Mitochondria-Derived Reactive Oxygen Species Contribute to Synergistic Interaction of Diabetes and Hypertension in Causing Chronic Kidney Injury.

Diabetes (DM) and hypertension (HTN) are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. The combination of DM and HTN significantly accelerates development of renal injury; however, the underlying mechanisms of this synergy are still poorly understood. This study assessed whether mitochondria (MT) dysfunction is essential in developing renal injury in a rat model with combined DM and HTN. Type 1 DM was induced in Wistar rats by streptozotocin (STZ). HTN was induced six weeks later by inter-renal aorta constriction between the renal arteries, so that right kidneys were exposed to HTN while left kidneys were exposed to normotension. Kidneys exposed to DM or HTN alone had only mild glomerular injury and urinary albumin excretion (UAE). In contrast, kidneys exposed to DM plus 8 weeks HTN had significantly increased UAE and glomerular structural damage with reduced glomerular filtration rate. Marked increases in MT-derived reactive oxygen species (ROS) were also observed in right kidneys exposed to HTN+DM. We further tested whether treatment with MT-targeted antioxidant (MitoTEMPO) after the onset of HTN attenuates renal injury in rats with DM+HTN. Results show that kidneys in DM+AC+MitoTEMPO rats had lower UAE, less glomerular damage, and preserved MT function compared to untreated DM+AC rats. Our studies indicate that MT-derived ROS play a major role in promoting kidney dysfunction when DM is combined with HTN. Preserving MT function might be a potential therapeutic approach to halt the development of renal injury when DM coexists with HTN.

Parental obesity predisposes offspring to kidney dysfunction and increased susceptibility to ischemia-reperfusion injury in a sex-dependent manner.

Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.

Bilateral Peters' anomaly, aniridia and Wilms tumour (WAGR syndrome) in monozygotic twins.

AIM: This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). METHODS: Two monozygotic female twins were referred at age 2 months with bilateral corneal opacity. A diagnosis of Peters' anomaly associated to aniridia was made in both eyes of both twins. Physical examination and ultrasonography were carried out at 12 months of age to explore the possibility of WAGR-related anomalies, specifically Wilms tumour. DNA were isolated and subjected to whole exome sequencing. RESULTS: Peters' anomaly associated to aniridia in both eyes as well as bilateral Wilms tumour in both children were diagnosed. Exome analyses showed a large heterozygous deletion encompassing 6 648 473 bp in chromosome 11p13, using Integrative Genomics Viewer and AnnotSV software. CONCLUSION: WAGR syndrome is a rare contiguous gene deletion syndrome with a greater risk of developing Wilms tumour associated with Peters' anomaly and congenital aniridia. However, co-occurrence of both anomalies was rarely reported in twins, and never in both eyes of monozygotic twins. Here, we report the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins with WAGR syndrome.

Clinical and radiographic outcomes of a two-piece ceramic implant: one year results from a prospective clinical trial.

OBJECTIVE: To describe the clinical and radiographic performance and survival rate of a new two-piece ceramic implant system after at least 12 months of follow-up. MATERIALS AND METHODS: Sixty-five implants were placed and followed up for at least 12 months (12.3 ± 1.5), in 50 patients. The implants were installed both in fresh extraction sockets and in healed sites and received provisional restoration when the clinical insertion torque was greater than 35Ncm. The primary results describe the survival rate of these implants. Clinical performance was evaluated through the evaluation of the Pink Esthetic Score (PES) and the degree of satisfaction of the patients. Bone loss was measured through radiographic measurements of the marginal bone loss in the mesial (MBLM) and distal (MBLD) sites. RESULTS: The survival rate was 98.5%. The average MBLM was 0.24 mm (± 0.53) and the MBLD was 0.27 mm (± 0.57). A statistical difference was observed only when comparing immediate implants with delayed ones (MBLM - p = 0.046 and MBLD - p = 0.028) and when they received immediate provisionalization or not (MBLM - p = 0.009 and MBLD - p = 0.040). The PES before the intervention (T0) was 13.4 (± 0.8) and the PES at T2 (12-month follow-up) was 12.9 (± 1.5) (p = 1.14). CONCLUSION: The new two-piece ceramic implant used in the present study showed predictable and reliable results, similar to those found with titanium implants after one year of follow-up. CLINICAL RELEVANCE: These implants can be used as an alternative to titanium implants in terms of the marginal bone loss and the degree of patient satisfaction.

