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Objectives: Homozygous familial hypercholesteremia (HoFH) is a rare, life-threatening metabolic disease, mainly caused by a mutation in the LDL receptor. If untreated, HoFH causes premature death from acute coronary syndrome. Lomitapide is approved by the FDA as a therapy to lower lipid levels in adult patients with HoFH. Nevertheless, the beneficial effect of lomitapide in HoFH models remains to be defined. In this study, we investigated the effect of lomitapide on cardiovascular function using LDL receptor-knockout mice (LDLr−/−). Methods: Six-week-old LDLr−/− mice were fed a standard diet (SD) or a high-fat diet (HFD) for 12 weeks. Lomitapide (1 mg/Kg/Day) was given by oral gavage for the last 2 weeks in the HFD group. Body weight and composition, lipid profile, blood glucose, and atherosclerotic plaques were measured. Vascular reactivity and markers for endothelial function were determined in conductance arteries (thoracic aorta) and resistance arteries (mesenteric resistance arteries (MRA)). Cytokine levels were measured by using the Mesoscale discovery V-Plex assays. Results: Body weight (47.5 ± 1.5 vs. 40.3 ± 1.8 g), % of fat mass (41.6 ± 1.9% vs. 31.8 ± 1.7%), blood glucose (215.5 ± 21.9 vs. 142.3 ± 7.7 mg/dL), and lipid levels (cholesterol: 600.9 ± 23.6 vs. 451.7 ± 33.4 mg/dL; LDL/VLDL: 250.6 ± 28.9 vs. 161.1 ± 12.24 mg/dL; TG: 299.5 ± 24.1 vs. 194.1 ± 28.1 mg/dL) were significantly decreased, and the % of lean mass (56.5 ± 1.8% vs. 65.2 ± 2.1%) was significantly increased in the HFD group after lomitapide treatment. The atherosclerotic plaque area also decreased in the thoracic aorta (7.9 ± 0.5% vs. 5.7 ± 0.1%). After treatment with lomitapide, the endothelium function of the thoracic aorta (47.7 ± 6.3% vs. 80.7 ± 3.1%) and mesenteric resistance artery (66.4 ± 4.3% vs. 79.5 ± 4.6%) was improved in the group of LDLr−/− mice on HFD. This was correlated with diminished vascular endoplasmic (ER) reticulum stress, oxidative stress, and inflammation. Conclusions: Treatment with lomitapide improves cardiovascular function and lipid profile and reduces body weight and inflammatory markers in LDLr−/− mice on HFD.

Abstract: The production of renin by the principal cells of the collecting duct has widened our understanding of the regulation of intrarenal angiotensin II (Ang II) generation and blood pressure. In the collecting duct, Ang II increases synthesis and secretion of renin by mechanisms involving the activation of Ang II type 1 receptors (AT1R) via stimulation of the PKCα, Ca2+ and cAMP/PKA/CREB pathways. Additionally, paracrine mediators, including vasopressin (AVP), prostaglandins, bradykinin (BK) and atrial natriuretic peptide (ANP) regulate renin in principal cells. During Ang II-dependent hypertension, despite plasma renin activity suppression, the renin and prorenin receptor (PRR) are upregulated in the collecting duct and promote de novo formation of intratubular Ang II. Furthermore, activation of PRR by its natural agonists, prorenin and renin, may contribute to the stimulation of profibrotic factors, independent of Ang II. Thus, the interactions of RAS components with paracrine hormones within the collecting duct enables tubular compartmentalization of the RAS to orchestrate complex mechanisms that increase intrarenal Ang II, Na+ reabsorption and blood pressure.

Understanding the complex elements affecting signal resolution in cytometry is key for quality experimental design and data. In this study, we incorporate autofluorescence as a contributing factor to our understanding of resolution in cytometry and corroborate its impact in fluorescence signal detection through mathematical predictions supported by empirical evidence. Our findings illustrate the critical importance of autofluorescence extraction via full spectrum unmixing in unmasking dim signals and delineating the expression and subset distribution of low abundance markers in discovery projects. We apply our findings to the precise definition of the tissue and cellular distribution of a weakly expressed fluorescent protein that reports on a low-abundance immunological gene. Exploiting the full spectrum coverage enabled by Aurora 5L, we describe a novel approach to the isolation of pure cell subset-specific autofluorescence profiles based on high dimensionality reduction algorithms. This method can also be used to unveil differences in the autofluorescent fingerprints of tissues in homeostasis and after immunological challenges.

To survive in nutrient-poor waters corals rely on a symbiotic association with intracellular microalgae. However, increased sea temperatures cause algal loss—known as coral bleaching—often followed by coral death. Some of the most compelling evidence in support of the ‘oxidative stress theory of coral bleaching’ comes from studies that exposed corals, cultures of their algal endosymbionts, or the coral modelExaiptasia diaphanato exogenous antioxidants during thermal stress. Here, we replicate these experiments usingE.diaphanawith the addition of the antioxidants ascorbate + catalase, catechin, or mannitol under ambient and elevated temperatures along with an antioxidant-free control. In the absence of exogenous antioxidants,E.diaphanaexposed to elevated temperatures bleached with no change in reactive oxygen species (ROS) levels associated with their microalgal cells. Ascorbate + catalase and mannitol treatments rescued the anemones from bleaching, although microalgal ROS levels increased in these antioxidant treatments under elevated temperature conditions. While bleaching was not associated with changes in net ROS for the intracellular algal symbionts, it is evident from our findings that excess ROS is connected to the bleaching phenotype as exogenous antioxidants were successful in mitigating the effects of thermal stress in cnidarians. This understanding may assist applied research that aims to reduce the impact of climate change on coral reefs.

