Assessing mucosal recovery in celiac disease - Time to diagnosis and histological severity as determining factors.

BACKGROUND AND OBJECTIVES: there is a huge disparity in mucosal recovery among celiac patients on a gluten-free diet. We report a study to identify associated factors. METHODS: celiac cases were collected that had positive celiac serology and villous atrophy at diagnosis, and had undergone a control biopsy after at least 12 months of follow-up. RESULTS: seventy celiac patients were included and had experienced symptoms for 9.05 ± 9.48 years before being diagnosed. After follow-up for 2.93 ± 1.94 years, 34.3 % had complete mucosal recovery and 57.1 % had partial mucosal recovery. In the comparative analysis, there was no relationship between mucosal recovery and sex, age, clinical manifestations or follow-up time from diagnosis to the second biopsy. Time with clinical manifestations before diagnosis was associated with a worse outcome: 2.64 years in patients with full recovery, 4.61 years in patients with partial recovery, and 14.26 years in patients with persistent villous atrophy. Higher transglutaminase antibody titers both at diagnosis and during follow-up were associated with poorer histologic outcomes. We observed higher mucosal recovery rates in patients with mild atrophy versus severe atrophy at diagnosis. CONCLUSIONS: in spite of a gluten-free diet, a significant proportion of patients have persistent histologic changes. Time with clinical manifestations before diagnosis is key for histological severity and recovery.

Implementing integrated hypertension and diabetes management using the World Health Organization's HEARTS model: protocol for a pilot study in the Guatemalan national primary care system.

BACKGROUND: The HEARTS technical package was developed by the World Health Organization to address the implementation gap in cardiovascular disease prevention in low- and middle-income countries. Guatemala is a middle-income country that is currently implementing HEARTS. National authorities in Guatemala are interested in exploring how hypertension and diabetes management can be integrated in HEARTS implementation. The objective of this study is to conduct a feasibility and acceptability pilot trial of integrated hypertension and diabetes management based on HEARTS in the publicly funded primary care system in Guatemala. METHODS: A single-arm pilot trial for 6 months will be carried out in 11 Ministry of Health primary care facilities starting in September 2023. A planned sample of 100 adult patients diagnosed with diabetes (n = 45), hypertension (n = 45), or both (n = 10) will be enrolled. The intervention will consist of HEARTS-aligned components: Training health workers on healthy-lifestyle counseling and evidence-based treatment protocols, strengthening access to medications and diagnostics, training on risk-based cardiovascular disease management, team-based care and task sharing, and systems monitoring and feedback, including implementation of a facility-based electronic monitoring tool at the individual level. Co-primary outcomes of feasibility and acceptability will be assessed using an explanatory sequential mixed-methods design. Secondary outcomes include clinical effectiveness (treatment with medication, glycemic control, and blood pressure control), key implementation outcomes (adoption, fidelity, usability, and sustainability), and patient-reported outcome measures (diabetes distress, disability, and treatment burden). Using an implementation mapping approach, a Technical Advisory Committee will develop implementation strategies for subsequent scale-up planning. DISCUSSION: This trial will produce evidence on implementing HEARTS-aligned hypertension and diabetes care in the MOH primary care system in Guatemala. Results also will inform future HEARTS projects in Guatemala and other low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06080451. The trial was prospectively registered on October 12, 2023.

Quinoline Derivatives: Promising Antioxidants with Neuroprotective Potential.

