HER2 overexpression in urothelial carcinoma with GATA3 and PPARG copy number gains.

HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.

Short-term outcomes of a multicentre prospective study using a "visible" polyvinylidene fluoride onlay mesh for the prevention of midline incisional hernia.

INTRODUCTION: Prophylactic meshes in high-risk patients prevent incisional hernias, although there are still some concerns about the best layer to place them in, the type of fixation, the mesh material, the significance of the level of contamination, and surgical complications. We aimed to provide answers to these questions and information about how the implanted material behaves based on its visibility under magnetic resonance imaging (MRI). METHOD: This is a prospective multicentre observational cohort study. Preliminary results from the first 3 months are presented. We included general surgical patients who had at least two risk factors for developing an incisional hernia. Multivariate logistic regression was used. A polyvinylidene fluoride (PVDF) mesh loaded with iron particles was used in an onlay position. MRIs were performed 6 weeks after treatment. RESULTS: Between July 2016 and June 2022, 185 patients were enrolled in the study. Surgery was emergent in 30.3% of cases, contaminated in 10.7% and dirty in 11.8%. A total of 5.6% of cases had postoperative wound infections, with the requirement of stoma being the only significant risk factor (OR = 7.59, p = 0.03). The formation of a seroma at 6 weeks detected by MRI, was associated with body mass index (OR = 1.13, p = 0.02). CONCLUSIONS: The prophylactic use of onlay PVDF mesh in midline laparotomies in high-risk patients was safe and effective in the short term, regardless of the type of surgery or the level of contamination. MRI allowed us to detect asymptomatic seromas during the early process of integration. STUDY REGISTRATION:  This protocol was registered at ClinicalTrials.gov (NCT03105895).

Small Organic Molecular Electrocatalysts for Fuels Production.

In recent years, heterocyclic organic compounds have been explored as molecular electrocatalysts in relevant reactions for energy conversion and storage. Merging mimetics of biological systems that perform hydride transfer with rational synthetic chemical design has opened many opportunities for organic molecules to be tuned at the atomic level conferring them interesting reactivities. These molecular electrocatalysts represent an alternative to traditional metallic materials and metal complexes employed for water oxidation, hydrogen production, and carbon dioxide reduction. This minireview describes recent reports concerning design, catalytic activity and the mechanism of synthetic molecular electrocatalysts towards solar fuels production.

Comparative Study of Machine Learning Models for Bee Colony Acoustic Pattern Classification on Low Computational Resources.

In precision beekeeping, the automatic recognition of colony states to assess the health status of bee colonies with dedicated hardware is an important challenge for researchers, and the use of machine learning (ML) models to predict acoustic patterns has increased attention. In this work, five classification ML algorithms were compared to find a model with the best performance and the lowest computational cost for identifying colony states by analyzing acoustic patterns. Several metrics were computed to evaluate the performance of the models, and the code execution time was measured (in the training and testing process) as a CPU usage measure. Furthermore, a simple and efficient methodology for dataset prepossessing is presented; this allows the possibility to train and test the models in very short times on limited resources hardware, such as the Raspberry Pi computer, moreover, achieving a high classification performance (above 95%) in all the ML models. The aim is to reduce power consumption and improves the battery life on a monitor system for automatic recognition of bee colony states.

Sleep quality and risk of recurrent aphthous ulcers: A Spanish cohort study.

OBJECTIVE: Recurrent aphthous stomatitis (RAS) is a condition that affects 20% of the world population and is characterized by painful ulcers in the oral mucosa. So far, the epidemiology and risk factors of RAS have been infrequently studied. Our objective was to determine whether sleep-related factors are related to the occurrence of RAS in the first prospective study carried out on this topic. METHODS: A cohort of 11210 Spanish students, 13-17 years old, was followed up for one year. Sleep disorders were assessed at baseline using a standard validated questionnaire. RESULTS: We detected 2655 new cases of RAS with a total of 287,262 person-week of follow-up. Subjects with high (4th quartile) Insomnia Index showed an incidence rate ratio (IRR) of RAS of 1.29 (95% confidence interval (CI) 1.15-1.45), while subjects with high Hypersomnia Index presented an IRR of 1.42 (95% CI 1.26-1.61). A high score of sleep-related phenomena was also associated with an increased IRR: 1.53 (95% CI 1.37-1.69). Adolescents with high level of sleep satisfaction were at lower risk of RAS: 0.88 (95% CI 0.77-1.01). CONCLUSION: These findings suggest that sleep disorders are moderately associated with RAS in adolescents.