Spontaneous pneumothorax is an uncommon complication of COVID-19 disease, and may be associated with worse outcomes. This can occur without a pre-existing lung disease or without mechanical ventilation. We present a series of 3 cases of spontaneous pneumothorax with Covid-19 pneumonia. All the cases in our series did not have any pre-existing lung disease. The timely identification of possible complications of COVID-19 is crucial to reduce mortality. Spontaneous pneumothorax should be suspected in all types of patients with SARS-CoV-2 pneumonia who present a sudden deterioration of hypoxia on their first admission to the health centers.

Oral lichen planus (OLP) is an inflammatory condition of unknown cause that has been associated with concurrent candidal infection. Mucosal-associated invariant T (MAIT) cells express the T cell receptor TCRVα7.2 and are activated by riboflavin intermediates produced by microbes. The interaction between MAIT cells, Candida, and OLP is unknown. This study aimed to determine mucosal-associated T cell presence in OLP and whether the abundance of these cells changed due to the presence of either Candida or symptoms, using multiplex immunohistochemistry (mIHC). Ninety formalin fixed-paraffin-embedded (FFPE) tissue samples were assessed using mIHC for the cellular markers CD3, interleukin 18 receptor one (IL18R1), TCRVα7.2, CD161, CD8, and major histocompatibility complex class I-related (MR-1) protein. The samples were stratified into five groups on the basis of clinical (presence/absence of symptoms) and microbiological (presence/absence of Candida) criteria. Results demonstrated the presence of MAIT cell phenotypes in OLP inflammatory infiltrate within the connective tissue. Significant differences existed between different OLP groups with the percentage of log(CD3+ CD161+) and log(CD3+ TCRVα7.2+) positive cells (p < 0.001 and p = 0.005 respectively). Significant differences also existed with the relative abundance of triple-stained log(CD3+ CD161+ IL18R1+) cells (p = 0.004). A reduction in log(CD3+ CD161+ IL18R1+) cells was observed in lesional tissue of patients with symptomatic OLP with and without Candida when compared to controls. When present in OLP, MAIT cells were identified within the connective tissue. This study demonstrates that mIHC can be used to identify MAIT cell phenotypes in OLP. Reduced percentage of log(CD3+ CD161+ IL18R1+) cells seen in symptomatic OLP with and without Candida suggests a role for these cells in OLP pathogenesis.

Growing evidence indicates that prorenin receptor (PRR) is upregulated in collecting duct (CD) of diabetic kidney. Prorenin is secreted by the principal CD cells, and is the natural ligand of the PRR. PRR activation stimulates fibrotic factors, including fibronectin, collagen, and transforming growth factor-β (TGF-β) contributing to tubular fibrosis. However, whether high glucose (HG) contributes to this effect is unknown. We tested the hypothesis that HG increases the abundance of PRR at the plasma membrane of the CD cells, thus contributing to the stimulation of downstream fibrotic factors, including TGF-β, collagen I, and fibronectin. We used streptozotocin (STZ) male Sprague–Dawley rats to induce hyperglycemia for 7 days. At the end of the study, STZ-induced rats showed increased prorenin, renin, and angiotensin (Ang) II in the renal inner medulla and urine, along with augmented downstream fibrotic factors TGF-β, collagen I, and fibronectin. STZ rats showed upregulation of PRR in the renal medulla and preferential distribution of PRR on the apical aspect of the CD cells. Cultured CD M-1 cells treated with HG (25 mM for 1 h) showed increased PRR in plasma membrane fractions compared to cells treated with normal glucose (5 mM). Increased apical PRR was accompanied by upregulation of TGF-β, collagen I, and fibronectin, while PRR knockdown prevented these effects. Fluorescence resonance energy transfer experiments in M-1 cells demonstrated augmented prorenin activity during HG conditions. The data indicate HG stimulates profibrotic factors by inducing PRR translocation to the plasma membrane in CD cells, which in perspective, might be a novel mechanism underlying the development of tubulointerstitial fibrosis in diabetes mellitus.

