Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin

Renal proximal tubule cells (PTECs) act as urine gatekeepers, constantly and efficiently avoiding urinary protein waste through receptor-mediated endocytosis. Despite its importance, little is known about how this process is modulated in physiologic conditions. Data suggest that the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway regulates PTEC protein reabsorption. Here, we worked on the hypothesis that the physiologic albumin concentration and PI3K/AKT pathway form a positive feedback loop to expand endocytic capacity. Using LLC-PK1 cells, a model of PTECs, we showed that the PI3K/AKT pathway is required for megalin recycling and surface expression, affecting albumin uptake. Inhibition of this pathway stalls megalin at EEA1+ endosomes. Physiologic albumin concentration (0.01 mg/mL) activated AKT; this depends on megalin-mediated albumin endocytosis and requires previous activation of PI3K/mTORC2. This effect is correlated to the increase in albumin endocytosis, a phenomenon that we refer to as “albumin-induced albumin endocytosis”. Mice treated with L-lysine present decreased albumin endocytosis leading to proteinuria and albuminuria associated with inhibition of AKT activity. Renal cortex explants obtained from control mice treated with MK-2206 decreased albumin uptake and promoted megalin internalization. Our data highlight the mechanism behind the capacity of PTECs to adapt albumin reabsorption to physiologic fluctuations in its filtration, avoiding urinary excretion.

Cross-sectional Analysis of Risk Factors for Surgical Site Infection Secondary to Spinal Internal Fixation via the Posterior Approach

Backgroud: The aim of this study was to investigate the risk factors related to surgical site infection (SSI) secondary to spinal internal fixation via the posterior approach.Methods: Patients who had undergone spinal internal fixation via the posterior approach at the spinal center of our hospital from January 2004 to December 2019 were selected in this cross-sectional study. Information about age, sex, body mass index (BMI), fused segment, hemoglobin concentration, serum albumin concentration, surgical duration, surgery beginning time, allogeneic blood transfusion, combined diabetes, peak blood glucose 72 h postoperatively ≥12 mmol/L, smoking history, and blood loss were included. The factors related to SSI were analyzed using univariate and multivariate analyses. P < 0.05 was considered to indicate statistical significance.Results: Among the 4,350 patients, 66 had SSI, with an infection prevalence of 1.5%. The subjects included 37 men and 29 women (age range, 22–84 y; average age, 47.4 ± 12.8 y). Univariate analysis showed that sex, BMI, fused segment, surgery beginning time, allogeneic blood transfusion, and smoking history were not correlated to infection (P > 0.05). However, age >60 y, surgical duration >3 h, serum albumin concentration <30 g/L, hemoglobin concentration <80 g/L, combined diabetes, peak blood glucose 72 h postoperatively ≥12 mmol/L, and blood loss >1,000 mL were correlated with infection (P < 0.05). Multivariate logistic regression analysis demonstrated that age >60 y, surgical duration >3 h, hemoglobin concentration <80 g/L, serum albumin concentration <30 g/L, combined diabetes, and blood loss >1,000 mL were significantly correlated with SSI secondary to spinal internal fixation via the posterior approach.Conclusion: This study provides information on SSI secondary to spinal internal fixation via the posterior approach. We found that age >60 y, surgical duration >3 h, hemoglobin concentration <80 g/L, serum albumin concentration <30 g/L, combined diabetes, and blood loss >1,000 mL are directly correlated with SSI secondary to spinal internal fixation via the posterior approach. These findings may contribute to discussions and actions that may help to reduce SSI secondary to spinal internal fixation via the posterior approach in the short or medium term.

The Effect of Adding Protected Amino Acids in the Rumen (Methionine and Lysine and their Mixtures) on Some Physiological Characteristics of Male Arabi Lambs

This study was conducted at the animal field of the Agriculture College / University of Basra / Karma Ali site for the period from 7/10/2019 to 1/5/2020 to investigation the effect of adding protected amino acids (methionine and lysine and their mixtures) on some physiological trails of male Arabi lambs. Sixteen male lambs with an average weight of (27.95) kg and an age of 5-6 months were selected, and randomly divided into four group (4 animals per group). The results indicated that there were no significant differences in the concentration of hemoglobin, packed cell volume, the number of red and white blood cells, cholesterol, triglycerides and the activity of the liver enzyme (ALT and AST) between the different treatments, while there was a significant (p <0.05) increase in the total protein and albumin concentration in the fourth treatment compared with the first treatment (control), while, there was a significant decrease (p <0.05) in the urea concentration for the fourth, third and second treatments compared with the first treatment. The concentrations of glucose, thyroxine and growth hormone increased significantly (p <0.05) in the fourth and second treatment compared with the first treatment. However, it can be concluded from the study that feeding the male lambs with 5g methionine or mixing it with lysine by 5g raises the concentration of glucose, growth hormones and thyroxine in the blood. Also, the levels of methionine and lysine used did not change the concentration of the studied biochemical parameters

