Complete mitochondrial genome of the introduced Indian walking stick Carausius morosus (Lonchodidae, Insecta) from California.

We present the complete mitochondrial genome of Carausius morosus from Salinas, CA. The mitochondrial genome of C. morosus is circular, AT rich (78.1%), and 16,671 bp in length. It consists of 13 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes and is identical in gene content to Carausius sp.

Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.

Psychostimulant use disorders (PSUD) are prevalent; however, no FDA-approved medications have been made available for treatment. Previous studies have shown that dual inhibitors of the dopamine transporter (DAT) and sigma receptors significantly reduce the behavioral/reinforcing effects of cocaine, which have been associated with stimulation of extracellular dopamine (DA) levels resulting from DAT inhibition. Here, we employ microdialysis and fast scan cyclic voltammetry (FSCV) procedures to investigate the effects of dual inhibitors of DAT and sigma receptors in combination with cocaine on nucleus accumbens shell (NAS) DA dynamics in naïve male Sprague Dawley rats. In microdialysis studies, administration of rimcazole (3, 10 mg/kg; i.p.) or its structural analog SH 3-24 (1, 3 mg/kg; i.p.), compounds that are dual inhibitors of DAT and sigma receptors, significantly reduced NAS DA efflux stimulated by increasing doses of cocaine (0.1, 0.3, 1.0 mg/kg; i.v.). Using the same experimental conditions, in FSCV tests, we show that rimcazole pretreatments attenuated cocaine-induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Under the same conditions, JJC8-091, a modafinil analog and dual inhibitor of DAT and sigma receptors, similarly attenuated cocaine-induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Our results provide the neurochemical groundwork towards understanding actions of dual inhibitors of DAT and sigma receptors on DA dynamics that likely mediate the behavioral effects of psychostimulants like cocaine.

MYT1L deficiency impairs excitatory neuron trajectory during cortical development.

Mutations that reduce the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. Furthermore, MYT1L is routinely used as a proneural factor in fibroblast-to-neuron transdifferentiation. MYT1L has been hypothesized to play a role in the trajectory of neuronal specification and subtype specific maturation, but this hypothesis has not been directly tested, nor is it clear which neuron types are most impacted by MYT1L loss. In this study, we profiled 313,335 nuclei from the forebrains of wild-type and MYT1L-deficient mice at two developmental stages: E14 at the peak of neurogenesis and P21, when neurogenesis is complete, to examine the role of MYT1L levels in the trajectory of neuronal development. We found that MYT1L deficiency significantly disrupted the relative proportion of cortical excitatory neurons at E14 and P21. Significant changes in gene expression were largely concentrated in excitatory neurons, suggesting that transcriptional effects of MYT1L deficiency are largely due to disruption of neuronal maturation programs. Most effects on gene expression were cell autonomous and persistent through development. In addition, while MYT1L can both activate and repress gene expression, the repressive effects were most sensitive to haploinsufficiency, and thus more likely mediate MYT1L syndrome. These findings illuminate the intricate role of MYT1L in orchestrating gene expression dynamics during neuronal development, providing insights into the molecular underpinnings of MYT1L syndrome.

Manejo clínico quirúrgico de la necrosis pancreática infectada en adultos: experiencia en un hospital especializado, Paraguay / Surgical clinical management of necrotizing pancreatitis in adults: experience in a specialized hospital, Paraguay