The intrarenal renin–angiotensin system is critical for the regulation of tubule sodium reabsorption, renal haemodynamics and blood pressure. The excretion of renin in urine can result from its increased filtration, the inhibition of renin reabsorption by megalin in the proximal tubule, or its secretion by the principal cells of the collecting duct. Modest increases in circulating or intrarenal angiotensin II (ANGII) stimulate the synthesis and secretion of angiotensinogen in the proximal tubule, which provides sufficient substrate for collecting duct-derived renin to form angiotensin I (ANGI). In models of ANGII-dependent hypertension, ANGII suppresses plasma renin, suggesting that urinary renin is not likely to be the result of increased filtered load. In the collecting duct, ANGII stimulates the synthesis and secretion of prorenin and renin through the activation of ANGII type 1 receptor (AT1R) expressed primarily by principal cells. The stimulation of collecting duct-derived renin is enhanced by paracrine factors including vasopressin, prostaglandin E2 and bradykinin. Furthermore, binding of prorenin and renin to the prorenin receptor in the collecting duct evokes a number of responses, including the non-proteolytic enzymatic activation of prorenin to produce ANGI from proximal tubule-derived angiotensinogen, which is then converted into ANGII by luminal angiotensin-converting enzyme; stimulation of the epithelial sodium channel (ENaC) in principal cells; and activation of intracellular pathways linked to the upregulation of cyclooxygenase 2 and profibrotic genes. These findings suggest that dysregulation of the renin–angiotensin system in the collecting duct contributes to the development of hypertension by enhancing sodium reabsorption and the progression of kidney injury.

Coral reefs are threatened by climate change, because it causes increasingly frequent and severe summer heatwaves, resulting in mass coral bleaching and mortality. Coral bleaching is believed to be driven by an excess production of reactive oxygen (ROS) and nitrogen species (RNS), yet their relative roles during thermal stress remain understudied. Here, we measured ROS and RNS net production, as well as activities of key enzymes involved in ROS scavenging (superoxide dismutase and catalase) and RNS synthesis (nitric oxide synthase) and linked these metrics to physiological measurements of cnidarian holobiont health during thermal stress. We did this for both an established cnidarian model, the sea anemone Exaiptasia diaphana, and an emerging scleractinian model, the coral Galaxea fascicularis, both from the Great Barrier Reef (GBR). Increased ROS production was observed during thermal stress in both species, but it was more apparent in G. fascicularis, which also showed higher levels of physiological stress. RNS did not change in thermally stressed G. fascicularis and decreased in E. diaphana. Our findings in combination with variable ROS levels in previous studies on GBR-sourced E. diaphana suggest G. fascicularis is a more suitable model to study the cellular mechanisms of coral bleaching.

Corals house a variety of microorganisms which they depend on for their survival, including endosymbiotic dinoflagellates (Symbiodiniaceae) and bacteria. While cnidarian–microorganism interactions are widely studied, Symbiodiniaceae–bacteria interactions are only just beginning to receive attention. Here, we describe the localization and composition of the bacterial communities associated with cultures of 11 Symbiodiniaceae strains from nine species and six genera. Three-dimensional confocal laser scanning and electron microscopy revealed bacteria are present inside the Symbiodiniaceae cells as well as closely associated with their external cell surface. Bacterial pure cultures and 16S rRNA gene metabarcoding from Symbiodiniaceae cultures highlighted distinct and highly diverse bacterial communities occur intracellularly, closely associated with the Symbiodiniaceae outer cell surface and loosely associated (i.e., in the surrounding culture media). The intracellular bacteria are highly conserved across Symbiodiniaceae species, suggesting they may be involved in Symbiodiniaceae physiology. Our findings provide unique new insights into the biology of Symbiodiniaceae.

The sea anemone, Exaiptasia diaphana, is a model of coral-dinoflagellate (Symbiodiniaceae) symbiosis. However, little is known of its potential to form symbiosis with Cladocopium—a key Indo-Pacific algal symbiont of scleractinian corals, nor the host nutritional consequences of such an association. Aposymbiotic anemones were inoculated with homologous algal symbionts, Breviolum minutum, and seven heterologous strains of Cladocopium C1acro (wild-type and heat-evolved) under ambient conditions. Despite lower initial algal cell density, Cladocopium C1acro-anemeones achieved similar cell densities as B. minutum-anemones by week 77. Wild-type and heat-evolved Cladocopium C1acro showed similar colonization patterns. Targeted LC-MS-based metabolomics revealed that almost all significantly different metabolites in the host and Symbiodiniaceae fractions were due to differences between Cladocopium C1acro and B. minutum, with little difference between heat-evolved and wild-type Cladocopium C1acro at week 9. The algal fraction of Cladocopium C1acro-anemones was enriched in metabolites related to nitrogen storage, while the host fraction of B. minutum-anemones was enriched in sugar-related metabolites. Compared to B. minutum, Cladocopium C1acro is likely slightly less nutritionally beneficial to the host under ambient conditions, but more capable of maintaining its own growth when host nitrogen supply is limited. Our findings demonstrate the value of E. diaphana to study experimentally evolved Cladocopium.

Mexico is currently emerging in the photovoltaic manufacturing market due to favorable geographical conditions like 5.5 hours of sun every day (5000W/m2) and a strategic commercial partner (USA) for exportation of photovoltaic products, therefore a gradual advance in the photovoltaic field as a source of clean energy generation in Mexico is inevitable, this causes a need to classify solar simulators located in photovoltaic manufacturing facilities across the whole country. The construction of a standard for the classification of large area solar simulators in non- uniformity irradiance (MMNU) was achieved, considering specifications of the international standards IEC90604-9 and IEC90604-2. The procedure for using this MMNU substantially improves the classification time of a large area solar simulation and its versatility of use in an industrial environment, resulting in suitable on-site measurements. The MMNU is composed of six electronic reading circuits and 36 cells which are connected individually, it can generate an irradiance map up to 72 regions and the measurement uncertainty within the operating temperature conditions of 29 C to 31 C was 1.1 % using the mathematical expression for non-uniformity in the standard IEC90604-9. Various strategies have been outlined to reduce the measurement uncertainty of the entire system, like reducing its thermal drift during measurement and improving the measurement uncertainty in electrical voltage by creating a new electronic reading module that would include a more robust microcontroller and A/D converter with higher resolution.

