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Kidney tubules have high metabolic activity to support solute transport and other cellular functions. Energy generation in the kidney is largely dependent on mitochondrial oxidative phosphorylation, particularly in the proximal tubules. Important alterations in the pathways of energy generation and cellular metabolism have been identified in early and late stages of kidney disease. This review provides a succinct summary of the current literature on the central role of energy metabolism in the pathophysiology of acute and chronic kidney disease.

Acute kidney injury (AKI) is a systemic inflammatory disease that contributes to remote organ failures. Multiple organ failure is the leading cause of death due to AKI, and lack of understanding of the mechanisms involved has precluded the development of novel therapies. Mitochondrial injury in AKI leads to mitochondrial fragmentation and release of damage-associated molecular patterns, which are known to active innate immune pathways and systemic inflammation. This review presents current evidence suggesting that extracellular mitochondrial damage-associated molecular patterns are mediators of remote organ failures during AKI that have the potential to be modifiable.

Acute respiratory distress syndrome (ARDS) is a common cause of mortality in patients with acute kidney injury (AKI). Inflammatory crosstalk from the kidney to the lung has been shown to contribute to lung injury after AKI, but anti-inflammatory therapies have not been proven beneficial in human studies. Recently, AKI was shown to alter mitochondria and related metabolic pathways in the heart, but the impact of AKI on lung metabolism has not been investigated to our knowledge. In this study, we evaluated the metabolomic profile of the lung following renal ischemia and reperfusion to identify novel pathways that may be modifiable. We randomized C57BL/6 mice to 20 minutes of bilateral renal arterial clamping or sham operation under ketamine/xylazine anesthesia. At 4 hours after reperfusion, we found a significant increase in markers of lung injury, as well as significant metabolomic changes across lung, kidney, plasma and bronchoalveolar lavage fluid (BALF) compared to shams. Comparative analyses revealed that the fatty acid oxidation pathway was the most significantly altered metabolic pathway, a finding which is consistent with mitochondrial dysfunction systemically and in the lung. These metabolomic changes correlated with the extracellular accumulation of the mitochondrial damage associated molecular patterns (mtDAMPs), mitochondrial DNA (mtDNA) and transcription factor A, mitochondria (TFAM). Finally, we found that intraperitoneal injection of renal mtDAMPs caused metabolomic changes consistent with mitochondrial dysfunction in the lung in vivo. Mitochondrial function and mtDAMPs warrant further investigation as potential therapeutic targets in preventing lung injury because of AKI.

Sepsis-associated acute kidney injury (s-AKI) has a staggering impact in patients and lacks any treatment. Incomplete understanding of the pathogenesis of s-AKI is a major barrier to the development of effective therapies. We address the gaps in knowledge regarding renal oxygenation, tubular metabolism, and mitochondrial function in the pathogenesis of s-AKI using the cecal ligation and puncture (CLP) model in mice. At 24 h after CLP, renal oxygen delivery was reduced; however, fractional oxygen extraction was unchanged, suggesting inefficient renal oxygen utilization despite decreased glomerular filtration rate and filtered load. To investigate the underlying mechanisms, we examined temporal changes in mitochondrial function and metabolism at 4 and 24 h after CLP. At 4 h after CLP, markers of mitochondrial content and biogenesis were increased in CLP kidneys, but mitochondrial oxygen consumption rates were suppressed in proximal tubules. Interestingly, at 24 h, proximal tubular mitochondria displayed high respiratory capacity, but with decreased mitochondrial content, biogenesis, fusion, and ATP levels in CLP kidneys, suggesting decreased ATP synthesis efficiency. We further investigated metabolic reprogramming after CLP and observed reduced expression of fatty acid oxidation enzymes but increased expression of glycolytic enzymes at 24 h. However, assessment of functional glycolysis revealed lower glycolytic capacity, glycolytic reserve, and compensatory glycolysis in CLP proximal tubules, which may explain their susceptibility to injury. In conclusion, we demonstrated significant alterations in renal oxygenation, tubular mitochondrial function, and metabolic reprogramming in s-AKI, which may play an important role in the progression of injury and recovery from AKI in sepsis.

