Impact of Tricuspid Repair on Surgical Death in Patients Undergoing Mitral Valve Surgery Due to Rheumatic Disease.

Background: Tricuspid valve repair during mitral valve replacement surgery remains a controversial topic. The risk-benefit ratio in some populations remains uncertain, especially in rheumatic heart disease patients. Therefore, we aimed to evaluate the impact of concomitant tricuspid repair on surgical mortality in patients undergoing cardiac surgery due to rheumatic mitral valve disease who have moderate to severe functional tricuspid regurgitation. Methods: This is a prospective cohort study from January 1, 2017, to December 30, 2022. All patients over 18 years of age who underwent cardiac surgery to correct rheumatic mitral valve disease with concomitant moderate to severe tricuspid regurgitation were included. The primary outcome was a surgical death. In an exploratory analysis, clinical and echocardiographic data were obtained 2 years after the procedure. Results: Of the 144 patients included, 83 (57.6%) underwent tricuspid valve repair. The mean age was 46.2 (±12.3) years with 107 (74.3%) female individuals, the median left ventricular ejection fraction was 61.0% (55-67), and systolic pulmonary artery pressure (sPAP) was 55.0 mmHg (46-74), with 45 (31.3%) individuals with right ventricular dysfunction. The total in-hospital mortality was 15 (10.4%) individuals, and there was no difference between the groups submitted or not to tricuspid repair: 10 (12.0%) vs. 5 (7.5%); p = 0.46, respectively. There was an association with one variable independently: the sPAP value, relative risk 1.04 (1.01-1.07), p = 0.01. The estimated cut-off value of sPAP that indicates higher early mortality through the receiver operating characteristic curve (area 0.70, p = 0.012) was 73.5 mmHg. Conclusions: Performing tricuspid repair in individuals who were undergoing cardiac surgery to correct rheumatic mitral valve disease was not associated with increased surgical mortality. Our results suggest the safety of tricuspid repair even in this high-risk population, reinforcing the recommendations in current guidelines.

Next-generation chemotherapy treatments based on black hole algorithms: From cancer remission to chronic disease management.

PROBLEM: Therapeutic planning strategies have been developed to enhance the effectiveness of cancer drugs. Nevertheless, their performance is highly limited by the inefficient biological representativeness of predictive tumor growth models, which hinders their translation to clinical practice. OBJECTIVE: This study proposes a disruptive approach to oncology based on nature-inspired control using realistic Black Hole physical laws, in which tumor masses are trapped to experience attraction dynamics on their path to complete remission or to become a chronic disease. This control method is designed to operate independently of individual patient idiosyncrasies, including high tumor heterogeneities and highly uncertain tumor dynamics, making it a promising avenue for advancing beyond the limitations of the traditional survival probabilistic paradigm. DESIGN: Here, we provide a multifaceted study of chemotherapy therapeutic planning that includes: (1) the design of a pioneering controller algorithm based on physical laws found in the Black Holes; (2) investigation of the ability of this controller algorithm to ensure stable equilibrium treatments; and (3) simulation tests concerning tumor volume dynamics using drugs with significantly different pharmacokinetics (Cyclophosphamide and Atezolizumab), tumor volumes (200 mm3 and 12 732 mm3) and modeling characterizations (Gompertzian and Logistic tumor growth models). RESULTS: Our results highlight the ability of this new astrophysical-inspired control algorithm to perform effective chemotherapy treatments for multiple tumor-treatment scenarios, including tumor resistance to chemotherapy, clinical scenarios modelled by time-dependent parameters, and highly uncertain tumor dynamics. CONCLUSIONS: Our findings provide strong evidence that cancer therapy inspired by phenomena found in black holes can emerge as a disruptive paradigm. This opens new high-impacting research directions, exploring synergies between astrophysical-inspired control algorithms and Artificial Intelligence applied to advanced personalized cancer therapeutics.