Anticancer drugs play an important role in reducing mortality rates and increasing life expectancy in cancer patients. Treatments include monotherapy and/or a combination of radiation therapy, chemotherapy, hormone therapy, or immunotherapy. Despite great advances in drug development, some of these treatments have been shown to induce cardiotoxicity directly affecting heart function and structure, as well as accelerating the development of cardiovascular disease. Such side effects restrict treatment options and can negatively affect disease management. Consequently, when managing cancer patients, it is vital to understand the mechanisms causing cardiotoxicity to better monitor heart function, develop preventative measures against cardiotoxicity, and treat heart failure when it occurs in this patient population. This review discusses the role and mechanism of major chemotherapy agents with principal cardiovascular complications in cancer patients.

Chronic enteropathies are a common problem in dogs, but many aspects of the pathogenesis remain unknown, making the therapeutic approach challenging in some cases. Environmental factors are intimately related to the development and perpetuation of gastrointestinal disease and the gut microbiome has been identified as a contributing factor. Previous studies have identified dysbiosis and reduced bacterial diversity in the gastrointestinal microbiota of dogs with chronic enteropathies. In this case-controlled study, we use flow cytometry and 16S rRNA sequencing to characterise bacteria highly coated with IgA or IgG in faecal samples from dogs with chronic enteropathy and evaluated their correlation with disease and resolution of the clinical signs. IgA and IgG-coated faecal bacterial counts were significantly higher during active disease compared to healthy dogs and decreased with the resolution of the clinical signs. Characterisation of taxa-specific coating of the intestinal microbiota with IgA and IgG showed marked variation between dogs and disease states, and different patterns of immunoglobulin enrichment were observed in dogs with chronic enteropathy, particularly for Erysipelotrichaceae, Clostridicaceae, Enterobacteriaceae, Prevotellaceae and Bacteroidaceae, families. Although, members of these bacterial groups have been associated with strong immunogenic properties and could potentially constitute important biomarkers of disease, their significance and role need to be further investigated.

Diabetes mellitus (DM) causes high glucose (HG) levels in the plasma and urine. The (pro)renin receptor (PRR) is a key regulator of renal Na+ handling. PRR is expressed in intercalated (IC) cells of the collecting duct (CD) and binds renin to promote angiotensin (Ang) II formation, thereby contributing to Na+ reabsorption. In DM, the Kreb's cycle is in a state of suppression in most tissues. However, in the CD, expression of glucose transporters is augmented, boosting the Kreb's cycle and consequently causing α-ketoglutarate (αKG) accumulation. The αKG receptor 1 (OXGR1) is a Gq-coupled receptor expressed on the apical membrane of IC cells of the CD. We hypothesize that HG causes αKG secretion and activation of OXGR1, which increases PRR expression in CD cells. This effect then promotes intratubular AngII formation and Na+ reabsorption. To test this hypothesis, streptozotocin (STZ)-induced diabetic mice were treated with or without montelukast (ML), an OXGR1 antagonist, for 6 days. STZ mice had higher urinary αKG and PRR expression along with augmented urinary AngII levels and Na+ retention. Treatment with ML prevented all these effects. Similarly, primary cultured inner medullary CD cells treated with HG showed increased PRR expression, while OXGR1 antagonist prevented this effect. αKG increases PRR expression, while treatments with ML, PKC inhibition, or intracellular Ca2+ depletion impair this effect. In silico analysis suggested that αKG binds to mouse OXGR1. These results indicate that HG conditions promote increased levels of intratubular αKG and OXGR1-dependent PRR upregulation, which impact AngII formation and Na+ reabsorption.

Patient: Male, 63 Final Diagnosis: Hypertensive cardiovenic pulmonary edema Symptoms: Shortness of breath Medication: — Clinical Procedure: — Specialty: General and Internal Medicine Objective: Management of emergency care Background: Pulmonary edema is the accumulation of fluid in the lung secondary to increased hydrostatic pressure. Hypertensive cardiogenic pulmonary edema presents with a sudden onset of severe dyspnea, tachycardia, and tachypnea, and can occur when the systolic blood pressure exceeds 160 mmHg in association with acute decompensated congestive cardiac failure (CCF). A case is presented of hypertensive cardiogenic pulmonary edema treated with high-dose nitroglycerin and includes a review of the literature. Case Report: A 63-year-old Hispanic male with a medical history of hypertension, coronary artery disease, heart failure with a reduced ejection fraction of 35%, chronic kidney disease (CKD) and diabetes mellitus, presented as an emergency with acute, severe dyspnea. The patient was initially managed with 100% oxygen supplementation and intravenous (IV) high-dose nitroglycerin (30 mcg/min), which was titrated every 3 minutes, increasing by 15 mcg/min until a dose of 120 mcg/min was reached. After 18 minutes of aggressive therapy, the patient’s condition improved and he no longer required mechanical ventilation. Conclusions: Hypertensive cardiogenic pulmonary edema is a challenging clinical condition that should be diagnosed and managed as early as possible, and distinguished from respiratory failure due to other causes. Although hypertensive cardiogenic pulmonary edema is usually managed acutely with high-dose diuretics, this case has highlighted the benefit of high-dose IV nitroglycerin, and review of the literature supports this treatment approach.