MOVE! Enhanced: A Virtual Multidisciplinary Weight and Diabetes Management Program for High-Risk Veterans. A Feasibility Pilot.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a feasibility study assessing a multidisciplinary, virtual weight and diabetes management program aimed at high-risk veterans with obesity and diabetes in Milwaukee, WI.

High recurrence rate after posterior component separation and keyhole mesh reconstruction for complex parastomal hernia: A case series study.

AIM: This study aimed to describe the results of complex parastomal hernia repair after posterior component separation and keyhole reconstruction. METHOD: We conducted a retrospective review of a prospectively sustained database in one single complex abdominal wall referral centre. We analysed the data of patients who underwent the posterior component separation technique using modified transversus abdominis release for complex parastomal hernia and retromuscular keyhole mesh repair from February 2014 to January 2017. Demographic data, hernia characteristics, operative details and outcomes were analysed. The primary outcome measured was the recurrence rate during the follow-up. RESULTS: Twenty patients were included in this study. Among the patients who underwent surgery for parastomal hernia, 17 patients had a colostomy (85%) and three patients had a ureteroileostomy after the Bricker procedure (15%). The mean body mass index was 33.2 kg/m2 (range 25-47). Twelve patients had an expected associated risk according to the Carolinas equation for determining associated risk classification of >60%. Sixty per cent of our patients had contaminated or dirty/infected wounds. The overall complication rate was 60%. Surgical site infection was observed in 25% of the cases. The mortality rate in our study group was 5% (n = 1). We found clinical or radiological evidence of parastomal hernia recurrence in nine out of 20 (45%) patients during follow-up. No hernia recurrence was detected in the concomitant incisional hernias. CONCLUSIONS: Although posterior component separation in the form of modified transversus abdominis muscle release allows abdominal wall reconstruction, keyhole mesh configuration at the stoma site does not offer satisfactory results in terms of long-term recurrence rate at the parastomal defect.

Using a Diabetes Risk Score to Identify Patients Without Diabetes at Risk for New Hyperglycemia in the Hospital.

OBJECTIVE: To assess the value of a validated diabetes risk test, the Cambridge Risk Score (CRS), to identify patients admitted to hospital without diabetes at risk for new hyperglycemia (NH). METHODS: This retrospective cross-sectional study included adults admitted to a hospital over a 4-year period. Patients with no diabetes diagnosis and not on antidiabetics were included. The CRS was calculated for each patient, and those with available glycated hemoglobin (HbA1C) results were investigated in a second analysis. Multivariate regression analyses were performed to assess the association among CRS, HbA1C, and the risk for NH. RESULTS: A total of 19,830 subjects comprised the sample, of which 38% were found to have developed NH, defined as a blood glucose level ≥140 mg/dL. After accounting for covariates, the CRS was significantly associated with NH (odds ratio [OR], 1.19 [1.16, 1.22]; P < .001). Only 17% of patients had their HbA1C values checked within 6 months of admission. Compared with patients without diabetes, patients with prediabetes based on their HbA1C level (OR, 1.59 [1.37, 1.86]; P < .001) and patients with undiagnosed diabetes (OR, 5.95 [3.50, 10.65]; P < .001) were also significantly more likely to have NH. CONCLUSION: Results of this study show that the CRS and HbA1C levels were significantly associated with the risk of developing NH in inpatient adults without diabetes. Given that an HbA1C level was missing in most medical records of hospitalized patients without diabetes, the CRS could be a useful tool for early identification and management of NH, possibly leading to better outcomes.

Functional neuroanatomy of racial categorization from visual perception: A meta-analytic study.