Quinoline has been proposed as a privileged molecular framework in medicinal chemistry. Although by itself it has very few applications, its derivatives have diverse biological activities. In this work, 8536 quinoline derivatives, strategically designed using the CADMA-Chem protocol, are presented. This large chemical space was sampled, analyzed and reduced using selection and elimination scores that combine their properties of bioavailability, toxicity and manufacturability. After applying several filters, 25 derivatives were selected to investigate their acid-base, antioxidant and neuroprotective properties. The antioxidant activity was predicted based on the ionization potential and bond dissociation energies, parameters directly related to the transfer of hydrogen atoms and of a single electron, respectively. These two mechanisms are typically involved in the radical scavenging processes. The antioxidant efficiency was compared with reference compounds, and the most promising antioxidants were found to be more efficient than Trolox but less efficient than ascorbate. In addition, based on molecular docking simulations, some derivatives are expected to act as inhibitors of catechol-O methyltransferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase type B (MAO-B) enzymes. Some structural insights about the compounds were found to enhance or decrease the neuroprotection activity. Based on the results, four quinoline derivatives are proposed as candidates to act as multifunctional antioxidants against Alzheimer's (AD) and Parkinson's (PD) diseases.

Unrestricted component count in multiphase lattice Boltzmann: A fugacity-based approach.

Studies of multiphase fluids utilizing the lattice Boltzmann method (LBM) are typically severely restricted by the number of components or chemical species being modeled. This restriction is particularly pronounced for multiphase systems exhibiting partial miscibility and significant interfacial mass exchange, which is a common occurrence in realistic multiphase systems. Modeling such systems becomes increasingly complex as the number of chemical species increases due to the increased role of molecular interactions and the types of thermodynamic behavior that become possible. The recently introduced fugacity-based LBM [Soomro et al., Phys. Rev. E 107, 015304 (2023)2470-004510.1103/PhysRevE.107.015304] has provided a thermodynamically consistent modeling platform for multicomponent, partially miscible LBM simulations. However, until now, this fugacity-based LB model had lacked a comprehensive demonstration of its ability to accurately reproduce thermodynamic behavior beyond binary mixtures and to remove any restrictions in a number of components for multiphase LBM. In this paper we closely explore these fugacity-based LBM capabilities by showcasing comprehensive, thermodynamically consistent simulations of multiphase mixtures of up to ten chemical components. The paper begins by validating the model against the Young-Laplace equation for a droplet composed of three components. The model is then applied to study mixtures with a range of component numbers from one to six, showing agreement with rigorous thermodynamic predictions and demonstrating linear scaling of computational time with the number of components. We further investigate ternary systems in detail by exploring a wide range of temperature, pressure, and overall composition conditions to produce various characteristic ternary diagrams. In addition, the model is shown to be unrestricted in the number of phases as demonstrated through simulations of a three-component three-phase equilibrium case. The paper concludes by demonstrating simulations of a ten-component, realistic hydrocarbon mixture, achieving excellent agreement with thermodynamics for both flat interface vapor-liquid equilibrium and curved interface spinodal decomposition cases. This study represents a significant expansion of the scope and capabilities of multiphase LBM simulations that encompass multiphase systems of keen interest in engineering.

Accuracy of ultrasound and visual inspection in antral follicular count in crossbred Holstein cows raised under grazing systems at high altitude.

The objective of this research was to investigate the diagnostic accuracy of post-mortem ultrasound in antral follicle count (AFC) determination and compare it with visual AFC in grazing crossbred Holstein cows, at high altitude in Ecuador. Pre-mortem blood from 80 cows was collected, and AFC and ovarian characteristics were analysed post-mortem by ultrasound and visual techniques. AFC counts were stratified as high, medium or low by terciles. Mean AMH concentration in pre-mortem blood was 280.1 ± 15.53 pg/mL. The AFC obtained by visual inspection (26.9 ± 9.49 follicles) was 23.8% higher than by ultrasound (20.5 ± 7.53 follicles) in all ovaries. Body condition score, age and weight of the cattle did not interact with the count technique. In the low AFC group, visual inspection and ultrasound provided similar AFC results. However, in the Medium- and High-AFC groups, AFC by ultrasound was 14.9% lower than AFC by visual inspection. We confirm that ultrasound can be used with great accuracy for AFC >3 mm (close to the resolution limit) in grazing crossbred Holstein cows at high altitude.

Rational Design of Multifunctional Ferulic Acid Derivatives Aimed for Alzheimer's and Parkinson's Diseases.

