Hypodescent or ingroup overexclusion?: Children's and adults' racial categorization of ambiguous black/white biracial faces.

Two processes describe racially ambiguous Black/White Biracial categorization-the one-drop rule, or hypodescent, whereby racially ambiguous people are categorized as members of their socially subordinated racial group (i.e., Black/White Biracial faces categorized as Black) and the ingroup overexclusion effect, whereby racially ambiguous people are categorized as members of a salient outgroup, regardless of the group's status. Without developmental research with racially diverse samples, it is unclear when these categorization patterns emerge. Study 1 included White, Black, and racially diverse Biracial children (aged 3- to 7-years) and their parents to test how racial group membership and social context influence face categorization biases. To provide the clearest test of hypodescent and ingroup overexclusion, White participants came from majority White neighborhoods and Black participants from majority Black neighborhoods (with Biracial participants from more racially diverse neighborhoods)-two samples with prominent racial ingroups. Study 2 aimed to replicate the parent findings with a separate sample of White, Black, Black/White Biracial, and Asian adults. Results suggest the ingroup overexclusion effect is present across populations early in development and persists into adulthood. Additionally, categorization was meaningfully related to parental context, pinpointing a pathway that potentially contributes to ingroup overexclusion. RESEARCH HIGHLIGHTS: White, Black, and racially diverse Biracial children and adults tended to categorize racially ambiguous Black/White Biracial faces as racial outgroup members, even if the outgroup was White. This contradicts most work arguing Black/White Biracial racially ambiguous people are more often seen as Black. Children and parents' categorizations were related, though children's categorizations were not related to socialization above and beyond parents' categorizations. Children showed similar categorization patterns across dichotomous and continuous measures.

Textural Characterization by Using an Alternative Langmuir Isotherm and a New Thickness Function.

Samples with micropores can not be adequately described by using the Langmuir isotherm. The Langmuir expression is obtained by using the monolayer assumption, which is not valid in samples with micropores. Then, we propose to include in the isotherm a corrective parameter related to the sample porosity. We show that the modified isotherm enables us to describe the experimental values for different samples (aluminas, clays, silicas, zeolites, and zirconias) in low and full relative pressure ranges. Indeed, a new thickness function for the adsorbate layer in terms of the relative pressure is proposed. Then, a better description of the external surface areas, mesopores, and micropores of the samples can be obtained with the new thickness function. The VBS model with this new thickness shows a better pore distribution description.

Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases.

An epidemiological relationship between urolithiasis and cardiovascular diseases has extensively been reported. Endothelial dysfunction is an early pathogenic event in cardiovascular diseases and has been associated with oxidative stress and low chronic inflammation in hypertension, coronary heart disease, stroke or the vascular complications of diabetes and obesity. The aim of this study is to summarize the current knowledge about the pathogenic mechanisms of urolithiasis in relation to the development of endothelial dysfunction and cardiovascular morbidities. METHODS: A non-systematic review has been performed mixing the terms "urolithiasis", "kidney stone" or "nephrolithiasis" with "cardiovascular disease", "myocardial infarction", "stroke", or "endothelial dysfunction". RESULTS: Patients with nephrolithiasis develop a higher incidence of cardiovascular disease with a relative risk estimated between 1.20 and 1.24 and also develop a higher vascular disease risk scores. Analyses of subgroups have rendered inconclusive results regarding gender or age. Endothelial dysfunction has also been strongly associated with urolithiasis in clinical studies, although no systemic serum markers of endothelial dysfunction, inflammation or oxidative stress could be clearly related. Analysis of urine composition of lithiasic patients also detected a higher expression of proteins related to cardiovascular disease. Experimental models of hyperoxaluria have also found elevation of serum endothelial dysfunction markers. CONCLUSIONS: Endothelial dysfunction has been strongly associated with urolithiasis and based on the experimental evidence, should be considered as an intermediate and changeable feature between urolithiasis and cardiovascular diseases. Oxidative stress, a key pathogenic factor in the development of endothelial dysfunction has been also pointed out as an important factor of lithogenesis. Special attention must be paid to cardiovascular morbidities associated with urolithiasis in order to take advantage of pleiotropic effects of statins, angiotensin receptor blockers and allopurinol.