We effortlessly sort people into different racial groups from their visual appearance and implicitly generate racial bias affecting cognition and behavior. As these mental activities provide the proximate mechanisms for social behaviours, it becomes essential to understand the neural activity underlying differences between own-race and other-race visual categorization. Yet intrinsic limitations of individual neuroimaging studies, owing to reduced sample size, inclusion of multiple races, and interactions between races in the participants and in the displayed visual stimuli, dampens generalizability of results. In the present meta-analytic study, we applied multimodal techniques to partly overcome these hurdles, and we investigated the entire functional neuroimaging literature on race categorization, therefore including more than 2000 Black, White and Asian participants. Our data-driven approach shows that own- and other-race visual categorization involves partly segregated neural networks, with distinct connectivity and functional profiles, and defined hierarchical organization. Categorization of own-race mainly engages areas related to cognitive components of empathy and mentalizing, such as the medial prefrontal cortex and the inferior frontal gyrus. These areas are functionally co-activated with cortical structures involved in auto-biographical memories and social knowledge. Conversely, other-race categorization recruits areas implicated in, and functionally connected with, visuo-attentive processing, like the fusiform gyrus and the inferior parietal lobule, and areas engaged in affective functions, like the amygdala. These results contribute to a better definition of the neural networks involved in the visual parcelling of social categories based on race, and help to situate these processes within a common neural space.

Challenges and Strategies for Inpatient Diabetes Management in Older Adults.

Adults older than 65 years of age are the fastest growing segment of the U.S. population. Aging is also one of the most important risk factors for diabetes, and about one-third of all individuals with diabetes are in this age-group. Older people with diabetes are more likely to have comorbidities such as hypertension, ischemic heart disease, chronic kidney disease, and cognitive impairment, which lead to higher rates of hospital admissions compared with individuals without diabetes. Professional organizations have recommended patient-centric individualized glycemic reduction approaches, with an emphasis on potential harms of intensive glycemic control and overtreatment in older adults. Insulin therapy remains a mainstay of diabetes management in the inpatient setting regardless of patients' age; however, there is uncertainty about optimal glycemic targets during the hospital stay. Increasing evidence supports selective use of dipeptidyl peptidase-4 inhibitors, alone or in combination with low-dose basal insulin, in older noncritically ill patients with mild to moderate hyperglycemia. This article reviews the prevalence, diagnosis, and monitoring of, and the available treatment strategies for, diabetes among elderly patients in the inpatient setting.

The influence of shade allocation or total shade plus overhead fan on growth performance, efficiency of dietary energy utilization, and carcass characteristics of feedlot cattle under tropical ambient conditions.

OBJECTIVE: The objective of this experiment was to evaluate the effect of shade allocation and shade plus fan on growth performance, dietary energy utilization and carcass characteristics of feedlot cattle under tropical ambient conditions. METHODS: Two trials were conducted, involving a total of 1,560 young bulls (289±22 kg BW) assigned to 24 pens (65 bulls/pen and 6 pens/treatment). Pens were 585 m2 with 15 m fence line feed bunks. Shade treatments (m2 shade/animal) were: i) limited shade (LS) to 1.2 m2shade/animal (LS1.2); ii) limited shade to 2.4 m2 shade/animal (LS2.4); iii) total shade (TS) which correspond to 9 m2/animal, and iv) total shade equipped with fans (TS+F). Trials lasted 158 and 183 days. In both studies, the average weekly maximum temperature exceeded 34°C. RESULTS: Increasing shade allocation tended (p = 0.08) to linearly increases average daily gain (ADG), and dry matter intake (DMI, quadratic effect, p = 0.03). This effect was most apparent between LS1.2 and LS2.4. Shade allocation, per se, did not affect gain efficiency or estimated dietary net energy (NE). Compared with TS, TS+F increased (p<0.05) ADG, gain efficiency, and tended (p = 0.06) to increase dietary NE. There was a quadratic effect of shade on longissimus area and marbling score, with values being lower (p<0.01) for LS2.4 than for LS1.2 or TS. Likewise, marbling score was lower for TS+F than for TS. Percentage kidney, pelvic, and heart (KPH) linearly decreased with increasing shade. In contrast, KPH was greater for TS than for TS+F. CONCLUSION: Providing more than 2.4 m2 shade/animal will not further enhance feedlot performance. The use of fans in combination with shade increases ADG and gain efficiency beyond that of shade, alone. These enhancements were not associated with increased DMI, but rather, to an amelioration of ambient temperature humidity index on maintenance energy requirement.

Assessing the relationship between adverse childhood experiences and life satisfaction, psychological well-being, and social well-being: United States Longitudinal Cohort 1995-2014.