Cutaneous involvement of dental sepsis is a rare occurrence in children. It often presents as a diagnostic dilemma, especially in the absence of oral symptoms, with initial presentation to non-dental professionals. This article discusses three cases of children presenting with cutaneous involvement of odontogenic origin to two paediatric dentistry departments in the UK. All cases had delayed presentations and were initially submitted to ineffective treatment, with significant impact on the children’s well-being. Final management included antibiotic therapy, drainage and extraction of the septic tooth. These three cases highlight the importance of considering a dental aetiology for localized inflammatory and purulent skin lesions of the mandible. Prompt diagnosis and early treatment are determinant for early resolution and avoidance of systemic or psychological complications. CPD/Clinical Relevance: This article discusses diagnosis and management of three different presentations of odontogenic sepsis with cutaneous involvement in children.

AimsTo review feedback from three Neurodevelopmental Psychiatry educational events attended by medical students and junior doctors, to establish their impact and whether they can influence interest in Psychiatry/Neurodevelopmental Psychiatry as a career.MethodsThree events were organised to a) increase understanding of Neurodevelopmental Psychiatry and b) promote career interest in the specialty, aiding recruitment efforts. Two were Face to Face Events (FFEs) whereas one was an Online Event (OE) in keeping with COVID-19 restrictions.The programme for the events was varied including key clinical topics such as Intellectual Disability, autism, ADHD and epilepsy as well as leadership, management, research and training information. Presentations were approximately 20 min in duration. 31 delegates attended the 2018 FFE, 28 attended the 2019 FFE and 65 attended the 2020 OE.The 2018 FFE and 2020 OE were primarily attended by medical students whereas the 2019 FFE was attended primarily by junior doctors.Delegates rated each presentation from 1 (poor) to 5(excellent) and provided comments. At the 2018 and 2019 FFEs we assessed impact on career interest.Results•The majority of delegates from both FFEs agreed that such events helped to facilitate understanding of neurodevelopmental psychiatry and encourage recruitment to psychiatry.•The majority of delegates at the 2019 FFE agreed that their interest in a career in neurodevelopmental psychiatry had increased following attendance•Attendance was highest at the 2020 OE and overall rating was 4.63/5.•Across the events, popular topics were Autism, Career path and Physical Health needs in Intellectual disability.•Themes in terms of comments included “friendly, inspiring speakers” and “opportunity for interactivity” (noted at OE).ConclusionBoth the OE and FFEs were enjoyed by medical students and junior doctors.Analysis showed key topics such as autism attract interest but also that diverse topics in different formats are important. Human factors that seemed important included inspiring, friendly speakers and a relaxed, interactive atmosphere. OEs are cost-effective and have the potential to attract a bigger audience but may present a challenge in terms of interaction. FFEs impact positively on career interest and this needs to be assessed further in terms of online events.

Acute kidney injury (AKI) significantly contributes to morbidity and mortality in critically ill patients. AKI is also an independent risk factor for the development and progression of chronic kidney disease. Effective therapeutic strategies for AKI are limited, but emerging evidence indicates a prominent role of mitochondrial dysfunction and altered tubular metabolism in the pathogenesis of AKI. Therefore, a comprehensive, mechanistic understanding of mitochondrial function and renal metabolism in AKI may lead to the development of novel therapies in AKI. In this review, we provide an overview of current state of research on the role of mitochondria and tubular metabolism in AKI from both pre-clinical and clinical studies. We also highlight current therapeutic strategies which target mitochondrial function and metabolic pathways for the treatment of AKI.

The role of the renal organic anion transporters OAT1 (also known as SLC22A6, originally identified as NKT) and OAT3 (also known as SLC22A8) in chronic kidney disease (CKD) remains poorly understood. This is particularly so from the viewpoint of residual proximal tubular secretion, a key adaptive mechanism to deal with protein-bound uremic toxins in CKD. Using the subtotal nephrectomy (STN) model, plasma metabolites accumulating in STN rats treated with and without the OAT inhibitor, probenecid, were identified. Comparisons with metabolomics data from Oat1-KO and Oat3-KO mice support the centrality of the OATs in residual tubular secretion of uremic solutes, such as indoxyl sulfate, kynurenate, and anthranilate. Overlapping our data with those of published metabolomics data regarding gut microbiome-derived uremic solutes - which can have dual roles in signaling and toxicity - indicates that OATs play a critical role in determining their plasma levels in CKD. Thus, the OATs, along with other SLC and ABC drug transporters, are critical to the movement of uremic solutes across tissues and into various body fluids, consistent with the remote sensing and signaling theory. The data support a role for OATs in modulating remote interorganismal and interorgan communication (gut microbiota-blood-liver-kidney-urine). The results also have implications for understanding drug-metabolite interactions involving uremic toxins.