Bone Density of the Midpalatal Suture After Surgically Assisted Rapid Maxillary Expansion: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the bone density in the midpalatal suture after 10 months of surgically assisted rapid maxillary expansion (SARME) with the separation of the maxilla into 2 segments. METHODS: Sixty multislice computed tomography (MCT) from 20 patients undergoing SARME were analyzed in 3 periods of time (1 MCT per patient on each occasion): (1) 1 week before surgery, (2) postsurgery immediately after completing the expander activation, and (3) 10 months after the expander activation. On all occasions, the bone density was measured in Hounsfield units on MCT scans in axial and coronal sections, in the anterior (A1), middle (A2), and posterior (A3) regions of the midpalatal suture. RESULTS: The mean percentage values of bone density in Hounsfield units, from the 10-month postactivation period to preoperative in the A1, A2, and A3 regions were 68.38%, 38.21%, and 55.90%, respectively, in the axial norm, and 64.06%, 36.81%, and 55.50% in coronal norm (A1 = A3>A2), with no significant difference in the tomographic cuts (P >0.05). There was no correlation between patient age or amount of expansion in the expander and bone density. CONCLUSIONS: The bone density in the midpalatal suture 10 months after SARME is lower than preexpansion. A denser new bone formation along the suture concentrates closer to the extremities rather than in the central region. Although the maturation of the new bone formation in the midpalatal suture is lower 10 months after SARME, it appears to be sufficient for satisfactory clinical results, regardless of patient age or the amount of expansion in the expander.

Sex differences in weight gain, blood pressure control, and responses to melanocortin-4 receptor antagonism in offspring from lean and obese parents.

We examined potential sex differences in appetite and blood pressure (BP) responses to melanocortin-4 receptor (MC4R) blockade in offspring from lean and obese parents. Offspring from normal (N) diet-fed parents were fed N (NN) or high-fat (H) diets (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were also fed N (HN) or H diets (HH). Adult male and female offspring were implanted with BP telemetry probes and intracerebroventricular cannulas to infuse MC4R antagonist or vehicle. Infusion of the MC4R antagonist SHU-9119 (1 nmol/h) for 7 days caused larger increases in calorie intake and body weight in obese compared with lean offspring. In male offspring, HH and HN groups exhibited higher baseline BP compared with NN and NH, and HH showed a greater reduction in BP during SHU-9119 infusion. In female offspring, HH also showed higher baseline BP and greater reduction in BP during MC4R blockade. SHU-9119 reduced heart rate in all groups, but reductions were more pronounced in offspring from lean parents. Combined α and ß-adrenergic blockade reduced BP more in male HH offspring compared with NN controls. Losartan reduced BP more in male NH, HN, and HH offspring compared with NN controls. Losartan and α- and ß-adrenergic blockade reduced BP similarly in all female groups. These results suggest that endogenous MC4R activity contributes to elevated BP in obese offspring from obese parents. Our findings also indicate important sex differences in the mechanisms of BP control in male and female offspring of obese parents.

Loss of hepatic PPARα in mice causes hypertension and cardiovascular disease.

The leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is cardiovascular disease (CVD). However, the mechanisms are unknown. Mice deficient in hepatocyte proliferator-activated receptor-α (PPARα) (PparaHepKO) exhibit hepatic steatosis on a regular chow diet, making them prone to manifesting NAFLD. We hypothesized that the PparaHepKO mice might be predisposed to poorer cardiovascular phenotypes due to increased liver fat content. Therefore, we used PparaHepKO and littermate control mice fed a regular chow diet to avoid complications with a high-fat diet, such as insulin resistance and increased adiposity. After 30 wk on a standard diet, male PparaHepKO mice exhibited elevated hepatic fat content compared with littermates as measured by Echo MRI (11.95 ± 1.4 vs. 3.74 ± 1.4%, P < 0.05), hepatic triglycerides (1.4 ± 0.10 vs. 0.3 ± 0.01 mM, P < 0.05), and Oil Red O staining, despite body weight, fasting blood glucose, and insulin levels being the same as controls. The PparaHepKO mice also displayed elevated mean arterial blood pressure (121 ± 4 vs. 108 ± 2 mmHg, P < 0.05), impaired diastolic function, cardiac remodeling, and enhanced vascular stiffness. To determine mechanisms controlling the increase in stiffness in the aorta, we used state-of-the-art PamGene technology to measure kinase activity in this tissue. Our data suggest that the loss of hepatic PPARα induces alterations in the aortas that reduce the kinase activity of tropomyosin receptor kinases and p70S6K kinase, which might contribute to the pathogenesis of NAFLD-induced CVD. These data indicate that hepatic PPARα protects the cardiovascular system through some as-of-yet undefined mechanism.

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID-19 therapy.

The immune response is crucial for coronavirus disease 19 (COVID-19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to induce neutrophil activation by CLEC5A and Toll-like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS-CoV-2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS-CoV-2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID-19 patients in comparison with mild COVID-19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID-19. In hamsters, we detected CLEC5A gene expression during 3-15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS-CoV-2, promoting inflammatory cytokine production, probably through an interaction with the receptor-binding domain in the N-acetylglucosamine binding site (NAG-601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID-19 progression; therapy with a monoclonal antibody could be a good strategy for COVID-19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.

Relative enhancement index can be used to quantify liver function in cirrhotic patients that undergo gadoxetic acid-enhanced MRI.

OBJECTIVES: To evaluate MRI with gadoxetic acid to quantify liver function in cirrhotic patients using the relative enhancement index (REI) compared with Child-Pugh score (CPS), MELD score, and indocyanine green plasma disappearance rate (ICG-PDR) and to establish cutoffs for REI to stratify cirrhotic patients into good and poor liver function groups. METHODS: We prospectively evaluated 60 cirrhotic patients and calculated CPS, MELD score, ICG-PDR, and REI for each patient. Spearman's correlation coefficient was used to assess correlation between REI, CPS, MELD, and ICG-PDR. Good and poor liver function groups were created by k-means clustering algorithm using CPS, MELD, and ICG-PDR. ROC curve analysis was performed and optimal cutoff was identified for group differentiation. RESULTS: Good correlations were found between REI and other liver function biomarkers: REI and CPS (rho = - 0.816; p < 0.001); REI and MELD score (rho = - 0.755; p < 0.001); REI and ICG-PDR (rho = 0.745; p < 0.001)]. REI correlation was stronger for patients with Child-Pugh A (rho = 0.642, p = 0.002) and B (rho = 0.798, p < 0.001) than for those with Child-Pugh C (rho = 0.336, p = 0.148). REI is significantly lower in patients with poor liver function (p < 0.001). ROC curve showed an AUC 0.94 to discriminate patients with poor liver function (REI cutoff < 100; 100% sensitivity; 76% specificity). CONCLUSIONS: REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. REI can be easily calculated and can be used to estimate liver function in clinical practice in the routine evaluation of cirrhotic patients that undergo MR imaging with gadoxetic acid contrast. KEY POINTS: • REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. • REI can be easily calculated in the routine evaluation of cirrhotic patients that undergo gadoxetic acid-enhanced MRI. • The REI enables stratification of cirrhotic patients into good and poor liver function groups and can be used as additional information, together with morphological and focal liver lesion evaluation.