BACKGROUND: More than half of the U.S. population has experienced adverse childhood experiences (ACE), which are linked to physical and mental health issues. This study examines the relationship between ACEs and life satisfaction, psychological well-being, and social well-being. METHODS: Data of 6323 participants from three waves of the Midlife Development in the United States (1995-1996, 2004-2006, and 2011-2014) were used. Repeated measures models were used to test the associations between ACEs and all three psychosocial scales. Generalized estimating equations (GEE) were used to account for multiple survey measures. Adjusting for demographics and survey wave, GEE models were run for each ACE construct. RESULTS: After controlling for demographic covariables, those reporting an ACE had significantly lower levels of life satisfaction (ß = - 0.20, 95% CI - 0.26 to - 0.15) compared to those without an ACE. Those reporting higher ACE counts were associated with lower life satisfaction compared to those with no ACE (ß = - 0.38, 95% CI - 0.56 to - 0.20; ß = - 0.36, 95% CI - 0.46 to - 0.27; and ß = - 0.13, 95% CI - 0.19 to - 0.08 for ACE counts of 3, 2, and 1, respectively). Abuse (ß = - 0.41, 95% CI - 0.48 to - 0.33) and household dysfunction (ß = - 0.18, 95% CI - 0.25 to - 0.10) were associated with significantly lower life satisfaction. Overall, those exposed to ACEs had significantly lower sense of social well-being. CONCLUSION: In this sample of adults, ACEs were significantly associated with lower life satisfaction, lower psychological well-being, and lower social well-being, especially for those who report abuse and household dysfunction during childhood.

Multidisciplinary Approach to Treating Severe Acute Pancreatitis in a Low-Volume Hospital.

BACKGROUND: Up to 25% of patients with acute pancreatitis develop severe complications and are classified as severe pancreatitis with a high death rate. To improve outcomes, patients may require interventional measures including surgical procedures. Multidisciplinary approach and best practice guidelines are important to decrease mortality. METHODS: We have conducted a retrospective analysis from a prospectively maintained database in a low-volume hospital. A total of 1075 patients were attended for acute pancreatitis over a ten-year period. We have analysed 44 patients meeting the criteria for severe acute pancreatitis and for intensive care unit (ICU) admittance. Demographics and clinical data were analysed. Patients were treated according to international guidelines and a multidisciplinary flowchart for acute pancreatitis and a step-up approach for pancreatic necrosis. RESULTS: Forty-four patients were admitted to the ICU due to severe acute pancreatitis. Twenty-five patients needed percutaneous drainage of peri-pancreatic or abdominal fluid collections or cholecystitis. Eight patients underwent endoscopic retrograde cholangiopancreatography for choledocholithiasis and biliary sepsis or pancreatic leakage, and one patient received endoscopic trans-gastric endoscopic prosthesis for pancreatic necrosis. Sixteen patients underwent surgery: six patients for septic abdomen, four patients for pancreatic necrosis and two patients due to abdominal compartment syndrome. Four patients had a combination of surgical procedures for pancreatic necrosis and for abdominal compartment syndrome. Overall mortality was 9.1%. CONCLUSION: Severe acute pancreatitis represents a complex pathology that requires a multidisciplinary approach. Establishing best practice treatments and evidence-based guidelines for severe acute pancreatitis may improve outcomes in low-volume hospitals.

Abdominal Wall Reconstruction Utilizing the Combination of Absorbable and Permanent Mesh in a Retromuscular Position: A Multicenter Prospective Study.

BACKGROUND: Optimal mesh reinforcement for abdominal wall reconstruction (AWR) in complex hernias remains questionable. Use of biologic, absorbable and synthetic meshes has been described. The idea of using an absorbable mesh (AM) under a permanent mesh (PM) in a retromuscular position may help in these challenging situations. METHODS: Between 2011 and 2016, consecutive patients undergoing open AWR utilizing an AM as posterior layer reinforcement and configuration of a large PM were identified in a multicenter prospectively maintained database in four hospitals. Main outcomes included demographics, ventral hernia classifications, perioperative data, complications and recurrences. RESULTS: A total of 169 complex incisional hernias were analyzed. Mean age was 60.9, with mean body mass index 30.7 (range: 20-46). Location of incisional hernias (IH) was: 80 midline, 59 lateral and 30 midline and lateral. 78% were grade I and II in Ventral Hernia Working Group classification. 52% of patients were discharged with no complication. There were 19% seromas, 13% hematomas, 12% surgical-site infection and 10% skin dehiscence. Only partial mesh removal was necessary in one patient. After a mean follow-up of 26 months (range 15-59), there were five (3.2%) recurrences. Reoperations on patients showed a band of fibrosis separating the peritoneum from the PM. CONCLUSION: The combination of AM with very large PM in the same retromuscular position in AWR seems to be safe. The efficacy with recurrence rates below 4% in complex midline and lateral IH may be explained by the use of larger PMs that are extended and configured with the support of AMs. Reoperations on patients have confirmed the previous experimental reports on the use of the AM.