Introducción: la necrosis pancreática se presenta entre 10 y 20 % de los pacientes con pancreatitis aguda, tiene una mortalidad de 10 a 25 % y si se agrega infección a la necrosis entre 40 y 70 %. Objetivo: describir el manejo clínico quirúrgico de la necrosis pancreática infectada en el Servicio de Cirugía General del Hospital Nacional entre el periodo 2021-2022. Metodología: estudio observacional descriptivo de corte temporal transversal. En pacientes internados en el Servicio de Cirugía General del Hospital Nacional por pancreatitis aguda grave con necrosis pancreática infectada. Resultados: se analizaron un total de 30 pacientes. La media de edad fue de 39 años. Predominó en nuestra población pacientes de sexo masculino en el 56.67 %. En cuanto a las comorbilidades asociadas un 33.3 % los pacientes presentaron principalmente Diabetes mellitus tipo 2 e Hipertensión arterial; en menor medida Obesidad en un 23.3 %. De la población en estudio 76.6 % recibieron tratamiento quirúrgico y 23.33% tratamiento médico principalmente antibiótico terapia. De los pacientes sometidos a tratamiento quirúrgico 9 fueron a necrosectomia abierta, 7 a drenaje percutáneo, y en menor medida drenaje biliar y endoscópico. En cuanto a la mortalidad por necrosis pancreática infectada encontramos un 10 % de mortalidad. Discusión: la mayor parte de los pacientes con pancreatitis aguda grave sufren de necrosis pancreática; la necrosis pancreática infectada se asocia con mayor riesgo de mortalidad y en su mayoría requieren tratamientos invasivos. Conclusión: el manejo mínimamente invasivo en el tratamiento inicial de la necrosis pancreática infectada podría resolver la mayoría de los casos sin necesidad de realizar necrosectomia; reservando esta última solo a los que fracasan en el tratamiento inicial.

Introduction: pancreatic necrosis occurs between 10 and 20 % of patients with pancreatitis, has a mortality of 10 to 25 % and if infection is added to the necrosis between 40 and 70 %. Objective: to describe the surgical and clinical management of infected necrotizing pancreatitis in patients admitted to the General Surgery Service of the Hospital Nacional between the period 2021-2022. Methodology: this was an observational, descriptive and cross-section study with a temporal cut. We included patients admitted to the general surgery service of the National Hospital with severe acute pancreatitis with infected necrotizing pancreatitis. Results: a total of 30 patients were included. The mean age was 39 years. Male patients prevailed in our population in 56.67 %. Regarding the associated comorbidities, 33.3 % of the patients presented mainly type 2 diabetes mellitus and arterial hypertension; to a lesser extent Obesity in 23.3 %. In the study population, 76.6 % received surgical treatment and 23.33 % medical treatment, mainly antibiotic therapy. Of the patients who underwent surgical treatment, 9 were open necrosectomy, 7 had percutaneous drainage, and to a lesser extent biliary and endoscopic drainage. Regarding mortality due to infected necrotizing pancreatitis, we found a 10% mortality. Discussion: most of the patients with severe acute pancreatitis suffer from necrotizing pancreatitis; infected necrotizing pancreatitis is associated with increased risk of mortality and most require invasive treatment. Conclusion: minimally invasive management in the initial treatment of infected necrotizing pancreatitis, which could resolve most cases without the need to perform necrosectomy; the latter should be reserved for those who fail the initial treatment.

KS-WNK1 is Required for the Renal Response to Extreme Changes in Potassium Intake.

KS-WNK1 is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies suggest that it could play a role in regulating potassium renal excretion by modulating the activity of the Na+-Cl- cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low potassium diet. In this study, we investigated the role of KS-WNK1 in regulating potassium excretion under extreme changes in potassium intake. After following a zero-potassium diet (0KD) for 10 days, KS-WNK1-/- mice had lower plasma levels of K+ and Cl-, while exhibiting higher urinary excretion of Na+, Cl-, and K+ compared to KS-WNK1+/+ mice. After 10 days of 0KD or normal-potassium diet (NKD), all mice were challenged with a high-potassium diet (HKD). Plasma K+ levels markedly increased after the HKD challenge only in mice previously fed with 0KD, regardless of genotype. KSWNK1+/+ mice adapt better to HKD-challenge than KS-WNK1-/- mice after a potassium-retaining state. The difference in the pNCC/NCC ratio between KS-WNK1+/+ and KS-WNK1-/- mice after 0KD and HKD indicates a role for KS-WNK1 in both, NCC phosphorylation and dephosphorylation. These observations show that KS-WNK1 helps the DCT to respond to extreme changes in potassium intake, such as those occurring in wildlife.