OBJECTIVE: Elevated circulating chromogranin A (CHGA) is observed in human hypertension. CHGA is critical for granulogenesis and exocytosis of catecholamine stores from secretory large dense core vesicles (LDCV). This study aims to understand the morphological, molecular and phenotypic changes because of excess CHGA and the mechanistic link eventuating in hyper-adrenergic hypertension. METHODS: Blood pressure and heart rate was monitored in mouse models expressing normal and elevated level of CHGA by telemetry. Catecholamine and oxidative stress radicals were measured. Adrenal ultrastructure, LDCV content and mitochondrial abundance were compared and respiration analyzed by Seahorse assay. Effect of CHGA dosage on adrenal ATP content, electron transport chain components and uncoupling protein 2 (UCP-2) were compared in vivo and in vitro. RESULTS: Mice with excess-CHGA displayed hypertensive phenotype, higher heart rate and increased sympathetic tone. They had elevated plasma catecholamine and adrenal ROS levels. Excess-CHGA caused an increase in size and abundance of LDCV and adrenal mitochondria. Nonetheless, they had attenuated levels of ATP. Isolated adrenal mitochondria from mice with elevated CHGA showed higher maximal respiration rates in the presence of protonophore, which uncouples oxidative phosphorylation. Elevated CHGA resulted in overexpression of UCP2 and diminished ATP. In vitro in chromaffin cells overexpressing CHGA, concomitant increase in UCP2 protein and decreased ATP was detected. CONCLUSION: Elevated CHGA expression resulted in underlying bioenergetic dysfunction in ATP production despite higher mitochondrial mass. The outcome was unregulated negative feedback of LDCV exocytosis and secretion, resulting in elevated levels of circulating catecholamine and consequently the hypertensive phenotype.

Background: The sexual minority status of the gay and bisexual community puts them into a unique vulnerability state for mental health problems. One of the factors associated with this stress is remaining in “closet” leading to a higher prevalence of depression. Aims: This study aimed to estimate the prevalence of depression in Indian men who have sex with men (MSM) and to assess the association of depression with disclosure, if any, in this community. Materials and Methods: This was a cross-sectional observational study of Indian men recruited through an advertisement on a dating website exclusive for gay men. Depression was assessed on self-reported scale of the Centre for Epidemiologic Studies Depression Scale-Revised (CESD-R). Results: Most of the men who took part in the study belonged to the age group of 25–35 years with mean age of the study sample being 30.31 years (standard deviation [SD] ±8.58). A majority of them were salaried, had higher education, and belonged to the Hindu religion. Most of the participants were either exclusively or predominantly homosexual (72%) followed by men with bisexual orientation (18%). On measures of disclosure/“outness,” out of 277 respondents, 171 (61.73%) were not open about their sexuality, 92 (33.21%) were sometimes open, while only 14 (5.05%) were always open about their sexual orientation in front of others. The average age of coming out of closet (n = 232) was 19.71 years (SD ± 6.67). The mean score on CESD-R scale was 25.65 (SD ± 16.38). Depression was present in 163 participants (58.84%) of the entire sample. The depression scores negatively correlated with age, with scores being higher in younger age group. Depression was not associated with the type of sexual orientation. Although the depression scores were higher in those who were in the closet, it was not statistically significant. Those who had negative experience of coming out of closet had significantly higher scores on CESD-R compared to those who had positive reaction on coming out. Conclusion: Depression is highly prevalent in Indian MSM.

The incretin hormone, glucagon-like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (glomerular filtration rate, GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv). Animals were pretreated with cyclooxygenase (COX) inhibitor (meclofenamate), NO synthase (NOS) inhibitor ( NG-monomethyl-l-arginine, l-NMMA), NO clamp (l-NMMA + sodium nitroprusside), or placebo. Effectiveness of COX inhibition was tested by measuring urinary prostaglandin E2 (UPGE2). Effectiveness of NOS blockade and NO clamp was determined by urinary NO degradation products (UNOx). Exenatide increased GFR, UV, UPGE2, and UNOx. Pretreatment with meclofenamate reduced UPGE2 by 75% and reduced the effect of exenatide on UPGE2 by 30% but did not modify the effects of exenatide on GFR or UV. Pretreatment with l-NMMA reduced UNOx and the impact of exenatide on GFR and UV by 50%. Pretreatment by NO clamp did not prevent UNOx from increasing during exenatide but blunted the effects of exenatide on GFR and UV. In conclusion, exenatide is a potent renal vasodilator and diuretic in the rat. These effects of exenatide are insensitive to COX inhibition but are mediated, in part, by NO.