La nutrición post alta del prematuro debe evitar el incremento excesivo o insuficiente de peso, con un crecimiento óptimo de circunferencia craneana y talla. En Chile los prematuros < 32 semanas reciben fórmulas enriquecidas durante el primer año si no se alimentan con lactancia materna exclusiva. Objetivo: describir el crecimiento e identificar precozmente el riesgo de malnutrición a los 24 meses. Pacientes y Método: Estudio de cohorte retrospectivo del crecimiento desde el nacimiento hasta los 2 años de edad corregida, de prematuros < 32 semanas de edad gestacional. Se analizó puntaje Z de peso, longitud, perímetro craneano e índice de masa corporal (IMC). Se analizaron los factores asociados al IMC a los 2 años; IMC entre -1 y +1: eutrofia; > +1: riesgo de malnutrición por exceso; < -1 malnutrición por déficit. Resultados: Se reclutaron 996 prematuros, 559 cumplieron control a los 24 meses. 64,5 % eutrófico, 18,4% riesgo de malnutrición por exceso, 17,1% malnutrición por déficit. En el análisis multivariado, el riesgo de malnutrición por exceso se asoció al peso de nacimiento > 1.460 g: OR 5,77 (2,11-15,77) y Z IMC > 1,6 a 6 meses: OR 2,67 (1,91-3,74); la malnutrición por déficit se asoció a peso de nacimiento < 1.000 g: OR 3,1(1,1-8,8) y Z IMC < -0,75 a 6 meses: OR 8,2 (4,3-16,3) Conclusiones: El mayor riesgo de malnutrición por exceso y por déficit puede ser anticipado con el peso de nacimiento y Z IMC a los 6 meses de edad corregida.

The growth of preterm newborns can be affected during the fetal period, hospitalization, and post discharge.to describe the anthropometric development of preterm newborns with or without intrauterine and postnatal growth restriction, and with or without recovery at 40 weeks from birth to 24 months of age.Retrospective, descriptive study with Z-scores (Fen ton and WHO) of weight, length, head circumference, and weight/length of preterm infants of less than 32 weeks of gestational age at birth up to 24 months of corrected age. 4 groups were defined ac cording to prenatal, postnatal, post-discharge growth as follows: Group AAA: newborns born AGA, with no postnatal growth restriction; Group APA: newborns born AGA, with postnatal growth res triction, weightp10 at discharge, and weightp10 at 40 weeks; Group APP: newborns born AGA, with postnatal growth restriction, weightp10 at discharge and at 40w; and Group PPP: newborns born with intrauterine growth restriction and who maintained postnatal growth restriction (p10 at birth, at discharge, and at 40w). We used descriptive statistics with ANOVA, Chi-squared, and linear mixed model analysis.710 preterm newborns were included, birth weight 1272 grams (SD 360) and gestational age 29 weeks (SD 1.9). Group AAA had weight, length, and head circumference Z-scores close to the median until 2 years of age. AGA preterm newborns and with postnatal growth restriction can evolve in two ways: one group presents recovery at 40 weeks (Group APA) while the other group presents weight Z-score-1 up to 6 months (Group APP). Group PPP (with intraute rine and postnatal growth restriction) presents slow weight and length Z-score recovery, weight Z- score -2.3 at discharge, and slow improvement to-1 at 2 years of age. All groups had weight/height Z-scores above the median in the first 2 months of corrected age.Preterm newborns with good fetal growth but restricted postnatal growth, may recover at 40 weeks, with subsequent normal development or recover at 6 months.

Diabetes mellitus (DM) causes high glucose (HG) levels in the plasma and urine. The (pro)renin receptor (PRR) is a key regulator of renal Na+ handling. PRR is expressed in intercalated (IC) cells of the collecting duct (CD) and binds renin to promote angiotensin (Ang) II formation, thereby contributing to Na+ reabsorption. In DM, the Kreb's cycle is in a state of suppression in most tissues. However, in the CD, expression of glucose transporters is augmented, boosting the Kreb's cycle and consequently causing α-ketoglutarate (αKG) accumulation. The αKG receptor 1 (OXGR1) is a Gq-coupled receptor expressed on the apical membrane of IC cells of the CD. We hypothesize that HG causes αKG secretion and activation of OXGR1, which increases PRR expression in CD cells. This effect then promotes intratubular AngII formation and Na+ reabsorption. To test this hypothesis, streptozotocin (STZ)-induced diabetic mice were treated with or without montelukast (ML), an OXGR1 antagonist, for 6 days. STZ mice had higher urinary αKG and PRR expression along with augmented urinary AngII levels and Na+ retention. Treatment with ML prevented all these effects. Similarly, primary cultured inner medullary CD cells treated with HG showed increased PRR expression, while OXGR1 antagonist prevented this effect. αKG increases PRR expression, while treatments with ML, PKC inhibition, or intracellular Ca2+ depletion impair this effect. In silico analysis suggested that αKG binds to mouse OXGR1. These results indicate that HG conditions promote increased levels of intratubular αKG and OXGR1-dependent PRR upregulation, which impact AngII formation and Na+ reabsorption.