Is dynapenic abdominal obesity a risk factor for cardiovascular mortality? A competing risk analysis.

BACKGROUND: Dynapenic abdominal obesity has been shown as a risk factor for all-cause mortality in older adults. However, there is no evidence on the association between this condition and cardiovascular mortality. OBJECTIVE: We aimed to investigate whether dynapenic abdominal obesity is associated with cardiovascular mortality in individuals aged 50 and older. METHODS: A longitudinal study with an 8-year follow-up was conducted involving 7,030 participants of the English Longitudinal Study of Ageing study. Abdominal obesity and dynapenia were respectively defined based on waist circumference (> 102 cm for men and > 88 cm for women) and grip strength (< 26 kg for men and < 16 kg for women). The sample was divided into four groups: non-dynapenic/non-abdominal obesity (ND/NAO), non-dynapenic/abdominal obesity (ND/AO), dynapenic/non-abdominal obesity (D/NAO) and dynapenic/abdominal obesity (D/AO). The outcome was cardiovascular mortality. The Fine-Grey regression model was used to estimate the risk of cardiovascular mortality as a function of abdominal obesity and dynapenia status in the presence of competing events controlled by socio-demographic, behavioural and clinical variables. RESULTS: The risk of cardiovascular mortality was significantly higher in individuals with D/AO compared with ND/NAO (SHR 1.85; 95% CI: 1.15-2.97). D/NAO was also associated with cardiovascular mortality (SHR: 1.62; 95% CI: 1.08-2.44). CONCLUSION: Dynapenic abdominal obesity is associated with cardiovascular mortality, with a larger effect size compared to dynapenia alone in individuals older than 50 years. Thus, prevention strategies and clinical interventions that enable mitigating the harmful effects of these conditions should be adopted to diminish such risk.

The role of glyphosate-resistant weeds and starvation on biological, reproductive, and preference parameters of Chrysodeixis includens (Lepidoptera: Noctuidae).

Glyphosate-resistant weeds are difficult to manage and can serve as hosts for pests that threaten cultivated crops. Chrysodeixis includens (Walker) (Lepidoptera: Noctuidae) is one of the main polyphagous pests of soybean in Brazil that can benefit from weeds' presence during season and off-season. Despite its pest status, little is known about C. includens survival and development on alternative hosts, including those resistant to glyphosate. Therefore, we assessed the biology, reproduction, preference, and survival at different feeding periods of C. includens on seven glyphosate-resistant weeds (Sumatran fleabane, Italian ryegrass, sourgrass, goosegrass, smooth pigweed, wild poinsettia, hairy beggarticks) commonly found in Brazilian agroecosystems, under laboratory conditions. Our results showed that C. includens survival and reproduction were similar on soybean and wild poinsettia. Survival and reproduction were lower on smooth pigweed and hairy beggarticks. Also, these plants prolonged the larval stage. Larvae did not pupate when fed on sourgrass, goosegrass, Italian ryegrass, and Sumatran fleabane. However, on Sumatran fleabane their biomass was higher. The mean generation time was lower on wild poinsettia. This weed was preferred to soybean. An antifeeding factor was observed on Sumatran fleabane. Larvae fed for 11 days on soybean, wild poinsettia and smooth pigweed developed into pupae. In agricultural systems, farmers must pay attention to the management of these weeds, especially wild poinsettia, smooth pigweed, and hairy beggarticks, to interrupt the cycle of this pest, since these plants can serve as main sources of infestation for the soybean crop.

Animal models and SARS-CoV-2-induced pulmonary and neurological injuries.