Ferulic acid has numerous beneficial effects on human health, which are frequently attributed to its antioxidant behavior. In this report, many of them are reviewed, and 185 new ferulic acid derivatives are computationally designed using the CADMA-Chem protocol. Consequently, their chemical space was sampled and evaluated. To that purpose, selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes directly related to the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and α-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directly related to the etiologies of Parkinson's and Alzheimer's diseases. These enzymes are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.

Fugacity-based lattice Boltzmann method for multicomponent multiphase systems.

The free-energy model can extend the lattice Boltzmann method to multiphase systems. However, there is a lack of models capable of simulating multicomponent multiphase fluids with partial miscibility. In addition, existing models cannot be generalized to honor thermodynamic information provided by any multicomponent equation of state of choice. In this paper, we introduce a free-energy lattice Boltzmann model where the forcing term is determined by the fugacity of the species, the thermodynamic property that connects species partial pressure to chemical potential calculations. By doing so, we are able to carry out multicomponent multiphase simulations of partially miscible fluids and generalize the methodology for use with any multicomponent equation of state of interest. We test this fugacity-based lattice Boltzmann method for the cases of vapor-liquid equilibrium for two- and three-component mixtures in various temperature and pressure conditions. We demonstrate that the model is able to reliably reproduce phase densities and compositions as predicted by multicomponent thermodynamics and can reproduce different characteristic pressure-composition and temperature-composition envelopes with a high degree of accuracy. We also demonstrate that the model can offer accurate predictions under dynamic conditions.

Relación de los factores demográficos e higiénico-dietéticos con la patología hallada en las colonoscopias ambulatorias realizadas en un centro del Servicio Castellano y Leonés de Salud / Relationship of demographic and dietary hygiene factors with the pathology found in outpatient colonoscopies performed in a Castilla y León Health Service center

Introducción: el cáncer colorrectal (CCR) es un tumor muy frecuente en términos de incidencia y mortalidad. Su patogenia se ha relacionado con diversos factores ambientales y hereditarios. Objetivos: analizar la asociación de edad, sexo y factores dietéticos con el diagnóstico de adenomas y CCR. Métodos: se realizó un estudio descriptivo prospectivo con los pacientes del Área Sanitaria de León que se sometieron a una colonoscopia ambulatoria entre 09/09/2012 y 30/06/2013. Mediante un formulario autoadministrado se recogieron datos sociodemográficos, tóxicos y dietéticos usando un cuestionario alimentario de frecuencia semicuantitativo. Se analizaron las diferencias en el diagnóstico según los datos sociodemográficos e higiénico-dietéticos, con análisis multivariante mediante regresión logística por pasos hacia delante. Resultados: se recogieron datos de 1390 pacientes cuya edad media fue de 57 (15) años; de ellos, el 47,8 % eran varones. Se diagnosticaron CCR en el 5 % de los pacientes y pólipos en el 20,4 % (9,4 % de adenomas de alto riesgo (AAR)). El hallazgo de pólipos y AAR fue más frecuente en los varones (26,9 % vs. 14,5 % y 12,6 % vs. 6,3 %, respectivamente (p < 0,001)). La edad media fue significativamente superior en los pacientes que presentaban pólipos (56.51 (15.45) vs. 63.22 (12.69) años; p < 0,001). En la población que refirió un consumo diario de carnes procesadas se duplicaba la proporción de pólipos detectados (2,9 % vs. 6,7 %; p = 0,02). Aquellos pacientes que consumían alcohol diariamente tenían mayor incidencia de pólipos frente al consumo ocasional y los abstemios (32 % vs. 20 % vs. 18,6 %; p = 0,002). Conclusiones: la edad se relacionaba con un mayor riesgo de pólipos, AAR y CCR. Los varones también tenían más riesgo de pólipos y AAR. El consumo de alcohol, carnes rojas y procesadas incrementaba el riesgo de pólipos. (AU)