Effectiveness of intracuff alkalinized lidocaine associated with intravenous dexamethasone in reducing laryngotracheal morbidity in children undergoing general anesthesia for tonsillectomy: a randomized controlled trial.

BACKGROUND: Postoperative sore throat is one of the main postoperative complaints in patients undergoing tonsillectomy. As the primary outcome, we aimed to determine whether endotracheal tube cuffs filled with alkalinized lidocaine are associated with a lower incidence of postoperative sore throat and anesthesia emergence phenomena in children undergoing tonsillectomy or adenotonsillectomy. We also assessed the potential additional benefits of IV dexamethasone in reducing postoperative laryngotracheal morbidity. METHODS: This is a clinical prospective, randomized, controlled trial. Patients were randomly allocated to one of four groups, as follows: air - endotracheal tube cuff filled with air; air/dex - endotracheal tube cuff filled with air and intravenous dexamethasone; lido - endotracheal tube cuff filled with alkalinized lidocaine; and lido/dex - endotracheal tube cuff filled with alkalinized lidocaine and intravenous dexamethasone. Perioperative hemodynamic parameters and the incidence of postoperative nausea and vomiting, coughing and hoarseness were recorded. Postoperative sore throat was assessed in the postanesthetic care unit and 24 hours post tracheal extubation. RESULTS: In total, 154 children aged 4-12 years, ASA physical status I or II, undergoing general anesthesia for elective tonsillectomy and adenotonsillectomy, were assessed for postoperative sore throat in this study. The incidence of postoperative sore throat 24 hours after tracheal extubation was significantly lower in the lido/dex group compared to groups air and air/dex (p = 0.01). However, no additional reduction in these symptoms was observed from the intravenous administration of dexamethasone when comparing the lido and lido/dex groups. Similarly, there were no differences among groups regarding perioperative hemodynamic variables or postoperative nausea and vomiting, coughing, and hoarseness during the study period. CONCLUSION: Intracuff alkalinized lidocaine, associated with intravenous dexamethasone, might be effective in reducing sore throat 24 hours post-tonsillectomy or adenotonsillectomy in children when compared to the use of air as the cuff insufflation media.

Cardiovascular predicted risk: A population-based comparison of the pooled cohorts equation and PREVENT.

BACKGROUND: While the new cardiovascular risk score (PREVENT) has improvements, its implementation may lead to significant changes in the distribution of atherosclerotic cardiovascular diseases (ASCVD) in the United States. We aimed to quantify and characterize the distribution of the 10-year predicted absolute ASCVD risk using the Pooled Cohorts Equation (PCE) and PREVENT. METHODS: We utilized the latest (2017-March 2020) round of the National Health and Nutrition Examination Survey (NHANES). Accounting for the complex survey design of the NHANES, we computed the mean predicted ASCVD risk overall and by sex, race, and education; similarly, we computed the prevalence of cardiovascular risk groups (<5%, 5%-7.4%, 7.5%-19.9%, and ≥ 20%). RESULTS: The study included 3845 observations, representing 109,692,509 people. Using the PREVENT calculator resulted in a reduction of the mean 10-year ASCVD absolute risk by half compared to the PCE: 9.1% vs 4.7%. Under the PCE, the high-risk category accounted for 12.5% of the population, whereas under PREVENT it fell to 0.4%. Among those previously classified as high-risk under the PCE, 3.5% would remain in this category with PREVENT, while 93% would be reclassified as intermediate risk. CONCLUSIONS: The adoption of the novel cardiovascular risk score, PREVENT, could lower the average predicted ASCVD risk and reduce the prevalence of high-risk individuals. While this shift might suggest improved cardiovascular health, it could also lead to complacency, potentially undermining ongoing public health efforts aimed at preventing cardiovascular disease.

Chassis-based fiber-coupled optical probe design for reproducible quantitative diffuse optical spectroscopy measurements.