Laboratory animals are essential mainly for experiments aiming to study pathogenesis and evaluate antivirals and vaccines against emerging human infectious diseases. Preclinical studies of coronavirus disease 19 (COVID-19) pathogenesis have used several animal species as models: transgenic human ACE2 mice (K18 mice), inbred BALB/c or C57BL/6N mice, ferrets, minks, domestic cats and dogs, hamsters, and macaques. However, the choice of an animal model relies on several limitations. Besides the host susceptibility, the researcher's experience with animal model management and the correct interpretation of clinical and laboratory records are crucial to succeed in preclinical translational research. Here, we summarise pathological and clinical findings correlated with virological data and immunological changes observed from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experimental infections using different well-established SARS-CoV-2 animal model species. This essay aims to critically evaluate the current state of animal model translation to clinical data, as described in the human SARS-CoV-2 infection.

Randomized clinical trial of surgically assisted rapid maxillary expansion with two and three segments for nasal breathing.

OBJECTIVES: To evaluate surgically assisted rapid maxillary expansion (SARME), with osteotomies separating the maxilla into two segments (SARME-2S) and three segments (SARME-3S), on obstruction symptoms and nasal cavity dimensions in patients with maxillary transverse skeletal deficiency (MTSD). MATERIALS AND METHODS: Sixteen patients with MTSD of 7 mm or above were evaluated in each group, for a total of 32 patients. All patients were evaluated pre- and postoperatively up to 10 months after the expander activations. The minimum cross-sectional area (MCA) and the volume of the nasal cavities were identified by acoustic rhinometry. The Nasal Obstruction Symptom Evaluation (NOSE) scale questionnaire was applied. The palate surface area (PSA) was measured, via digitized maxillary models, as a criterion for comparison with the other variables studied. RESULTS: There was no difference between the groups (p = 0.370) and was verified a significant increase in PSA postoperatively. MCA showed a small increase without statistical significance, and together with the volume of the nasal cavities remained constant during the study. NOSE scale scores decreased significantly in the postoperative periods, implying a decrease in nasal obstruction symptoms in both groups. CONCLUSIONS: SARME with two and three segments show similar results, and both may improve nasal obstruction symptoms when present in patients with MTSD. CLINICAL RELEVANCE: SARME, regardless of the chosen surgical technique, should follow the recommendation to correct just the MTSD. While an improvement in nasal breathing is expected, this must be understood as likely, but not certain.

Decoupling of Temperature and Strain Effects on Optical Fiber-Based Measurements of Thermomechanical Loaded Printed Circuit Board Assemblies.

This study investigated the use of distributed optical fiber sensing to measure temperature and strain during thermomechanical processes in printed circuit board (PCB) manufacturing. An optical fiber (OF) was bonded to a PCB for simultaneous measurement of temperature and strain. Optical frequency-domain reflectometry was used to interrogate the fiber optic sensor. As the optical fiber is sensitive to both temperature and strain, a demodulation technique is required to separate both effects. Several demodulation techniques were compared to find the best one, highlighting their main limitations. The importance of good estimations of the temperature sensitivity coefficient of the OF and the coefficient of thermal expansion of the PCB was highlighted for accurate results. Furthermore, the temperature sensitivity of the bonded OF should not be neglected for accurate estimations of strains. The two-sensor combination model provided the best results, with a 2.3% error of temperature values and expected strain values. Based on this decoupling model, a methodology for measuring strain and temperature variations in PCB thermomechanical processes using a single and simple OF was developed and tested, and then applied to a trial in an industrial environment using a dynamic oven with similar characteristics to those of a reflow oven. This approach allows the measurement of the temperature profile on the PCB during oven travel and its strain state (warpage).

Transient receptor potential cation channel 6 contributes to kidney injury induced by diabetes and hypertension.