Background: colorectal cancer (CRC) is one of the most frequent tumors in terms of incidence and mortality. Several elements, both inherited and environmental, have been related with its pathogenesis. Aims: to analyze the influence of age, gender and nutritional factors on the diagnosis of colonic polyps and CRC. Methods: a prospective, descriptive study over outpatients from the Health Area of León who took a colonoscopy between 09/09/2012 and 06/30/2013. Patients were asked to fill a semiquantitative food frecuency questionnaire with data such a sociodemographic, toxic and dietetic facts. Differences in diagnosis according to sociodemographic and hygiene-dietetic data were analyzed with a multivariate analysis by forward stepwise logistic regression. Results: data were collected from 1390 patients. Mean age was 57.88 (15.17) years and 47.8 % were male. CRC was diagnosed in 5 % of colonoscopies, and polyps in 20.4 %, with 9.4 % of them being HRA. Risk of polyps and HRA was higher in males (26.9 % vs 14.5 %) and (12.6 % vs 6.3 %), respectively (p < 0.001). Mean age was significantly higher in patients who presented polyps (56.51 (15.45) vs 63.22 (12.69) years; p < 0.001). Among the group who reported intake of smoked and salted food, the risk of polyps doubled (2.9 % vs 6.7 %, p = 0.002). In relation to alcohol intake we found that subjects with daily alcohol consumption showed a higher incidence of polyps whe compared to occasional drinkers and teetotallers (32 % vs 20 % vs 18.6 %, p = 0.002) Conclusions: age correlated with higher risk of polyps, HRA and CRC. Moreover, male gender also was associated with a high risk of polyps and HRA. Alcohol and red and processed meat intake increased polyp risk. (AU)

Health-related quality of life decline in clinically stable inflammatory bowel disease patients during the COVID-19 outbreak.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) affects many aspects of a patient's life and impairs their health-related quality of life (HRQoL). The COVID-19 outbreak has led to important mobility restrictions and a dramatic re-adjustment of social habits and health systems. This study aimed to assess the influence of the outbreak and mobility restrictions on the HRQoL of IBD patients with stable clinical remission on biologic treatment. Their self-perceived stress scores during the outbreak were also assessed. METHODS: A prospective, observational study was performed in IBD patients on biologic treatment with stable clinical remission. Patients with both Crohn's disease and Ulcerative Colitis patients were included. Patients filled in the IBDQ9 and the Perceived stress scale (PSS) electronically. To determine any changes, the results of the IBDQ9 during the outbreak were compared with the last IBDQ9 before the outbreak. RESULTS: 106 patients in clinical remission were included, with a median age of 42 year, 42% were female and 77% had CD. Median preCOVID-19 IBDQ9 was 72.1[66.5-80.12] and decreased to 69.2 [63.1-77.10] during the outbreak (p<0.001). The median PSS score was 12 [9-19]. There was a significant negative correlation between the PSS and the outbreak IBDQ9 (r=-0.66, p< 0.001). Regression analysis showed that the PSS score was associated with a lower IBDQ-9 during the outbreak(p<0.001) Conclusion: There was a negative impact of the COVID19 outbreak on the HRQoL of IBD patients in remission, with higher self-perceived stress scores associated with a lower QoL. The COVID-19 outbreak may have long-term implications for the HRQoL in these patients.

[Relationship of demographic and dietary hygiene factors with the pathology found in outpatient colonoscopies performed in a Castilla y León Health Service center]. / Relación de los factores demográficos e higiénico-dietéticos con la patología hallada en las colonoscopias ambulatorias realizadas en un centro del Servicio Castellano y Leonés de Salud.

