Standardization of the Norwood Procedure Improves Outcomes in a Medium-Sized Volume Center.

The Norwood operation has become common practice to palliate patients with hypoplastic left heart structures. Surgical technique and postoperative care have improved; yet, there remains significant attrition prior to stage II palliation. The objective of this study is to report outcomes before and after standardizing our approach to the Norwood operation. Patients who underwent the Norwood operation at Children's of Alabama were identified, those who underwent hybrid palliation operations were excluded. Pre- (2015-2020) and post- (2020-January 2023) standardization groups were compared and outcomes analyzed. Ninety-one patients were included (pre-standardization 44 (48.3%) and 47 (51.7%) post-standardization). There were no differences in baseline and intraoperative characteristics at Norwood between the pre- and post-standardization groups. Compared with pre-standardization, post-standardization was associated with decreased time to extubation (OR 0.87, 95%CI 0.79-0.96), inotrope duration (OR 0.92, 95%CI 0.86-0.98) and hospital length of stay (OR 0.98, 95%CI 0.96-0.99). There was a trend toward decreased cardiac arrest, reintervention rates, and interstage mortality for the post-standardization group. A standardized approach to complex neonatal cardiac operations such as the Norwood procedure may improve morbidity and decrease hospital resource utilization. We recommend establishing protocols at an institutional level to optimize outcomes in such high-risk patient populations.

Pharmacogenomics of coronary artery response to intravenous gamma globulin in kawasaki disease.

Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The mechanism of coronary artery aneurysms (CAA) in KD despite intravenous gamma globulin (IVIG) treatment is not known. We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z ≥ 2.5 and large coronary aneurysm (CAA/L) (N = 92) as z ≥ 5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. The top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p < 6.32E-08 most significant). Variants in SMAT4, LOC100127, PTPRD, TCAF2 and KLRC2 were the most significant non-intergenic SNPs. Functional mapping and annotation (FUMA) analysis identified 12 genomic risk loci with eQTL or chromatin interactions mapped to 48 genes. Of these NDUFA5 has been implicated in KD CAA and MICU and ZMAT4 has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an area under the receiver operating characteristic curve (AUC) of 0.86. This pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD and shows that genomics can help define the cause of CAA/L to guide management and improve risk stratification of KD patients.

Silencing of Sporothrix schenckii GP70 Reveals Its Contribution to Fungal Adhesion, Virulence, and the Host-Fungus Interaction.

Sporothrix schenckii is one of the etiological agents of sporotrichosis, a cutaneous and subcutaneous infection distributed worldwide. Like other medically relevant fungi, its cell wall is a molecular scaffold to display virulence factors, such as protective pigments, hydrolytic enzymes, and adhesins. Cell wall proteins with adhesive properties have been previously reported, but only a handful of them have been identified and characterized. One of them is Gp70, an abundant cell wall protein mainly found on the surface of yeast-like cells. Since the protein also has a role in the activity of 3-carboxy-cis,cis-muconate cyclase and its abundance is low in highly virulent strains, its role in the Sporothrix-host interaction remains unclear. Here, a set of GP70-silenced strains was generated, and the molecular and phenotypical characterization was performed. The results showed that mutants with high silencing levels showed a significant reduction in the adhesion to laminin and fibrinogen, enzyme activity, and defects in the cell wall composition, which included reduced mannose, rhamnose, and protein content, accompanied by an increment in ß-1,3-glucans levels. The cell wall N-linked glycan content was significantly reduced. These strains induced poor TNFα and IL-6 levels when interacting with human peripheral blood mononuclear cells in a dectin-1-, TLR2-, and TLR4-dependent stimulation. The IL-1ß and IL-10 levels were significantly higher and were stimulated via dectin-1. Phagocytosis and stimulation of neutrophil extracellular traps by human granulocytes were increased in highly GP70-silenced strains. Furthermore, these mutants showed virulence attenuation in the invertebrate model Galleria mellonella. Our results demonstrate that Gp70 is a versatile protein with adhesin properties, is responsible for the activity of 3-carboxy-cis,cis-muconate cyclase, and is relevant for the S. schenckii-host interaction.