Advanced optical neuromonitoring of cerebral hemodynamics with hybrid diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) methods holds promise for non-invasive characterization of brain health in critically ill patients. However, the methods' fiber-coupled patient interfaces (probes) are challenging to apply in emergent clinical scenarios that require rapid and reproducible attachment to the head. To address this challenge, we developed a novel chassis-based optical probe design for DOS/DCS measurements and validated its measurement accuracy and reproducibility against conventional, manually held measurements of cerebral hemodynamics in pediatric swine (n = 20). The chassis-based probe design comprises a detachable fiber housing which snaps into a 3D-printed, circumferential chassis piece that is secured to the skin. To validate its reproducibility, eight measurement repetitions of cerebral tissue blood flow index (BFI), oxygen saturation (StO2), and oxy-, deoxy- and total hemoglobin concentration were acquired at the same demarcated measurement location for each pig. The probe was detached after each measurement. Of the eight measurements, four were acquired by placing the probe into a secured chassis, and four were visually aligned and manually held. We compared the absolute value and intra-subject coefficient of variation (CV) of chassis versus manual measurements. No significant differences were observed in either absolute value or CV between chassis and manual measurements (p > 0.05). However, the CV for BFI (mean ± SD: manual, 19.5% ± 9.6; chassis, 19.0% ± 10.8) was significantly higher than StO2 (manual, 5.8% ± 6.7; chassis, 6.6% ± 7.1) regardless of measurement methodology (p<0.001). The chassis-based DOS/DCS probe design facilitated rapid probe attachment/re-attachment and demonstrated comparable accuracy and reproducibility to conventional, manual alignment. In the future, this design may be adapted for clinical applications to allow for non-invasive monitoring of cerebral health during pediatric critical care.

Progressive verbal apraxia of reading.

We identified a syndrome characterized by a relatively isolated progressive impairment of reading words that the patient was able to understand and repeat but without other components of speech apraxia. This cluster of symptoms fits a new syndrome designated Progressive Verbal Apraxia of Reading. A right-handed man (AB) came with a 2.5-year history of increasing difficulties in reading aloud. He was evaluated twice, 2 years apart, using multimodal neuroimaging techniques and quantitative neurolinguistic assessment. In the laboratory, reading difficulties arose in the context of intact visual and auditory word recognition as well as intact ability to understand and repeat words he was unable to read aloud. The unique feature was the absence of dysarthria or speech apraxia in tasks other than reading. Initial imaging did not reveal statistically significant atrophy. Structural magnetic resonance and FDG-PET imaging at the second assessment revealed atrophy and hypometabolism in the right posterior cerebellum, in areas shown to be part of his language network by task-based functional neuroimaging at initial assessment. This syndromic cluster can be designated Progressive Verbal Apraxia of Reading, an entity that has not been reported previously to the best of our knowledge. We hypothesize a selective disconnection of the visual word recognition system from the otherwise intact articulatory apparatus, a disconnection that appears to reflect the disruption of multisynaptic cerebello-cortical circuits.

Epidemiology of cardiometabolic health in Latin America and strategies to address disparities.

In Latin America and the Caribbean (LAC), sociodemographic context, socioeconomic disparities and the high level of urbanization provide a unique entry point to reflect on the burden of cardiometabolic disease in the region. Cardiovascular diseases are the main cause of death in LAC, precipitated by population growth and ageing together with a rapid increase in the prevalence of cardiometabolic risk factors, predominantly obesity and diabetes mellitus, over the past four decades. Strategies to address this growing cardiometabolic burden include both population-wide and individual-based initiatives tailored to the specific challenges faced by different LAC countries, which are heterogeneous. The implementation of public policies to reduce smoking and health system approaches to control hypertension are examples of scalable strategies. The challenges faced by LAC are also opportunities to foster innovative approaches to combat the high burden of cardiometabolic diseases such as implementing digital health interventions and team-based initiatives. This Review provides a summary of trends in the epidemiology of cardiometabolic diseases and their risk factors in LAC as well as context-specific disease determinants and potential solutions to improve cardiometabolic health in the region.

Fungemia due to opportunistic fungi in patients with cancer.

