Big Data-Planetary Health approach for evaluating the Brazilian Dengue Control Program.

OBJECTIVE: This study aims to integrate the concepts of planetary health and big data into the Donabedian model to evaluate the Brazilian dengue control program in the state of São Paulo. METHODS: Data science methods were used to integrate and analyze dengue-related data, adding context to the structure and outcome components of the Donabedian model. This data, considering the period from 2010 to 2019, was collected from sources such as Department of Informatics of the Unified Health System (DATASUS), the Brazilian Institute of Geography and Statistics (IBGE), WorldClim, and MapBiomas. These data were integrated into a Data Warehouse. K-means algorithm was used to identify groups with similar contexts. Then, statistical analyses and spatial visualizations of the groups were performed, considering socioeconomic and demographic variables, soil, health structure, and dengue cases. OUTCOMES: Using climate variables, the K-means algorithm identified four groups of municipalities with similar characteristics. The comparison of their indicators revealed certain patterns in the municipalities with the worst performance in terms of dengue case outcomes. Although presenting better economic conditions, these municipalities held a lower average number of community healthcare agents and basic health units per inhabitant. Thus, economic conditions did not reflect better health structure among the three studied indicators. Another characteristic of these municipalities is urbanization. The worst performing municipalities presented a higher rate of urban population and human activity related to urbanization. CONCLUSIONS: This methodology identified important deficiencies in the implementation of the dengue control program in the state of São Paulo. The integration of several databases and the use of Data Science methods allowed the evaluation of the program on a large scale, considering the context in which activities are conducted. These data can be used by the public administration to plan actions and invest according to the deficiencies of each location.

Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies.

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.

Short- and Long-Term Effects of Subchronic Stress Exposure in Male and Female Brain-Derived Neurotrophic Factor Knock-In Val66Met Mice.

Stress is an important risk factor for the onset of anxiety and depression. The ability to cope with stressful events varies among different subjects, probably depending on different genetic variants, sex and previous life experiences. The Val66Met variant of Brain-Derived Neurotrophic Factor (BDNF), which impairs the activity-dependent secretion of BDNF, has been associated with increased susceptibility to the development of various neuropsychiatric disorders. Adult male and female wild-type Val/Val (BDNFV/V) and heterozygous Val/Met (BDNFV/M) mice were exposed to two sessions of forced swimming stress (FSS) per day for two consecutive days. The mice were behaviorally tested 1 day (short-term effect) or 11 days (long-term effect) after the last stress session. Protein and mRNA levels were measured in the hippocampus 16 days after the end of stress exposure. Stressed mice showed a higher anxiety-like phenotype compared to non-stressed mice, regardless of the sex and genotype, when analyzed following the short period of stress. In the prolonged period, anxiety-like behavior persisted only in male BDNFV/M mice (p < 0.0001). Interestingly, recovery in male BDNFV/V mice was accompanied by an increase in pCREB (p < 0.001) and Bdnf4 (p < 0.01) transcript and a decrease in HDAC1 (p < 0.05) and Dnmt3a (p = 0.01) in the hippocampus. Overall, our results show that male and female BDNF Val66Met knock-in mice can recover from subchronic stress in different ways.

The influence of thioether-substituted ligands in dicopper(II) complexes: Enhancing oxidation and biological activities.