Acute kidney injury (AKI) continues to be a major therapeutic challenge. Despite significant advances made in cellular and molecular pathophysiology of AKI, major gaps in knowledge exist regarding the changes in renal hemodynamics and oxygenation in the early stages and through the continuum of AKI. Particular features of renal hemodynamics and oxygenation increase the susceptibility of the kidney to sustain injury due to oxygen demand-supply mismatch and also play an important role in the recovery and repair from AKI as well as the transition of AKI to chronic kidney disease. However, lack of well-established physiological biomarkers and noninvasive imaging techniques limit our understanding of the interactions between renal macro and microcirculation and tissue oxygenation in AKI. Advances in our ability to assess these parameters in preclinical and clinical AKI will enable the development of targeted therapeutics to improve clinical outcomes.

Sepsis-associated acute kidney injury (AKI) is frequently observed and has poor prognosis with no effective treatments. The lack of complete understanding of its pathogenesis is a significant barri...

Introduction Diabetes is a major cause of chronic kidney disease. Recent data reports that sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin (EMPA), slows down the progression of diab...

Renal hypoxia contributes to chronic kidney disease (CKD) progression, as validated in experimental and human CKD. In the early stages, increased oxygen consumption causes oxygen demand/supply mismatch, leading to hypoxia. Hence, early targeting of the determinants and regulators of oxygen consumption in CKD may alter the disease course before permanent damage ensues. Here, we focus on hypoxia inducible factor-1α (HIF-1α) and AMP-activated protein kinase (AMPK) and on the mechanisms by which they may facilitate cellular hypoxia adaptation. We found that HIF-1α activation in the subtotal nephrectomy (STN) model of CKD limits protein synthesis, inhibits apoptosis, and activates autophagy, presumably for improved cell survival. AMPK activation was diminished in the STN kidney and was remarkably restored by HIF-1α activation, demonstrating a novel role for HIF-1α in the regulation of AMPK activity. We also investigated the independent and combined effects of HIF-1α and AMPK on cell survival and death pathways by utilizing pharmacological and knockdown approaches in cell culture models. We found that the effect of HIF-1α activation on autophagy is independent of AMPK, but on apoptosis it is partially AMPK dependent. The effects of HIF-1α and AMPK activation on inhibiting protein synthesis via the mTOR pathway appear to be additive. These various effects were also observed under hypoxic conditions. In conclusion, HIF-1α and AMPK appear to be linked at a molecular level and may act as components of a concerted cellular response to hypoxic stress in the pathophysiology of CKD.

Electronic (e)-cigarettes theoretically may be safer than conventional tobacco. However, our prior studies demonstrated direct adverse effects of e-cigarette vapor (EV) on airway cells, including decreased viability and function. We hypothesize that repetitive, chronic inhalation of EV will diminish airway barrier function, leading to inflammatory protein release into circulation, creating a systemic inflammatory state, ultimately leading to distant organ injury and dysfunction. C57BL/6 and CD-1 mice underwent nose only EV exposure daily for 3–6 mo, followed by cardiorenal physiological testing. Primary human bronchial epithelial cells were grown at an air-liquid interface and exposed to EV for 15 min daily for 3–5 days before functional testing. Daily inhalation of EV increased circulating proinflammatory and profibrotic proteins in both C57BL/6 and CD-1 mice: the greatest increases observed were in angiopoietin-1 (31-fold) and EGF (25-fold). Proinflammatory responses were recapitulated by daily EV exposures in vitro of human airway epithelium, with EV epithelium secreting higher IL-8 in response to infection (227 vs. 37 pg/ml, respectively; P < 0.05). Chronic EV inhalation in vivo reduced renal filtration by 20% ( P = 0.017). Fibrosis, assessed by Masson’s trichrome and Picrosirius red staining, was increased in EV kidneys (1.86-fold, C57BL/6; 3.2-fold, CD-1; P < 0.05), heart (2.75-fold, C57BL/6 mice; P < 0.05), and liver (1.77-fold in CD-1; P < 0.0001). Gene expression changes demonstrated profibrotic pathway activation. EV inhalation altered cardiovascular function, with decreased heart rate ( P < 0.01), and elevated blood pressure ( P = 0.016). These data demonstrate that chronic inhalation of EV may lead to increased inflammation, organ damage, and cardiorenal and hepatic disease.

