Degree of food processing and breast cancer risk: a prospective study in 9 European countries.

Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk, although some studies also reported no association. Furthermore, the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited. Thus, we investigated the associations between dietary intake by degree of food processing and breast cancer risk, overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intake of EPIC participants was assessed via questionnaires at baseline. More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system: unprocessed/minimally processed (NOVA 1), culinary ingredients (NOVA 2), processed (NOVA 3) and ultra-processed (NOVA 4). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer per standard deviation increase in daily consumption (grams) of foods from each NOVA group. The current analysis included 14,933 breast cancer cases, diagnosed among the 318,686 EPIC female participants, (median follow-up of 14.9 years). No associations were found between breast cancer risk and the level of dietary intake from NOVA 1 [HR per 1 SD=0.99 (95% CI 0.97 - 1.01)], NOVA 2 [HR per 1 SD =1.01 (95% CI 0.98 - 1.03)] and NOVA 4 [HR per 1 SD =1.01 (95% CI 0.99 - 1.03)] foods. However, a positive association was found between NOVA 3 and breast cancer risk [HR per 1 SD =1.05 (95% CI 1.03 - 1.07)] which became non-significant after adjustment for alcohol intake [HR per 1 SD =1.01 (95% CI 0.98 - 1.05)] or when beer and wine were excluded from this group [HR per 1 SD =0.99 (95% CI 0.97 - 1.01)]. The associations did not differ by breast cancer subtype, menopausal status or body mass index. Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption. Supplementary Information: The online version contains supplementary material available at 10.1186/s43014-024-00264-2.

Ruthenium complexes with triazenide ligands bearing an N-heterocyclic moiety, and their catalytic properties in the reduction of nitroarenes.

A series of ruthenium complexes of formulae [RuCl(triazenide)(p-cymene)] have been synthesized using as ligand a triazenide monofunctionalized with an N-heterocyclic moiety. Nuclear magnetic resonance, high resolution mass spectrometry and X-ray diffraction were used to characterize the triazenide ligands and their complexes. In addition, these ruthenium complexes catalyzed the reduction of nitrobenzene to aniline in the presence of sodium borohydride and ethanol as solvent at room temperature. Notably, complex 5 was especially active in the reduction of nitroarenes substituted at the aromatic ring with electron-withdrawing or electron-donating fuctional groups affording the desired arylamines in good to excellent yields (80-100%). The role of the N-heterocyclic moiety on catalysis was explored.

Food biodiversity and gastrointestinal cancer risk in nine European countries: Analysis within a prospective cohort study.

BACKGROUND: Food biodiversity in human diets has potential co-benefits for both public health and sustainable food systems. However, current evidence on the potential relationship between food biodiversity and cancer risk, and particularly gastrointestinal cancers typically related to diet, remains limited. This study evaluated how dietary species richness (DSR) was associated with gastrointestinal cancer risk in a pan-European population. METHODS: Associations between DSR and subsequent gastrointestinal cancer risk were examined among 450,111 adults enrolled in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC, initiated in 1992), free of cancer at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires. DSR of an individual's yearly diet was calculated based on the absolute number of unique biological species in each food and drink item. Associations between DSR and cancer risk were assessed by multivariable Cox proportional hazards regression models. FINDINGS: During a median follow-up time of 14.1 years (SD=3.9), 10,705 participants were diagnosed with gastrointestinal cancer. Hazard ratios (HRs) and 95 % confidence intervals (CIs) comparing overall gastrointestinal cancer risk in the highest versus lowest quintiles of DSR indicated inverse associations in multivariable-adjusted models [HR (95 % CI): 0.77 (0.69-0.87); P-value < 0·0001] (Table 2). Specifically, inverse associations were observed between DSR and oesophageal squamous cell carcinoma, proximal colon, colorectal, and liver cancer risk (p-trend<0.05 for all cancer types). INTERPRETATION: Greater food biodiversity in the diet may lower the risk of certain gastrointestinal cancers. Further research is needed to replicate these novel findings and to understand potential mechanisms.

Primary central nervous system germ cell tumors in Central America and the Caribbean Region: an AHOPCA 20-year experience.