A meta-analysis on global change drivers and the risk of infectious disease.

Anthropogenic change is contributing to the rise in emerging infectious diseases, which are significantly correlated with socioeconomic, environmental and ecological factors1. Studies have shown that infectious disease risk is modified by changes to biodiversity2-6, climate change7-11, chemical pollution12-14, landscape transformations15-20 and species introductions21. However, it remains unclear which global change drivers most increase disease and under what contexts. Here we amassed a dataset from the literature that contains 2,938 observations of infectious disease responses to global change drivers across 1,497 host-parasite combinations, including plant, animal and human hosts. We found that biodiversity loss, chemical pollution, climate change and introduced species are associated with increases in disease-related end points or harm, whereas urbanization is associated with decreases in disease end points. Natural biodiversity gradients, deforestation and forest fragmentation are comparatively unimportant or idiosyncratic as drivers of disease. Overall, these results are consistent across human and non-human diseases. Nevertheless, context-dependent effects of the global change drivers on disease were found to be common. The findings uncovered by this meta-analysis should help target disease management and surveillance efforts towards global change drivers that increase disease. Specifically, reducing greenhouse gas emissions, managing ecosystem health, and preventing biological invasions and biodiversity loss could help to reduce the burden of plant, animal and human diseases, especially when coupled with improvements to social and economic determinants of health.

Concordancia inter- e intraobservador del puntaje PI-RADS 2.1 del Colegio Americano de Radiología / Intraobserver and interobserver agreement of the American College of Radiology PI-RADS 2.1 score

Resumen Antecedentes: La resonancia magnética (RM) de próstata es uno de los métodos diagnósticos para la identificación del carcinoma de próstata. La escala PI-RADS (Prostate Imaging and Reporting Data System) es el sistema usado para la interpretación de estas imágenes. Es importante, para su reproducibilidad, la estandarización y la evaluación de dicha escala. Objetivo: Determinar la concordancia inter- e intraobservador de la versión 2.1 del PI-RADS. Material y métodos: Estudio observacional retrospectivo, evaluando 129 RM de pacientes con sospecha de cáncer de próstata por tres radiólogos con diferentes años de experiencia y en dos momentos del tiempo, usando el puntaje PI-RADS 2.1. Se evaluó la concordancia intra- e interobservador. Resultados: La concordancia interobservador fue sustancial (kappa > 0,6) en todos los observadores, siendo la categoría 5 la de mayor acuerdo interobservador. Se observó una alta reproducibilidad intraobservardor, con la mayor kappa siendo de 0,856. Cuando se realizó el análisis según años de experiencia de los radiólogos, la concordancia interobservador fue significativa en todos los casos. Conclusiones: El sistema de clasificación PI-RADS 2.1 es reproducible para las diferentes categorías y aumenta la concordancia cuando se trata de lesiones con mayor probabilidad de cáncer clínicamente significativo.

Abstract Background: Magnetic Resonance Imaging (MRI) of the prostate is a key diagnostic tool for identifying prostate carcinoma. The Prostate Imaging-Reporting and Data System (PI-RADS) scale is the standard system for interpreting these images. Standardizing and evaluating this scale is crucial for ensuring consistent and reproducible results. Objective: This study aims to assess both the interobserver and intraobserver agreement of the PI-RADS version 2.1. Material and methods: In this retrospective observational study, 129 prostate MRI scans from patients with suspected prostate cancer were evaluated. Three radiologists, each with different levels of experience, analyzed these scans at two separate times using the PI-RADS 2.1 scoring system. Both intraobserver and interobserver agreements were measured. Results: The study found substantial interobserver agreement (kappa > 0.6) across all categories, with category 5 showing the highest level of agreement. Intraobserver reproducibility was also high, with the highest kappa value reaching 0.856. Further analysis based on the radiologists’ years of experience revealed significant interobserver agreement in all instances. Conclusions: The PI-RADS 2.1 classification system demonstrates high reproducibility across different categories, particularly for lesions more likely to be clinically significant cancers. This underscores its reliability in varied diagnostic scenarios.

