Effects of high salt diet on blood pressure and the renal handling of sodium

Introduction: The association between elevated dietary salt consumption and high blood pressure is well known. Hypertension carries elevated risk for stroke, cardiovascular disease, liver disease, and nervous disorders. Interestingly, sex differences in many areas of pathophysiology. Pre-menopausal women have shown to be protected against hypertension and renal diseases compared to age matched men. It is reasonable to expect that how the kidney handles sodium in presence of high-salt consumption plays a key role in sex differences. The purpose of this study was to determine sex differences in the renal handling of sodium in mice consuming a high-salt diet. We also investigated the effects of high-salt consumption on blood pressure in these mice.Methods: Intact male and female mice (n=6/group) consumed a high-salt (4%, HarlanTeklad) diet for 30 days. Mice were placed individually in metabolic cages where urine could be collected for volume and measurement of Na+ concentration. Urinary Na+ excretion (NAE, mg/day) was determined from daily measurements of urine sodium concentration and urine volume. Sodium intake (Nai, mg/day) was determined from daily food intake of 4% salt diet ad libitum. Blood pressure was measured daily via the tail-cuff method. Expression of key sodium transport proteins in the kidney was measured via real-time quantitative PCR.Results: From the data accumulated during the 30-day period of high salt consumption, female mice showed a significantly lower average of the output-to-input Na+ ratio (NAE/Nai) compared to male mice (53.3 ± 2.7 vs 68.1 ± 1.8, respectively, p<0.0001). Female mice showed lower mean blood pressure (MBP, mmHg) compared to male mice over the 30-day period (78.4 ± 1.0 vs 84.9 ± 1.2 respectively, <0.0005). Molecular expression of the key sodium transporter Na+ -2Cl- -K + (NKCC) in the thick ascending limb was over 5-fold higher in the female kidney.Conclusion: Interestingly, results from this study demonstrated that female mice retained more ingested sodium compared to male mice while on a high-salt diet. Moreover, female mice had lower MBP compared to male mice while on a high-salt diet. We suspect that sex steroids are playing important roles in the renal handling of sodium and in the control of blood pressure. This study suggests that females are protected from deleterious effects of high-salt consumption

Cross sectional analysis of the impact of a language barrier in the osteoarthritic Latina population

Background: Osteoarthritis (OA) is a very prominent musculoskeletal disorder that affects approximately 303 million people worldwide. Numerous studies have shown language barriers interfere with the ability of Spanish speakers to communicate their pain symptoms to non-Spanish speaking physicians. The challenge that language barriers present to the Latina population in regard to the diagnosis and treatment of osteoarthritis remain largely unknown.Hypothesis: We hypothesize that the presence of a language barrier will negatively affect the diagnosis and treatment of osteoarthritis, leading to worse health outcomes for the Latina population.Methods: We analyzed data from the CDC’s Behavioral Risk Screening and Surveillance System, combining the 2017-2020 cycles using sampling weights provided by BRFSS, adjusted for multiple cycles. Determination of English- or Spanish-speaking groups was based on the language of the survey submitted with 20,659 and 18,559 in each group respectively (n=39,218). We calculated population estimates for arthritis diagnosis, physical limitations, and mean joint pain among language groups and by age (40+ and 65+), and determined associations via odds ratios.Results: Rates of arthritis diagnosis between groups were similar for both age groups; however, we found that Spanish speaking Latinas 65+ were statistically more likely to report being limited by pain. Further, Spanish speaking Latinas in both age groups reported higher pain scores than the English speaking group (p < .001).Conclusions: Results from this study show that while there were no significant differences in rates of diagnosis, Spanish-speaking Latinas were more likely to be limited by joint pain and report higher pain scores. Given potential language barriers and potentially later diagnosis, emphasizing the holistic nature of osteopathic medicine should strive to provide equitable treatment and support for Spanish-speaking women. When language barriers exist, incorporating translators in medical settings may improve outcome

Investigation of acetate sensitivity within shf1 Chlamydomonas mutants

Cilia and flagella are essential for human health. Defects in the assembly and function of these organelles are associated with a collection of disorders called ciliopathies. Studies have suggested that regulation of ciliary size is associated with external environmental factors. Although TOR signaling pathway has recently been implicated as playing a pivotal role in linking the cellular environment with determination of cell and organelle size, additional biological pathways involved in this process remain largely unknown. Short flagellar (shf) mutants of Chlamydomonas assemble flagella that are half the length of wild-type cells. Consistent with the observation that ciliary length and cell size are interconnected, shf1 cell volume is increased compared to wild-type cells. Interestingly, shf1 mutants are aflagellate when grown in the presence of acetate. To learn more about the acetate sensitivity, we examined the ultrastructure of shf1 mutants following the addition of acetate. Microscopic analysis revealed notable deformities in the flagellar ultrastructure. Currently, we are using a biochemical and global proteomic approach to learn more about the function of the SHF1 gene product