Background: Primary central nervous system germ cell tumors (GCT) are rare neoplasms in pediatrics. Treatment depends on the histological subtype and extent of the disease. Overall survival (OS) is above 90% for germinomas and 70%-80% for nongerminomatous GCT (NGGCT) in high-income countries (HIC) while data are usually lacking for patients in Low-Middle Income country (LMIC). Objective: This study aims to describe the experience of treating patients with CNS GCT in four of eight countries, members of the Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA), and determine their 5-year OS. Design/methods: We conducted a retrospective chart review of patients treated for CNS GCT. Epidemiological and clinical characteristics, histology, treatment modalities, and outcomes were analyzed. Results: From 2001 to 2021, 48 patients were included: 22 from Guatemala, 18 from Nicaragua, three from the Dominican Republic, and five from El Salvador. Thirty-one (64.6%) were boys; the median age at diagnosis was 10.2 years (range: 1 to 17 years). Presenting symptoms were headaches (n = 24, 50%), visual disturbances (n = 17, 35.4%), vomiting (n = 12, 25%), nausea (n = 8, 16.7%), and diabetes insipidus (n = 7, 14.6%). Two patients with NGGCT presented with precocious puberty. Biopsy or tumor resection was performed in 38 cases (79.2%): 23 (88.4%) germinomas, 11 (78.6%) NGGCT, and four (50%) CNS GCT. Eight patients were diagnosed and treated based on CSF tumor marker elevation; four germinomas (BHCG 11.32-29.41 mUI/mL) and four NGGCT (BHCG 84.43-201.97 mUI/mL or positive AFP > 10 UI/mL). Tumor locations included suprasellar (n = 17, 35.4%), pineal (n = 13, 27.1%), thalamus/basal ganglia (n = 5, 10.4%), other (n = 12, 25%), and one bifocal. Four (8.3%) had metastatic disease, and six had positive CSF; staging data were incomplete in 25 patients (52%). Patients were treated with varied chemotherapy and radiotherapy modalities. Nine patients had incomplete data regarding treatment. Five-year OS was 65% (68% for germinoma, 50.6% for NGGCT, and 85.7% for unclassified GCT). Conclusions: Germinoma was the most common histology, and there was a male predominance. More than half of patients had incomplete staging data and treatment was variable across the region. OS is lower compared to HIC. Standardized treatment protocols will aid in adequate staging and treatment planning, prevent complications, and improve survival.

Effects of inclusion of the blend of essential oils, organic acids, curcumin, tannins, vitamin E, and zinc in the maternal diet, and of incubation temperature on early and late development of quail.

The maternal diet and egg incubation temperature are some of the factors that can influence the embryonic development and performance of the newly chicks at 15 d of age. This study evaluated the effects of adding a blend of organic acids, essential oils, curcumin, tannins, vitamin E, and zinc microencapsulated in to the diet of female quails (Coturnix coturnix japonica) on their productive, reproductive performance and redox parameters of their eggs and the interaction of maternal diet × incubation temperature on embryo (E16 and E18) and chicks development. At 98 d of age, 64 female quails with a mean body weight of 150 g ± 0.5 were distributed into two treatments: a Basal diet or a diet supplemented with blend (Sannimix). The eggs from each female were incubated at 37.5°C (Control) and 38.5°C (High Temperature) throughout the incubation period. After hatching, chicks were distributed in a 2 (maternal diet) × 2 (incubation temperature) factorial design. Female quails supplemented with Sannimix showed better productive and reproductive performance and produced higher-quality embryos. Their offspring had greater weight at hatch and at 15 d of age. The eggs and offspring of supplemented with Sannimix female quails showed better oxidative stability. At E16 and E18, High Temperature increased yolk sac utilization and gene expression of the growth hormone receptor (GHR). At E16, embryos from supplemented with Sannimix female quail had higher expression of insulin-like growth factor type I (IGFI) and heat shock protein 70 kDa genes. At 15 d of age, highest expression of the GHR and IGFI genes was observed in chicks from female quails fed the Sannimix diet, regardless of incubation temperature. Regarding the maternal diet × incubation temperature an improved result was observed for chicks from female quails fed with Sannimix even when eggs are exposed to High Temperature during the incubation. The supplementation of quail diets with blend Sannimix improves productive and reproductive performance, egg quality and their embryos, as well as their offspring quality.