Impact of Personal Protective Equipment on Surgical Performance During the COVID-19 Pandemic.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has exposed surgeons to hazardous working conditions, imposing the need for personal protective equipment (PPE) use during surgery. The use of such equipment may affect their non-technical skills, augment fatigue, and affect performance. This study aimed to assess the surgeons' perceptions of the impact of wearing PPE during emergency surgery throughout the pandemic. METHODS: An international cooperation group conducted an anonymous online survey among surgeons from over 30 countries, to assess perceptions about the impact of PPE use on non-technical skills, overall comfort, decision making, and surgical performance during emergency surgery on COVID-19 patients. RESULTS: Responses to the survey (134) were received from surgeons based on 26 countries. The vast majority (72%) were males. More than half of the respondents (54%) felt that their surgical performance was hampered with PPE. Visual impairment was reported by 63%, whereas 54% had communication impediments. Less than half (48%) felt protected with the use of PPE, and the same proportion perceived that the use of such equipment influenced their decision making. Decreased overall comfort was cited by 66%, and 82% experienced increased surgical fatigue. CONCLUSIONS: Surgeons perceived impediment for both visibility and communication, and other non-technical skills while using PPE on emergency surgery in COVID-19 patients. Their perceived lack of protection and comfort and increased fatigue may have inhibited their optimal surgical performance. More attention should be placed in the design of more user-friendly equipment, given the possibility of a second wave of the pandemic.

Endothelin A (ET(A)) receptors are involved in augmented adrenergic vasoconstriction and blunted nitric oxide-mediated relaxation of penile arteries from insulin-resistant obese zucker rats.

INTRODUCTION: Endothelin 1 (ET-1) levels and receptors are up-regulated in the erectile tissue of diabetic patients and animal models of erectile dysfunction (ED). AIM: The present study assessed the role of ET-1 receptors in the impaired adrenergic vasoconstriction and nitrergic relaxation of penile arteries from a rat model of insulin resistance. METHODS: The effect of ET receptor antagonists was evaluated on the contractile responses to electrical field stimulation (EFS) of penile arteries from obese Zucker rats (OZRs) compared with lean Zucker rats (LZRs). ET receptor expression was determined by immunohistochemistry. MAIN OUTCOME MEASURES: Changes in neural nitrergic relaxation and adrenergic vasoconstriction and the expression of ET receptors in perivascular nerves were assessed. RESULTS: ET-1 (10(-10) M) enhanced EFS-induced vasoconstriction, and treatment with the adrenergic neurotoxin guanethidine reduced the contractions induced by ET-1 in penile arteries from both LZRs and OZRs, thus supporting the hypothesis that ET-1 releases noradrenaline from adrenergic nerves. ET-1 antagonized neural nitric oxide (NO)-mediated relaxant responses in LZR arteries, antagonizing relaxations induced by the NO donor S-nitroso-N-acetylpenicillamine to a larger extent in arteries from OZRs. ET(A) and ET(B) receptors were expressed in perivascular fibers colocalized with the neuronal marker protein gene product 9.5 in penile arteries from OZRs. The ET(A) receptor antagonist BQ-123 reversed the enhancing effect of ET-1 on the vasoconstriction elicited by EFS and the ET-1-induced inhibition of nitrergic relaxations in LZRs, restoring them to control levels in penile arteries of OZRs. CONCLUSIONS: ET-1 enhances adrenergic vasoconstriction through presynaptic ET(A) receptors and antagonizes neural NO-mediated relaxation through postsynaptic smooth muscle ET(A) receptors in penile arteries from OZRs, which likely contributes to the augmented vasoconstriction and blunted nitrergic relaxation of erectile tissue under conditions of insulin resistance.

Is the reflux disease questionnaire useful for identifying GERD according to the Montreal definition?