BACKGROUND: Fungemia due to uncommon fungi and secondary to multiple risk factors has become an emergent health problem, particularly in oncology patients. AIMS: This study shows the following data collected during an 11-year period in a tertiary care oncologic center from patients with fungemia: demographic data, clinical characteristics, and outcome. METHODS: A retrospective study was performed at Instituto Nacional de Cancerología, a 135-bed referral cancer center in Mexico City, from July 2012 to June 2023. All episodes of non-Candida fungemia were included. RESULTS: Sixteen cases with uncommon fungemia were found in the database, representing 0.3% from all the blood cultures positive during the study period, and 8.5% from all the fungi isolated. The most common pathogens identified in our series were Histoplasma capsulatum, Acremonium spp., Trichosporon asahii, and Saccharomyces cerevisiae. Eight patients had hematologic malignancies, and five had severe neutropenia. In eight cases fungemia was considered catheter-related, in four cases was classified as primary, and in the last four it was diagnosed as disseminated fungal diseases. Mortality at 30 days was 43.8%. CONCLUSIONS: The improved diagnostic tools have led to a better diagnosis of uncommon fungal infections. More aggressive therapeutic approaches, particularly in patients with malignancies, would increase survival rates in these potentially fatal diseases.

Identifying intraoperative events in a simulated laparotomy video: a multinational study of inattentional blindness among anesthesiologists.

PURPOSE: Medical errors may be occasionally explained by inattentional blindness (IB), i.e., failing to notice an event/object that is in plain sight. We aimed to determine whether age/experience, restfulness/fatigue, and previous exposure to simulation education may affect IB in the anesthetic/surgical setting. METHODS: In this multicentre/multinational study, a convenience sample of 280 anesthesiologists watched an attention-demanding video of a simulated trauma patient undergoing laparotomy and (independently/anonymously) recorded the abnormalities they noticed. The video contained four expected/common abnormalities (hypotension, tachycardia, hypoxia, hypothermia) and two prominently displayed unexpected/rare events (patient's head movement, leaky central venous line). We analyzed the participants' ability to notice the expected/unexpected events (primary outcome) and the proportion of expected/unexpected events according to age group and prior exposure to simulation education (secondary outcomes). RESULTS: Anesthesiologists across all ages noticed fewer unexpected/rare events than expected/common ones. Overall, younger anesthesiologists missed fewer common events than older participants did (P = 0.02). There was no consistent association between age and perception of unexpected/rare events (P = 0.28), although the youngest cohort (< 30 yr) outperformed the other age groups. Prior simulation education did not affect the proportion of misses for the unexpected/rare events but was associated with fewer misses for the expected/common events. Self-perceived restfulness did not impact perception of events. CONCLUSION: Anesthesiologists noticed fewer unexpected/rare clinical events than expected/common ones in an attention-demanding video of a simulated trauma patient, in keeping with IB. Prior simulation training was associated with an improved ability to notice anticipated/expected events, but did not reduce IB. Our findings may have implications for understanding medical mishaps, and efforts to improve situational awareness, especially in acute perioperative and critical care settings.