The integrated mechanisms of heart contraction are some of the most complex processes for undergraduate biomedical students to understand. Visual models have the potential to enhance learning environments by providing visual representations of complex mechanisms. Despite their benefits, the use of visual models in undergraduate classrooms is still limited. For this study, we tested the effect of a learning sequence of activities related to the cardiac cycle using an augmented reality (AR) application for smartphones and tablets. We were interested in understanding the ability of students to draw and label figures reflecting cardiac function after experiencing the learning sequence using AR. Undergraduate students of the biomedical sciences (control n = 43, experimental n = 58) were enrolled in the course, and their drawings were evaluated using multiple levels of complexity (1 = basic to 5 = complex) through a pre-/posttest structure that included a learning sequence based on AR in the experimental group and regular lecture-based activities in the control group. The complexity of students’ drawings was evaluated on the anatomical, physiological, and molecular aspects of heart contraction. We used Cohen’s kappa index for interrater reliability when determining the complexity of drawings. Control and experimental groups showed no differences in baseline knowledge (preexamination quiz). The students who experienced the AR activities showed an increase in the complexity of representation levels in posttest results and also showed a significant difference in scores for the final exam in the heart physiology course. Our results indicate that using AR enhances the comprehension of anatomical and physiological concepts of the cardiac cycle for undergraduate biomedical students.

Vasopressin, also named antidiuretic hormone (ADH), arginine vasopressin (AVP) is the main hormone responsible for water maintenance in the body through the antidiuretic actions in the kidney. The posterior pituitary into the blood releases vasopressin formed in the hypothalamus. Hypothalamic osmotic neurons are responsible to initiate the cascade for AVP actions. The effects of AVP peptide includes activation of V2 receptors which stimulate the formation of cyclic AMP (cAMP) and phosphorylation of water channels aquaporin 2 (AQP2) in the collecting duct. AVP also has vasoconstrictor effects through V1a receptors in the vasculature, while V1b is found in the nervous system. V1a and b receptors increases intracellular Ca

Vasopressin, also named antidiuretic hormone (ADH), arginine vasopressin (AVP) is the main hormone responsible for water maintenance in the body through the antidiuretic actions in the kidney. The posterior pituitary into the blood releases vasopressin formed in the hypothalamus. Hypothalamic osmotic neurons are responsible to initiate the cascade for AVP actions. The effects of AVP peptide includes activation of V2 receptors which stimulate the formation of cyclic AMP (cAMP) and phosphorylation of water channels aquaporin 2 (AQP2) in the collecting duct. AVP also has vasoconstrictor effects through V1a receptors in the vasculature, while V1b is found in the nervous system. V1a and b receptors increases intracellular Ca2+ while activation of V2 receptors of signaling pathways are related to cAMP-dependent phosphorylation in kidney collecting ducts acting in coordination to stimulate water and electrolyte homeostasis. AVP potentiate formation of intratubular angiotensin II (Ang II) through V2 receptors-dependent distal tubular renin formation, contributing to Na+ reabsorption. On the same way, Ang II receptors are able to potentiate the effects of V2-dependent stimulation of AQP2 abundance in the plasma membrane. The role of AVP in hypertension and renal disease has been demonstrated in pathological states with the involvement of V2 receptors in the progression of kidney damage in diabetes and also on the stimulation of intracellular pathways linked to the development of polycystic kidney.

El crecimiento de recién nacidos prematuros puede afectarse durante período fetal, la hospitalización y post alta. Objetivo: describir el crecimiento de prematuros, con o sin restricción de crecimiento intrauterino y postnatal, y con o sin recuperación a las 40 semanas desde el nacimiento hasta los 24 meses de vida. Pacientes y Método:Estudio descriptivo retrospectivo de crecimiento en puntaje Z (según Fenton y OMS) de peso, longitud, perímetro craneano y peso/talla de prematuros < 32 semanas al nacer, hasta los 2 años de edad corregida. Se definieron cuatro grupos según crecimiento prenatal, postnatal y postalta. Grupo AAA: lactantes nacidos AEG, sin restricción postnatal; Grupo APA: lactantes nacidos AEG con restricción postnatal, con peso al alta < p10, y a las 40 semanas con peso > p10; Grupo APP: lactantes nacidos AEG, con restricción postnatal, con peso al alta < p10, que se mantienen bajo percentil 10 a las 40 semanas, y Grupo PPP: lactantes nacidos con restricción intrauterina y que mantuvieron restricción postnatal (al nacer, al alta y 40 semanas con peso < p10). Se utilizó estadística descriptiva, ANOVA y Chi cuadrado, y análisis de Modelos Lineales Mixtos. Resultados: Se incluyeron 721 prematuros, peso de 1272 g. (DE 360) y edad gestacional 29 (DE 1,9) semanas al nacer. El grupo AAA mantiene puntaje Z de peso, longitud y perímetro craneano alrededor de la mediana, hasta los 2 años. Los prematuros adecuados al nacer y restricción postnatal, pueden tener dos trayectorias: un grupo presenta recuperación a las 40 semanas (Grupo APA) y otro grupo presenta puntaje Z peso < -1 hasta los 6 meses (Grupo APP). El grupo PPP (con restricción intrauterina y postnatal) presenta lenta recuperación de puntaje Z de peso y longitud con Z de peso alta de -2,3 y lenta mejoría hasta < -1 a los 2 años. Todos los grupos presentaron Z peso/talla sobre la mediana en los primeros 2 meses corregidos. Conclusión: Los prematuros con buen crecimiento intrauterino en peso, pero deterioro postnatal, pueden recuperarse a las 40 semanas, con evolución normal posterior o recuperarse a los 6 meses. El grupo de prematuros con restricción de crecimiento pre y post natal (PPP) mantiene el compromiso nutricional en los 2 primeros años de vida.