Clinical characteristics of, prognostic factors for, and long-term outcome of dogs with multiple acquired portosystemic shunts: 72 cases (2000–2018)

OBJECTIVE To identify clinical characteristics of, prognostic factors for, and long-term outcome of dogs with multiple acquired portosystemic shunts (MAPSSs) and determine whether survival time was associated with previous portosystemic shunt attenuation. ANIMALS 72 client-owned dogs with MAPSSs. PROCEDURES Medical records of dogs in which MAPSSs had been diagnosed between January 2000 and August 2018 were reviewed for signalment, historic and diagnostic findings, management methods, and outcome. RESULTS Median survival time of dogs (n = 23) that died of causes related to MAPSSs was 580 days (range, 156 to 1,363 days). Factors significantly associated with dying of MAPSS-related versus unrelated causes included body weight, albumin concentration at the first and last recheck examinations, and cholesterol, total solids, and glucose concentrations at the last recheck examination. Dogs not receiving medical management or without signs of depressed mentation at the time of initial presentation were less likely to die of causes related to MAPSSs. Patient status (alive vs dead of causes related to MAPSSs vs dead of causes unrelated to MAPSSs vs dead of unknown causes) was not significantly associated with survival time. CONCLUSIONS AND CLINICAL RELEVANCE Survival time for dogs with MAPSSs was not shortened by previous portosystemic shunt attenuation surgery and was not different when death was versus was not related to MAPSSs. Dogs with MAPSSs that had progression of biochemical changes consistent with liver dysfunction were more likely to die of causes related to MAPSSs and were unlikely to live a normal lifespan.

Impact of Dry Sugar Beet Pulp on Milk Production, Digestibility Traits, and Blood Constituents of Dairy Holstein Cows

Thirty multiparous lactating Holstein cows with an average live body weight of 642 ± 21 kg and an average daily milk yield of 30.46 ± 0.59 kg were used in this study. Cows with parities of 2 and 4 were used following their peak period, and were divided into three groups, with ten cows in each group. The control group was fed yellow corn grain rations (YCG), while for the 2nd and 3rd groups, 25 and 50% of YCG was replaced with dry sugar beet pulp (DSBP), denoted as DSBP25 and DSBP50, respectively. The contents of dry matter, organic matter, ether extract, nitrogen-free extract, and fiber carbohydrate in the experimental rations tended to decrease; however, crude protein, crude fiber, ash, and fiber fractions tended to increase in the DSBP25 and DSBP50 groups. Only crude fiber digestibility increased (p < 0.05) in the DSBP rations. Rumen pH value and concentration of ammonia nitrogen (NH3-N) decreased, while the concentration of total volatile fatty acids (TVFAs) increased in the DSBP25 and DSBP50 groups. The concentrations of total protein and globulin in blood plasma were higher (p < 0.05) in DSBP25 and DSBP50 than in YCG. However, plasma albumin concentration, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities were lower (p < 0.05) in DSBP50 than in YCG. Milk yield and yield of 4% fat-corrected milk (4% FCM) were higher (p < 0.05) in DSBP25 and DSBP50 than in YCG. Fat, protein, solids not fat (SNF), and total solids (TS) contents in milk increased significantly (p < 0.05) for feeding rations containing DSBP. Feed cost was reduced, but the output of milk yield increased with DSBP. In conclusion, introducing DSBP into the rations of Holstein dairy cows led to significant improvements in their productive performance.

Prevalence and Correlates of Zinc Deficiency Among Vietnamese Women of Reproductive Age in Ho Chi Minh City: A Single Hospital-Based Survey

Background and Objectives: Zinc is a micronutrient that plays an important role in metabolism, cell growth regulation, and differentiation. Vietnam has many population groups living in poverty. The daily food of Vietnamese people is mainly rice, which contains very little zinc. This cross-sectional study was conducted to determine the prevalence of, and factors related to, zinc deficiency in women of reproductive age.Methods and Study Design: The sample population was non-pregnant women of reproductive age (18–49 years old) who visited Nguyen Tri Phuong Hospital Gynecological Outpatient Clinic. The subjects were interviewed and data on background characteristics, anthropometric measurements, and blood tests (serum zinc concentration, complete blood count, albumin, and ferritin) were collected.Results: The prevalence of zinc deficiency, as defined by the International Zinc Nutrition Consultative Group (IZiNCG), was 85% [61/72; 95% confidence interval (CI) = 74–91%], and the prevalence of severe zinc deficiency was 37% (27/72; 95% CI = 26–50%). There were significant associations of albumin concentration, marital status, and past pregnancy history with severe zinc deficiency.Conclusions: More than three-fourths of Vietnamese women of reproductive age had zinc deficiency at our study site in Ho Chi Minh City. This health issue requires greater attention in order to swiftly promote preventive actions, and further surveillance to confirm our study findings.