How we do it: down to up posterior components separation.

BACKGROUND: Posterior component separation with transversus abdominis release technique is increasingly being used for abdominal wall reconstruction in complex abdominal wall repair. The main purpose of this study is to present a modification of the surgical technique originally described that facilitates the surgical procedure and offers additional advantages. METHODS: Based on the knowledge of the anatomy of the retromuscular space and the preperitoneal aerolar tissue distribution, we start the incision on the posterior rectus sheath from the arcuate line in a down to up direction. The posterior rectus sheath is incised 0,5-1 cm medial to the linea semilunaris and cut longitudinally as far as the fibers of transversus abdominis muscle that are divided in the superior part of the abdomen. It is also possible to avoid cutting the fibers of this muscle if we incise the posterior rectus sheath in an oblique direction to the midline from the umbilical area. Since 2012 to 2016, 69 consecutive patients with down to up TAR have been prospectively followed. Main outcome measures included demographics, perioperative details, wound complications, and recurrences. RESULTS: Between 2012 and 2016, we have operated 69 patients with down to up TAR technique. Mean operative time was 251 (range 65-566) minutes. Mean hospital stay was 9,8 (2-98) days. 10 patients presented surgical site events (14,5%): 6 patients had superficial site infection, 3 deep and 1 organ space. During follow-up, 3 patients (4,3%) presented incisional hernia recurrence. CONCLUSIONS: This novel modification allows a simpler dissection of the preperitoneal retromuscular space and makes the TAR technique easier to perform. It also enables to incise only the insertion of the transversalis fascia cranially.

Postoperative Day 1 Glucose May Be Associated With Wound Complications in Sarcomas Treated With Preoperative Radiation.

BACKGROUND: Uncontrolled blood glucose impacts key phases of the wound healing process. Various factors have been associated with postoperative wound complications in soft tissue sarcomas; however, the association of postoperative early morning blood glucose with wound complications, if any, remains to be determined. Because blood glucose levels may be modified, understanding whether glucose levels are associated with wound complications has potential therapeutic importance. QUESTIONS/PURPOSES: The purposes of this study were (1) to evaluate if postoperative early morning blood glucose is associated with the development of wound complications in soft tissue sarcomas; (2) to determine a blood glucose cutoff that may be associated with an increased risk of wound complications; and (3) to evaluate if patients with diabetes have higher postoperative blood glucose and an associated increased risk of wound complications. METHODS: From 2000 to 2015, 298 patients with Stage I to III soft tissue sarcomas of the extremity or chest wall were treated with preoperative radiation ± chemotherapy followed by limb-sparing resection. Of those, 191 (64%) patients had demographic, treatment, and postoperative variables and wound outcomes available; these patients' results were retrospectively evaluated. None of the 191 patients were lost to followup. Early morning blood glucose levels on postoperative day (POD) 1 were available in all patients. Wound complications were defined as those resulting in an operative procedure or prolonged wound care for 6 months postresection. Variables that may be associated with wound complications were evaluated using logistic regression for multivariate analysis. Receiver operative curve (ROC) analysis was used to assess the early morning blood glucose level that best was associated postoperative wound complications. RESULTS: After controlling for potentially relevant confounding variables such as patient comorbidities, tumor size, and location, lower extremity soft tissue sarcomas (p = 0.002, odds ratio [OR], 6.4; 95% confidence interval [CI], 1.97-20.84) and elevated POD 1 early morning blood sugars (p < 0.001; OR, 1.1; 95% CI, 1.04-1.11) were associated with increased wound complications postoperatively. ROC analysis revealed that early morning POD 1 blood glucose of > 127 mg/dL was associated with postoperative wound complications with a sensitivity of 89% (area under the curve 0.898, p < 0.001). Median POD 1 early morning blood glucose in patients without diabetes was 118 mg/dL and 153 mg/dL in patients with diabetes (p = 0.023). However, with the numbers available, there was no increase in wound complications in patients with diabetes compared with those without it. CONCLUSIONS: Our study provides preliminary information suggesting that POD 1 early morning blood glucose in patients with soft tissue sarcomas may be associated with a slightly increased risk of postoperative wound complications. An early morning blood glucose of > 127 mg/dL may be a threshold associated with this outcome. Although patients with diabetes had higher POD 1 early morning blood glucose levels, diabetes itself was not associated with the development of wound complications. We cannot conclude that better glycemic control will reduce wound complications in patients who receive preoperative radiation, but our data suggest this should be further studied in a larger, prospective study. LEVEL OF EVIDENCE: Level III, therapeutic study.