Arginine vasopressin regulates the renal Na+-Cl- and Na+-K+-Cl- cotransporters through with-no-lysine kinase 4 and inhibitor 1 phosphorylation.

Vasopressin regulates water homeostasis via the V2 receptor in the kidney at least in part through protein kinase A (PKA) activation. Vasopressin, through an unknown pathway, upregulates the activity and phosphorylation of Na+-Cl- cotransporter (NCC) and Na+-K+-2Cl- cotransporter 2 (NKCC2) by Ste20-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase 1 (OSR1), which are regulated by the with-no-lysine kinase (WNK) family. Phosphorylation of WNK4 at PKA consensus motifs may be involved. Inhibitor 1 (I1), a protein phosphatase 1 (PP1) inhibitor, may also play a role. In human embryonic kidney (HEK)-293 cells, we assessed the phosphorylation of WNK4, SPAK, NCC, or NKCC2 in response to forskolin or desmopressin. WNK4 and cotransporter phosphorylation were studied in desmopressin-infused WNK4-/- mice and in tubule suspensions. In HEK-293 cells, only wild-type WNK4 but not WNK1, WNK3, or a WNK4 mutant lacking PKA phosphorylation motifs could upregulate SPAK or cotransporter phosphorylation in response to forskolin or desmopressin. I1 transfection maximized SPAK phosphorylation in response to forskolin in the presence of WNK4 but not of mutant WNK4 lacking PP1 regulation. We observed direct PP1 regulation of NKCC2 dephosphorylation but not of NCC or SPAK in the absence of WNK4. WNK4-/- mice with desmopressin treatment did not increase SPAK/OSR1, NCC, or NKCC2 phosphorylation. In stimulated tubule suspensions from WNK4-/- mice, upregulation of pNKCC2 was reduced, whereas upregulation of SPAK phosphorylation was absent. These findings suggest that WNK4 is a central node in which kinase and phosphatase signaling converge to connect cAMP signaling to the SPAK/OSR1-NCC/NKCC2 pathway.NEW & NOTEWORTHY With-no-lysine kinases regulate the phosphorylation and activity of the Na+-Cl- and Na+-K+-2Cl- cotransporters. This pathway is modulated by arginine vasopressin (AVP). However, the link between AVP and WNK signaling remains unknown. Here, we show that AVP activates WNK4 through increased phosphorylation at putative protein kinase A-regulated sites and decreases its dephosphorylation by protein phosphatase 1. This work increases our understanding of the signaling pathways mediating AVP actions in the kidney.

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis.

PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

Biofortified Beverage with Chlorogenic Acid from Stressed Carrots: Anti-Obesogenic, Antioxidant, and Anti-Inflammatory Properties.

Using wounding stress to increase the bioactive phenolic content in fruits and vegetables offers a promising strategy to enhance their health benefits. When wounded, such phenolics accumulate in plants and can provide antioxidant, anti-inflammatory, and anti-obesogenic properties. This study investigates the potential of using wounding stress-treated carrots biofortified with phenolic compounds as a raw material to extract carrot juice with increased nutraceutical properties. Fresh carrots were subjected to wounding stress via slicing and then stored at 15 °C for 48 h to allow phenolic accumulation. These phenolic-enriched slices were blanched, juiced, and blended with orange juice (75:25 ratio) and 15% (w/v) broccoli sprouts before pasteurization. The pasteurized juice was characterized by its physicochemical attributes and bioactive compound content over 28 days of storage at 4 °C. Additionally, its antioxidant, anti-inflammatory, and anti-obesogenic potentials were assessed using in vitro assays, both pre- and post-storage. The results reveal that juice derived from stressed carrots (SJ) possessed 49%, 83%, and 168% elevated levels of total phenolics, chlorogenic acid, and glucosinolates, respectively, compared to the control juice (CJ) (p < 0.05). Both juices reduced lipid accumulation in 3T3-L1 cells and nitric oxide production in Raw 264.7 cells, without significant differences between them. SJ further displayed a 26.4% increase in cellular antioxidant activity. The juice's bioactive characteristics remained stable throughout storage time. In conclusion, the utilization of juice obtained from stressed carrots in a blend with orange juice and broccoli sprouts offers a promising method to produce a beverage enriched in bioactive compounds and antioxidant potential.