Atrial fibrillation detected at screening is not a benign condition: outcomes in screen-detected versus clinically detected atrial fibrillation. Results from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study

AimsIt is unknown whether screen-detected atrial fibrillation (AF) carries cardiovascular risks similar to clinically detected AF. We aimed to compare clinical outcomes between individuals with screen-detected and clinically detected incident AF.MethodsWe studied 8265 participants (age 49 ± 13 years, 50% women) without prevalent AF from the community-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study. By design of the PREVEND study, 70% of participants had a urinary albumin concentration >10 mg/L. Participants underwent 12-lead ECG screening at baseline and every 3 years. AF was considered screen-detected when first diagnosed during a study visit and clinically detected when first diagnosed during a hospital visit. We analysed data from the baseline visit (1997–1998) up to the third follow-up visit (2008). We used Cox regression with screen-detected and clinically detected AF as time-varying covariates to study the association of screen-detected and clinically detected AF with all-cause mortality, incident heart failure (HF) and vascular events.ResultsDuring a follow-up of 9.8 ± 2.3 years, 265 participants (3.2%) developed incident AF, of whom 60 (23%) had screen-detected AF. The majority of baseline characteristics were comparable between individuals with screen-detected and clinically detected AF. Unadjusted, both screen-detected and clinically detected AF were strongly associated with mortality, incident HF, and vascular events. After multivariable adjustment, screen-detected and clinically detected AF remained significantly associated with mortality (HR 2.21 (95% CI 1.09 to 4.47) vs 2.95 (2.18 to 4.00), p for difference=0.447) and incident HF (4.90 (2.28 to 10.57) vs 3.98 (2.49 to 6.34), p for difference=0.635). After adjustment, screen-detected AF was not significantly associated with vascular events, whereas clinically detected AF was (1.12 (0.46 to 2.71) vs 1.92 (1.21 to 3.06), p for difference=0.283).ConclusionScreen-detected incident AF was associated with an increased risk of adverse outcomes, especially all-cause mortality and incident HF. The risk of outcomes was not significantly different between screen-detected AF and clinically detected AF.

The Relationship between the Presence of White Nails and Mortality among Rural, Older, Admitted Patients: A Prospective Cohort Study

White nails are a sign of various physical deteriorations, including poor nutrition, organ damage, and aging. During a physical examination, white nails can be a helpful health indicator in older patients with vague and multiple symptoms. In this prospective cohort study of patients admitted to the Department of General Medicine in a rural community hospital, we investigated the relationship between white nails and patient mortality. Patient data, including age, sex, condition, and bloodwork results, were collected. Trained family physicians confirmed the presence of white nails. Logistic regression analysis was performed to determine the relationship between white nails and death during hospitalization. Of 711 study participants, 74 died during hospitalization. White nails, male sex, and caregiver dependence were associated with high in-hospital mortality (odds ratio (OR) = 3.47, p < 0.001; OR 2.05, p = 0.01; OR 1.92, p = 0.049, respectively). High albumin concentration was associated with low in-hospital mortality (OR = 0.44, p < 0.001). White nails, along with serum albumin concentration, male sex, and caregiver dependence, are associated with mortality. The identification of white nails can predict the deterioration of patients. Various professionals should learn to identify the presence of white nails to facilitate the care of elderly patients.

Hypoalbuminemia Predicts Adverse Events following Unicompartmental Knee Arthroplasty

Hypoalbuminemia is a potentially modifiable risk factor associated with adverse events following total knee arthroplasty. The present study aimed to evaluate whether hypoalbuminemia similarly predisposes to adverse events following unicompartmental knee arthroplasty (UKA). Patients who underwent UKA during 2006–2018 were identified through the American College of Surgeons National Surgical Quality Improvement Program. Only patients with preoperative serum albumin concentration were included. Outcomes were compared between patients with and without hypoalbuminemia (serum albumin concentration < 3.5 g/dL). All associations were adjusted for demographic, comorbidity, and laboratory differences between populations. A total of 11,342 patients were identified, of whom 6,049 (53.3%) had preoperative serum albumin laboratory values available for analysis. After adjustment for potential confounders, patients with hypoalbuminemia had a greater than 2-fold increased probability for occurrence of any complication (7.02% vs. 2.23%, p = 0.009) and a 4-fold increased probability of receiving a blood transfusion (1.81% vs. 0.25%, p = 0.045). Among procedures performed as inpatients, mean postoperative length of stay (LOS) was longer in patients with hypoalbuminemia (2.2 vs. 1.8 days; p = 0.031). Hypoalbuminemia is independently associated with complications and increased LOS following UKA and a marker for patients at higher risk of postoperative complications. Patients should be screened for hypoalbuminemia and nutritional deficiencies addressed prior to UKA.