This paper describes the synthesis, structural analysis, as well as the magnetic and spectroscopic characterizations of three new dicopper(II) complexes with dinucleating phenol-based ligands containing different thioether donor substituents: aromatic (1), aliphatic (2) or thiophene (3). Temperature-dependent magnetometry reveals the presence of antiferromagnetic coupling for 1 and 3 (J = -2.27 cm-1 and -5.01 cm-1, respectively, H = -2JS1S2) and ferromagnetic coupling for 2 (J = 5.72 cm-1). Broken symmetry DFT calculations attribute this behavior to a major contribution from the dz2 orbitals for 1 and 3, and from the dx2-y2 orbitals for 2, along with the p orbitals of the oxygens. The bioinspired catalytic activities of these complexes related to catechol oxidase were studied using 3,5-di-tert-butylcatechol as substrate. The order of catalytic rates for the substrate oxidation follows the trend 1 > 2 > 3 with kcat of (90.79 ± 2.90) × 10-3 for 1, (64.21 ± 0.99) × 10-3 for 2 and (14.20 ± 0.32) × 10-3 s-1 for 3. The complexes also cleave DNA through an oxidative mechanism with minor-groove preference, as indicated by experimental and molecular docking assays. Antimicrobial potential of these highly active complexes has shown that 3 inhibits both Staphylococcus aureus bacterium and Epidermophyton floccosum fungus. Notably, the complexes were found to be nontoxic to normal cells but exhibited cytotoxicity against epidermoid carcinoma cells, surpassing the activity of the metallodrug cisplatin. This research shows the multifaceted properties of these complexes, making them promising candidates for various applications in catalysis, nucleic acids research, and antimicrobial activities.

WNT pathway in focal cortical dysplasia compared to perilesional nonlesional tissue in refractory epilepsies.

BACKGROUND: Focal cortical dysplasia (FCD) is a malformation of cortical development that causes medical refractory seizures, and one of the main treatments may be surgical resection of the affected area of the brain. People affected by FCD may present with seizures of variable severity since childhood. Despite many medical treatments available, only surgery can offer cure. The pathophysiology of the disease is not yet understood; however, it is known that several gene alterations may play a role. The WNT/ß-catenin pathway is closely related to the control and balance of cell proliferation and differentiation in the central nervous system. The aim of this study was to explore genes related to the WNT/ß-catenin pathway in lesional and perilesional brain tissue in patients with FCD type II. METHODS: Dysplastic and perilesional tissue from the primary dysplastic lesion of patients with FCD type IIa were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array (super array) containing 84 genes related to the WNT pathway. RESULTS: Our results suggest the existence of molecular alteration in some genes of the WNT pathway in tissue with dysplastic lesions and of perilesional tissue. We call this tissue of normal-appearing adjacent cortex (NAAC). Of all genes analyzed, a large number of genes show similar behavior between injured, perilesional and control tissues. However, some genes have similar characteristics between the perilesional and lesional tissue and are different from the control brain tissue, presenting the perilesional tissue as a molecularly altered material. CONCLUSION: Our results suggest that the perilesional area after surgical resection of tissue with cortical dysplasia presents molecular changes that may play a role in the recurrence of seizures in these patients. The perilesional tissue should receive expanded attention beyond the somatic mutations described and associated with FCD, such as mTOR, for example, to new signaling pathways that may play a crucial role in seizure recurrence.

Spectroscopical and Molecular Studies of Four Manganese(I) PhotoCORMs with Bioinspired Ligands Containing Non-Coordinated Phenol Groups.

Carbonyl compounds are widely explored in medicinal inorganic chemistry and have drawn attention due to their signaling functions in homeostasis. Carbon-monoxide-releasing molecules (CORMs) were developed with the purpose of keeping the CO inactive until its release in the intracellular environment, considering its biological relevance. However, for therapeutic applications, the mechanisms of photorelease and which electronic and structural variations influence its rates must be fully understood. In this work, four ligands containing a pyridine, a secondary amine, and a phenolic group with different substituents were used to prepare new Mn(I) carbonyl compounds. Structural and physicochemical characterization of these complexes was carried out and confirmed the proposed structures. X-ray diffractometry structures obtained for the four organometallic compounds revealed that the substituents in the phenolic ring promote only negligible distortions in their geometry. Furthermore, UV-Vis and IR kinetics showed the direct dependence of the electron-withdrawing or donating ability of the substituent group, indicating an influence of the phenol ring on the CO release mechanism. These differences in properties were also supported by theoretical studies at the DFT, TD-DFT, and bonding situation analyses (EDA-NOCV). Two methods were used to determine the CO release constants (kCO,old and kCO,new), where Mn-HbpaBr (1) had the greatest kCO by both methods (Kco,old = 2.36 × 10-3 s-1 and kCO,new = 2.37 × 10-3 s-1). Carbon monoxide release was also evaluated using the myoglobin assay, indicating the release of 1.248 to 1.827 carbon monoxides upon light irradiation.

