Can curcumin supplementation break the vicious cycle of inflammation, oxidative stress, and uremia in patients undergoing peritoneal dialysis?

BACKGROUND & AIMS: Turmeric (a source of curcumin) is an excellent food to modulate oxidative stress, inflammation, and gut dysbiosis in patients with chronic kidney disease (CKD). However, no studies report the benefits of curcumin in patients undergoing peritoneal dialysis (PD). This study aims to evaluate the effects of curcuminoid supplementation on oxidative stress, inflammatory markers, and uremic toxins originating from gut microbiota in patients with CKD undergoing PD. METHODS: This longitudinal, randomized, single-blind, placebo-controlled trial evaluated 48 patients who were randomized into two groups: Curcumin (three capsules of 500 mg of Curcuma longa extract, with 98.42 % total curcuminoids) or placebo (three capsules of 500 mg of starch) for twelve weeks. In the peripheral blood mononuclear cells (PBMCs), the transcriptional expression levels of Nrf2, HOX-1 and NF-κB were evaluated by quantitative real-time PCR. Oxidative stress was evaluated by malondialdehyde (MDA) and total Thiol (T-SH). TNF-α and IL-6 plasma levels were measured by ELISA. P-cresyl sulphate plasma level, a uremic toxin, was evaluated by high-performance liquid chromatography (HPLC) with fluorescent detection. RESULTS: Twenty-four patients finished the study: 10 in the curcumin group (57.5 ± 11.6 years) and 14 in the placebo group (56.5 ± 10.0 years). The plasma levels of MDA were reduced after 12 weeks in the curcumin group (p = 0.01), while the placebo group remained unchanged. However, regarding the difference between the groups at the endpoint, no change was observed in MDA. Still, there was a trend to reduce the p-CS plasma levels in the curcumin group compared to the placebo group (p = 0.07). Likewise, the concentrations of protein thiols, mRNA expression of Nrf2, HOX-1, NF-κB, and cytokines plasma levels did not show significant changes. CONCLUSION: Curcuminoid supplementation for twelve weeks attenuates lipid peroxidation and might reduce uremic toxin in patients with CKD undergoing PD. This study was registered on Clinicaltrials.gov as NCT04413266.

Low peripheral blood chemokine (C-C motif) ligand 5 and tumor necrosis factor α gene expression is associated with unfavorable progression of respiratory syncytial virus bronchiolitis in infants.

OBJECTIVES: We aimed to analyze whether the expression of inflammatory and antiviral genes in respiratory syncytial virus (RSV)-infected infants' peripheral blood is associated with bronchiolitis progression. METHODS: We conducted a prospective study on 117 infants between 2015 and 2023. The expression levels of nine genes were quantified by quantitative polymerase chain reaction. Infants were classified according to their clinical evolution during hospital admission: (i) non-progression (n = 74), when the RSV bronchiolitis severity remained stable or improved; (ii) unfavorable progression (n = 43), when the RSV bronchiolitis severity increased. The association analysis was performed by logistic regression, adjusted by age, gender, prematurity, and RSV bronchiolitis severity in the emergency room. RESULTS: Infants were 57.3% male, and the median age of the study population was 61 days. Thirty-five infants (30.7%) were admitted to the intensive care unit after hospital admission. Univariate logistic models showed that tumor necrosis factor (TNFα) and chemokine (C-C motif) ligand (CCL5) gene expression at baseline were inversely associated with unfavorable progression, which was confirmed by multivariate analyses: TNFα (adjusted odds ratio = 0.8 [95% confidence interval = 0.64-0.99], P-value = 0.038) and CCL5 (adjusted odds ratio = 0.76 [95% confidence interval = 0.62-0.93], P-value = 0.007). CONCLUSIONS: An inadequate immune response to RSV, characterized by reduced gene expression levels of CCL5 and TNFα in peripheral blood, was associated with an unfavorable progression of RSV bronchiolitis.

Renocardiac Effects of p-Cresyl Sulfate Administration in Acute Kidney Injury Induced by Unilateral Ischemia and Reperfusion Injury In Vivo.

