategies that would guarantee the immunization of the entire child population.

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The shiitake mushroom has gained popularity in the last decade, ranking second in the world for mushrooms consumed, providing consumers with a wide variety of nutritional and healthy benefits. It is often not clear the origin of these mushrooms, so it becomes of great importance to the consumers. In this research, different machine learning algorithms were developed to determine the geographical origin of shiitake mushrooms (Lentinula edodes) consumed in Korea, based on experimental data reported in the literature (δ13C, δ15N, δ18O, δ34S, and origin). Regarding the origin of shiitake in three categories (Korean, Chinese, and mushrooms from Chinese inoculated sawdust blocks), the random forest model presents the highest accuracy value (0.940) and the highest kappa value (0.908) for the validation phase. To determine the origin of shiitake mushrooms in two categories (Korean and Chinese, including mushrooms from Chinese inoculated sawdust blocks in the latter ones), the support vector machine model is chosen as the best model due to the high accuracy (0.988) and kappa (0.975) values for the validation phase. Finally, to determine the origin in two categories (Korean and Chinese, but this time including the mushrooms from Chinese inoculated sawdust blocks in the Korean ones), the best model is the random forest due to its higher accuracy value (0.952) in the validation phase (kappa value of 0.869). The accuracy values in the testing phase for the best selected models are acceptable (between 0.839 and 0.964); therefore, the predictive capacity of the models could be acceptable for their use in real applications. This allows us to affirm that machine learning algorithms would be suitable modeling instruments to determine the geographical origin of shiitake.

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The effect of peptide toxins on voltage-gated ion channels can be reliably assessed using electrophysiological assays, such as the patch-clamp technique. However, much of the toxinological research done in Central and South America aims at purifying and characterizing biochemical properties of the toxins of vegetal or animal origin, lacking electrophysiological approaches. This may happen due to technical and infrastructure limitations or because researchers are unfamiliar with the techniques and cellular models that can be used to gain information about the effect of a molecule on ion channels. Given the potential interest of many research groups in the highly biodiverse region of Central and South America, we reviewed the most relevant conceptual and methodological developments required to implement the evaluation of the effect of peptide toxins on mammalian voltage-gated ion channels using patch-clamp. For that, we searched MEDLINE/PubMed and SciELO databases with different combinations of these descriptors: "electrophysiology", "patch-clamp techniques", "Ca2+ channels", "K+ channels", "cnidarian venoms", "cone snail venoms", "scorpion venoms", "spider venoms", "snake venoms", "cardiac myocytes", "dorsal root ganglia", and summarized the literature as a scoping review. First, we present the basics and recent advances in mammalian voltage-gated ion channel's structure and function and update the most important animal sources of channel-modulating toxins (e.g. cnidarian and cone snails, scorpions, spiders, and snakes), highlighting the properties of toxins electrophysiologically characterized in Central and South America. Finally, we describe the local experience in implementing the patch-clamp technique using two models of excitable cells, as well as the participation in characterizing new modulators of ion channels derived from the venom of a local spider, a toxins' source less studied with electrophysiological techniques. Fostering the implementation of electrophysiological methods in more laboratories in the region will strengthen our capabilities in many fields, such as toxinology, toxicology, pharmacology, natural products, biophysics, biomedicine, and bioengineering.

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The purpose of this study was to confirm that blood lactate concentrations can be maintained at moderate to high steady state values during an entire interval training (IT) session (repetitions + rest). Forty-eight trained swimmers and track athletes performed four IT protocols consisting of 6-10 bouts between 1 and 3-min at ~5-10 mmol/L blood lactate concentrations with a passive recovery of 60 to 180-sec. Performance times were measured at every bout, while blood lactate concentrations and heart rate during recovery every other bout. One-way ANOVA was performed for comparisons and r-squared for the effect size (ES). Performance times were stable throughout each IT protocol (75 ± 8 and 77 ± 5-sec [swimmers and track athletes]; 67 ± 3-sec [swimmers]; 64 ± 3-sec [swimmers]; and 135 ± 6-sec [swimmers]). Despite some minor differences (p<0.05; ES, 0.28 to 0.37, large), blood lactate concentrations were maintained stable at moderate to high values during each IT protocol (5.85 ± 1.47 mmol/L; 5.64 ± 1.03 mmol/L; 9.29 ± 1.07 mmol/L; and 9.44 ± 1.12 mmol/L). HR decreased significantly from the beginning to the end of recovery (p<0.05; ES, 0.93 to 0.96, large). In conclusion, moderate to high blood lactate steady state concentrations can be sustained for ~20 to 60-min during an entire IT session (repetitions + rest) at a stable performance. This approach can optimize performance by stimulating the metabolic demands and the pace strategy during the middle section of endurance competitive events.

