Effects of Propolis Supplementation on Gut Microbiota and Uremic Toxin Profiles of Patients Undergoing Hemodialysis.

BACKGROUND: Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota profile and uremic toxin plasma levels in HD patients. These are secondary analyses from a previous double-blind, randomized clinical study, with 42 patients divided into two groups: the placebo and propolis group received 400 mg of green propolis extract/day for eight weeks. Indole-3 acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) plasma levels were evaluated by reversed-phase liquid chromatography, and cytokines were investigated using the multiplex assay (Bio-Plex Magpix®). The fecal microbiota composition was analyzed in a subgroup of patients (n = 6) using a commercial kit for fecal DNA extraction. The V4 region of the 16S rRNA gene was then amplified by the polymerase chain reaction (PCR) using short-read sequencing on the Illumina NovaSeq PE250 platform in a subgroup. Forty-one patients completed the study, 20 in the placebo group and 21 in the propolis group. There was a positive correlation between IAA and TNF-α (r = 0.53, p = 0.01), IL-2 (r = 0.66, p = 0.002), and between pCS and IL-7 (r = 0.46, p = 0.04) at the baseline. No significant changes were observed in the values of uremic toxins after the intervention. Despite not being significant, microbial evenness and observed richness increased following the propolis intervention. Counts of the Fusobacteria species showed a positive correlation with IS, while counts of Firmicutes, Lentisphaerae, and Proteobacteria phyla were negatively correlated with IS. Two months of propolis supplementation did not reduce the plasma levels of uremic toxins (IAA, IS, and p-CS) or change the fecal microbiota.

Short-term results of unroofing and marsupialization compared to the Karydakis technique in the treatment of pilonidal sinus. A randomized prospective study.

INTRODUCTION: The treatment of pilonidal sinus (PS) is usually surgical, but no procedure is considered the gold standard. The Karydakis (K) technique is widely used, and unroofing and marsupialization (UM) is a simple surgery with good results. PRIMARY OBJECTIVE: To evaluate early postoperative complications (EPC) 30 days after UM surgery compared to the K technique. SECONDARY OBJECTIVES: To evaluate surgical time, postoperative pain, patient satisfaction, return to daily activity and early recurrence within 3 months. METHOD: Prospective, single-center, randomized study in patients who underwent surgery for primary PS with no abscess between June 2016 and November 2017. They were randomized using a computer-generated block method. To analyze the main objective, a non-inferiority analysis was performed. RESULTS: 122 patients with symptomatic primary PS were randomized: 60 in the K group and 62 in the UM group. Both groups were homogeneous. There were statistically significant differences between surgery and postoperative complications at 15 and 30 days in favor of UM. There were also differences in favor of UM in surgical time and return to daily activity. During the 90-day follow-up, there were 3 recurrences in the UM group and 0 in the K group. CONCLUSIONS: UM is a simple, minimally invasive, easily reproducible technique that has a lower rate of early complications, with a shorter operative time and an earlier return to daily activity.

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.

Reduced antiviral gene expression and elevated CXCL8 expression in peripheral blood are associated with severe hypoxemia in RSV-infected children.

The pathology of respiratory syncytial virus (RSV) infection remains unclear. An unbalanced immune response to RSV infection can lead to immunopathology, causing airway damage and impaired exchange of oxygen and carbon dioxide between the air and the bloodstream. We aimed to evaluate the association of the expression of inflammatory and antiviral genes in peripheral blood with severe hypoxemia in children with RSV infection seen in the hospital emergency room. We conducted a cross-sectional study on 121 RSV-infected children seen in hospital emergency rooms between 2015 and 2023. Total RNA was extracted from whole blood samples, and gene expression (IL-6, TNFα, CXCL8, ISG15, IFIT1, RIGI, IFNß, CCL5, and CXCL10) was quantified using quantitative RT-PCR. The outcome variable was having severe hypoxemia (SpO2 ≤ 90%). The association analysis was performed using a volcano plot, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLS-DA). We found that 26 of 121 children had severe hypoxemia (SpO2 ≤ 90%). CXCL8 was overexpressed [fold changes (FC) > 2; q-value < 0.05], and ISG15, IFIT1, RIGI, IFNß, CCL5, and CXCL10 were underexpressed (FC <0.5; q-value <0.05) in children with severe hypoxemia. These associations were ratified using adjusted logistic regression. The OPLS-DA showed that the gene expressions of CXCL8, ISG15, IFIT1, RIGI, and CXCL10 had values of variable importance in projection (VIP) ≥1, being the most relevant features. In conclusion, an imbalance favoring inflammation over antiviral defense may contribute to the pathogenesis of severe hypoxemia in RSV-infected children. These findings provide valuable insights into the pathology of RSV infection.

Late rectal and bladder toxicity following radiation therapy for prostate cancer: Predictive factors and treatment results.