The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected to AKI induced by ischemia and reperfusion (IR) injury. C57BL6 mice were subjected to distinct protocols: (i) administration with PCS (20, 40, or 60 mg/L/day) for 15 days and (ii) AKI due to unilateral IR injury associated with PCS administration for 15 days. The 20 mg/L dose of PCS led to a decrease in renal mass, an increase in the gene expression of Cystatin C and kidney injury molecule 1 (KIM-1), and a decrease in the α-actin in the heart. During AKI, PCS increased the renal injury biomarkers compared to control; however, it did not exacerbate these markers. Furthermore, PCS did not enhance the cardiac hypertrophy observed after 15 days of IR. An increase, but not potentialized, in the cardiac levels of interleukin (IL)-1ß and IL-6 in the IR group treated with PCS, as well as in the injured kidney, was also noticed. In short, PCS administration did not intensify kidney injury, inflammation, and cardiac outcomes after AKI.

Alergia alimentaria: importancia de los cofactores / Food allergy: the importance of cofactors

Las LTP (lipid transfer proteins) son una familia de proteínas presentes en diferentes alimentos. La sintomatología de la alergia a las LTP es muy variable, desde clínica leve hasta sistémica, en ocasiones, presentando síntomas únicamente en presencia de cofactores. Se presenta el caso de una paciente de 11 años que acude a urgencias con clínica de anafilaxia tras ingesta previa de fruta mientras realizaba ejercicio físico, destacando la importancia de la historia clínica y la sospecha diagnóstica en el enfoque de esta entidad (AU)

LTP (lipid transfer proteins) are a family of proteins present in different foods. The symptomatology of allergy to LTP is highly variable, ranging from mild to systemic. Sometimes, symptoms are only present in the presence of cofactors.We present the case of an 11-year-old female patient who presented to the emergency department with anaphylaxis following previous ingestion of fruit while doing physical exercise, highlighting the importance of the clinical history and diagnostic suspicion in the approach to this entity. (AU)

Efficacy of Bromhexine versus Standard of Care in Reducing Viral Load in Patients with Mild-to-Moderate COVID-19 Disease Attended in Primary Care: A Randomized Open-Label Trial.

A 28-day randomized open-label multicenter study was conducted to assess the efficacy of bromhexine plus standard of care (SOC) (n = 98) vs. SOC alone (n = 93) in 191 outpatients with mild-to-moderate COVID-19 in the primary health care setting. Bromhexine three daily doses of 10 mL (48 mg/day) were administered for seven days. The primary efficacy endpoint was the reduction of viral load estimated as the cycle thresholds (Ct) to detect ORF1ab, N Protein, and S Protein genes by RT-qPCR in saliva samples on day 4 as compared with baseline. Ct values of the three genes increased from baseline throughout days 4 to 14 (p < 0.001) but significant differences between the study groups were not found. Differences in the percentages of patients with low, medium, and high viral loads at 4, 7, and 14 days were not found either. In summary, treatment with bromhexine plus SCO was associated with a viral load reduction of ORF1ab, N Protein, and S Protein genes at day 4, which was not significantly different than similar viral load reductions observed with SOC alone. The present findings do not seem to favor the use of bromhexine as an antiviral in patients with COVID-19.

¿Podría ser el maltrato animal un indicador policial de violencia de género? Análisis de casos en España / Could animal abuse be a police indicator of gender violence? Analysis of cases in Spain / O abuso de animais poderia ser um indicador policial da violência baseada no gênero? Análise de casos na Espanha

La concurrencia entre el maltrato animal y la violencia de género, cometidos por el mismo maltratador, ha sido señalada en los últimos años en diversas sociedades, principalmente en EE. UU., Reino Unido y Australia. En este estudio analizamos esta relación en España, con la idea de investigar la posible utilización del maltrato animal como indicador policial de violencia de género. Hemos vislumbrado la perpetración del maltrato animal, de forma instrumental, con el fin de controlar a la (ex)pareja, o de forma expresiva para causar daño de forma indirecta a la (ex)pareja. Creemos pertinente avanzar en esta clase de estudios mediante la recolección de más datos y la realización de análisis cualitativos.