Early Life Nutrition Factors and Risk of Acute Leukemia in Children: Systematic Review and Meta-Analysis.

Acute leukemia commonly occurs in young children with peak incidence at the age of 2-5 years. However, the etiology is still unclear and many preventable risk factors still deserve to be reviewed. The focus of this systematic review and meta-analysis is to summarize the evidence concerning early life nourishment (breastfeeding, early life diet), neonatal vitamin K administration and the risk of acute leukemia. All epidemiological studies published up to June 2023 and assessing diet-related risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science), with no limits on publication year or language. A total of 38 studies (37 case-control studies and 1 study with pooled analysis) were included. The published risk estimates were combined into a meta-analysis using the Generic Inverse Variance method. The current evidence shows that breastfeeding (yes vs. no) has a protective effect against acute lymphoblastic leukemia (odds ratio = 0.85; 95% CI, 0.76-0.94). Evidence related to the role of other studied factors (foods and supplements) is inconclusive. Further research into the potential role of diet in early life and the risk of acute leukemia is needed to develop prevention strategies at population level. Review Registration: PROSPERO registration no. CRD42019128937.

Calling Cards: A Customizable Platform to Longitudinally Record Protein-DNA Interactions Over Time in Cells and Tissues.

Calling Cards is a platform technology to record a cumulative history of transient protein-DNA interactions in the genome of genetically targeted cell types. The record of these interactions is recovered by next-generation sequencing. Compared with other genomic assays, readouts of which provide a snapshot at the time of harvest, Calling Cards enables correlation of historical molecular states to eventual outcomes or phenotypes. To achieve this, Calling Cards uses the piggyBac transposase to insert self-reporting transposon "Calling Cards" into the genome, leaving permanent marks at interaction sites. Calling Cards can be deployed in a variety of in vitro and in vivo biological systems to study gene regulatory networks involved in development, aging, and disease. Out of the box, it assesses enhancer usage but can be adapted to profile-specific transcription factor (TF) binding with custom TF-piggyBac fusion proteins. The Calling Cards workflow has five main stages: delivery of Calling Cards reagents, sample preparation, library preparation, sequencing, and data analysis. Here, we first present a comprehensive guide for experimental design, reagent selection, and optional customization of the platform to study additional TFs. Then, we provide an updated protocol for the five steps, using reagents that improve throughput and decrease costs, including an overview of a newly deployed computational pipeline. This protocol is designed for users with basic molecular biology experience to process samples into sequencing libraries in 2 days. Familiarity with bioinformatic analysis and command line tools is required to set up the pipeline in a high-performance computing environment and to conduct downstream analyses. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Preparation and delivery of Calling Cards reagents Support Protocol 1: Next-generation sequencing quantification of barcode distribution within self-reporting transposon plasmid pool and adeno-associated virus genome Basic Protocol 2: Sample collection and RNA purification Support Protocol 2: Library density quantitative PCR Basic Protocol 3: Sequencing library preparation Basic Protocol 4: Library pooling and sequencing Basic Protocol 5: Data analysis.

Calling Cards: a customizable platform to longitudinally record protein-DNA interactions over time in cells and tissues.