RéSUMé: OBJECTIF: Les erreurs médicales peuvent parfois s'expliquer par la cécité d'inattention, soit le fait de ne pas remarquer un événement/objet qui est à la vue de tous et toutes. Notre objectif était de déterminer si l'âge/l'expérience, le repos/la fatigue et l'exposition antérieure à l'enseignement par simulation pouvaient affecter la cécité d'inattention dans le cadre de l'anesthésie/chirurgie. MéTHODE: Dans cette étude multicentrique/multinationale, un échantillon de convenance de 280 anesthésiologistes ont visionné une vidéo exigeant l'attention portant sur un patient de trauma simulé bénéficiant d'une laparotomie et ont enregistré (de manière indépendante/anonyme) les anomalies qu'ils et elles ont remarquées. La vidéo contenait quatre anomalies attendues/courantes (hypotension, tachycardie, hypoxie, hypothermie) et deux événements inattendus/rares bien en vue (mouvement de la tête du patient, fuite du cathéter veineux central). Nous avons analysé la capacité des participant·es à remarquer les événements attendus/inattendus (critère d'évaluation principal) et la proportion d'événements attendus/inattendus selon le groupe d'âge et l'exposition antérieure à l'enseignement par simulation (critères d'évaluation secondaires). RéSULTATS: Les anesthésiologistes de tous âges ont remarqué moins d'événements inattendus/rares que d'événements attendus/courants. Globalement, les anesthésiologistes plus jeunes ont manqué moins d'événements courants que leurs congénères plus âgé·es (P = 0,02). Il n'y avait pas d'association constante entre l'âge et la perception d'événements inattendus ou rares (P = 0,28), bien que la cohorte la plus jeune (< 30 ans) ait surpassé les autres groupes d'âge. La formation antérieure par simulation n'a pas eu d'incidence sur la proportion d'inobservation des événements inattendus ou rares, mais a été associée à moins de cécité d'inattention envers les événements attendus ou courants. Le repos perçu n'a pas eu d'impact sur la perception des événements. CONCLUSION: Les anesthésiologistes ont remarqué moins d'événements cliniques inattendus/rares que d'événements attendus/courants dans une vidéo exigeant l'attention portant sur la simulation d'un patient traumatisé, ce qui s'inscrit dans la cécité d'inattention. La formation préalable par simulation était associée à une meilleure capacité à remarquer les événements anticipés/attendus, mais ne réduisait pas la cécité d'inattention. Nos résultats peuvent avoir des implications pour la compréhension des accidents médicaux et les efforts visant à améliorer la conscience situationnelle, en particulier dans les contextes de soins périopératoires aigus et de soins intensifs.

Recognition of Patient Gender: A Machine Learning Preliminary Analysis Using Heart Sounds from Children and Adolescents.

Research has shown that X-rays and fundus images can classify gender, age group, and race, raising concerns about bias and fairness in medical AI applications. However, the potential for physiological sounds to classify sociodemographic traits has not been investigated. Exploring this gap is crucial for understanding the implications and ensuring fairness in the field of medical sound analysis. We aimed to develop classifiers to determine gender (men/women) based on heart sound recordings and using machine learning (ML). Data-driven ML analysis. We utilized the open-access CirCor DigiScope Phonocardiogram Dataset obtained from cardiac screening programs in Brazil. Volunteers < 21 years of age. Each participant completed a questionnaire and underwent a clinical examination, including electronic auscultation at four cardiac points: aortic (AV), mitral (MV), pulmonary (PV), and tricuspid (TV). We used Mel-frequency cepstral coefficients (MFCCs) to develop the ML classifiers. From each patient and from each auscultation sound recording, we extracted 10 MFCCs. In sensitivity analysis, we additionally extracted 20, 30, 40, and 50 MFCCs. The most effective gender classifier was developed using PV recordings (AUC ROC = 70.3%). The second best came from MV recordings (AUC ROC = 58.8%). AV and TV recordings produced classifiers with an AUC ROC of 56.4% and 56.1%, respectively. Using more MFCCs did not substantially improve the classifiers. It is possible to classify between males and females using phonocardiogram data. As health-related audio recordings become more prominent in ML applications, research is required to explore if these recordings contain signals that could distinguish sociodemographic features.

Universe-inspired algorithms for control engineering: A review.