Experiencia en el manejo de fístulas enterocutáneas postoperatorias en el Hospital Nacional del 2017 al 2022

Introducción: la mayoría de las fistulas enterocutáneas se producen como complicación de una o varias cirugías previas. La mortalidad sigue siendo muy elevada. Su tratamiento supone un reto para el cirujano y gran uso de recursos humanos, económicos y prolongada estancia hospitalaria. Objetivo: determinar la experiencia del manejo de las fístulas enterocutáneas postoperatorias en el servicio de cirugía general del Hospital Nacional de Itauguá durante el periodo 2017-2022. Metodología: estudio observacional descriptivo retrospectivo de corte transversal, con muestreo no probabilístico. Solo hubo 30 casos con fichas completas, las cuales sometimos a procesamiento y análisis de las variables de interés. Resultados: de la muestra final 70 % fueron hombres, el promedio de edad fue de 49,6 años y de días de internación 28,6. Solo 5 pacientes consultaron por secreción fecaloide, los demás refirieron secreción seropurulenta por herida o cicatriz operatoria. Del total, 9 fueron de alto débito. El 100 % recibió antibioticoterapia; obitaron 4 de los 14 pacientes intervenidos quirúrgicamente con fin terapéutico. La técnica quirúrgica mayormente utilizada fue: laparotomía + liberación de adherencias e identificación de la fístula + resección intestinal + anastomosis. De los antecedentes la mayoría fueron postoperados de oclusión intestinal mecánica alta o peritonitis aguda de origen apendicular. Conclusión: debido a su alto impacto en la capacidad laboral y social las fístulas enterocutáneas representan patologías quirúrgicas muy complejas y relevantes con bajas tasas de curación definitiva. La mayoría se presentan como complicación de cirugías de urgencia; requiere intervención multidisciplinaria adaptada para cada caso en particular.

Introduction: the occur enterocutaneous fistula as a complication of one or several previous surgeries. Mortality is still very high. Its treatment represents a challenge for the surgeon and great use of human and economic resources and a long hospital stay. Objective: to determine the experience in the management of postoperative enterocutaneous fistulae in the general surgery service of the Itauguá National Hospital during the period 2017-2022. Methodology: retrospective, cross-sectional, descriptive, observational study with non-probabilistic sampling. There were only 30 cases with complete records, which we subjected to processing and analysis of the variables of interest. Results: of the final sample, 70 % were men, the average age was 49,6 years and 28,6 days of hospitalization. Only 5 patients consulted due to fecaloid discharge, the rest reported seropurulent discharge from wound or surgical scar. Of the total, 9 were high debit. 100 % received antibiotic therapy, 4 of the 14 patients who underwent surgery as therapeutics, died. The most commonly used surgical technique was: laparotomy + release of adhesions and identification of the fistula + intestinal resection + anastomosis. Most of the antecedents were post-operated for high mechanical intestinal occlusion or acute peritonitis of appendiceal origin. Conclusion: due to their high impact on work and social capacity, enterocutaneous fistulas represent very complex and relevant surgical pathologies with low definitive cure rates. Most present as a complication in emergency surgeries; requires multidisciplinary intervention adapted to each particular case.

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.

Características clínicas de niños con apendicitis aguda que acuden al Servicio de Urgencias del Hospital Regional de Pilar en el periodo 2020 al 2023

Introducción: La apendicitis aguda, definida como la inflamación del apéndice vermiforme, es la causa más frecuente de abdomen agudo quirúrgico y es la patología aguda quirúrgica más común en la infancia y en el niño mayor. Objetivo: Determinar las características clínicas de niños con apendicitis aguda que acuden al Servicio de Urgencias del Hospital Regional de Pilar durante el periodo 2020 al 2023. Materiales y métodos: Estudio observacional descriptivo, retrospectivo, de corte transversal en pacientes pediátricos que acuden al servicio de urgencias del Hospital Regional de Pilar. Incluyó pacientes de 4 a 15 años que acudieron al servicio de urgencias por cuadro de dolor abdominal agudo durante el periodo enero 2020 a julio 2023. Resultados: Se realizaron 80 apendicetomías en niños de 4 a 15 años, la media de edad fue 11±3años; predominó el sexo femenino en el 34,4%; el principal motivo de consulta fue dolor abdominal más vómitos con un tiempo promedio de evolución de 29,6±22horas; se presentó signo de defensa muscular en el 77,5%; la característica apendicular predominante fue flegmonosa en el 51,3%; el tiempo promedio de estancia hospitalaria fue de 3±1,2días y el 71,3% de los niños no presentó complicación aguda. Conclusión : El conocimiento de las características clínicas de la apendicitis aguda resultan de suma importancia para el médico en el Servicio de Urgencias para un diagnóstico precoz y; por ende, una apendicetomía temprana minimizando tanto las tazas de complicaciones intraoperatorias como posoperatorias.