New dimethacrylate monomers based on phenolphthalein and resveratrol for the application of dental materials.

Potential estrogenic effects and changes in fertility are some of the health problems associated with bisphenol A (BPA) derivatives used to produce some polymers, including dental materials that contain Bis-GMA. Those issues drove this study proposing the synthesis of methacrylate resveratrol and phenolphthalein monomers that, combined with diluent monomers, generate copolymers. Their key characteristics were determined and analyzed on the chemical structure-property perspective considering monomer planarity and flexibility based on molecular dynamic simulations. METHODS: Methacrylate resveratrol ((E)-5-(4-(methacryloyloxy)styryl)-1,3-phenylenebis(2-methylacrylate)), EMPM) and methacrylate phenolphthalein ((3-oxo-1,3-dihydroisobenzofuran-1,1-diyl)bis(4,1-phenylene)bis(2-methylacrylate)), DIFPM) were synthesized through the reaction of precursors with methacryloyl chloride. After monomers purification and spectroscopic characterization (FTIR and NMR), the following copolymers were produced: DIFPM/TEGDMA and Bis-GMA/TEGDMA, EMPM/HEMA and Bis-GMA/HEMA. Microhardness, degree of conversion, water sorption and contact angle data were statistically analyzed through one-way ANOVA and Tukey's test (p ≤ 0.05). RESULTS: The DIFPM molecular structure's reduced flexibility proved to be an important factor to inhibit TEGDMA cyclization. In turn, the EMPM molecule's high planarity modified the spatial organization of the HEMA copolymer, altering the water diffusion and, therefore, the water sorption when compared to Bis-GMA copolymers. CONCLUSION: The scientific findings contribute to better understand the effect of monomer chemical structures, molecular geometry, and planarity on some physicochemical properties of copolymers. Knowledge that can contribute to the design of new monomers to replace Bis-GMA.

In vitro anti-Leishmania activity of new isomeric cobalt(II)complexes and in silico insights: Mitochondria impairment and apoptosis-like cell death of the parasite.

The synthesis, physico-chemical characterization and in vitro antiproliferative activity against the promastigote form of Leishmania amazonensis of two new cobalt(II) coordination compounds (i.e. [Co(HL1)Cl2]0.4,2H2O (1) and [Co(HL2)(Cl)(CH3OH)](ClO4).2H2O (2)) are reported, where HL1 = 4-{3-[bis(pyridin-2-ylmethyl)amino]-2-hydroxypropoxy}-2H-chromen-2-one and HL2 = 7-{3-[bis(pyridin-2-ylmethyl)amino]-2-hydroxypropoxy}-2H-chromen-2-one. X-ray diffraction studies were performed for complex (2) and the structure of complex (1) was built through Density Functional Theory (DFT) calculations. Complex (1) presented no cytotoxicity to LLC-MK2, but complex (2) was toxic. IC50 against promastigotes of L. amazonensis for complex (1) were 4.90 (24 h), 3.50 (48 h) and 3. 80 µmol L-1 (72 h), and for complex (2) were 2.09, 4.20 and 2.80 µmol L-1, respectively. Due to the high toxicity presented by complex (2) against LLC-MK2 host cells, mechanistic studies, to shed light on the probable mode of leishmanicidal activity, were carried out only for the non-cytotoxic complex. Complex (1) was able to elevate mitochondrial membrane potential of the parasites after treatment. Transmission electron microscopy revealed typical apoptotic condensation of chromatin, altered kinetoplast and mitochondria structures, suggesting that apoptosis-like cell death of the protozoa is probably mediated by an apoptotic mechanism associated with mitochondrial dysfunction (intrinsic pathway). Molecular docking studies with complex (1) upon protein tyrosine phosphatase (LmPRL-1) suggests a plausible positive complex anchoring mainly by hydrophobic and hydrogen bond forces close to the enzyme's catalytic site. These promising results for complex 1 will prompt future investigations against amastigote form of L. amazonensis.