Pharmacogenomics of Coronary Artery Response to Intravenous Gamma Globulin in Kawasaki Disease.

Background: Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The pathological walls of afflicted coronary arteries show propensity for forming thrombosis and aneurysms. The mechanism of coronary artery aneurysms (CAA) despite intravenous gamma globulin (IVIG) treatment is not known. Methods: We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z>2.5 and large coronary aneurysm (CAA/L) (N = 92) as z>5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. We performed functional mapping and annotation (FUMA) analysis and further assessed the predictive risk score of genomic risk loci using the area under the receiver operating characteristic curve (AUC). Results: The top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p<6.32E-08 most significant). Variants in SMAT4, LOC100127 , PTPRD, TCAF2 and KLRC2 were the most significant non-intergenic SNPs. FUMA identified 12 genomic risk loci with eQTL or chromatin interactions mapped to 48 genes. Of these NDUFA5 has been implicated in KD CAA and MICU and ZMAT4 has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an AUC of 0.86. Conclusions: This pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD patients. We have identified multiple novel SNPs associated with CAA/L and related genes with potential functional implications. The study shows that genomics can help define the cause of CAA/L to guide management and improve risk stratification of KD patients.

substance use and recidivism of intimate partner violence in Peru: A cross-sectional study.

Background: Intimate Partner Violence (IPV) carries significant global burden, with approximately 27% of women who have ever had a partner experiencing IPV. Additionally, substance use (alcohol and drugs) is often associated with aggressive attitudes and serves as a risk factor for IPV. Objective: Determine the association between substance use and the recurrence of IPV in the Peruvian population in 2022. Methods: A cross-sectional study was conducted using public data from the Ministry of Women, employing regression based on generalized linear models to calculate crude and adjusted Odds Ratios. Results: A total of 65,290 cases of IPV were analyzed, the results revealed that 93.70% of the reports were cases of recidivism. A relationship was identified between substance use and IPV, with an Odds Ratio of 2.24 for the perpetrator's alcohol consumption and an Odds Ratio of 2.33 for drug use. Conclusion: Based on these findings, it can be concluded that a relationship exists between substance use and IPV, and national strategies should incorporate proper monitoring after the initial report of violence, as well as effective control of substance use among perpetrators.

The Potential of Electrospinning to Enable the Realization of Energy-Autonomous Wearable Sensing Systems.

The market for wearable electronic devices is experiencing significant growth and increasing potential for the future. Researchers worldwide are actively working to improve these devices, particularly in developing wearable electronics with balanced functionality and wearability for commercialization. Electrospinning, a technology that creates nano/microfiber-based membranes with high surface area, porosity, and favorable mechanical properties for human in vitro and in vivo applications using a broad range of materials, is proving to be a promising approach. Wearable electronic devices can use mechanical, thermal, evaporative and solar energy harvesting technologies to generate power for future energy needs, providing more options than traditional sources. This review offers a comprehensive analysis of how electrospinning technology can be used in energy-autonomous wearable wireless sensing systems. It provides an overview of the electrospinning technology, fundamental mechanisms, and applications in energy scavenging, human physiological signal sensing, energy storage, and antenna for data transmission. The review discusses combining wearable electronic technology and textile engineering to create superior wearable devices and increase future collaboration opportunities. Additionally, the challenges related to conducting appropriate testing for market-ready products using these devices are also discussed.

Hybrid Thrombectomy and Central Extracorporeal Membrane Oxygenation for Massive Pulmonary Embolism in a Child.

We describe a hybrid thrombectomy and central extracorporeal membrane oxygenation for a child in cardiogenic shock due to a massive pulmonary embolism.

[Neurovascular decompression in trigeminal neuralgia: Functional outcome]. / Descompresión neurovascular en neuralgia trigeminal: resultado funcional.