Calling Cards is a platform technology to record a cumulative history of transient protein-DNA interactions in the genome of genetically targeted cell types. The record of these interactions is recovered by next generation sequencing. Compared to other genomic assays, whose readout provides a snapshot at the time of harvest, Calling Cards enables correlation of historical molecular states to eventual outcomes or phenotypes. To achieve this, Calling Cards uses the piggyBac transposase to insert self-reporting transposon (SRT) "Calling Cards" into the genome, leaving permanent marks at interaction sites. Calling Cards can be deployed in a variety of in vitro and in vivo biological systems to study gene regulatory networks involved in development, aging, and disease. Out of the box, it assesses enhancer usage but can be adapted to profile specific transcription factor binding with custom transcription factor (TF)-piggyBac fusion proteins. The Calling Cards workflow has five main stages: delivery of Calling Card reagents, sample preparation, library preparation, sequencing, and data analysis. Here, we first present a comprehensive guide for experimental design, reagent selection, and optional customization of the platform to study additional TFs. Then, we provide an updated protocol for the five steps, using reagents that improve throughput and decrease costs, including an overview of a newly deployed computational pipeline. This protocol is designed for users with basic molecular biology experience to process samples into sequencing libraries in 1-2 days. Familiarity with bioinformatic analysis and command line tools is required to set up the pipeline in a high-performance computing environment and to conduct downstream analyses. Basic Protocol 1: Preparation and delivery of Calling Cards reagentsBasic Protocol 2: Sample preparationBasic Protocol 3: Sequencing library preparationBasic Protocol 4: Library pooling and sequencingBasic Protocol 5: Data analysis.

Evaluation of the antioxidant, anti-inflammatory, and anti-tumoral properties of bioactive compounds extracted from murta berries (Ugni molinae T.) dried by different methods.

This study evaluated the effects of different drying methods (freeze drying, vacuum drying, infrared drying, convective drying, and sun drying) on the biological properties of berries from the Chilean murta (Ugni molinae Turcz) shrub. Physical-chemical properties (proximal composition, dietary fiber, sugars) were determined. Total phenolic content through the method of Folin-Ciocalteau, the profile of phenol compounds was determined by HPLC, and antioxidant potential by DPPH and ORAC assays were also evaluated. The topic anti-inflammatory effect was evaluated by mice´s ear edema, and in vitro anti-tumoral activity was tested by MTT assay. The chemical properties of dried berries differed significantly based on the drying method: freeze-dried murta berries showed increased total phenolic content extracted over fresh and dried samples. In addition, this lyophilized extract stood out in its antioxidant potential, in both assays evaluated (DPPH and ORAC), compared to the other drying methods. Notwithstanding, vacuum- and infrared-dried murta also showed a higher ORAC value. Antioxidant potential was significantly associated with phenolic compounds catechin and pyrogallol, which were the most abundant phenolic compounds present in all samples. The anti-inflammatory activity was most effective under freeze-drying and vacuumdrying conditions. Moreover, vacuum drying and infrared drying best preserved the anti-tumoral effect on cancer cells.

Experiencia actual en el abordaje laparoscópico transabdominal preperitoneal de hernias inguinales en el Servicio de Cirugía General del Hospital Nacional: periodo 2018-2022

Introducción: la hernia inguinal es uno de los principales motivos de consulta quirúrgica y su reparación es uno de los procedimientos más comunes en cirugía. Objetivo: determinar la experiencia en el abordaje laparoscópico de las hernias inguinales por técnica transabdominal preperitoneal en el Servicio de Cirugía General del Centro Médico Nacional-Hospital Nacional. Metodología: estudio observacional descriptivo retrospectivo de corte temporal transversal. En pacientes de 16 a 90 años de edad con diagnóstico de hernia inguinal internados en el Servicio de Cirugía General del Centro Médico Nacional-Hospital Nacional para hernioplastia electiva. Resultados: se llevaron a cabo 30 hernioplastias por técnica técnica trans-abdominal pre-peritoneal de los cuales el 73 % fue realizado en hombres y 27 % en mujeres; se identificó una media de edad de 48,4 años, el grupo etario con mayor frecuencia fue de 38 a 48 años. En el examen físico pre quirúrgico se encontraron hernias inguinales unilaterales en el 76.6 % y bilaterales en el 23.3 %; en la mayor parte de los pacientes las hernias fueron primarias en el 86.6 %y recidivada en el 13.3 %. El tiempo quirúrgico en promedio fue de 93.1 minutos; con un tiempo máximo de 120 minutos y mínimo de 60 minutos. El tiempo de hospitalización en el 100 % de los pacientes fue de 48 h. De las complicaciones post operatorias se establece que el 76.6 % no presento ningún tipo de complicación; el 20 % presentó seroma como complicación principal y 3.3 % infección del sitio quirúrgico. Conclusión: debido a su alta frecuencia y a su impacto en la incapacidad laboral y social, las hernias inguinales representan una de las patologías quirúrgicas más importantes con bajas tasas de complicaciones post operatorias y corta estancia hospitalaria.