Six new whole aromatic poly(azomethine)s with different rigidity were prepared from three diamines and two dialdehydes, all of them containing a diphenylsilane moiety as a central structural element. Two amines containing biphenyl moieties were obtained for the first time. Thus, the synthesized polymers contain two silicon atoms in the repeat unit, where methyl and/or phenyl groups bonded to them, complete the tetra-valence of the heteroatom. The new materials were structurally characterized by means of FT-IR, solid NMR and elemental analysis. Solubility was tested in several organic solvents at room temperature and 40 °C and the inherent viscosity was determined. GPC analysis showed oligomeric chains of five repetitive units for the tested samples. Additionally, thermal behavior was studied by TGA and DSC analysis, by evidencing materials highly stable and rigid. Band gaps values ranging between 2.71 and 3.14 eV were obtained from UV/Vis and DRS analysis. The spin-coating technique was used to prepare films from soluble samples in NMP and their thicknesses were determined by the ellipsometric method. From these samples, and using AFM and four-point techniques, the effect of the annealing time on the roughness and conductivity of the films was studied. In accordance with the appropriate thermal and conductivity properties of the new silylated materials (which has a whole aromatic structure), could be proposed as an alternative for applications in the optoelectronics field.

Increasing evidence shows that antigen-presenting cells (APCs) are involved in the development of inflammation associated to hypertension. However, the potential role of APCs in the modulation of renal sodium transport has not been addressed. We hypothesized that APCs participate in renal sodium transport and, thus, development of high blood pressure in response to angiotensin II plus a high-salt diet. Using transgenic mice that allow the ablation of CD11c high APCs, we studied renal sodium transport, the intrarenal renin–angiotensin system components, blood pressure, and cardiac/renal tissue damage in response to angiotensin II plus a high-salt diet. Strikingly, we found that APCs are required for the development of hypertension and that the ablation/restitution of APCs produces rapid changes in the blood pressure in mice with angiotensin II plus a high-salt diet. Moreover, APCs were necessary for the induction of intrarenal renin–angiotensin system components and affected the modulation of natriuresis and tubular sodium transporters. Consistent with the prevention of hypertension, the ablation of APCs also prevented cardiac hypertrophy and the induction of several indicators of renal and cardiac damage. Thus, our findings indicate a prominent role of APCs as modulators of blood pressure by mechanisms including renal sodium handling, with kinetics that suggest the involvement of tubular cell functions in addition to the modulation of inflammation and adaptive immune response.

The aim of this study was to investigate the methane (CH(4)) reducing potential of a combination of prenatal and/or postnatal treatment with coconut oil medium chain fatty acids (CO MCFA) in goat kids. The hypothesis is that influencing rumen function during early life has more chances for success than in the adult life, related to the resilience of the mature rumen microbiota. Forty-eight pregnant does were split into two experimental groups: treated does (D+) received 40 g/d of CO MCFA in a test compound feed, while control does (D−) received a control compound feed, during the last 3 wk of gestation. Twin kids from 10 does of each group were split up into a treated (K+) and nontreated (K−) group, resulting in four experimental groups: D+K+, D+K−, D−K+, and D−K−. The K+ kids received 1.8 mL/d of CO MCFA from birth until 2-wk postweaning (11 wk). Irrespective of treatment, the experimental rearing conditions resulted in absence of rumen protozoa at all sampling times, assessed by quantitative PCR (qPCR). In vitro incubations with rumen fluid at 4 wk old showed 82% lower CH(4) production of inoculum from D+K+ kids compared to D−K− kids (P = 0.01). However, this was accompanied by lower total volatile fatty acids (tVFA) production (P = 0.006) and higher hydrogen accumulation (P = 0.008). QPCR targeting the mcrA and rrs genes confirmed a lower abundance of total methanogens (P < 0.02) and total eubacteria (P = 0.02) in D+K+ kids at 4 wk old. Methanogenic activity, as assessed by mcrA expression by RT-qPCR, was also lower in these kids. However, activity did not always reflect methanogen abundance. At 11 and 28 wk old, prenatal and postnatal effects on in vitro fermentation and rumen microbiota disappeared. Nevertheless, lower milk replacer intake in the first 4 wk resulted in reduced BW in K+ kids, persisting until 28 wk of age. Additionally, differences assigned to postnatal treatment were found in papillae density, width, and length in different areas of the rumen, recorded at 28 wk old. Conclusion: prenatal and postnatal supplementation with CO MCFA reduced in vitro CH(4) emissions until 4 wk old by depressing methanogen abundance and activity but at the expense of rumen fermentation and eubacterial abundance. Unfortunately, daily gain of K+ kids was suppressed. Some rumen papillae characteristics differed at 28 wk old due to postnatal treatment which ended at 11 wk old, indicating rumen papillary development can be affected by the early-life nutritional circumstances.