BACKGROUND: Scales for aiding physicians diagnose gastro-oesophageal reflux disease (GERD) have not been evaluated in terms of their ability to discriminate between troublesome symptoms (TS) and non-troublesome symptoms (NTS). Our objective is to evaluate the ability of the Reflux Disease Questionnaire (RDQ) to identify GERD according to referral of TS, in patients without previous proton pump inhibitor (PPI) treatment and in patients on PPI treatment. METHODS: Patients consulting physicians because of heartburn or acid regurgitation were recruited at 926 primary-care centres in Spain. They were asked to complete several questionnaires including the RDQ, and to define which of their symptoms were troublesome. Information on drug treatment was collected by the physician. We performed a receiver operating characteristic (ROC) curve analysis to ascertain the RDQ's optimum cut-point for identifying TS. RESULTS: 4574 patients were included, 1887 without PPI and 2596 on PPI treatment. Among those without PPI treatment, 1722 reported TS. The area under the curve (AUC) was 0.79 for the RDQ, and the optimum RDQ cut-point for identifying TS was 3.18 (sensitivity, 63.2%; specificity, 80.2%). A total of 2367 patients on PPI treatment reported TS, and the optimum RDQ cut-off value was 3.06 (sensitivity, 65.4%; specificity, 71.8%). CONCLUSIONS: An RDQ score higher than 3 shows good sensitivity and specificity for differentiating TS from NTS among patients without PPI or on PPI treatment. The RDQ is useful in primary care for diagnosis of GERD based on the Montreal definition.

Activation of mitoKATP channels induces penile vasodilation and inhibits mitochondrial respiration and ROS production: Role of NO.

OBJECTIVE: Mitochondrial ATP-sensitive K+ (mitoKATP) channels are involved in neuronal and cardiac protection from ischemia and oxidative stress. Penile erection is a neurovascular event mediated by relaxation of the erectile tissue via nitric oxide (NO) released from nerves and endothelium. In the present study, we investigated whether mitoKATP channels play a role in the control of penile vascular tone and mitochondrial dynamics, and the involvement of NO. METHODS: The effect of the selective mitoKATP activator BMS191095 was examined on vascular tone, on mitochondrial bioenergetics by real-time measurements with Agilent Seahorse and on ROS production by MitoSOX fluorescence in freshly isolated microarteries. RESULTS: BMS191095 and diazoxide relaxed penile arteries, BMS191095 being one order of magnitude more potent. BMS191095-induced relaxations were reduced by mechanical endothelium removal and by inhibitors of the nitric oxide synthase (NOS) and PI3K enzymes. The NO-dependent component of the relaxation to BMS191095 was impaired in penile arteries from insulin resistant obese rats. The blockers of mitoKATP channel 5-HD, sarcolemma KATP (sarcKATP) channel glibenclamide, and large conductance Ca2+-activated K+ (BKCa) channel iberiotoxin, inhibited relaxations to BMS191095 and to the NO donor SNAP. BMS191095 reduced the mitochondrial bioenergetic profile of penile arteries and attenuated mitochondrial ROS production. Blockade of endogenous NO impaired and exogenous NO mimicked, respectively, the inhibitory effects of BMS191095 on basal respiration and oxygen consumed for ATP synthesis. Exogenous NO exhibited dual inhibitory/stimulatory effects on mitochondrial respiration. CONCLUSIONS: These results demonstrate that selective activation of mitoKATP channels causes penile vasodilation, attenuates ROS production and inhibits mitochondrial respiration in part by releasing endothelial NO. These mechanisms couple blood flow and metabolism in penile arterial wall and suggest that activation of vascular mitoKATP channels may protect erectile tissue against ischemic injury.

Updated Review and Clinical Recommendations for the Diagnosis and Treatment of Patients with Retroperitoneal Sarcoma by the Spanish Sarcoma Research Group (GEIS).

Soft tissue sarcomas (STS) are an uncommon and biologically heterogeneous group of tumors arising from mesenchymal cells. The incidence is estimated at five cases per 100,000 people per year. Retroperitoneal sarcomas (RPS) account for 10-15% of all STS, and their management depends on their anatomical characteristics and histotype. Due to their very low incidence, it is recommended that RPS be treated in reference centers and evaluated by an experienced multidisciplinary team (MDT). In Spain, the Spanish Group for Research in Sarcomas (GEIS) brings together experts from various specialties to promote research on sarcomas and improve treatment results. This paper summarizes the GEIS recommendations for the diagnosis, treatment, and follow-up of patients with RPS.

Hyperoxaluria Induces Endothelial Dysfunction in Preglomerular Arteries: Involvement of Oxidative Stress.