INTRODUCTION: The most frequent pathology of the fifth cranial nerve is trigeminal neuralgia (TN), characterized by unilateral orofacial pain, of a paroxysmal nature, with distribution in one or more divisions of the trigeminal nerve. The main objective of this work is to demonstrate the efficacy and safety of neurovascular decompressive surgery (NVD). METHODS: Retrospective analytical study, patients operated on for NVD by TN (n: 155), from January 2006 - 2022, using a retrosigmoid approach and clinicalradiological follow-up, whose intraoperative recording was in 3D system (n: 42). RESULTS: 83.3% (n=35) presented classic NT and 16.7% (n = 7) idiopathic. The right side prevailed with 59.5% (n = 25) and paroxysmal pain with 81% (n=34) of representation in the entire series. Compression of arterial origin represented 76.2% (n: 32) of the cases, the superior cerebellar artery represented the first cause of neurovascular compression (NVC) in 52.4% (n: 22) in the exit zone of the trigeminal nerve. The validity of the magnetic resonance imaging (MRI) protocol selected for this series was analyzed; evidencing a high sensitivity of MRI with 97%, and a specificity of 86%. CONCLUSION: The sensitivity and specificity of highdefinition MRI studies and with special protocols for the evaluation of TN, as gold standard paraclinical, were presented. The DNV offered safe results, a high percentage of the patients were described as successful. The 3D recording allowed retrospective analysis with a vision identical to that of the surgeon during the intraoperative period, the type of NVC.

Introducción: La afección más frecuente del V nervio craneal es la neuralgia del trigémino (NT), se caracteriza por dolor orofacial unilateral, paroxístico, distribuyéndose en una o más divisiones del nervio trigémino. El objetivo de presente trabajo es demostrar la eficacia y seguridad de la cirugía descompresiva neurovascular (DNV). Métodos: Estudio analítico retrospectivo, pacientes intervenidos para DNV por NT (n: 155), desde enero de 2006 - 2022, mediante un abordaje retrosigmoideo y seguimiento clínico-radiológico, cuyo registro intraoperatorio fue en sistema 3D (n: 42). Resultados: 83.3% (n=35) presentó NT clásica y 16.7% (n = 7) idiopática. La mayoría con afectación del lado derecho 59.5% (n = 25) y el dolor paroxístico con 81% (n = 34). La compresión de origen arterial representó 76.2% (n: 32) de los casos, la arteria cerebelosa superior representó la primera causa de compresión neurovascular (CNV) en un 52.4% (n:22) en la zona de salida del nervio trigémino. Se analizó la validez del protocolo de resonancia magnética (RM) seleccionado para esta serie; evidenciando una alta sensibilidad de la RM con 97%, y una especificidad del 86%. Conclusión: Se demostró la sensibilidad y especificidad de los estudios de resonancia magnética (RM) de alta definición y con protocolos especiales para la evaluación de la NT, como paraclínico estándar de oro. La DNV ofreció resultados seguros, un alto porcentaje de los pacientes se calificaron como exitosos. El registro 3D permitió analizar en retrospectiva con una visión idéntica a la del cirujano durante el intraoperatorio, el tipo de CNV.

Drug-Induced Linear IgA Bullous Dermatosis in an Oncologic Patient.

Blister formation in the skin can result from various conditions, such as autoimmune disorders, drug reactions, infections, etc. A comprehensive patient assessment may offer clues for diagnosis. Linear IgA bullous dermatosis (LABD) is a rare subepidermal blistering disorder characterized by the deposition of IgA at the basement membrane zone of the skin and mucous membranes. Here, we describe a case of a patient with a new onset of painless blisters located in the skin and oral mucosa after initiating antibiotic treatment.