Since the prorenin receptor (PRR) was first reported, its physiological role in many cellular processes has been under intense scrutiny. The PRR is currently recognized as a multifunctional receptor with major roles as an accessory protein of the vacuolar-type H+-ATPase and as an intermediary in the Wnt signaling pathway. As a member of the renin-angiotensin system (RAS), the PRR has demonstrated to be of relevance in cardiovascular diseases (CVD) because it can activate prorenin and enhance the enzymatic activity of renin, thus promoting angiotensin II formation. Indeed, there is an association between PRR gene polymorphisms and CVD. Independent of angiotensin II, the activation of the PRR further stimulates intracellular signals linked to fibrosis. Studies using tissues and cells from a variety of organs and systems have supported its roles in multiple functions, although some remain controversial. In the brain, the PRR appears to be involved in the central regulation of blood pressure via activation of RAS- and non-RAS-dependent mechanisms. In the heart, the PRR promotes atrial structural and electrical remodeling. Nonetheless, animals overexpressing the PRR do not exhibit cardiac injury. In the kidney, the PRR is involved in the development of ureteric bud branching, urine concentration, and regulation of blood pressure. There is great interest in the PRR contributions to T cell homeostasis and to the development of visceral and brown fat. In this mini-review, we discuss the evidence for the pathophysiological roles of the PRR with emphasis in CVD.

In this study, four new silicon-containing poly(ether-azomethine)s with linear structures were prepared using original silicon and biphenyl moiety-containing monomers: two diamines and two dialdehydes. The oligomeric natures of the samples were established by GPC analysis, which showed chains containing 3 to 5 repetitive units. The monomers and the oligomeric samples were structurally characterized by NMR and FT-IR spectroscopy. The solubilities of the samples in common organic solvents and their thermal behavior enable improvement of their industrial and technological processability. The optical band gaps of the oligomeric samples were estimated from optical measurements (UV-vis), and their electrical behavior in films was determined using the four-point method. The surface arrangements and morphological characteristics of the films were determined via atomic force microscopy measurements. The roughness, area increase percentage and layer stiffness of the films were also measured using this technique.

During the early phase of ANG II-dependent hypertension, tubular PGE2is increased. Renin synthesis and secretion in the collecting duct (CD) are upregulated by ANG II, contributing to further intratubular ANG II formation. However, what happens first and whether the triggering mechanism is independent of tubular ANG II remain unknown. PGE2stimulates renin synthesis in juxtaglomerular cells via E-prostanoid (EP) receptors through the cAMP/cAMP-responsive element-binding (CREB) pathway. EP receptors are also expressed in the CD. Here, we tested the hypothesis that renin is upregulated by PGE2in CD cells. The M-1 CD cell line expressed EP1, EP3, and EP4 but not EP2. Dose-response experiments, in the presence of ANG II type 1 receptor blockade with candesartan, demonstrated that 10−6M PGE2maximally increases renin mRNA (approximately 4-fold) and prorenin/renin protein levels (approximately 2-fold). This response was prevented by micromolar doses of SC-19220 (EP1 antagonist), attenuated by the EP4 antagonist, L-161982, and exacerbated by the highly selective EP3 antagonist, L-798106 (~10-fold increase). To evaluate further the signaling pathway involved, we used the PKC inhibitor calphostin C and transfections with PKCα dominant negative. Both strategies blunted the PGE2-induced increases in cAMP levels, CREB phosphorylation, and augmentation of renin. Knockdown of the EP1 receptor and CREB also prevented renin upregulation. These results indicate that PGE2increases CD renin expression through the EP1 receptor via the PKC/cAMP/CREB pathway. Therefore, we conclude that during the early stages of ANG II-dependent hypertension, there is augmentation of PGE2that stimulates renin in the CD, resulting in increased tubular ANG II formation and further stimulation of renin.

The aim of this study was to evaluate the dose response on in vitro methane (CH) production of PUFA to which the inoculum donor animals had been exposed early in life. Sixteen Holstein calves (160 ± 3 and 365 ± 2 kg BW) at 6 and 12 mo of age were used as inoculum donors. Half of the calves were given increasing amounts of extruded linseed from birth (22 g/d) until 4 mo of age (578 g/d) first mixed with milk and then included in their concentrate. Linseed oil (LSO) was supplemented in vitro at 5 different doses (0, 0.6, 1.2, 2.4, and 4.8 mg/mL). Supplementation of LSO in the rumen inocula at both ages linearly decreased ( < 0.05) the in vitro CH production. Total in vitro VFA production was not affected by LSO supplementation. Inhibition of CH was smaller when using the rumen inoculum from calves that had received a similar treatment early in life ( < 0.05). Differences in response to in vitro supplementation of a type of fatty acids similar to those applied during early life suggest some "changes" in the functioning of the rumen microbial community.