Urolithiasis is a worldwide problem and a risk factor for kidney injury. Oxidative stress-associated renal endothelial dysfunction secondary to urolithiasis could be a key pathogenic factor, similar to obesity and diabetes-related nephropathy. The aim of the present study was to characterize urolithiasis-related endothelial dysfunction in a hyperoxaluria rat model of renal lithiasis. EXPERIMENTAL APPROACH: Endothelial dysfunction was assessed in preglomerular arteries isolated from control rats and in which 0.75% ethylene glycol was administered in drinking water. Renal interlobar arteries were mounted in microvascular myographs for functional studies; superoxide generation was measured by chemiluminescence and mRNA and protein expression by RT-PCR and immunofluorescence, respectively. Selective inhibitors were used to study the influence of the different ROS sources, xanthine oxidase, COX-2, Nox1, Nox2 and Nox4. Inflammatory vascular response was also studied by measuring the RNAm expression of NF-κB, MCP-1 and TNFα by RT-PCR. RESULTS: Endothelium-dependent vasodilator responses were impaired in the preglomerular arteries of the hyperoxaluric group along with higher superoxide generation in the renal cortex and vascular inflammation developed by MCP-1 and promoted by NF-κB. The xanthine oxidase inhibitor allopurinol restored the endothelial relaxations and returned superoxide generation to basal values. Nox1 and Nox2 mRNA were up-regulated in arteries from the hyperoxaluric group, and Nox1 and Nox2 selective inhibitors also restored the impaired vasodilator responses and normalized NADPH oxidase-dependent higher superoxide values of renal cortex from the hyperoxaluric group. CONCLUSIONS: The current data support that hyperoxaluria induces oxidative stress-mediated endothelial dysfunction and inflammatory response in renal preglomerular arteries which is promoted by the xanthine oxidase, Nox1 and Nox2 pathways.

Promoting Inclusive Outdoor Recreation in National Park Governance: A Comparative Perspective from Canada and Spain.

While national parks (NPs) have for a long time made substantial contributions to visitor well-being, many spaces remain out of reach of people with disabilities (PwDs). This is partly due to a lack of policies that take accessibility for broader intersectional audiences into consideration. This paper evaluates governance and legal frameworks in NPs in both Canada and Spain. A decision-making framework based on intersectionality realities is proposed to assess current conditions of environmental good governance using a set of descriptors created to scrutinize laws and technical documents that can promote equitable access to NPs. To validate results derived from the regulatory evaluation, semistructured interviews with park managers were carried out. Results revealed the importance of incorporating equity discourses into policies that regulate NP networks to guarantee that all the intersectional realities for park uses are considered in their management. Furthermore, when a country develops a well-structured federal framework under which the rights of PwDs are ensured, it transcends other fields of law. Differences between the Canadian and the Spanish situation are highlighted, as well as the need for links between higher-level policies and laws and on-the-ground implementation, with NP management plans playing an important role.

Differential contribution of renal cytochrome P450 enzymes to kidney endothelial dysfunction and vascular oxidative stress in obesity.

Arachidonic acid (AA)-derived cytochrome P450 (CYP) derivatives, epoxyeicosatrienoic acids (EETs) and 20-hidroxyeicosatetranoic acid (20-HETE), play a key role in kidney tubular and vascular functions and blood pressure. Altered metabolism of CYP epoxygenases and CYP hydroxylases has differentially been involved in the pathogenesis of metabolic disease-associated vascular complications, although the mechanisms responsible for the vascular injury are unclear. The present study aimed to assess whether obesity-induced changes in CYP enzymes may contribute to oxidative stress and endothelial dysfunction in kidney preglomerular arteries. Endothelial function and reactive oxygen species (ROS) production were assessed in interlobar arteries of obese Zucker rats (OZR) and their lean counterparts lean Zucker rats (LZR) and the effects of CYP2C and CYP4A inhibitors sulfaphenazole and HET0016, respectively, were examined on the endothelium-dependent relaxations and O2- and H2O2 levels of preglomerular arteries. Non-nitric oxide (NO) non-prostanoid endothelium-derived hyperpolarization (EDH)-type responses were preserved but resistant to the CYP epoxygenase blocker sulfaphenazole in OZR in contrast to those in LZR. Sulfaphenazole did not further inhibit reduced arterial H2O2 levels, and CYP2C11/CYP2C23 enzymes were downregulated in intrarenal arteries from OZR. Renal EDH-mediated relaxations were preserved in obese rats by the enhanced activity and expression of endothelial calcium-activated potassium channels (KCa). CYP4A blockade restored impaired NO-mediated dilatation and inhibited augmented O2- production in kidney arteries from OZR. The current data demonstrate that both decreased endothelial CYP2C11/ CYP2C23-derived vasodilator H2O2 and augmented CYP4A-derived 20-HETE contribute to endothelial dysfunction and vascular oxidative stress in obesity. CYP4A inhibitors ameliorate arterial oxidative stress and restore endothelial function which suggests its therapeutic potential for the vascular complications of obesity-associated kidney injury.