Control algorithms have been proposed based on knowledge related to nature-inspired mechanisms, including those based on the behavior of living beings. This paper presents a review focused on major breakthroughs carried out in the scope of applied control inspired by the gravitational attraction between bodies. A control approach focused on Artificial Potential Fields was identified, as well as four optimization metaheuristics: Gravitational Search Algorithm, Black-Hole algorithm, Multi-Verse Optimizer, and Galactic Swarm Optimization. A thorough analysis of ninety-one relevant papers was carried out to highlight their performance and to identify the gravitational and attraction foundations, as well as the universe laws supporting them. Included are their standard formulations, as well as their improved, modified, hybrid, cascade, fuzzy, chaotic and adaptive versions. Moreover, this review also deeply delves into the impact of universe-inspired algorithms on control problems of dynamic systems, providing an extensive list of control-related applications, and their inherent advantages and limitations. Strong evidence suggests that gravitation-inspired and black-hole dynamic-driven algorithms can outperform other well-known algorithms in control engineering, even though they have not been designed according to realistic astrophysical phenomena and formulated according to astrophysics laws. Even so, they support future research directions towards the development of high-sophisticated control laws inspired by Newtonian/Einsteinian physics, such that effective control-astrophysics bridges can be established and applied in a wide range of applications.

Preliminary profile of the gut microbiota from amerindians in the Brazilian amazon experiencing a process of transition to urbanization.

The Yanomami are one of the oldest indigenous tribes in the Amazon and are direct descendants of the first people to colonize South America 12,000 years ago. They are located on the border between Venezuela and Brazil, with the Venezuelan side remaining uncontacted. While they maintain a hunter-gatherer society, they are currently experiencing contact with urbanized populations in Brazil. The human gut microbiota of traditional communities has become the subject of recent studies due to the Westernization of their diet and the introduction of antibiotics and other chemicals, which have affected microbial diversity in indigenous populations, thereby threatening their existence. In this study, we preliminarily characterized the diversity of the gut microbiota of the Yanomami, a hunter-gatherer society from the Amazon, experiencing contact with urbanized populations. Similarly, we compared their diversity with the population in Manaus, Amazonas. A metabarcoding approach of the 16 S rRNA gene was carried out on fecal samples. Differences were found between the two populations, particularly regarding the abundance of genera (e.g., Prevotella and Bacteroides) and the higher values of the phyla Bacteroidetes over Firmicutes, which were significant only in the Yanomami. Some bacteria were found exclusively in the Yanomami (Treponema and Succinivibrio). However, diversity was statistically equal between them. In conclusion, the composition of the Yanomami gut microbiota still maintains the profile characteristic of a community with a traditional lifestyle. However, our results suggest an underlying Westernization process of the Yanomami microbiota when compared with that of Manaus, which must be carefully monitored by authorities, as the loss of diversity can be a sign of growing danger to the health of the Yanomami.

Maize yield prediction and condition monitoring at the sub-county scale in Kenya: synthesis of remote sensing information and crop modeling.

Agricultural production assessments are crucial for formulating strategies for closing yield gaps and enhancing production efficiencies. While in situ crop yield measurements can provide valuable and accurate information, such approaches are costly and lack scalability for large-scale assessments. Therefore, crop modeling and remote sensing (RS) technologies are essential for assessing crop conditions and predicting yields at larger scales. In this study, we combined RS and a crop growth model to assess phenology, evapotranspiration (ET), and yield dynamics at grid and sub-county scales in Kenya. We synthesized RS information from the Food and Agriculture Organization (FAO) Water Productivity Open-access portal (WaPOR) to retrieve sowing date information for driving the model simulations. The findings showed that grid-scale management information and progressive crop growth could be accurately derived, reducing the model output uncertainties. Performance assessment of the modeled phenology yielded satisfactory accuracies at the sub-county scale during two representative seasons. The agreement between the simulated ET and yield was improved with the combined RS-crop model approach relative to the crop model only, demonstrating the value of additional large-scale RS information. The proposed approach supports crop yield estimation in data-scarce environments and provides valuable insights for agricultural resource management enabling countermeasures, especially when shortages are perceived in advance, thus enhancing agricultural production.

Characterization of antimalarial activity of artemisinin-based hybrid drugs.