Bioinspired oxidation of benzyl alcohol: The role of environment and nuclearity of the catalyst evaluated by multivariate analysis.

Inspired by copper-containing enzymes such as galactose oxidase and catechol oxidase, in which distinct coordination environments and nuclearities lead to specific catalytic activities, we summarize here the catalytic properties of dinuclear and mononuclear copper species towards benzyl alcohol oxidation using a multivariate statistical approach. The new dinuclear [Cu2(µ-L1)(µ-pz)]2+ (1) is compared against the mononuclear [CuL2Cl] (2), where (L1)- and (L2)- are the respective deprotonated forms of 2,6-bis((bis(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol, and 3-((bis(pyridin-2-ylmethyl)amino)methyl)-2-hydroxy-5-methylbenzaldehyde and (pz)- is a pyrazolato bridge. Copper(II) perchlorate (CP) is used as control. The catalytic oxidation of benzyl alcohol is pursued, aiming to assess the role of the ligand environment and nuclearity. The multivariate statistical approach allows for the search of optimal catalytic conditions, considering variables such as catalyst load, hydrogen peroxide load, and time. Species 1, 2 and CP promoted selective production of benzaldehyde at different yields, with only negligible amounts of benzoic acid. Under normalized conditions, 2 showed superior catalytic activity. This species is 3.5-fold more active than the monometallic control CP, and points out to the need for an efficient ligand framework. Species 2 is 6-fold more active than the dinuclear 1, and indicates the favored nuclearity for the conversion of alcohols into aldehydes.

Enhancing the biological properties of zinc complexes with bis(indolyl)methane groups: Synthesis, characterization, DNA interaction, and biocide activity.

The unprecedented mononucleated ligand (6,6-di(1H-indol-3-yl)-N,N-bis(pyridin-2-ylmethyl)hexan-1-amine (LC5) with an N3-donor set and its complexes [Zn(LC5)Cl2] • 2CH3OH (1) and [Zn(LC5)2](ClO4)2 (2), were successfully prepared. All compounds were fully characterized by a suite of physicochemical methods. Fluid 1H and 13C NMR spectroscopy, as well as DFT and TD-DFT calculations, were carried out to propose a viable structural arrangement for both complexes. The interaction between these compounds and DNA was monitored in the UV region where binding constants (Kb) were estimated (2 > 1 > LC5). These data were corroborated by DNA cleavage assays using groove binders, circular dichroism, and docking studies. Both complexes confirmed their biocide activity against selected microorganisms: Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria, the filamentous fungi A. fumigatus and S. cerevisiae. Finally, the cytotoxic activities of 1 and 2 were tested against the erythroleukemia K562 cell line. For all biological studies, it was probed that the presence of the indole moieties and the zinc atoms in the chemical composition of the complexes studied could increase the magnitude of the activity following the order: 2 > 1 > LC5, where a linear relationship between the biological activity upon K562 cells (IC50) and DNA binding studies (Kb) was found.

Hydrolytic activity of new bioinspired MnIIIMnII and FeIIIMnII complexes as mimetics of PAPs: Biological and environmental interest.

Coordination compounds that mimic Purple Acid Phosphatases (PAPs) have drawn attention in the bioinorganic field due to their capacity to cleave phosphodiester bonds. However, their catalytic activity upon phosphate triesters is still unexplored. Thus, we report the synthesis and characterization of two binuclear complexes, [MnIIMnIII(L1)(OAc)2]BF4 (1) and [MnIIFeIII(L1)(OAc)2]BF4 (2) (H2L1 = 2-[N,N-bis-(2- pyridilmethyl)aminomethyl]-4-methyl-6-[N-(2-hydroxy-3-formyl-5-methylbenzyl)-N-(2-pyridylmethyl)aminomethyl]phenol), their hydrolytic activity and antioxidant potential. The complexes were fully characterized, including the X-Ray diffraction (XRD) of 1. Density functional theory (DFT) calculations were performed to better understand their electronic and structural properties and phosphate conjugates. The catalytic activity was analyzed for two model substrates, a diester (BDNPP) and a triester phosphate (DEDNPP). The results suggest enhancement of the hydrolysis reaction by 170 to 1500 times, depending on the substrate and complex. It was possible to accompany the catalytic reaction of DEDNPP hydrolysis by phosphorus nuclear magnetic resonance (31P NMR), showing that both 1 and 2 are efficient catalysts. Moreover, we also addressed that 1 and 2 present a relevant antioxidant potential, protecting the yeast Saccharomyces cerevisiae, used as eukaryotic model of study, against the exposure of cells to acute oxidative stress.