A comparison of budesonide/formoterol maintenance and reliever therapy versus conventional best practice in asthma management in Spain.

OBJECTIVE: To study the effectiveness and safety in a real-life setting of budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy® (Symbicort SMART®), a simplified management approach with one inhaler, compared with conventional best practice (CBP) with multiple inhalers in patients with persistent asthma. DESIGN: Open-label randomized controlled parallel-group trial, 6-month treatment. PARTICIPANTS: A total of 654 adult patients, with persistent asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in conjunction with long-acting ß(2)-agonist. MAIN OUTCOME MEASURES: Time to first severe asthma exacerbation and number of severe asthma exacerbations. RESULTS: No difference between groups was seen in time to first severe exacerbation (p = .2974). Exacerbation rates were low in both groups. A total of 22 patients in the Symbicort SMART group experienced a total of 24 severe asthma exacerbations, and 31 patients in the CBP group experienced a total of 34 severe asthma exacerbations (annual rate 0.16 vs. 0.22, p = .2869). The mean daily dose of ICS expressed in beclomethasone dipropionate equivalent was significantly lower in the Symbicort SMART group (including as-needed use) versus the CBP group (799 µg vs.1184 µg; p < .001). Mean scores in Asthma Control Questionnaire, five-question version, improved significantly in the SMART group compared with the CBP group (p = .0292). Symbicort SMART and CBP were equally well tolerated. The mean drug cost per patient per 6 months was lower for the patients in the SMART group compared with patients receiving CBP (€295.32 vs. €387.98, p < .0001). CONCLUSIONS: A simplified regimen using budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and lower drug costs.

AMPK, metabolism, and vascular function.

Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor activated during energy stress that plays a key role in maintaining energy homeostasis. This ubiquitous signaling pathway has been implicated in multiple functions including mitochondrial biogenesis, redox regulation, cell growth and proliferation, cell autophagy and inflammation. The protective role of AMPK in cardiovascular function and the involvement of dysfunctional AMPK in the pathogenesis of cardiovascular disease have been highlighted in recent years. In this review, we summarize and discuss the role of AMPK in the regulation of blood flow in response to metabolic demand and the basis of the AMPK physiological anticontractile, antioxidant, anti-inflammatory, and antiatherogenic actions in the vascular system. Investigations by others and us have demonstrated the key role of vascular AMPK in the regulation of endothelial function, redox homeostasis, and inflammation, in addition to its protective role in the hypoxia and ischemia/reperfusion injury. The pathophysiological implications of AMPK involvement in vascular function with regard to the vascular complications of metabolic disease and the therapeutic potential of AMPK activators are also discussed.

Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity.