Introduction: Background: colorectal cancer (CRC) is one of the most frequent tumors in terms of incidence and mortality. Several elements, both inherited and environmental, have been related with its pathogenesis. Aims: to analyze the influence of age, gender and nutritional factors on the diagnosis of colonic polyps and CRC. Methods: a prospective, descriptive study over outpatients from the Health Area of León who took a colonoscopy between 09/09/2012 and 06/30/2013. Patients were asked to fill a semiquantitative food frecuency questionnaire with data such a sociodemographic, toxic and dietetic facts. Differences in diagnosis according to sociodemographic and hygiene-dietetic data were analyzed with a multivariate analysis by forward stepwise logistic regression. Results: data were collected from 1390 patients. Mean age was 57.88 (15.17) years and 47.8 % were male. CRC was diagnosed in 5 % of colonoscopies, and polyps in 20.4 %, with 9.4 % of them being HRA. Risk of polyps and HRA was higher in males (26.9 % vs 14.5 %) and (12.6 % vs 6.3 %), respectively (p < 0.001). Mean age was significantly higher in patients who presented polyps (56.51 (15.45) vs 63.22 (12.69) years; p < 0.001). Among the group who reported intake of smoked and salted food, the risk of polyps doubled (2.9 % vs 6.7 %, p = 0.002). In relation to alcohol intake we found that subjects with daily alcohol consumption showed a higher incidence of polyps whe compared to occasional drinkers and teetotallers (32 % vs 20 % vs 18.6 %, p = 0.002) Conclusions: age correlated with higher risk of polyps, HRA and CRC. Moreover, male gender also was associated with a high risk of polyps and HRA. Alcohol and red and processed meat intake increased polyp risk.

Introducción: Introducción: el cáncer colorrectal (CCR) es un tumor muy frecuente en términos de incidencia y mortalidad. Su patogenia se ha relacionado con diversos factores ambientales y hereditarios. Objetivos: analizar la asociación de edad, sexo y factores dietéticos con el diagnóstico de adenomas y CCR. Métodos: se realizó un estudio descriptivo prospectivo con los pacientes del Área Sanitaria de León que se sometieron a una colonoscopia ambulatoria entre 09/09/2012 y 30/06/2013. Mediante un formulario autoadministrado se recogieron datos sociodemográficos, tóxicos y dietéticos usando un cuestionario alimentario de frecuencia semicuantitativo. Se analizaron las diferencias en el diagnóstico según los datos sociodemográficos e higiénico-dietéticos, con análisis multivariante mediante regresión logística por pasos hacia delante. Resultados: se recogieron datos de 1390 pacientes cuya edad media fue de 57 (15) años; de ellos, el 47,8 % eran varones. Se diagnosticaron CCR en el 5 % de los pacientes y pólipos en el 20,4 % (9,4 % de adenomas de alto riesgo (AAR)). El hallazgo de pólipos y AAR fue más frecuente en los varones (26,9 % vs. 14,5 % y 12,6 % vs. 6,3 %, respectivamente (p < 0,001)). La edad media fue significativamente superior en los pacientes que presentaban pólipos (56.51 (15.45) vs. 63.22 (12.69) años; p < 0,001). En la población que refirió un consumo diario de carnes procesadas se duplicaba la proporción de pólipos detectados (2,9 % vs. 6,7 %; p = 0,02). Aquellos pacientes que consumían alcohol diariamente tenían mayor incidencia de pólipos frente al consumo ocasional y los abstemios (32 % vs. 20 % vs. 18,6 %; p = 0,002). Conclusiones: la edad se relacionaba con un mayor riesgo de pólipos, AAR y CCR. Los varones también tenían más riesgo de pólipos y AAR. El consumo de alcohol, carnes rojas y procesadas incrementaba el riesgo de pólipos.

Health-related quality of life decline in clinically stable inflammatory bowel disease patients during the COVID-19 outbreak