AIM: This study aimed at investigating factors associated to late rectal and bladder toxicity following radiation therapy and the effectiveness of Hyperbaric Oxygen Therapy (HBOT) when toxicity is grade ≥2. BACKGROUND: Radiation is frequently used for prostate cancer, but a 5-20% incidence of late radiation proctitis and cystitis exists. Some clinical and dosimetric factors have been defined without a full agreement. For patients diagnosed of late chronic proctitis and/or cystitis grade ≥2 treatment is not well defined. Hyperbaric Oxygen Therapy (HBOT) has been used, but its effectiveness is not well known. MATERIALS AND METHODS: 257 patients were treated with radiation therapy for prostate cancer. Clinical, pharmacological and dosimetric parameters were collected. Patients having a grade ≥2 toxicity were treated with HBOT. Results of the intervention were measured by monitoring toxicity by Common Toxicity Criteria v3 (CTCv3). RESULTS: Late rectal toxicity was related to the volume irradiated, i.e. V50 > 53.64 (p = 0.013); V60 > 38.59% (p = 0.005); V65 > 31.09% (p = 0.002) and V70 > 22.81% (p = 0.012). We could not correlate the volume for bladder. A total of 24 (9.3%) patients experienced a grade ≥2. Only the use of dicumarinic treatment was significant for late rectal toxicity (p = 0.014). A total of 14 patients needed HBOT. Final percentage of patients with a persistent toxicity grade ≥2 was 4.5%. CONCLUSION: Rectal volume irradiated and dicumarinic treatment were associated to late rectal/bladder toxicity. When toxicity grade ≥2 is diagnosed, HBOT significantly ameliorate symptoms.

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.

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.

New gene targets for glucagon-like peptide-1 during embryonic development and in undifferentiated pluripotent cells.

In humans, glucagon-like peptide (GLP-1) functions during adult life as an incretin hormone with anorexigenic and antidiabetogenic properties. Also, the therapeutic potential of GLP-1 in preventing the adipocyte hyperplasia associated with obesity and in bolstering the maintenance of human mesenchymal stem cell (hMSC) stores by promoting the proliferation and cytoprotection of hMSC seems to be relevant. Since these observations suggest a role for GLP-1 during developmental processes, the aim of the present work was to characterize GLP-1 in early development as well as its gene targets in mouse embryonic stem (mES) cells. Mouse embryos E6, E8, and E10.5 and pluripotent mES were used for the inmunodetection of GLP-1 and GLP-1 receptor. Quantitative real-time PCR was used to determine the expression levels of GLP-1R in several tissues from E12.5 mouse embryos. Additionally, GLP-1 gene targets were studied in mES by multiple gene expression analyses. GLP-1 and its receptors were identified in mES and during embryonic development. In pluripotent mES, GLP-1 modified the expression of endodermal, ectodermal, and mesodermal gene markers as well as sonic hedgehog, noggin, members of the fibroblast and hepatic growth factor families, and others involved in pancreatic development. Additionally, GLP-1 promoted the expression of the antiapoptotic gene bcl2 and at the same time reduced proapoptotic caspase genes. Our results indicate that apart from the effects and therapeutic benefits of GLP-1 in adulthood, it may have additional gene targets in mES cells during embryonic life. Furthermore, the pathophysiological implications of GLP-1 imbalance in adulthood may have a counterpart during development.

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.

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.

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.

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.

PAS Kinase: A Nutrient and Energy Sensor "Master Key" in the Response to Fasting/Feeding Conditions.

The protein kinase with PAS domains (PASK) is a nutrient and energy sensor located in the cells of multiple organs. Many of the recent findings for understanding PASK functions in mammals have been reported in studies involving PASK-deficient mice. This minireview summarizes the PASK role in the control of fasting and feeding responses, focusing especially on the hypothalamus and liver. In 2013, PASK was identified in the hypothalamic areas involved in feeding behavior, and its expression was regulated under fasting/refeeding conditions. Furthermore, it plays a role in coordinating the activation/inactivation of the hypothalamic energy sensors AMPK and mTOR/S6K1 pathways in response to fasting. On the other hand, PASK deficiency prevents the development of obesity and non-alcoholic fatty liver in mice fed with a high-fat diet. This protection is explained by the re-establishment of several high-fat diet metabolic alterations produced in the expression of hepatic transcription factors and key enzymes that control the main metabolic pathways involved in maintaining metabolic homeostasis in fasting/feeding responses. This minireview covers the effects of PASK inactivation in the expression of certain transcription factors and target enzymes in several metabolic pathways under situations such as fasting and feeding with either a standard or a high-fat diet.

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.

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.

The Women Neuroscientists in the Cajal School.