Introduction: inguinal hernia is one of the main reasons TAPP, e-TEP (Totally extraperitoneal with extended vision) for surgical consultation and its repair is one of the most common surgical procedures. Objective: to determine the experience in the laparoscopic approach of inguinal hernias by preperitoneal transabdominal technique in the Servicio de Cirugía General of the Centro Médico Nacional-Hospital Nacional. Methodology: retrospective descriptive observational study of cross-sectional time. In patients from 16 to 90 years of age with a diagnosis of inguinal hernia admitted to the Servicio de Cirugía General of the Centro Médico Nacional-Hospital Nacional for elective hernioplasty. Results: 30 hernioplasties were carried out by the TAPP technique, of which 73 % were performed in men and 27 % in women; a mean age of 48.4 years was identified, the age group most frequently being 38 to 48 years. In the pre-surgical physical examination, unilateral inguinal hernias were found in 76.6 % and bilateral in 23.3 %; in most of the patients the hernias were primary in 86.6 % and recurred in 13.3 %. Average surgical time was 93.1 minutes; with a maximum time of 120 minutes and a minimum of 60 minutes. The hospitalization time in 100 % of the patients was 48 hours. Of the post-operative complications, it is established that 76.6% did not present any type of complication; 20 % presented seroma as the main complication and 3.3 % surgical site infection. Conclusion: due to its high frequency and its impact on work and social disability, inguinal hernias represent one of the most important surgical pathologies with low rates of postoperative complications and short hospital stay.

Role of Maternal Diet in the Risk of Childhood Acute Leukemia: A Systematic Review and Meta-Analysis.

Many studies have investigated the etiology of acute leukemia, one of the most common types of cancer in children; however, there is a lack of clarity regarding preventable risk factors. This systematic review and meta-analysis aimed to summarize the current evidence regarding the role of maternal dietary factors in the development of childhood leukemia. All epidemiological studies published until July 2022 that evaluated maternal dietary risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science) without limits of publication year or language. A total of 38 studies (1 prospective cohort study, 34 case-control studies and 3 studies with pooled analysis) were included. The published risk estimates were combined into a meta-analysis, using the Generic Inverse Variance method. The maternal consumption of fruits (two or more daily servings vs. less) was inversely associated with acute lymphoblastic leukemia (odds ratio = 0.71; 95% CI, 0.59-0.86), whereas maternal coffee intake (higher than two cups per day vs. no consumption) was associated with an increased risk of acute lymphoblastic leukemia (odds ratio = 1.45; 95% CI, 1.12-1.89). Despite these findings, more high-quality research from cohort studies and the identification of causal factors are needed to develop evidence-based and cost-effective prevention strategies applicable at the population level. Review Registration: PROSPERO registration no. CRD42019128937.