Background and aims: Inflammatory bowel disease (IBD) affects many aspects of a patient’s life and impairs their health-related quality of life (HRQoL). The COVID-19 outbreak has led to important mobility restrictions and a dramatic re-adjustment of social habits and health systems. This study aimed to assess the influence of the outbreak and mobility restrictions on the HRQoL of IBD patients with stable clinical remission on biologic treatment. Their self-perceived stress scores during the outbreak were also assessed. Methods: A prospective, observational study was performed in IBD patients on biologic treatment with stable clinical remission. Patients with both Crohn’s disease and Ulcerative Colitis patients were included. Patients filled in the IBDQ9 and the Perceived stress scale (PSS) electronically. To determine any changes, the results of the IBDQ9 during the outbreak were compared with the last IBDQ9 before the outbreak. Results: 106 patients in clinical remission were included, with a median age of 42 year, 42% were female and 77% had CD. Median preCOVID-19 IBDQ9 was 72.1[66.5-80.12] and decreased to 69.2 [63.1-77.10] during the outbreak (p<0.001). The median PSS score was 12 [9-19]. There was a significant negative correlation between the PSS and the outbreak IBDQ9 (r=-0.66, p< 0.001). Regression analysis showed that the PSS score was associated with a lower IBDQ-9 during the outbreak(p<0.001) Conclusion: There was a negative impact of the COVID19 outbreak on the HRQoL of IBD patients in remission, with higher self-perceived stress scores associated with a lower QoL. The COVID-19 outbreak may have long-term implications for the HRQoL in these patients (AU)

Chalcone Derivatives with a High Potential as Multifunctional Antioxidant Neuroprotectors.

A systematic, rational search for chalcone derivatives with multifunctional behavior has been carried out, with the support of a computer-assisted protocol (CADMA-Chem). A total of 568 derivatives were constructed by incorporating functional groups into the chalcone structure. Selection scores were calculated from ADME properties, toxicity, and manufacturability descriptors. They were used to select a subset of molecules (23) with the best drug-like behavior. Reactivity indices were calculated for this subset. They were chosen to account for electron and hydrogen atom donating capabilities, which are key processes for antioxidant activity. The indexes showed that four chalcone derivatives (dCHA-279, dCHA-568, dCHA-553, and dCHA-283) are better electron and H donors than the parent molecule and some reference antioxidants (Trolox, ascorbic acid, and α-tocopherol). In addition, based on molecular docking, they are predicted to act as catechol-O-methyltransferase (COMT), acetylcholinesterase (AChE), and monoamine oxidase B (MAO-B) inhibitors. Therefore, these four molecules are proposed as promising candidates to act as multifunctional antioxidants with neuroprotective effects.

CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants.

A computational protocol aimed to design new antioxidants with versatile behavior is presented. It is called Computer-Assisted Design of Multifunctional Antioxidants and is based on chemical properties (CADMA-Chem). The desired multi-functionality consists of in different methods of antioxidant protection combined with neuroprotection, although the protocol can also be used to pursue other health benefits. The dM38 melatonin derivative is used as a study case to illustrate the protocol in detail. This was found to be a highly promising candidate for the treatment of neurodegeneration, in particular Parkinson's and Alzheimer's diseases. This also has the desired properties of an oral-drug, which is significantly better than Trolox for scavenging free radicals, and has chelates redox metals, prevents the ●OH production, via Fenton-like reactions, repairs oxidative damage in biomolecules (lipids, proteins, and DNA), and acts as a polygenic neuroprotector by inhibiting catechol-O-methyl transferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase B (MAOB). To the best of our best knowledge, CADMA-Chem is currently the only protocol that simultaneously involves the analyses of drug-like behavior, toxicity, manufacturability, versatile antioxidant protection, and receptor-ligand binding affinities. It is expected to provide a starting point that helps to accelerate the discovery of oral drugs with the potential to prevent, or slow down, multifactorial human health disorders.

Casiopeinas® third generation, with indomethacin: synthesis, characterization, DFT studies, antiproliferative activity, and nanoencapsulation.