Estrategias nutricionales implementadas en los paisesandinos. Una mirada a la nutrición escolar en Ecuador, Perú y Bolivia / Nutritional strategies implemented in Andean countries. A look at schoolnutrition in Ecuador, Peru and Bolivia

Introducción: La nutrición es sumamente importantepara el normal desarrollo de los seres humanos, por lo tanto,es importante conocer el proceso que se ha llevado a cabopara mejorar los procesos de alimentación escolar en AméricaLatina, tomando como referencia a los países andinos. Se manifiesta que en América Latina el Programa de Alimentación Escolar (PAE) es de gran envergadura por losobjetivos, la cobertura y los recursos que asigna el Estadopara su operación, haciendo de este uno de los programas sociales de mayor importancia en la región. La presente investigación cumple con los siguientes objetivos: Descripción sobre estrategias nutricionales que han mejorado los índices de nutrición escolar en Ecuador, Boliviay Perú. Identificación de los alimentos que no contribuyen a unanutrición adecuada para los niños. Material y métodos: Se realizó una búsqueda bibliográfica en bases de datos de la Organización de Naciones Unidas(ONU), Organización de las Naciones Unidas para la Agri cultura y la Alimentación (FAO) y Ministerios de Educación de lospaíses sudamericanos. Para complementar la investigacióntambién se buscaron artículos en Association for Computing Machinery (ACM) y Scopus, empleando los términos: estrategias nutricionales, nutrición infantil, escolares en Sudamérica,malnutrición, PAE. En la presente investigación se aplica la descripción histórica y comparativa de ciertos proyectos de nutrición escolarque han sido ejecutados desde el 2008 hasta 2018 en los países andinos. Resultados: Los países sudamericanos, especialmente losandinos han reformado sus procesos de alimentación escolar,mejorando así también aspectos sociales como la economía y la educación, basados en estrategias de equidad que promueven la incorporación y estabilidad de los estudiantes alsector académico.(AU)

Introduction: Nutrition is extremely important for thenormal development of human beings, therefore, it is important to know the process that has been carried out to improveschool feeding processes in Latin America, taking the Andeancountries as a reference.It is clear that in Latin America the School Feeding Program(PAE) is of great importance due to its objectives, coverageand the resources allocated by the State for its operation,making it one of the most important social programs in theregion. This research has the following objectives: Description on nutritional strategies that have improvedschool nutrition indices in Ecuador, Bolivia and Peru. Identification of foods that do not contribute to adequatenutrition for children. Material and methods: A bibliographic search was carried out in databases of the United Nations (UN), Food andAgriculture Organization of the United Nations (FAO) andMinistries of Education of South American countries. To complement the research, articles were also searched in theAssociation for Computing Machinery (ACM) and Scopus, using the terms: nutritional strategies, child nutrition, schoolchildren in South America, malnutrition, PAE.The present research applies the historical and comparativedescription of certain school nutrition projects that have beenimplemented from 2008 to 2018 in the Andean countries. Results: South American countries, especially the Andeancountries have reformed their school nutrition processes, thusalso improving social aspects such as economy and education, based on equity strategies that promote the incorporation and stability of students to the academic sector. Discussion / conclusions: The PAE, work under thecomprehensive protection approach, contributing mainly tothe guarantee of two fundamental rights: education and foodfor children and adolescents enrolled in the public education system.(AU)

Hydrogen-atom and oxygen-atom transfer reactivities of iron(IV)-oxo complexes of quinoline-substituted pentadentate ligands.