In response to the spread of artemisinin (ART) resistance, ART-based hybrid drugs were developed, and their activity profile was characterized against drug-sensitive and drug-resistant Plasmodium falciparum parasites. Two hybrids were found to display parasite growth reduction, stage-specificity, speed of activity, additivity of activity in drug combinations, and stability in hepatic microsomes of similar levels to those displayed by dihydroartemisinin (DHA). Conversely, the rate of chemical homolysis of the peroxide bonds is slower in hybrids than in DHA. From a mechanistic perspective, heme plays a central role in the chemical homolysis of peroxide, inhibiting heme detoxification and disrupting parasite heme redox homeostasis. The hybrid exhibiting slow homolysis of peroxide bonds was more potent in reducing the viability of ART-resistant parasites in a ring-stage survival assay than the hybrid exhibiting fast homolysis. However, both hybrids showed limited activity against ART-induced quiescent parasites in the quiescent-stage survival assay. Our findings are consistent with previous results showing that slow homolysis of peroxide-containing drugs may retain activity against proliferating ART-resistant parasites. However, our data suggest that this property does not overcome the limited activity of peroxides in killing non-proliferating parasites in a quiescent state.

Infrared spectroscopy as a predictive tool for the severity of COVID-19 using patient's saliva: A strategy to avoid hyperinflammation.

Discriminate the severity level of COVID-19 disease is still a challenge. Here we investigate the capability of micro-infrared absorption spectroscopy (micro-FTIR) to probe COVID-19 severity level and predict hyperinflammation, correlating the assigned vibrational data to relevant biomolecules related to the immune system. Saliva of 184 patients was analysed by ELISA assay (Hepcidin) and micro-FTIR. Vibrational bands related to IgM and IgA can discriminate healthy from Severe individuals (sensitivity ≥ 0.749, specificity ≥ 0.945) and are less effective in discriminating Mild or Moderate individuals from the Severe group (sensitivity ≥ 0.628, specificity ≥ 0.867). Analysis of the second derivative of spectra probed increased levels of IL-6 in the saliva a key additional information for the degree of severity prediction. Because the model discriminates all the groups regarding the Severe group, it predicts an intense state of inflammation based on FTIR analysis. It is a powerful tool for predicting hyperinflammation conditions related to SARS-CoV-2 infection and may be an ally in implementing drugs or therapeutic approaches to manage COVID-19 in the Severe stage in healthcare facilities.

Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain.

Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, lrp6 mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor-interacting protein that regulates lateralized neuronal identity in the zebrafish brain.

Should a Stoma Be Used After Intestinal Transplant.

As we all acknowledge benefits of ostomies, they can come with significant morbidity, quality of life issues, and major complications, especially during reversal procedures. In recent years, we have started to observe that similar graft and patient survival can be achieved without ostomies in certain cases. This observation and practice adopted in a few large-volume transplant centers opened a new discussion about the necessity of ostomies in intestinal transplantation. There is still more time and randomized studies will be needed to better understand and analyze the risk/benefits of "No-ostomy" approach in intestinal transplantation.

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

Dimethyl fumarate modulates the regulatory T cell response in the mesenteric lymph nodes of mice with experimental autoimmune encephalomyelitis.

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients.

A rat model of cirrhosis with well-differentiated hepatocellular carcinoma induced by thioacetamide.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA. These rats received bi-weekly injections of either 200 mg/kg TAA or saline (as a control) over a period of 34 weeks. The development of cirrhosis and hepatocarcinogenesis was monitored through histopathological examinations, biochemical markers, and immunohistochemical analyses. Our results demonstrated that chronic TAA administration induced cirrhosis and well-differentiated HCC, characterized by increased fibrosis, altered liver architecture, and enhanced hepatocyte proliferation. Biochemical analyses revealed significant alterations in liver function markers, including elevated alpha-fetoprotein (AFP) levels, without affecting kidney function or causing significant weight loss or mortality in rats. This TAA-induced cirrhosis and HCC rat model successfully replicates the clinical progression of human HCC, including liver function impairment and early-stage liver cancer characteristics. It presents a valuable tool for future research on the mechanisms of antitumor drugs in tumor initiation and development.