BACKGROUND: Mechanical ventilation is associated with significant increases in the risk of acute kidney injury (AKI). The rate of AKI due to mechanical ventilation and the associated mortality remain unacceptably high. Preventative and therapeutic strategies are clearly lacking. SUMMARY: Ventilator induced kidney injury (VIKI) is believed to occur due to changes in hemodynamics that impair renal perfusion, neurohumoral mediated alterations in intra-renal blood flow, and systemic inflammatory mediators generated by ventilator induced lung injury (VILI). The risk of injury to the kidney by these mechanisms may be modified by open lung protective ventilation with low tidal volumes and high positive end expiratory pressure (PEEP). However, these strategies may also increase risk of injury in some settings, and clinicians have limited means to identify the optimal ventilator strategy for each specific patient. Novel urinary biomarkers have demonstrated the ability to predict AKI prior to classic clinical signs such as decreased urine output and increased creatinine. These biomarkers may serve as an early indication to intensivists of an injurious ventilator strategy and failure of traditional management. KEY MESSAGES: VIKI remains a common and serious problem in critically ill patients. Open lung protective ventilation is the only proven strategy to improve renal outcomes in mechanically ventilated patients, and novel strategies are urgently needed. Interventional trials focused on using early biomarkers of renal injury to guide ventilator management may offer important insights and improve outcomes.

Cloud computing is a model on which association and people can work with application from anywhere on demand. The real issue of cloud computing is preserving integrity and confidentiality of data in data security. The essential solution for this issue is data encryption on cloud. Security in cloud computing being one of the great research subjects. Numerous strategies have been proposed on attribute-based encryption systems. Attribute Based Encryption (ABE) is a cryptographic crude that understands the thought of cryptographic access control. This research work proposed attribute-based encryption method based on hash function associated with asymmetric encryption. The performance of the proposed algorithm has been evaluated by simulation using Cloudsim toolkit. For simulation we have analyzed the results on the basis of different File Size and simulated the results of proposed algorithm. Encryption Time, Key Generation Time and decryption time are evaluated and compared with the existing algorithm. Performance of proposed hash-based ABE algorithm is compared with the existing ABE algorithm. Experimental results demonstrate that proposed technique takes less time for encryption, decryption and for computing key than the existing technique and hence, performs better than existing algorithm. The average improvement is 13.54% in the proposed ABE with hashing as compared to existing ABE on the basis of encryption time; average approximate increase in the efficiency of key computation time is 3.72% as compared with the existing; 11.08% of improvement in decryption time.

This paper proposes a new WSN-based Landslide Prediction Algorithm, developed using Fuzzy Logic Inference System. Three factors conditioning landslides are considered, namely: slope angle, soil moisture and topographical elevation. These conditioning factors are sensed using WSN and analysed using proposed algorithm at sink node. A Mamdani-type Fuzzy Inference System (FIS) is used to develop the algorithm. Triangular membership functions are considered for all FIS parameters. A total of 45 rules have been developed in this FIS, which holds capability to generate a three-level alarm to warn residents of area about any impeding danger due to landslide. For results, surface plots are generated which show us the variation of landslide susceptibility with the change in three parameters considered.

In this paper, a computationally efficient range-free localization algorithm in 2D plane has been proposed for wireless sensor networks using fuzzy logic system (FLS) and invasive weed optimization (IWO). The received signal strength (RSS) value is used to find out the distance between nodes in the network. To reduce the nonlinearity between RSS values and distances between nodes, and to model the edge weight of the anchor nodes based on the RSS value, FLS is used. Further IWO is used to optimize the edge weights of anchors to achieve the high localization accuracy. Radio propagation is considered as circular for all nodes in the proposed method. It is observed from the simulation results, proposed algorithm performs better in localization accuracy than some existing range free localization algorithms, i.e. centroid method, weighted centroid and range-free localization based on biogeography-based optimization.