BACKGROUND AND PURPOSE: Obesity is a risk factor for the development of chronic kidney disease independent of diabetes, hypertension and other co-morbidities. Obesity-associated nephropathy is linked to dysregulation of the cell energy sensor AMP-activated protein kinase (AMPK). We aimed here to assess whether impairment of AMPK activity may cause renal arterial dysfunction in obesity and to evaluate the therapeutic potential of activating renal AMPK. EXPERIMENTAL APPROACH: Effects of the AMPK activator A769662 were assessed on intrarenal arteries isolated from ob/ob mice and obese Zucker rats and then mounted in microvascular myographs. Superoxide and hydrogen peroxide production were measured by chemiluminescence and fluorescence, respectively, and protein expression was analysed by western blotting. KEY RESULTS: Endothelium-dependent vasodilation and PI3K/Akt/eNOS pathway were impaired in preglomerular arteries from genetically obese rats and mice, along with impaired arterial AMPK activity and blunted relaxations induced by the AMPK activator A769662. Acute ex vivo exposure to A769662 restored endothelial function and enhanced activity of PI3K/Akt/eNOS pathway in obese rats, whereas in vivo treatment with A769662 improved metabolic state and ameliorated endothelial dysfunction, reduced inflammatory markers and vascular oxidative stress in renal arteries and restored redox balance in renal cortex of obese mice. CONCLUSION AND IMPLICATIONS: These results demonstrate that AMPK dysregulation underlies obesity-associated kidney vascular dysfunction and activation of AMPK improves metabolic state, protects renal endothelial function and exerts potent vascular antioxidant and anti-inflammatory effects. The beneficial effects of vascular AMPK activation might represent a promising therapeutic approach to the treatment of obesity-related kidney injury.

Endothelial KCa 1.1 and KCa 3.1 channels mediate rat intrarenal artery endothelium-derived hyperpolarization response.

AIM: Endothelium-derived hyperpolarization (EDH)-mediated response plays an essential role in the control of kidney preglomerular circulation, but the identity of the K+ channels involved in this response is still controversial. We hypothesized that large- (KCa 1.1), intermediate- (KCa 3.1) and small (KCa 2.3) -conductance Ca2+ -activated K+ (KCa ) channels are expressed in the endothelium of the preglomerular circulation and participate in the EDH-mediated response. METHODS: We study the functional expression of different K+ channels in non-cultured, freshly isolated native endothelial cells (ECs) of rat intrarenal arteries using immunofluorescence and the patch-clamp technique. We correlate this with vasorelaxant responses ex vivo using wire myography. RESULTS: Immunofluorescence revealed the expression of KCa 1.1, KCa 3.1 and KCa 2.3 channels in ECs. Under voltage-clamp conditions, acetylcholine induced a marked increase in the outward currents in these cells, sensitive to the blockade of KCa 1.1, KCa 3.1 and KCa 2.3 channels respectively. Isometric myography experiments, under conditions of endothelial nitric oxide synthase and cyclooxygenase inhibition, showed that blockade either of KCa 1.1 or KCa 3.1 channels was able to reduce the endothelium-derived vasorelaxation of isolated interlobar arteries, while their combined blockade completely abolished it. In contrast, blockade of KCa 2.3 channels did not reduce this vasorelaxant response, despite being functionally expressed in the endothelial cells. CONCLUSION: This study shows that KCa 1.1 and KCa 3.1 channels are functionally expressed at the renal vascular endothelium and play a central role in the EDH-mediated relaxation of kidney preglomerular arteries, which is important in the control of renal blood flow and glomerular filtration rate.

Fabrication of Green Diatomite/Chitosan-Based Hybrid Foams with Dye Sorption Capacity.

The latest tendency of the scientific community regards the development of different classes of green materials able to solve pollution problems caused by industrial and human activity. In this paper, chitosan and diatomite were used to produce a broad-spectrum hybrid adsorbent, either in powder or in monolithic form for environmental pollutant removal. Diatomite-chitosan-based powders and porous diatomite-chitosan hybrids were prepared and characterized by chemical-physical, thermal and morphological analysis. Moreover, their adsorbent capacity towards anionic dye (Indigo Carmine) was also evaluated. Obtained data showed that chitosan improves the adsorption capacity of both systems, increasing the uptake of dye in both diatomite-chitosan systems.

Differential contribution of Nox1, Nox2 and Nox4 to kidney vascular oxidative stress and endothelial dysfunction in obesity.