Preoperative Diabetes Optimization Program.

IN BRIEF "Quality Improvement Success Stories" are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc., and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a successful effort to improve glycemic control in presurgical patients with an A1C >8%.

Management of Type 1 Diabetes in the Hospital Setting.

PURPOSE OF REVIEW: The purpose of this article was to review recent guideline recommendations on glycemic target, glucose monitoring, and therapeutic strategies, while providing practical recommendations for the management of medical and surgical patients with type 1 diabetes (T1D) admitted to critical and non-critical care settings. RECENT FINDINGS: Studies evaluating safety and efficacy of insulin pump therapy, continuous glucose monitoring, electronic glucose management systems, and closed loop systems for the inpatient management of hyperglycemia are described. Due to the increased prevalence and life expectancy of patients with type 1 diabetes, a growing number of these patients require hospitalization every year. Inpatient diabetes management is complex and is best provided by a multidisciplinary diabetes team. In the absence of such resource, providers and health care staff must become familiar with the features of this condition to avoid complications such as severe hyperglycemia, ketoacidosis, hypoglycemia, or glycemic variability. We reviewed most recent guidelines and relevant literature in the topic to provide practical recommendations for the inpatient management of patients with T1D.

ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin.

Adrenocorticotropic hormone (ACTH) treatment has been proven to promote paxillin dephosphorylation and increase soluble protein tyrosine phosphatase (PTP) activity in rat adrenal zona fasciculata (ZF). Also, in-gel PTP assays have shown the activation of a 115-kDa PTP (PTP115) by ACTH. In this context, the current work presents evidence that PTP115 is PTP-PEST, a PTP that recognizes paxillin as substrate. PTP115 was partially purified from rat adrenal ZF and PTP-PEST was detected through Western blot in bioactive samples taken in each purification step. Immunohistochemical and RT-PCR studies revealed PTP-PEST expression in rat ZF and Y1 adrenocortical cells. Moreover, a PTP-PEST siRNA decreased the expression of this phosphatase. PKA phosphorylation of purified PTP115 isolated from non-ACTH-treated rats increased KM and VM . Finally, in-gel PTP assays of immunoprecipitated paxillin from control and ACTH-treated rats suggested a hormone-mediated increase in paxillin-PTP115 interaction, while PTP-PEST and paxillin co-localize in Y1 cells. Taken together, these data demonstrate PTP-PEST expression in adrenal ZF and its regulation by ACTH/PKA and also suggest an ACTH-induced PTP-PEST-paxillin interaction. J. Cell. Biochem. 117: 2170-2181, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

Hyperglycemia and Acute Kidney Injury During the Perioperative Period.

Hyperglycemia and acute kidney injury (AKI) are frequently observed during the perioperative period. Substantial evidence indicates that hyperglycemia increases the prevalence of AKI as a surgical complication. Patients who develop hyperglycemia and AKI during the perioperative period are at significantly elevated risk for poor outcomes such as major adverse cardiac events and all-cause mortality. Early observational and interventional trials demonstrated that the use of intensive insulin therapy to achieve strict glycemic control resulted in remarkable reductions of AKI in surgical populations. However, more recent interventional trials and meta-analyses have produced contradictory evidence questioning the renal benefits of strict glycemic control. Although the exact mechanisms through which hyperglycemia increases the risk of AKI have not been elucidated, multiple pathophysiologic pathways have been proposed. Hypoglycemia and glycemic variability may also play a significant role in the development of AKI. In this literature review, the complex relationship between hyperglycemia and AKI as well as its impact on clinical outcomes during the perioperative period is explored.