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Interest in remimazolam has surged in recent years, thanks to its advantageous pharmacologic profile. This ultra-short-acting benzodiazepine is noted for its rapid onset and termination of action, organ-independent elimination, availability of a reversal agent, and excellent hemodynamic stability. Although the use of remimazolam has been explored in various anesthesia settings and procedures, data on its application in cardiovascular anesthesia and catheterization laboratory procedures remain limited. This review evaluates the latest literature to assess remimazolam's role in cardiovascular anesthesia across different settings and procedures. The analysis shows that remimazolam offers anesthesia without significant hemodynamic instability and a reduced need for vasopressors, with an incidence of perioperative adverse events comparable to that of other agents. These findings are relevant for both the induction and maintenance of general anesthesia in catheterization laboratory procedures and general anesthesia in elective cardiac surgery. Although further research is needed to fully understand remimazolam's role in cardiovascular anesthesia, its favorable hemodynamic and safety profile suggests that it is a promising option for cardiac anesthesiologists in both the catheterization laboratory and the operating room.

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Lignin valorization through heterogeneous photocatalysis is a promising pathway for obtaining value-added products, including chemical building blocks, biofuels, etc. However, several challenges still demand attention and resolution in this field. One of the key parameters in the heterogeneous photocatalytic process is the synthesis of efficient photocatalysts that can accomplish efficient and selective reactions. Selective conversion of lignin can be achieved by using heterojunction photocatalysts which can efficiently separate charge carriers' and promote selective reactions by band structure modulation. This work details a straightforward approach for synthesizing heterojunction photocatalysts based on Bi4Ti3O12 and BiOI involving the hydrothermal and co-precipitation methods. Additionally, the synthesized composites were employed in the selective oxidation of veratryl alcohol, a lignin-derived model compound, to produce high-value-added veratraldehyde. The experimental results showed that the BiOI/Bi4Ti3O12 heterojunction (12.5 mol % BiOI) showed superior activity with a veratraldehyde yield of 5.4 and 27.2 times higher than those of Bi4Ti3O12 and BiOI, respectively. The mechanistic studies revealed that the improved activity and selectivity were due to the enhanced charge carriers' separation and the suppression of reactive oxygen species formation through modulation of band structure. This study allows a green approach to lignin-derived biomass valorization to obtain high-value chemicals.

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This article explores how the leadership learning framework can scaffold leadership development training toward meaningful, observable change. This change occurs when students have opportunities to take their existing leadership knowledge and combine it with new information to increase their leadership metacognition both conceptually and in practice. To bring these concepts to reality, we provide examples of the philosophies and priorities influencing LeaderShape's curriculum design. Examining core curricular themes of identity development, technology, and process-based learning, the authors share the rationale for implementation. They also provide suggestions for leadership operationalization based on LeaderShape's most utilized training programs, all grounded in critical elements of the LLF.

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BACKGROUND: Mindfulness skills training is a core component of Dialectical Behavior Therapy and aims to improve emotion dysregulation (ED) in people with Borderline Personality Disorder (BPD). However, the underlying mechanisms of change are not fully understood. METHODS: A total of 75 BPD outpatients participated in a 10-week mindfulness skills training. Multilevel models with a time-lagged approach were conducted to examine the temporal dynamics between the proposed mechanisms and ED. Decentering, nonjudgment, body awareness and attention awareness as putative mechanisms and ED as outcome were assessed on a session-by-session basis. RESULTS: Greater nonjudgment and body awareness showed within-person effects; participants who reported higher nonjudgement of inner experience and body awareness than their own personal average at a given week showed improvement in ED at the following week. Notably, decentering moderated these associations, such that increased nonjudgment and body awareness predicted improvements in ED more strongly in those participants with high decentering ability. Lastly, a bidirectional relationship between the mechanisms and ED was found; when participants were more emotionally dysregulated than their usual state, they showed less gain in the mechanisms at the following week. CONCLUSIONS: Knowing how mindfulness training works is relevant to optimize treatments. Clinicians may use strategies to increase these mechanisms when the goal is to improve emotion regulation difficulties in BPD.