Diabetes mellitus (DM) and hypertension (HTN) are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed whether DM and HTN interact synergistically to promote kidney dysfunction and whether transient receptor potential cation channel 6 (TRPC6) contributes to this synergism. In wild-type (WT; B6/129s background) and TRPC6 knockout (KO) mice, DM was induced by streptozotocin injection to increase fasting glucose levels to 250-350 mg/dL. HTN was induced by aorta constriction (AC) between the renal arteries. AC increased blood pressure (BP) by ∼25 mmHg in the right kidney (above AC), whereas BP in the left kidney (below AC) returned to near normal after 8 wk, with both kidneys exposed to the same levels of blood glucose, circulating hormones, and neural influences. Kidneys of WT mice exposed to DM or HTN alone had only mild glomerular injury and urinary albumin excretion. In contrast, WT kidneys exposed to DM plus HTN (WT-DM + AC mice) for 8 wk had much greater increases in albumin excretion and histological injury. Marked increased apoptosis was also observed in the right kidneys of WT-DM + AC mice. In contrast, in TRPC6 KO mice with DM + AC, right kidneys exposed to the same levels of high BP and high glucose had lower albumin excretion and less glomerular damage and apoptotic cell injury compared with right kidneys of WT-DM + AC mice. Our results suggest that TRPC6 may contribute to the interaction of DM and HTN to promote kidney dysfunction and apoptotic cell injury.NEW & NOTEWORTHY A major new finding of this study is that the combination of moderate diabetes and hypertension promoted marked renal dysfunction, albuminuria, and apoptotic cell injury, and that these effects were greatly ameliorated by transient receptor potential cation channel 6 deficiency. These results suggest that transient receptor potential cation channel 6 may play an important role in contributing to the interaction of diabetes and hypertension to promote kidney injury.

Transient receptor potential cation channel 6 deficiency leads to increased body weight and metabolic dysfunction.

Transient receptor potential cation channel 6 (TRPC6), a member of the TRPC family, is expressed in the hypothalamus and modulates cell Ca2+ influx. However, the role of TRPC6 in controlling metabolic and cardiovascular functions under normal conditions has not been previously determined. Thus the impacts of TRPC6 deletion on energy balance, metabolic, and cardiovascular regulation as well as the anorexic responses to leptin and melanocortin 3/4 receptor (MC3/4R) activation were investigated in this study. Extensive cardiometabolic phenotyping was conducted in male and female TRPC6 knockout (KO) and control mice from 6 to 24 wk of age to assess mechanisms by which TRPC6 influences regulation of energy balance and blood pressure (BP). We found that TRPC6 KO mice are heavier with greater adiposity, are hyperphagic, and have reduced energy expenditure, impaired glucose tolerance, hyperinsulinemia, and increased liver fat compared with controls. TRPC6 KO mice also have smaller brains, reduced proopiomelanocortin mRNA levels in the hypothalamus, and impaired anorexic response to leptin but not to MC3/4R activation. BP and heart rate, assessed by telemetry, were similar in TRPC6 KO and control mice, and BP responses to air-jet stress were attenuated in TRPC6 KO mice despite increased body weight and metabolic disorders that normally raise BP and increase BP responses to stress. Our results provide evidence for a novel and important role of TRPC6 in controlling energy balance, adiposity, and glucose homeostasis, which suggests that normal TRPC6 function may be necessary to link weight gain and hyperleptinemia with BP responses to acute stress.

Parental obesity alters offspring blood pressure regulation and cardiovascular responses to stress: role of P2X7R and sex differences.

We examined the impact of parental obesity on offspring blood pressure (BP) regulation and cardiovascular responses to stress. Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were also fed N (HN) or H diet (HH). Body weight, calorie intake, and fat mass were measured at 22 wk of age when cardiovascular phenotyping was performed. Male and female HH offspring were 15% heavier than NH and 70% heavier than NN offspring. Male HH and HN offspring had elevated BP (121 ± 2 and 115 ± 1 mmHg, by telemetry) compared with male NH and NN offspring (108 ± 6 and 107 ± 3 mmHg, respectively) and augmented BP responses to angiotensin II, losartan, and hexamethonium. Male HH and HN offspring also showed increased BP responses to air-jet stress (37 ± 2 and 38 ± 2 mmHg) compared with only 24 ± 3 and 25 ± 3 mmHg in NH and NN offspring. Baseline heart rate (HR) and HR responses to air-jet stress were similar among groups. In females, BP and cardiovascular responses to stress were similar among all offspring. Male H diet-fed offspring from obese H diet-fed purinoreceptor 7-deficient (HH-P2X7R-KO) parents had normal BP that was similar to control NN-P2X7R-KO offspring from lean parents. These results indicate that parental obesity leads to increased BP and augmented BP responses to stress in their offspring in a sex-dependent manner, and the impact of parental obesity on male offspring BP regulation is markedly attenuated in P2X7R-KO mice.