The concurrence between animal abuse and gender violence, committed by the same abuser, has been reported in recent years in several societies, mainly in the USA, United Kingdom and Australia. In this study we analyze this relationship in Spain, with the idea of investigating the possible use of animal abuse as a police indicator of gender violence. We have glimpsed the perpetration of animal abuse, in an instrumental way, in order to control the (ex)partner, or in an expressive way to indirectly cause harm to the (ex)partner. We believe it is pertinent to advance in this kind of studies by collecting more data and conducting qualitative analyses.

A concorrência entre o abuso de animais e a violência de gênero, cometida pelo mesmo abusador, tem sido relatada nos últimos anos em várias sociedades, principalmente nos EUA, no Reino Unido e na Austrália. Neste estudo analisamos esta relação na Espanha, com a idéia de investigar o possível uso de abuso de animais como um indicador policial de violência de gênero. Vislumbramos a perpetração de abuso de animais, de forma instrumental, a fim de controlar o (ex)parceiro, ou de forma expressiva para causar indiretamente danos ao (ex)parceiro. Acreditamos que é pertinente avançar neste tipo de estudos, coletando mais dados e realizando análises qualitativas.

Preventing Oxidative Stress in the Liver: An Opportunity for GLP-1 and/or PASK.

The liver's high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant's effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress.

Desprendimiento de retina: la importancia del cribado de la agudeza visual / Retinal detachment: the importance of visual acuity screening

El desprendimiento de retina es una patología infrecuente en Pediatría y presenta diferencias con respecto a los casos que se dan en la edad adulta. Predomina en varones escolares. El subtipo más frecuente es el regmatógeno y la principal causa son los traumatismos, sin olvidar otras causas como las sindrómicas y lesiones no accidentales. El abordaje de esta patología es quirúrgico, aunque el éxito anatómico de la cirugía no implica buen resultado funcional. Presentamos el caso de un niño en el que se detectó una disminución unilateral importante de la agudeza visual en consulta programada (AU)

The retinal detachment is an infrequent pathology in pediatrics and presents differences with the cases that occur in adulthood. It predominates in school-age boys. The most frequent subtype is rhegmatogenous and the main cause is trauma, without forgetting other causes such as syndromic and non-accidental injuries. The approach to this pathology is surgical, although the anatomical success of the surgery does not imply a good functional result. We present the case of a child in whom a significant unilateral decrease in visual acuity was detected in a scheduled consultation (AU)

Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent.

Glucagon-like peptide 1 (GLP-1) and PAS kinase (PASK) control glucose and energy homeostasis according to nutritional status. Thus, both glucose availability and GLP-1 lead to hepatic glycogen synthesis or degradation. We used a murine model to discover whether PASK mediates the effect of exendin-4 (GLP-1 analogue) in the adaptation of hepatic glycogen metabolism to nutritional status. The results indicate that both exendin-4 and fasting block the Pask expression, and PASK deficiency disrupts the physiological levels of blood GLP1 and the expression of hepatic GLP1 receptors after fasting. Under a non-fasted state, exendin-4 treatment blocks AKT activation, whereby Glucokinase and Sterol Regulatory Element-Binding Protein-1c (Srebp1c) expressions were inhibited. Furthermore, the expression of certain lipogenic genes was impaired, while increasing Glucose Transporter 2 (GLUT2) and Glycogen Synthase (GYS). Moreover, exendin-4 treatment under fasted conditions avoided Glucose 6-Phosphatase (G6pase) expression, while maintaining high GYS and its activation state. These results lead to an abnormal glycogen accumulation in the liver under fasting, both in PASK-deficient mice and in exendin-4 treated wild-type mice. In short, exendin-4 and PASK both regulate glucose transport and glycogen storage, and some of the exendin-4 effects could therefore be due to the blocking of the Pask expression.

The Usefulness of Mesenchymal Stem Cells beyond the Musculoskeletal System in Horses.

The differentiation ability of mesenchymal stem cells (MSCs) initially raised interest for treating musculoskeletal injuries in horses, but MSC paracrine activity has widened their scope for inflammatory and immune-mediated pathologies in both equine and human medicine. Furthermore, the similar etiopathogenesis of some diseases in both species has advanced the concept of "One Medicine, One Health". This article reviews the current knowledge on the use of MSCs for equine pathologies beyond the locomotor system, highlighting the value of the horse as translational model. Ophthalmologic and reproductive disorders are among the most studied for MSC application. Equine asthma, equine metabolic syndrome, and endotoxemia have been less explored but offer an interesting scenario for human translation. The use of MSCs in wounds also provides a potential model for humans because of the healing particularities in both species. High-burden equine-specific pathologies such as laminitis have been suggested to benefit from MSC-therapy, and MSC application in challenging disorders such as neurologic conditions has been proposed. The available data are preliminary, however, and require further development to translate results into the clinic. Nevertheless, current evidence indicates a significant potential of equine MSCs to enlarge their range of application, with particular interest in pathologies analogous to human conditions.