Introduction: Acute appendicitis, defined as inflammation of the vermiform appendix, is the most common cause of acute surgical abdomen and is the most common acute surgical pathology in childhood and older children. Objective: Determine the clinical characteristics of children with acute appendicitis who attend the Emergency Service of the Pilar Regional Hospital during the period 2020 to 2023. Materials and methods: Descriptive, retrospective, cross-sectional observational study in pediatric patients attending the emergency service of the Pilar Regional Hospital. It included patients aged 4 to 15 years who attended the emergency department due to acute abdominal pain during the period January 2020 to July 2023. Results: 80 appendectomies were performed in children from 4 to 15 years old, the average age was 11±3 years; The female sex predominated in 34.4%; The main reason for consultation was abdominal pain plus vomiting with an average duration of 29.6±22 hours; sign of muscular defense was present in 77.5%; the predominant appendiceal characteristic was phlegmonous in 51.3%; The average length of hospital stay was 3±1.2 days and 71.3% of the children did not present acute complications. Conclusion: Knowledge of the clinical characteristics of acute appendicitis is of utmost importance for the doctor in the Emergency Department for early diagnosis and therefore, an early appendectomy minimizes both intraoperative and postoperative complication rates.

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.

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.

Repercussões psicológicas de adultos que sofreram abuso sexual na infância / Psychological repercussions of adults who suffered sexual abuse in childhood

Objetivo: correlacionar o abuso sexual na infância com as repercussões psicológicas na idade adulta, das vítimas e destacar a importância de abordar o despreparo do sistema judiciário, a culpabilização das vítimas e as falhas no acesso à educação e à informação sobre sexualidade. Métodos: uma revisão de literatura foi conduzida utilizando métodos descritivos e analíticos, com a utilização de dados publicados nos últimos 10 anos, nas bases de dados PubMed e Scielo Brasil. Resultados: foram selecionados 13 artigos do PubMed e 10 artigos do Scielo Brasil para análise. Observa-se que o abuso sexual na infância tem repercussões que vão além do nível psicológico e cognitivo, afetando outras áreas, como mudanças na estrutura cerebral, problemas de saúde física, desenvolvimento de comportamentos de risco e dificuldades em estabelecer relações sociais, além de redução na expectativa de vida. Conclusões: são muitos os impactos negativos na vida de vítimas de abuso sexual infantil. O cuidado físico e psicológico voltado às vítimas de abuso infantil vai além da infância, demandando atenção nos anos subsequentes e durante a vida adulta, uma vez que o trauma repercute de formas diferentes, gerando repercussões negativas na qualidade de vida dos abusados. Verifica-se a necessidade de implementação de estratégias de ensino e capacitação para profissionais da área da educação, a fim de identificar e denunciar casos de violência sexual, bem como a imprescindibilidade em criar espaços para abordagem desse tema nas escolas.

Objectives: to correlate sexual abuse in childhood with the psychological repercussions of the victims in adulthood and highlight the importance of addressing the lack of preparation of the judicial system, the blaming of victims, and failures in access to education and information about sexuality. Methods: a literature review was conducted using descriptive and analytical methods using data published in the last ten (10) years in the PubMed and Scielo Brasil databases. Results: 13 articles from PubMed and ten (10) articles from Scielo Brasil were selected for analysis. It is observed that sexual abuse in childhood has repercussions that go beyond the psychological and cognitive level, affecting other areas, such as changes in brain structure, physical health problems, development of risk behaviors, and difficulties in establishing relationships and social benefits, in addition to a reduction in life expectancy. Conclusions: there are many negative impacts on the lives of victims of child sexual abuse. Physical and psychological care aimed at victims of child abuse goes beyond childhood, demanding attention in subsequent years and during adult life since the trauma has repercussions in different ways, generating negative epercussions on the quality of life of those abused. There is a need to implement teaching and training strategies for professionals in the field of education to identify and report cases of sexual violence, as well as the essential need to create spaces to address this issue in schools.

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.

Kidney-specific with-no-lysine kinase 1 (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 have suggested 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 with 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 phosphorylated NCC-to-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 distal convoluted tubule to respond to extreme changes in potassium intake, such as those occurring in wildlife.NEW & NOTEWORTHY The findings of this study demonstrate that kidney-specific with-no-lysine kinase 1 plays a role in regulating urinary electrolyte excretion during 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.

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.