Are Serum 25-Hydroxyvitamin D Deficiency and Insufficiency Risk Factors for the Incidence of Dynapenia?

Epidemiological evidence showing the association between low 25(OH)D and age-related reduction in neuromuscular strength (dynapenia) is a paucity and controversial and, to date, the effect of osteoporosis and vitamin D supplementation on these associations has not been measured. Thus, we analyze whether serum 25(OH)D deficiency and insufficiency are risk factors for the incidence of dynapenia in individuals aged 50 or older and whether osteoporosis or vitamin D supplementation modify these associations. For that, 3205 participants of the ELSA study who were non-dynapenic at baseline were followed for 4 years. Vitamin D was measured at baseline by the serum concentration of 25(OH)D and classified as sufficient (> 50 nmol/L), insufficient (≥ 30 and ≤ 50 nmol/L) or deficient (< 30 nmol/L). The incidence of dynapenia was determined by a grip strength < 26 kg for men and < 16 kg for women at the end of the 4-year follow-up. Poisson regression models were adjusted by sociodemographic, behavioral, clinical and biochemical characteristics. Serum 25(OH)D deficient was a risk factor for the incidence of dynapenia (IRR = 1.70; 95% CI 1.04-2.79). When only individuals without osteoporosis and those who did not use vitamin D supplementation were analyzed, both serum 25(OH)D deficiency (IRR = 1.78; 95% CI 1.01-3.13) and insufficiency (IRR = 1.77; 95% CI 1.06-2.94) were risk factors for the incidence of dynapenia. In conclusion, a serum level of 25(OH)D < 30 nmol/L is a risk factor for the incidence of dynapenia. Among individuals without osteoporosis and those who do not take vitamin D supplementation, the threshold of risk is higher (≤ 50 nmol/L).

Higher hemoglobin levels are associated with better physical performance among older adults without anemia: a longitudinal analysis.

BACKGROUND: Anemia is the most common hematological abnormality among older adults, and it is associated with decreased physical performance. But the role of hemoglobin in the absence of anemia remains unclear. Thus, this study aimed to assess the impact of hemoglobin levels on physical performance in Brazilian older adults without anemia. METHODS: The study is longitudinal in that it relies on two waves of the Saúde, Bem-Estar e Envelhecimento (SABE; Health, Well-being, and Aging) study: 2010 and 2015-2016. Mixed-effects linear regression was used to determine the effects of the hemoglobin concentrations on the Short Physical Performance Battery-SPPB over time among the 1,023 who had complete data and did not have anemia in 2010. In the follow-up, there were 567 without anemia. RESULTS: In analyses adjusted for age, education, comorbidities, body mass index, and physical inactivity, we found a differential association between hemoglobin concentration and SBBP by sex, with a positive interaction (ß Hb*female= 0.20, 95% CI 0.04,0.37). At lower levels of hemoglobin, women have lower levels of SPPB than men, but at higher levels of hemoglobin concentration, there are no sex differences in physical performance. In addition, higher age was negatively associated with SPPB levels and cardiometabolic diseases, other diseases, and physical inactivity. Education was positively associated with physical performance. CONCLUSION: Our study demonstrates that higher hemoglobin levels were associated with better physical performance among older adults without anemia in Brazil. However, there were sex differences in this association. This finding is important because, in clinical practice, most health professionals focus on the World Health Organization definition of anemia. Our study suggests the importance of hemoglobin levels among older adults, even those without anemia, and highlights sex differences.