The pathophysiology of chronic kidney disease (CKD) is driven by alterations in surviving nephrons to sustain renal function with ongoing nephron loss. Oxygen supply-demand mismatch, due to hemodynamic adaptations, with resultant hypoxia, plays an important role in the pathophysiology in early CKD. We sought to investigate the underlying mechanisms of this mismatch. We utilized the subtotal nephrectomy (STN) model of CKD to investigate the alterations in renal oxygenation linked to sodium (Na) transport and mitochondrial function in the surviving nephrons. Oxygen delivery was significantly reduced in STN kidneys because of lower renal blood flow. Fractional oxygen extraction was significantly higher in STN. Tubular Na reabsorption was significantly lower per mole of oxygen consumed in STN. We hypothesized that decreased mitochondrial bioenergetic capacity may account for this and uncovered significant mitochondrial dysfunction in the early STN kidney: higher oxidative metabolism without an attendant increase in ATP levels, elevated superoxide levels, and alterations in mitochondrial morphology. We further investigated the effect of activation of hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular hypoxia response. We observed significant improvement in renal blood flow, glomerular filtration rate, and tubular Na reabsorption per mole of oxygen consumed with HIF-1α activation. Importantly, HIF-1α activation significantly lowered mitochondrial oxygen consumption and superoxide production and increased mitochondrial volume density. In conclusion, we report significant impairment of renal oxygenation and mitochondrial function at the early stages of CKD and demonstrate the beneficial role of HIF-1α activation on renal function and metabolism.

There are unique features of renal oxygenation that render the kidney susceptible to oxygen demand-supply mismatch and hypoxia. Renal oxygen consumption by oxidative metabolism is closely coupled to and driven by tubular transport, which is linked to the filtered solute load and glomerular filtration rate (GFR). In turn, filtered solute load and GFR are dependent on the renal blood flow. Hence, changes in renal blood flow increase oxygen delivery but also increase oxygen demand (consumption) simultaneously by increasing the tubular workload of solute transport. The renal blood flow to different regions of kidney is also inhomogeneous, increasing the oxygen demand-supply mismatch in particular areas such as the outer medulla which become more susceptible to injury. Thus, tubular transport and oxidative metabolism by miochondria are closely coupled in the kidney and are the principal determinants of intrarenal oxygenation. Here we review the published literature characterizing renal oxygenation and mitochondrial function in ischemic and sepsis-associated acute kidney injury (AKI). However, the coupling of transport and metabolism in AKI has not been examined. This is a potentially fruitful area of research that should become increasingly active given the emerging data linking renal oxygenation and hypoxia to acute and chronic dysfunction in the kidney.

Diabetes mellitus with its attendant complications is a significant cause of morbidity and mortality with diabetic nephropathy being the leading cause of end stage renal disease in the Western world. Characteristic structural and functional changes in the kidney early in the course of diabetes have been shown to have enduring effects on the progression of disease. A better understanding of the mechanisms underlying these changes is imperative to the development of new therapeutic strategies. Renal hypertrophy and hyperfiltration along with proximal tubular hyperreabsorption are among the distinctive features of early diabetic nephropathy. Additionally, there are particular alterations in the sensitivity of the glomerular and tubular function to dietary salt intake in early diabetes. Herein, we focus on these early physiologic changes and discuss some of the primary and secondary mechanisms discovered in recent years which lead to these alterations in kidney function.

In critical illness, such as sepsis or the acute respiratory distress syndrome, acute kidney injury (AKI) is common and associated with increased morbidity and mortality. Mechanical ventilation in critical illnesses is also a risk factor for AKI, but it is potentially modifiable. Injurious ventilation strategies may lead to the systemic release of inflammatory mediators from the lung due to ventilator induced lung injury (VILI). The systemic consequences of VILI are difficult to differentiate clinically from other systemic inflammatory syndromes, such as sepsis. The purpose of this study was to identify unique changes in the expression of inflammatory mediators in kidney tissue in response to VILI compared with systemic sepsis to gain insight into direct effects of VILI on the kidney. Four groups of mice were compared—mice with sepsis from cecal ligation and puncture (CLP), mice subjected to injurious mechanical ventilation with high tidal volumes (VILI), mice exposed to CLP followed by VILI (CLP+VILI), and sham controls. Protein expression of common inflammatory mediators in kidneys was analyzed using a proteome array and confirmed by Western blot analysis or ELISA. VEGF and VCAM-1 were found to be significantly elevated in kidneys from VILI mice compared with sham and CLP. Angiopoietin-2 was significantly increased in CLP+VILI compared with CLP alone and was also correlated with higher levels of AKI biomarker, neutrophil gelatinase-associated lipocalin. These results suggest that VILI alters the renal expression of VEGF, VCAM-1, and angiopoietin-2, and these proteins warrant further investigation as potential biomarkers and therapeutic targets.