Descompresión neurovascular en neuralgia trigeminal: resultado funcional / Neurovascular decompression in trigeminal neuralgia: Functional outcome

Resumen Introducción : La afección más frecuente del V nervio craneal es la neuralgia del trigémino (NT), se caracteriza por dolor orofacial unilateral, paroxístico, distribuyén dose en una o más divisiones del nervio trigémino. El objetivo de presente trabajo es demostrar la eficacia y seguridad de la cirugía descompresiva neurovascular (DNV). Métodos : Estudio analítico retrospectivo, pacientes intervenidos para DNV por NT (n: 155), desde enero de 2006 - 2022, mediante un abordaje retrosigmoideo y seguimiento clínico-radiológico, cuyo registro intraope ratorio fue en sistema 3D (n: 42). Resultados : 83.3% (n=35) presentó NT clásica y 16.7% (n = 7) idiopática. La mayoría con afectación del lado derecho 59.5% (n = 25) y el dolor paroxístico con 81% (n = 34). La compresión de origen arterial representó 76.2% (n: 32) de los casos, la arteria cerebelosa superior representó la primera causa de compresión neurovas cular (CNV) en un 52.4% (n:22) en la zona de salida del nervio trigémino. Se analizó la validez del protocolo de resonancia magnética (RM) seleccionado para esta serie; evidenciando una alta sensibilidad de la RM con 97%, y una especificidad del 86%. Conclusión : Se demostró la sensibilidad y especi ficidad de los estudios de resonancia magnética (RM) de alta definición y con protocolos especiales para la evaluación de la NT, como paraclínico estándar de oro. La DNV ofreció resultados seguros, un alto porcentaje de los pacientes se calificaron como exitosos. El registro 3D permitió analizar en retrospectiva con una visión idéntica a la del cirujano durante el intraoperatorio, el tipo de CNV.

Abstract Introduction : The most frequent pathology of the fifth cranial nerve is trigeminal neuralgia (TN), characterized by unilateral orofacial pain, of a paroxysmal nature, with distribution in one or more divisions of the trigeminal nerve. The main objective of this work is to demonstrate the efficacy and safety of neurovascular decompressive surgery (NVD). Methods : Retrospective analytical study, patients operated on for NVD by TN (n: 155), from January 2006 - 2022, using a retrosigmoid approach and clinical-radiological follow-up, whose intraoperative recording was in 3D system (n: 42). Results : 83.3% (n=35) presented classic NT and 16.7% (n = 7) idiopathic. The right side prevailed with 59.5% (n = 25) and paroxysmal pain with 81% (n=34) of rep resentation in the entire series. Compression of arte rial origin represented 76.2% (n: 32) of the cases, the superior cerebellar artery represented the first cause of neurovascular compression (NVC) in 52.4% (n: 22) in the exit zone of the trigeminal nerve. The validity of the magnetic resonance imaging (MRI) protocol selected for this series was analyzed; evidencing a high sensitivity of MRI with 97%, and a specificity of 86%. Conclusion : The sensitivity and specificity of high-definition MRI studies and with special protocols for the evaluation of TN, as gold standard paraclinical, were presented. The DNV offered safe results, a high percent age of the patients were described as successful. The 3D recording allowed retrospective analysis with a vision identical to that of the surgeon during the intraoperative period, the type of NVC.

Central Extracorporeal Membrane Oxygenation Support Following Calcium Channel Blocker Overdose in Children.

Refractory vasodilatory shock (RVS) following massive calcium channel blocker (CCB) overdose remains a challenging clinical entity. Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) has proven useful in several cases of CCB intoxication, however, its use in the pediatric population poses unique challenges given the generally small size of pediatric peripheral vasculature in comparison to the high flow rates necessary for adequate mechanical circulatory support. As a result of these challenges, our group has adopted a "primary" central ECMO cannulation approach to the treatment of children and adolescents admitted to our center with profound RVS after CCB ingestion. We present four cases within the last year using this approach. All patients were successfully discharged from the hospital with no late morbidity at most recent follow-up. Central ECMO support in cases of massive vasodilatory shock following CCB overdose is safe and effective and should be considered early in the clinical course of these critically ill patients.

Phylogenetic classification of natural product biosynthetic gene clusters based on regulatory mechanisms.