A series of iron(II) complexes with the general formula [FeII(L2-Qn)(L)]n+ (n = 1, L = F-, Cl-; n = 2, L = NCMe, H2O) have been isolated and characterized. The X-ray crystallographic data reveals that metal-ligand bond distances vary with varying ligand field strengths of the sixth ligand. While the complexes with fluoride, chloride and water as axial ligand are high spin, the acetonitrile-coordinated complex is in a mixed spin state. The steric bulk of the quinoline moieties forces the axial ligands to deviate from the Fe-Naxial axis. A higher deviation/tilt is noted for the high spin complexes, while the acetonitrile coordinated complex displays least deviation. This deviation from linearity is slightly less in the analogous low-spin iron(II) complex [FeII(L1-Qn)(NCMe)]2+ of the related asymmetric ligand L1-Qn due to the presence of only one sterically demanding quinoline moiety. The two iron(II)-acetonitrile complexes [FeII(L2-Qn)(NCMe)]2+ and [FeII(L1-Qn)(NCMe)]2+ generate the corresponding iron(IV)-oxo species with higher thermal stability of the species supported by the L1-Qn ligand. The crystallographic and spectroscopic data for [FeIV(O)(L1-Qn)](ClO4)2 bear resemblance to other crystallographically characterized S = 1 iron(IV)-oxo complexes. The hydrogen atom transfer (HAT) and oxygen atom transfer (OAT) reactivities of both the iron(IV)-oxo complexes were investigated, and a Box-Behnken multivariate optimization of the parameters for catalytic oxidation of cyclohexane by [FeII(L2-Qn)(NCMe)]2+ using hydrogen peroxide as the terminal oxidant is presented. An increase in the average Fe-N bond length in [FeII(L1-Qn)(NCMe)]2+ is also manifested in higher HAT and OAT rates relative to the other reported complexes of ligands based on the N4Py framework. The results reported here confirm that the steric influence of the ligand environment is of critical importance for the reactivity of iron(IV)-oxo complexes, but additional electronic factors must influence the reactivity of iron-oxo complexes of N4Py derivatives.

Hallazgos ultraestructurales renales de pacientes con nefritis intersticial crónica de las comunidades agrícolas en El Salvador / Renal ultrastructural findings of patients with chronic interstitial nephritis from farming communities in El Salvador

Introducción: Desde hace 20 años se presenta en Centroamérica una enfermedad renal crónica que fundamentalmente afecta a hombres agricultores y no asociada a las causas tradicionales. Se caracteriza por presentar una nefritis intersticial crónica, en tanto las características ultraestructurales no se conocen con exactitud. En su origen se invoca el uso de agroquímicos y otros agentes nefrotóxicos, la deshidratación crónica, el consumo de medicamentos, entre otros factores. Objetivo: Describir las características ultraestructurales de la nefritis intersticial crónica en comunidades agrícolas. Método: Se realizó un estudio descriptivo de corte transversal. Se estudiaron muestras de biopsias renales de ocho pacientes con diagnóstico de nefritis intersticial crónica de las comunidades agrícolas. Resultados: De los ocho pacientes estudiados, dos (25 por ciento) trabajaban en labores agrícolas y cinco eran del sexo femenino (62,5 por ciento). Dos de los pacientes (25 por ciento) presentaban una enfermedad renal crónica estadio 2, y seis (75 por ciento) estadio 3. En cinco pacientes se hallaron fagolisosomas con presencia de componente lipídico entremezclado con material electrodenso en células del túbulo distal. En igual cantidad de pacientes se observaron cuerpos mieloides con zonas laminadas y núcleo central en células de túbulo proximal y de los vasos sanguíneos. Conclusiones: En pacientes de comunidades agrícolas que padecen nefritis intersticial crónica se evidencian fagolisosomas y estructuras mieloides en túbulos y vasos renales, cuyo contenido y origen se desconocen(AU)