In this paper, use of drone as a relay node in Network Coded Cooperation (NCC) for upcoming wireless networks is proposed to achieve additional diversity as well as improve throughput. Unlike static relay cases, in drone assisted scenarios, better performance can be achieved simply by changing the position of relay. In order to quantify the network performance in drone assisted NCC, analytical closed form expression of outage probability has been calculated using two approaches namely, Analytical and Semi-analytical. Using a generalized system model, Probability Density Function (PDF) of Signal to Noise Ratio (SNR) of the path from source to destination via drone (relay) is derived. Closed form expression for outage probability in absence of direct link is also investigated. By analyzing Analog Network Coding (ANC) noise, statistical parameters of variance of ANC-noise have been obtained. Analytical findings have been verified through extensive simulations using MATLAB. Effects of drone height on system performance is also investigated through simulations. Framework presented here can be useful while analysing networks having resource constraint devices. PDF of SNR of relay path can be utilized for performing diversity calculations. Two outage expressions derived may be useful in determining system parameters for achieving any particular Quality of Service (QoS) in next generation wireless networks. Valuable insights obtained through the analysis of optimum height of drone are conducive while deploying the nodes in deterministic fashion for NCC.

Background: The lesbian, gay, bisexual, and transgender (LGBT) community faces unique stressors in the form of nondisclosure of their sexual orientation, relationship dissatisfaction, social isolation, and low self-esteem. Data regarding this community in India is scarce due to fear of discrimination and abuse. Aims: To describe the pattern of sexual orientation, relationships, social connectedness, and disclosure in men and to assess their self-esteem and its association with “coming out”. Method: This was a cross-sectional observational study of Indian men who use a gay dating website. Results: Majority of the 277 respondents were salaried, had higher education, unmarried, and belonged to Hindu religion. Seventy two per cent of the subjects expressed their orientation as either exclusively or predominantly homosexual and 18% as bisexual. Among those in relationship, an equal number reported being satisfied with the relationship (40%) and felt socially connected (53%). Seventy to 80% of them had a feeling of missing companionship and being left out. Sixty one per cent were not open about their orientation at all times. Eighty per cent of the subjects were not open at workplace and with family. The average age of coming out of the closet was 19.71 years (SD±6.67). The mean scores on the Rosenberg Self-Esteem Scale of the entire sample was 28.49 (SD±5.55). There was no association between age of coming out and self-esteem scores. Self-esteem scores were significantly lower in subjects who were in the closet and those who had negative coming out experiences. Conclusion: There is a need to address the sexual minority stress faced by this community due to social isolation and concealment which affects the self-esteem.

The 5/6thnephrectomy or ablation/infarction (A/I) preparation has been used as a classic model of chronic kidney disease (CKD). We observed increased kidney oxygen consumption (QO2) and altered renal hemodynamics in the A/I kidney that were normalized after combined angiotensin II (ANG II) blockade. Studies suggest hypoxia inducible factor as a protective influence in A/I. We induced hypoxia-inducible factor (HIF) and HIF target proteins by two different methods, cobalt chloride (CoCl2) and dimethyloxalyglycine (DMOG), for the first week after creation of A/I and compared the metabolic and renal hemodynamic outcomes to combined ANG II blockade. We also examined the HIF target proteins expressed by using Western blots and real-time PCR. Treatment with DMOG, CoCl2, and ANG II blockade normalized kidney oxygen consumption factored by Na reabsorption and increased both renal blood flow and glomerular filtration rate. At 1 wk, CoCl2and DMOG increased kidney expression of HIF by Western blot. In the untreated A/I kidney, VEGF, heme oxygenase-1, and GLUT1 were all modestly increased. Both ANG II blockade and CoCl2therapy increased VEGF and GLUT1 but the cobalt markedly so. ANG II blockade decreased heme oxygenase-1 expression while CoCl2increased it. By real-time PCR, erythropoietin and GLUT1 were only increased by CoCl2therapy. Cell proliferation was modestly increased by ANG II blockade but markedly after cobalt therapy. Metabolic and hemodynamic abnormalities were corrected equally by ANG II blockade and HIF therapies. However, the molecular patterns differed significantly between ANG II blockade and cobalt therapy. HIF induction may prove to be protective in this model of CKD.