Perfil cognitivo y social en niños y niñas con Trastorno del Espectro Autista / Cognitive and social profile in children with autism spectrum disorder

El Trastorno del Espectro Autista (TEA) es una condición que se caracteriza por presentar fallas en la conducta social y comportamientos repetitivos. Su perfil neuropsicológico muestra hallaz-gos heterogéneos que dependen de la severidad del trastorno. El objetivo del presente trabajo es describir el funcionamiento neuropsicológico de una muestra de niños y niñas con TEA que asisten al Instituto para el Desarrollo Integral del Niño en condición de Autismo (DINA). La muestra estuvo conformada por 78 participantes, 15.4% de género femenino y 84.6% de géne-ro masculino, con edades entre los 6 y los 16 años. Los instrumentos utilizados fueron protocolo neuropsicológico adaptado de la ENI, prorrateo de inteligencia del WISC-IV, Test de Sally y Ann, Test de Expresiones faciales adaptadopor Paul Ekman y el Test de la Mirada para niños, El Test de Metidas de Pata, e Historias Extrañas de Happé. Los resultados se discuten a la luz de la li-teratura científica sobre el tema.

Autism Spectrum Disorder (ASD) is a condition that is characterized by failures in social behav-ior and repetitive behaviors. The neuropsychological profile shows heterogeneous findings that depends on the severity of the disorder. The objective of this paper is to describe the neuropsychological functioning of a sample of children with ASD who attend the Institute for the Integral Development of Children with Autism (DINA). The sample consisted of 78 partici-pants, 15.4% female and 84.6% male, aged between6 and 16 years. The instruments used were the neuropsychological protocol adapted from the ENI, intelligence apportionment from the WISC-IV, Sally and Ann Test, Facial Expressions Test adapted by Paul Ekman and Reading the Mind in the Eye for children, Faux Pas Test, and The Happé’s Strange Stories test. The re-sults are discussed considering the scientific literature on the subject. (AU)

Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets.

During aging, changes in gene expression are associated with a decline in physical and cognitive abilities. Here, we investigate the connection between changes in mRNA and protein expression in the brain by comparing the transcriptome and proteome of the mouse cortex during aging. Our transcriptomic analysis revealed that aging mainly triggers gene activation in the cortex. We showed that an increase in mRNA expression correlates with protein expression, specifically in the anterior cingulate cortex, where we also observed an increase in cortical thickness during aging. Genes exhibiting an aging-dependent increase of mRNA and protein levels are involved in sensory perception and immune functions. Our proteomic analysis also identified changes in protein abundance in the aging cortex and highlighted a subset of proteins that were differentially enriched but exhibited stable mRNA levels during aging, implying the contribution of aging-related post- transcriptional and post-translational mechanisms. These specific genes were associated with general biological processes such as translation, ribosome assembly and protein degradation, and also important brain functions related to neuroplasticity. By decoupling mRNA and protein expression, we have thus characterized distinct subsets of genes that differentially adjust to cellular aging in the cerebral cortex.

How should childhood acute lymphoblastic leukemia relapses in low-income and middle-income countries be managed: The AHOPCA-ALL study group experience.

BACKGROUND: Children with relapsed acute lymphoblastic leukemia (ALL) in low-income and middle-income countries rarely survive. The Pediatric Hematology-Oncology Association of Central America (AHOPCA) developed the AHOPCA-ALL REC 2014 protocol to improve outcomes in resource-constrained settings without access to stem cell transplantation. METHODS: The AHOPCA-ALL REC 2014 protocol was based on a modified frontline induction phase 1A, a consolidation therapy with six modified R-blocks derived from the ALL-Berlin-Frankfurt-Munster REZ 2002 protocol and intermittent maintenance therapy. Children with B-lineage ALL were eligible after a late medullary relapse, an early or late combined relapse, or any extramedullary relapses. Those with T-lineage ALL were eligible after early and late extramedullary relapses, as were those with both B-lineage and T-lineage relapses occurring at least 3 months after therapy abandonment. RESULTS: The study population included 190 patients with T-lineage (n = 3) and B-lineage (n = 187) ALL. Of those with B-lineage ALL, 25 patients had a very early extramedullary relapse, 40 had an early relapse (32 extramedullary and 8 combined), and 125 had a late relapse (34 extramedullary, 19 combined, and 72 medullary). The main cause of treatment failure was second relapse (52.1%). The 3-year event-free survival rate (± standard error) was 25.9% ± 3.5%, and the 3-year overall survival rate was 36.7% ± 3.8%. The 3-year event-free survival rate was 47.2% ± 4.7% for late relapses. The most frequently reported toxicity was grade 3 or 4 infection. Mortality during treatment occurred in 17 patients (8.9%), in most cases because of infectious complications. CONCLUSIONS: Selected children with relapsed ALL in Central America can be cured with second-line regimens even without access to consolidation with stem cell transplantation. Children in low-income and middle-income countries who have lower risk relapses of ALL should be treated with curative intent.