Seven new Casiopeinas® were synthesized and properly characterized. These novel compounds have a general formula [Cu(N-N)(Indo)]NO3, where Indo is deprotonated indomethacin and N-N is either bipyridine or phenanthroline with some methyl-substituted derivatives, belonging to the third generation of Casiopeinas®. Spectroscopic characterization suggests a square-based pyramid geometry and voltammetry experiments indicate that the redox potential is strongly dependent on the N-N ligand. All the presented compounds show high cytotoxic efficiency, and most of them exhibit higher efficacy compared to the well-known cisplatin drug and acetylacetonate analogs of the first generation. Computational calculations show that antiproliferative behavior can be directly related to the volume of the molecules. Besides, a chitosan (CS)-polyacrylamide (PNIPAAm) nanogel was synthesized and characterized to examine the encapsulation and release properties of the [Cu(4,7-dimethyl-1,10-phenanthroline)(Indo)]NO3 compound. The results show good encapsulation performance in acidic conditions and a higher kinetic drug release in acidic media than at neutral pH. This result can be described by the Peppas-Sahlin model and indicates a release mechanism predominantly by Fick diffusion.

Treatment of a genetic brain disease by CNS-wide microglia replacement.

Hematopoietic cell transplantation after myeloablative conditioning has been used to treat various genetic metabolic syndromes but is largely ineffective in diseases affecting the brain presumably due to poor and variable myeloid cell incorporation into the central nervous system. Here, we developed and characterized a near-complete and homogeneous replacement of microglia with bone marrow cells in mice without the need for genetic manipulation of donor or host. The high chimerism resulted from a competitive advantage of scarce donor cells during microglia repopulation rather than enhanced recruitment from the periphery. Hematopoietic stem cells, but not immediate myeloid or monocyte progenitor cells, contained full microglia replacement potency equivalent to whole bone marrow. To explore its therapeutic potential, we applied microglia replacement to a mouse model for Prosaposin deficiency, which is characterized by a progressive neurodegeneration phenotype. We found a reduction of cerebellar neurodegeneration and gliosis in treated brains, improvement of motor and balance impairment, and life span extension even with treatment started in young adulthood. This proof-of-concept study suggests that efficient microglia replacement may have therapeutic efficacy for a variety of neurological diseases.

COVID-19 lockdown and housing deprivation across European countries.

Housing deprivation is a key determinant of the capacity to prevent infection and to recover from a disease because poor housing prevents adequate sheltering during a quarantine. We analyze the degree of housing deprivation faced by households in European countries when COVID-19 lockdown measures were enacted. To do so, we propose a synthetic measure that includes more dimensions than the official Eurostat indicator of severe housing deprivation. We use a fuzzy set approach to measure housing deprivation so that, unlike traditional deprivation approaches, based on a dichotomous variable, we can identify different degrees of housing deprivation for each household in the population. We find similar orderings of housing deprivation dimensions by country with the highest degree of deprivation in the living space dimension and the lowest one in the standard housing or technology deprivation dimension. Nonetheless, housing deprivation levels differ across countries, with Eastern European households being significantly more housing deprived than the rest when the lockdown began. This result shows that the effects of the lockdown on social well-being have not affected all Europeans equally and emphasizes the need for government measures that promote decent housing.

Adiponectin Influences FGF2 in the Developing Porcine Corpus Luteum.

Luteal angiogenesis is regulated by pro-angiogenic hormones including fibroblast growth factor 2 (FGF2) and angiopoietin 1 (Ang1), which are regulated by the adipokine leptin during development. Another adipokine, adiponectin, exhibits an inverse relationship with leptin and has been identified in the CL. Therefore, it is hypothesized that adiponectin will influence pro-angiogenic hormones in the developing porcine CL. Crossbred sows were randomly allocated to one of two days of the estrous cycle, day 5 (D5; n = 4) or day 7 (D7; n = 5) for CL collection. Tissue was processed for immunohistochemical localization of adiponectin receptor 2 (AdipoR2), gene expression of FGF2, Ang1, leptin, AdipoR2, and cell culture for adiponectin treatment. The expression of AdipoR2 tended (p = 0.09) to be higher in D7 lutea and was more prevalently localized to the cell surface of large and small luteal cells than in D5 tissue. Adiponectin influenced (p ≤ 0.05) FGF2, leptin, and AdipoR2 gene expression relative to the dose and day (D5 or D7). Collectively, the evidence supports the supposition that adiponectin influences angiogenic factors in the developing CL.