The natural products (NPs) biosynthetic gene clusters (BGCs) represent the adapting biochemical toolkit for microorganisms to thrive different microenvironments. Despite their high diversity, particularly at the genomic level, detecting them in a shake-flask is challenging and remains the primary obstacle limiting our access to valuable chemicals. Studying the molecular mechanisms that regulate BGC expression is crucial to design of artificial conditions that derive on their expression. Here, we propose a phylogenetic analysis of regulatory elements linked to biosynthesis gene clusters, to classify BGCs to regulatory mechanisms based on protein domain information. We utilized Hidden Markov Models from the Pfam database to retrieve regulatory elements, such as histidine kinases and transcription factors, from BGCs in the MIBiG database, focusing on actinobacterial strains from three distinct environments: oligotrophic basins, rainforests, and marine environments. Despite the environmental variations, our isolated microorganisms share similar regulatory mechanisms, suggesting the potential to activate new BGCs using activators known to affect previously characterized BGCs.

Association between weight status and migraine in the paediatric population: a systematic review and meta-analysis.

Introduction: An association between weight status and migraine has been previously reported; however, this relationship has only been studied in adults, not in the paediatric population. Objective: To evaluate the association between weight status and migraine in the paediatric population. Methods: We searched PubMed/Medline, Scopus, Web of Science, Ovid Medline, and Embase using a cut-off date of May 2023. We included observational studies that evaluated the association between weight status (underweight, overweight, obese, and excess weight) and migraine in the paediatric population (children and adolescents). Normal weight was the comparator. The outcome was migraine (all types, episodic and chronic). We performed meta-analyses using a random-effects model to estimate the pooled effects for each outcome. Sensitivity analysis was performed based on study design and risk of bias (using the Newcastle-Ottawa Scale). Certainty of evidence was assessed using the GRADE approach. Results: Eight studies (6 cross-sectional, 1 case-control and 1 cohort) covering 16,556 patients were included. The overall certainty of evidence was very low for the association between overweight, obesity, and excess weight with migraine. In the sensitivity analysis, meta-analyses of studies with a low risk of bias found that the overweight population probably had an increased odds of migraine (OR: 1.70; 95% CI: 1.14 to 2.53; I2 = 32.3%, p = 0.224) and that excess weight may increase the odds of migraine (OR: 1.58; 95% CI: 1.06 to 2.35; I2 = 83.7%, p = 0.002). Additionally, cohort and case-control studies found that obesity probably increases the odds of migraine. No studies analysed the association between underweight and migraine. Conclusion: The associations between overweight, obesity, excess weight and migraine were uncertain, but studies with better methodological quality reported increased odds. Future longitudinal studies with proper confounding control are needed to disentangle their causal relationship. Systematic review registration: PROSPERO, identifier CRD42021271533.

Community-Based Workshops to Involve Rural Communities in Wildlife Management Case Study: Bighorn Sheep in Baja California, Mexico.

The description of natural history, and information on the factors threatening conservation, the distribution area, and the status of species population are necessary for proper wildlife management. The objective of this research was to generate such information in two rural communities and to engage residents in bighorn sheep management through a program of three workshops. The first one covered training regarding natural history and management of the species. The second one consisted in the description of the habitat of the species through a dynamic of participatory mapping. The third, include a design of a one strategy to monitor the bighorn sheep population. The workshops were attended by 37 people from the two rural communities. The results suggest the economic element was the main interest of the inhabitants regarding the bighorn sheep. Eleven risk factors were identified to the bighorn sheep in the study sites, a participatory map with relevant information for the management of the species on each community was developed, and a monitoring strategy of the bighorn sheep population was prepared. The workshop program proposed in this research is a tool that can be applied in rural communities to lay the groundwork for a long-term management project of wildlife species.

Pilot study on the efficacy and safety of berberine in people with metabolic syndrome and human immunodeficiency virus infection.