Introduction: Chronic kidney disease mainly affecting male farmers and not associated to traditional causes has been present in Central America for twenty years. The condition is characterized by the presence of chronic interstitial nephritis, but its ultrastructural features are not fully known. Factors suggested as responsible for its occurrence include the use of agrochemicals and other nephrotoxic agents, chronic dehydration and medicine consumption. Objective: Describe the ultrastructural characteristics of chronic interstitial nephritis in farming communities. Method: A cross-sectional descriptive study was conducted of renal biopsy samples from eight patients diagnosed with chronic interstitial nephritis in farming communities. Results: Of the eight patients studied, two (25 percent) were farm workers and five (62.5percent) were female. Two of the patients (25 percent) had stage 2 and six (75 percent) stage 3 chronic kidney disease. In five patients evidence was found of phagolysosomes with lipid component mixed with electrodense material in distal tubule cells. An equal number of patients had myeloid bodies with laminated areas and central nucleus in proximal tubule and blood vessel cells. Conclusions: Evidence of phagolysosomes and myeloid structures of unknown content and origin was found in renal tubules and vessels of patients from farming communities diagnosed with chronic interstitial nephritis(AU)

Luminescent PhotoCORMs: Enabling/Disabling CO Delivery upon Blue Light Irradiation.

The new luminescent carbonyl compounds [Mn(Oxa-H)(CO)3Br] (1) and [Mn(Oxa-NMe2)(CO)3Br] (2) were synthesized and fully characterized. Complexes 1 and 2 showed CO release under blue light (λ453). Spectroscopic techniques and TD-DFT and SOC-TD-DFT calculations indicated that 1 and 2 release the Oxa-H and Oxa-NMe2 coligands in addition to the carbonyl ligands, increasing the luminescence during photoinduction.

Nicotinamide riboside with pterostilbene (NRPT) increases NAD+ in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI.

BACKGROUND: Preclinical studies have identified both NAD+ and sirtuin augmentation as potential strategies for the prevention and treatment of AKI. Nicotinamide riboside (NR) is a NAD+ precursor vitamin and pterostilbene (PT) is potent sirtuin activator found in blueberries. Here, we tested the effect of combined NR and PT (NRPT) on whole blood NAD+ levels and safety parameters in patients with AKI. METHODS: We conducted a randomized, double-blind, placebo-controlled study of escalating doses of NRPT in 24 hospitalized patients with AKI. The study was comprised of four Steps during which NRPT (5 subjects) or placebo (1 subject) was given twice a day for 2 days. NRPT dosing was increased in each Step: Step 1250/50 mg, Step 2500/100 mg, Step 3750/150 mg and Step 41,000/200 mg. Blood NAD+ levels were measured by liquid chromatography-mass spectrometry and safety was assessed by history, physical exam, and clinical laboratory testing. RESULTS: AKI resulted in a 50% reduction in whole blood NAD+ levels at 48 h compared to 0 h in patients receiving placebo (p = 0.05). There was a trend for increase in NAD+ levels in all NRPT Steps individually at 48 h compared to 0 h, but only the change in Step 2 reached statistical significance (47%, p = 0.04), and there was considerable interindividual variability in the NAD+ response to treatment. Considering all Steps together, NRPT treatment increased NAD+ levels by 37% at 48 h compared to 0 h (p = 0.002). All safety laboratory tests were unchanged by NRPT treatment, including creatinine, estimated glomerular filtration rate (eGFR), electrolytes, liver function tests, and blood counts. Three of 20 patients receiving NRPT reported minor gastrointestinal side effects. CONCLUSION: NRPT increases whole blood NAD+ levels in hospitalized patients with AKI. In addition, NRPT up to a dose of 1000 mg/200 mg twice a day for 2 days is safe and well tolerated in these patients. Further studies to assess the potential therapeutic benefit of NRPT in AKI are warranted. TRIAL REGISTRATION: NCT03176628 , date of registration June 5th, 2017.