Glucose/Fructose Delivery to the Distal Nephron Activates the Sodium-Chloride Cotransporter via the Calcium-Sensing Receptor.

BACKGROUND: The calcium-sensing receptor (CaSR) in the distal convoluted tubule (DCT) activates the NaCl cotransporter (NCC). Glucose acts as a positive allosteric modulator of the CaSR. Under physiologic conditions, no glucose is delivered to the DCT, and fructose delivery depends on consumption. We hypothesized that glucose/fructose delivery to the DCT modulates the CaSR in a positive allosteric way, activating the WNK4-SPAK-NCC pathway and thus increasing salt retention. METHODS: We evaluated the effect of glucose/fructose arrival to the distal nephron on the CaSR-WNK4-SPAK-NCC pathway using HEK-293 cells, C57BL/6 and WNK4-knockout mice, ex vivo perfused kidneys, and healthy humans. RESULTS: HEK-293 cells exposed to glucose/fructose increased SPAK phosphorylation in a WNK4- and CaSR-dependent manner. C57BL/6 mice exposed to fructose or a single dose of dapagliflozin to induce transient glycosuria showed increased activity of the WNK4-SPAK-NCC pathway. The calcilytic NPS2143 ameliorated this effect, which was not observed in WNK4-KO mice. C57BL/6 mice treated with fructose or dapagliflozin showed markedly increased natriuresis after thiazide challenge. Ex vivo rat kidney perfused with glucose above the physiologic threshold levels for proximal reabsorption showed increased NCC and SPAK phosphorylation. NPS2143 prevented this effect. In healthy volunteers, cinacalcet administration, fructose intake, or a single dose of dapagliflozin increased SPAK and NCC phosphorylation in urinary extracellular vesicles. CONCLUSIONS: Glycosuria or fructosuria was associated with increased NCC, SPAK, and WNK4 phosphorylation in a CaSR-dependent manner.

Comparison of Emotion Recognition in Young People, Healthy Older Adults, and Patients with Mild Cognitive Impairment.

BACKGROUND: The basic discrete emotions, namely, happiness, disgust, anger, fear, surprise, and sadness, are present across different cultures and societies. Facial emotion recognition is crucial in social interactions, but normal and pathological aging seem to affect this ability. The present research aims to identify the differences in the capacity for recognition of the six basic discrete emotions between young and older healthy controls (HOC) and mildly cognitively impaired patients (MCI). METHOD: The sample (N = 107) consisted of 47 young adults, 27 healthy older adults, and 33 MCI patients. Several neuropsychological scales were administered to assess the cognitive state of the participants, followed by the emotional labeling task on the Ekman 60 Faces test. RESULTS: The MANOVA analysis was significant and revealed the presence of differences in the emotion recognition abilities of the groups. Compared to HOC, the MCI group obtained a significantly lower number of hits on fear, anger, disgust, sadness, and surprise. The happiness emotion recognition rate did not differ significantly among the three groups. Surprisingly, young people and HOC did not show significant differences. CONCLUSIONS: Our results demonstrated that MCI was associated with facial emotion recognition impairment, whereas normal aging did not seem to affect this ability.