B-Cell Regeneration Profile and Minimal Residual Disease Status in Bone Marrow of Treated Multiple Myeloma Patients.

B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (≥50y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations. BM hemodilution was detected in 41 out of 177 (23%) patient samples, leading to lower total B-cell, B-cell precursor (BCP) and normal plasma cell (nPC) counts. Among MM BM, decreased percentages (vs. HD) of BCP, transitional/naïve B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP increased after induction therapy, whereas TBC/NBC counts remained abnormally low. At day+100 postautologous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC cell numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19- nPC counts vs. non-CR specimens. MRD positivity was associated with higher BCP and nPC percentages. Hemodilution showed a negative impact on BM B-cell distribution. Different BM B-cell regeneration profiles are present in MM at diagnosis and after therapy with no significant association with patient outcome.

Population-based survival of lymphoid neoplasms: Twenty years of epidemiological data in the Girona province, Spain.

BACKGROUND: The aim of this study was to describe survival of lymphoid neoplasms (LNs) in the Girona province (Spain) during 1996-2015. METHODS: Data were extracted from the Girona cancer registry. LN incident cases were registered using the ICD-O-3, following the 2008 WHO classification scheme and HAEMACARE grouping. Follow-up was available until the 31/12/2015. Observed and relative survival (RS) were estimated with Kaplan-Meier and Pohar Perme methods, respectively. RESULTS: 4294 LNs diagnosed over a 20-year period were included in the survival analyses. 5-year RS was 62.3 % (95 % confidence interval (CI): 60.4-64.4), and ranged from 88.5%-41.1% according to subtype. Findings were similar between men and women, while survival decreased markedly with age. RS for all LNs improved during the first two periods of study, being 56.5 % (95 % CI: 53.1-60.0) in 1996-2002, 64.8 % (95 % CI: 61.7-68.2) in 2003-2008, and 65.6 % (95 % CI: 62.0-69.5) in 2009-2015. This pattern was mostly attributed to an improved survival of mature B-cell neoplasms, yet only statistically significant differences were reported for follicular lymphoma and mantle cell lymphoma subtypes. CONCLUSIONS: Our study provides estimates of survival in LNs and its subtypes, allowing comparisons between countries. Survival for overall cases improved across the period of study, yet rates are still poor for most subtypes, evidencing the need of therapeutic research programs.

PAS kinase deficiency reduces aging effects in mice.

Several signaling pathways may be affected during aging. All are regulated by nutrient levels leading to a decline in mitochondrial function and autophagy and to an increase in oxidative stress. PAS Domain Kinase (PASK) is a nutrient and bioenergetic sensor. We have previously found that PASK plays a role in the control of hepatic metabolic balance and mitochondrial homeostasis. To investigate PASK's role in hepatic oxidative stress during aging, we analyzed the mitochondrial function, glucose tolerance, insulin resistance, and lipid-related parameters in aged PASK-deficient mice. Hepatic Pask mRNA decreased in step with aging, being undetectable in aged wild-type (WT) mice. Aged PASK-deficient mice recorded lower levels of ROS/RNS compared to aged WT. The regulators of mitochondrial biogenesis, PGC1a, SIRT1 and NRF2, decreased in aged WT, while aged PASK-deficient mice recorded a higher expression of NRF2, GCLm and HO1 proteins and CS activity under fasted conditions. Additionally, aged PASK-deficient mice recorded an overexpression of the longevity gene FoxO3a, and maintained elevated PCNA protein, suggesting that hepatic cell repair mechanisms might be functional. PASK-deficient mice have better insulin sensitivity and no glucose intolerance, as confirmed by a normal HOMA-IR index. PASK may be a good target for reducing damage during aging.