Oxidative stress-associated endothelial dysfunction is a key pathogenic factor underlying the microvascular complications of metabolic disease. NADPH oxidase (Nox) is a major source of oxidative stress in diabetic nephropathy and chronic kidney disease, despite Nox4 and Nox2 have been identified as relevant sources of vasodilator endothelial H2O2.The present study was sought to investigate the role of Nox enzymes in renal vascular oxidative stress and endothelial dysfunction in a rat model of genetic obesity. Endothelial function was assessed in intrarenal arteries of obese Zucker rats (OZR) and their counterparts lean Zucker rats (LZR) mounted in microvascular myographs, and superoxide (O2.-) and H2O2 production were measured. Impaired endothelium-dependent relaxations to acetylcholine (ACh) were associated to augmented O2.- generation, but neither ROS scavengers nor the Nox inhibitor apocynin significantly improved these relaxant responses in renal arteries of OZR. Whereas NO contribution to endothelial relaxations was blunted, catalase-sensitive non-NO non-prostanoid relaxations were enhanced in obese rats. Interestingly, NADPH-dependent O2.- production was augmented while NADPH-dependent H2O2 generation was reduced, and cytosolic and mitochondrial SOD were up-regulated in kidney of obese rats. Nox4 was down-regulated in renal arteries and Nox4-dependent H2O2 generation and endothelial relaxation were reduced in OZR. Up-regulation of both Nox2 and Nox1 was associated with augmented O2.- production but reduced H2O2 generation and blunted endothelial Nox2-derived H2O2-mediated in obese rats. Moreover, increased Nox1-derived O2.- contributed to renal endothelial dysfunction in OZR. In summary, the current data support a main role for Nox1-derived O2.- in kidney vascular oxidative stress and renal endothelial dysfunction in obesity, while reduced endothelial Nox4 expression associated to decreased H2O2 generation and H2O2-mediated vasodilatation might hinder Nox4 protective renal effects thus contributing to kidney injury. This suggests that effective therapies to counteract oxidative stress and prevent microvascular complications must identify the specific Nox subunits involved in metabolic disease.

Activation of the AMP-related kinase (AMPK) induces renal vasodilatation and downregulates Nox-derived reactive oxygen species (ROS) generation.

AMP-activated protein kinase (AMPK) is a cellular energy sensor activated during energy stress to stimulate ATP production pathways and restore homeostasis. AMPK is widely expressed in the kidney and involved in mitochondrial protection and biogenesis upon acute renal ischemia, AMPK activity being blunted in metabolic disease-associated kidney disease. Since little is known about AMPK in the regulation of renal blood flow, the present study aimed to assess the role of AMPK in renal vascular function. Functional responses to the selective AMPK activator A769662 were assessed in intrarenal small arteries isolated from the kidney of renal tumour patients and Wistar rats and mounted in microvascular myographs to perform simultaneous measurements of intracellular calcium [Ca2+]i and tension. Superoxide (O2.-) and hydrogen peroxide (H2O2) production were measured by chemiluminescence and fluorescence and protein expression by Western blot. Activation of AMPK with A769662 increased AMPKα phosphorylation at Thr-172 and induced potent relaxations compared to AICAR in isolated human and rat intrarenal arteries, through both endothelium-dependent mechanisms involving nitric oxide (NO) and intermediate-conductance calcium-activated potassium (IKCa) channels, as well as activation of ATP-sensitive (KATP) channels and sarcoplasmic reticulum Ca2+-ATPase (SERCA) in vascular smooth muscle (VSM). Furthermore, AMPK activator reduced NADPH oxidase 4 (Nox4) and Nox2-derived reactive oxygen species (ROS) production. These results demonstrate that A769662 has potent vasodilator and antioxidant effects in intrarenal arteries. The benefits of AMPK activation in rat kidney are reproduced in human arteries and therefore vascular AMPK activation might be a therapeutic target in the treatment of metabolic disease-associated kidney injury.

Methodology Proposal for the Management of Nursing Competencies towards a Strategic Training. A Theoretical Analysis.

Professional and academic legislation relating to nursing skills reflects conceptual and professional developments. In this sense, conceptual and methodological analyses are required to describe the concept of nursing competencies, the individual or group self-perception of competencies, to identify training needs, and to specify the nursing professional profile within the health organization. A sequential mixed methodology was proposed combining qualitative and quantitative approaches. The qualitative methodology involves the Focus Group and the Delphi technique. The quantitative methodology involves surveying and analyzing self-perception (descriptive and analytical in relation to personal and professional variables and levels of excellence). The methodology was piloted among primary care nurses. Competencies were analyzed and distributed across the training program. The combination of qualitative and quantitative methods showed that obtaining a deep insight into the nurses' competencies would be a good process. This proposal is applicable as an approach to global nursing competencies or to a particular specialty.