At the beginning of the 20th century, in view of the growing international recognition of Santiago Ramón y Cajal, the Spanish authorities took some important steps to support Cajal's scientific work. This recognition peaked in 1906, when Camillo Golgi and Santiago Ramón y Cajal shared the Nobel Prize in Physiology or Medicine. The Spanish government provided Cajal a state-of-the-art laboratory in Madrid to allow him to continue with his research and they funded salaries to pay his first tenured collaborators, the number of which increased further after the creation of the Junta para Ampliación de Estudios (JAE). The JAE was an organism set up to help promising researchers develop their careers in different ways, thereby contributing to the development of science in Spain. Although largely forgotten or relatively unknown, there has been a recent revival in the recognition of the school that developed around Cajal, collectively referred to as the Spanish Neurological School (or colloquially, as the Cajal School or School of Madrid). Almost all Cajal's collaborators were men, although a limited number of female scientists spent part of their careers at the heart of the Cajal School. Here we discuss these women and their work in the laboratory in Madrid. We have tracked the careers of Laura Forster (from Australia/United Kingdom), Manuela Serra, María Soledad Ruiz-Capillas and María Luisa Herreros (all Spanish), through their scientific publications, both in the journal founded by Cajal and elsewhere, and from other documentary sources. To complete the picture, we also outline the careers of other secondary figures that contributed to the production and running of Cajal's laboratory in Madrid. We show here that the dawn of Spanish neuroscience included a number of contributions from female researchers who to date, have received little recognition.

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

BACKGROUND: The aim of this study was to describe incidence patterns of lymphoid neoplasms in the Girona province (Spain) (1996-2015), and to predict the number of cases in Spain during 2020. METHODS: Data were extracted from the Girona cancer registry. Incident cases were classified using the ICD-O-3, third revision, and grouped according to the WHO 2008 classification scheme. Age-adjusted incidence rates to the European standard population (ASRE) were estimated and incidence trends were modeled using Joinpoint. RESULTS: 4367 lymphoid neoplasms were diagnosed in the Girona province. The ASRE for overall lymphoma was 37.1 (95% CI: 36.0; 38.2), with a marked male predominance in almost all subtypes. During 1996-2015, incidence trends remained stable for broader lymphoma categories. According to our predictions, 17,950 new cases of LNs will be diagnosed in Spain in 2020. CONCLUSIONS: This 'real-world' data will provide valuable information to better inform etiological hypotheses and plan future health-care services.

Does my patient really need this at admission? Seven opportunities for improving value in patient care during their hospitalization.

INTRODUCTION: Besides the main treatment for their disease, hospital patients receive multiple care measures which include venous lines (VL), urinary catheters (UC), dietary restrictions (DR), mandatory bed rest (BR), deep venous thrombosis prophylaxis (VTP), stress ulcer prophylaxis (SUP) and anticoagulation bridge therapy for atrial fibrillation (BAF). In many cases these practices are of low value. METHODS: We analysed patients admitted to Internal Medicine wards throughout 2018 (2714 inpatients). We used different methodologies to identify low-value clinical practices. RESULTS: BR or DR at admission were recommended in 37% (32-44) and 24% (19-30) of the patients respectively. In 81% (71-87) and 33% (21-45) of the cases this restriction was deemed unnecessary. Ninety-six percent (92-98) had VL and 25% (19-32) UC. VL were not used in 10% (6-12), UC had no indications for insertion in 21% (11-35) and for maintenance in 31% (12-46) patients. Fifty-seven percent (49-64) of the patients were administered VTP and 69% (62-76) were prescribed SUP. Twenty-two percent (15-31) of patients with VTP and 52% (43-60) with SUP had no indication. Chronic anticoagulation for AF was interrupted in 65% (53-75) with BAF was prescribed in 38% (25-52) of them. An intervention to reduce low-value care supporting clinical practices addressed only to the Internal Medicine Wards showed very poor results. CONCLUSION: These results demonstrate that there is ample room for reduction of low-value care. Interventions to implement clinical guidelines at admissions should be addressed to cover the entire admission process, from the emergency room to the ward. Partial approaches are discouraged.

Leptin but not neuropeptide Y up-regulated glucagon-like peptide 1 receptor expression in GT1-7 cells and rat hypothalamic slices.

In an attempt to gain better insight into the central effects of glucagon-like peptide (GLP-1), we studied the action of glucose and of regulatory peptides on the expression of its receptor (GLP-1R) in hypothalamic GT1-7 cells and in ventromedial (VMH) and lateral (LH) rat hypothalamus slices. The promoter activity of GLP-1R in transfected GT1-7 cells increased with leptin, whereas neuropeptide Y (NPY) did not modify it. Interestingly, when cells were incubated with both NPY and leptin, NPY blocked the stimulating effect of leptin. The effects of leptin and NPY were also confirmed at messenger RNA levels. In hypothalamic slices, GLP-1R messenger RNA levels increased at higher glucose concentrations in the VMH. In addition, leptin exerted a stimulating effect; and NPY did not modify receptor expression. By contrast, in the LH, the opposite effects were found for those parameters, except at 20 mmol/L glucose. These findings suggest that the stimulating effect of leptin on GLP-1R expression, with no changes in NPY-induced activity, could enhance the anorexic actions generated through this receptor. In addition, the different responses of the VMH and LH may be related to specific functions of these structures, as already known in vivo, highlighting the interest of hypothalamic slices for this kind of study.