BACKGROUND: Antiretroviral therapy has increased the life expectancy of people living with HIV. However, this increase is not free of comorbidities, and metabolic syndrome is one of the most prevalent. Berberine is an alkaloid nutraceutical that has been shown to ameliorate metabolic disorders such as prediabetes, polycystic ovary syndrome, and non-alcoholic fatty liver disease. However, it has not been tested in HIV infection. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of berberine in improving metabolic syndrome. METHODS AND RESULTS: In this double-blind, placebo-controlled trial, adults living with HIV under virological suppression and metabolic syndrome received either berberine 500 mg TID or placebo for 20 weeks. The primary outcomes were a composite of weight reduction, insulin resistance decrease, and lipid profile improvement. A total of 43 participants were randomized (22 in the berberine group and 21 in the placebo group); 36 participants completed the follow-up and were analyzed. The berberine group showed a reduction in weight and body mass index, lower insulin resistance, and a reduction in TNF-alpha. The control group had higher total cholesterol, c-LDL, and IL-6 concentration. CONCLUSION: In people living with HIV under virological suppression, berberine was safe and improves clinical and biochemical components of metabolic syndrome. However, further studies with more participants and longer intervention periods need to be explored.

Rictor induces AKT signaling to regulate lymphatic valve formation.

Lymphatic valves are specialized structures of the collecting lymphatic vessels and are crucial for preventing retrograde lymph flow. Mutations in valve-forming genes have been clinically implicated in the pathology of congenital lymphedema. Lymphatic valves form when oscillatory shear stress (OSS) from lymph flow signals through the PI3K/AKT pathway to promote the transcription of valve-forming genes that trigger the growth and maintenance of lymphatic valves throughout life. Conventionally, in other tissue types, AKT activation requires dual kinase activity and the mammalian target of rapamycin complex 2 (mTORC2) commands this process by phosphorylating AKT at Ser473. Here we showed that embryonic and postnatal lymphatic deletion of Rictor , a critical component of mTORC2, led to a significant decrease in lymphatic valves and prevented the maturation of collecting lymphatic vessels. RICTOR knockdown in human lymphatic endothelial cells (hdLECs) not only significantly reduced the level of activated AKT and the expression of valve-forming genes under no-flow conditions, but also abolished the upregulation of AKT activity and valve-forming genes in response to flow. We further showed that the AKT target, FOXO1, a repressor of lymphatic valve formation, had increased nuclear activity in Rictor knockout mesenteric LECs, in vivo . Deletion of Foxo1 in Rictor knockout mice restored the number of valves to control levels in both mesenteric and ear lymphatics. Our work revealed a novel role of RICTOR signaling in the mechanotransduction signaling pathway, wherein it activates AKT and prevents the nuclear accumulation of the valve repressor, FOXO1, which ultimately allows the formation and maintenance of a normal lymphatic valve.

Lauroylated, Acetylated, and Succinylated Agave tequilana Fructans Fractions: Structural Characterization, Prebiotic, Antibacterial Activity and Their Effect on Lactobacillus paracasei under Gastrointestinal Conditions.

The effect of chemical modification of fractions of native agave fructans (NAF), high performance (HPAF), and a high degree of polymerization (HDPAF) by lauroylation, acetylation, and succinylation reactions on their prebiotic activity, antibacterial properties were evaluated and survival of L. paracasei in a simulated gastrointestinal system. The characterization of the reactions was confirmed by NMR and FTIR. The lauroylated and succinylated fructan fractions showed higher antibacterial activity against pathogenic bacteria such as Escherichia coli, Enterococcus faecalis and Staphylococcus aureus than the unmodified ones. Analyses with L. paracasei showed that the acetylated fructan fractions had a greater prebiotic effect, and simulated gastrointestinal tests demonstrated that the acetylated and succinylated fractions favored the survival of L. paracasei during the gastrointestinal phase. The effect of modifying the agave fructans fractions on the evaluated properties depended on the structure, size, and polarity of each incorporated functional group, as well as the degree of polymerization and substitution of each fraction. These results show that the chemical modification of the fructan fractions analyzed improves their functional properties, offering an alternative in the food and pharmaceutical industry.