Infusion of l-arginine produces an increase in glomerular filtration via kidney vasodilation, correlating with increased kidney excretion of nitric oxide (NO) metabolites, but the specific underlying mechanisms are unknown. We utilized clearance and micropuncture techniques to examine the whole kidney glomerular filtration rate (GFR) and single nephron GFR (SNGFR) responses to 1) l-arginine (ARG), 2) ARG+octreotide (OCT) to block insulin release, 3) ARG+OCT+insulin (INS) infusion to duplicate ARG-induced insulin levels, and 4) losartan (LOS), an angiotensin AT-1 receptor blocker, +ARG+OCT. ARG infusion increased GFR, while increasing insulin levels. OCT coinfusion prevented this increase in GFR, but with insulin infusion to duplicate ARG induced rise in insulin, the GFR response was restored. Identical insulin levels in the absence of ARG had no effect on GFR. In contrast to ARG infusion alone, coinfusion of OCT with ARG reduced proximal tubular fractional and absolute reabsorption potentially activating tubuloglomerular feedback. Losartan infusion, in addition to ARG and OCT (LOS+ARG+OCT), restored the increase in both SNGFR and proximal tubular reabsorption, without increasing insulin levels. In conclusion, 1) hyperfiltration responses to ARG require the concurrent, modest, permissive increase in insulin; 2) inhibition of insulin release after ARG reduces proximal reabsorption and prevents the hyperfiltration response; and 3) inhibition of ANG II activity restores the hyperfiltration response, maintains parallel increases in proximal reabsorption, and overrides the arginine/octreotide actions.

To retrospectively determine whether postoperative ultrasonography (US) of clinically immature dialysis fistulas can be used to identify potential anatomic origins of immaturity and whether correction of immature fistulas promotes fistula maturation.Institutional review board approval was obtained for this retrospective study, with waiver of informed consent. Postoperative US was performed in 95 consecutive subjects (52 men, 43 women; mean age, 58 years) with clinically immature fistulas. Fistulas were deemed sonographically mature if they had a diameter of at least 4 mm, an access flow of at least 500 mL/min, and a depth of no more than 5 mm from the skin surface. Fistulas were deemed clinically mature if they could be used for dialysis for at least 1 month. The proportion of subjects in different US subgroups with fistulas that matured during follow-up was compared with chi2 analysis.Sixty-seven clinically immature fistulas were deemed sonographically immature. One or more remediable anatomic problems were detected with US in 60 subjects with sonographically immature fistulas; these problems included focal stenosis in 23, accessory veins in 34, and excessively deep veins in 19. Multiple abnormalities were present in 13 subjects. Of 58 subjects with sonographically immature fistulas and known clinical outcomes, 32 underwent an intervention. In those subjects who did not undergo a salvage procedure, only eight fistulas were usable for dialysis. Among those who underwent a salvage procedure, 25 fistulas were subsequently usable for dialysis (P.001).Clinically immature fistulas frequently have one or more potentially remediable problems seen at postoperative US. Problem-specific salvage procedures increase the proportion of fistulas that are usable for dialysis.

Purpose of review The imbalances in the activities of various components of the neurohormonal system that maintain renal homeostasis may have important implications in pathophysiology. This review aims to examine the evidence for disparities between angiotensin II and nitric oxide in acute and chronic kidney diseases. Recent findings Low nitric oxide generation and activity characterize chronic kidney disease, whereas decreasing angiotensin activity is known to be beneficial. High oxygen consumption and hypoxia are thought to play important roles in progression of kidney disease, and angiotensin II and nitric oxide appear to influence oxygen consumption in these models. The common etiologic models of acute kidney injury, such as ischemia, nephrotoxic drug administration, radiocontrast exposure and sepsis, also demonstrate significant imbalances in the activities of angiotensin II and nitric oxide. Summary Disparities between the activities of angiotensin II and nitric oxide are pervasive in a variety of acute and chronic kidney diseases. A better understanding of these interactions and their net effect on renal pathophysiology can lead to therapeutic interventions aimed at preventing or correcting such imbalances.

Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.

Increased renal oxygen consumption (QO2) and hypoxia have been observed in early diabetes, but underlying mechanisms are still being investigated. Nearly 80% of QO2 is used for active sodium transp...

We have shown in subtotal nephrectomy (STN), a model of chronic kidney disease, there is increased oxygen consumption (QO2) factored for tubular Na reabsorption (TNa) leading to hypoxia. To demonst...