Sex differences in protein excretion in mice consuming high protein diet

Background: Normally, the renal excretion of protein (or proteinuria) is absent or very small. Ingesting high-protein diets can elevate proteinuria and in the long term, increase the work on the kidney by increasing glomerular filtration and higher energy requirement to handle the protein. Sex differences in renal function are well known and thus, differences in proteinuria may exist. The purpose of this study was to determine if sex differences exist in proteinuria in mice consuming high protein diet and investigate the potential roles of the sex steroids 17beta-estrogen (E2) and testosterone.Methods: Healthy 3-4-week-old male and female intact and gonadectomized mice were used. Mice were placed in individual metabolic cages where the urine of each mouse could be collected and measured for protein concentration. Mice consumed a 40% casein protein diet for 25 days (normal protein = 20% protein). Some gonadectomized female mice received exogenous E2 and gonadectomized male mice received exogenous testosterone. Proteinuria was measured via dipstick measurement and protein excretion (mg/day) i.e., urine flow rate (ml/day) x urine protein concentration(mg/day).Results: Intact male mice had significantly higher proteinuria compared to intact female mice (5-10 mg/day vs 25-30 mg/day, p<0.001). Gonadectomized male and female mice had very low proteinuria (3- 5 mg/day). Gonadectomized testosterone-treated male mice had high proteinuria not different from the intact male mice. Gonadectomized E2-treated female mice had similar proteinuria compared to intact female mice and slightly though not significantly higher than gonadectomized placebo-treated female mice.Conclusion: The results of this study suggest that the male sex steroid induces high proteinuria in mice consuming high protein levels. The female sex steroid plays no role or only a minor role in proteinuria under these experimental conditions. Our results suggest that androgens may account for the higher incidence of kidney disease in males compared to age-matched pre-menopausal females

Sex differences in blood pressure and renal handling of sodium in mice on a high salt and high fructose diet

Background: High consumption of either fructose or salt can have deleterious consequences on health and consuming high levels of both leads to serious health problems. Research demonstrates that important sex differences exist with respect to renal metabolism of high fructose intake which directly effects renal handling of sodium. The objective of this study was to investigate sex differences in blood pressure and renal handling of sodium in mice consuming a high-salt and high-fructose (HSHF) diet. We set out to determine if females are protected from high blood pressure when consuming HSHF.Methods: Healthy 4-week-old male and female mice (n=6/group) were placed in metabolic cages for six weeks. For the first week (baseline), all mice consumed a normal diet (0.25% salt) with water. Mice were then placed on the HSHF diet consisting of 4% salt chow with a drinking solution of 20% fructose and 1% NaCl for the next 4 weeks. This was followed by a recovery week with mice on the normal diet with water. Blood pressure was measured daily via the tail cuff technique and averaged weekly. Daily measurements of sodium intake and output were measured. Sodium intake (Nai, mEq/day) was calculated from daily food and fluid consumptionand output was measured by sodium excretion (Nae, mEq/day) (urine volume, ml/day x urine sodium concentration, mEq/day). Sodium concentration was measured using the EasyLyte Na/K analyzer. The ratio Nae/Nai indicates sodium retention. Real-time PCR was conducted using custom-made PCR arrays made by Qiagen SA Biosciences) designed with specific primers for mouse renal Na+ transporters.Results: Mean blood pressure (MBP) was not different between male and female mice in the baseline week and in the first week on HSHF diet. MBP significantly increased in female mice in the 2nd week on the HSHF diet whereas MBP increased in male mice only slightly from baseline. In the 3rd week on HSHF diet male MBP increased to that of the females and MBP in both sexes remained high in the 4th week. In the recovery week, MBP remained elevated in females whereas MBP in males decreased significantly (p<0.01 compared to females). Female mice showed higher sodium retention during the HSHF period via the Nae/Nai (62±5% vs 75±5%, p<0.001). Molecular expression of renal sodium transporters showed significantly higher expression of the NKCC and the NCC transporter in the female kidney.Conclusion: Results indicate that the HSHF diet significantly increased MBP in female and male mice. MBP in females increased before that in males and remained elevated during the recovery period whereas blood pressure decreased in males in the recovery period. Females had higher retention of sodium and higher expression of renal sodium transporters. We conclude that female mice are not protected from the HSHF dietary-induced increase in blood pressure. This study challenges the current position that females possess protective mechanisms against dietary induced increase in blood pressure

Adverse childhood experiences and subjective cognitive decline: An analysis of the Behavioral Risk Factor Surveillance System

Background: Cognitive functioning plays a crucial role in maintaining a healthy, active, and independent lifestyle. A 2017 study found the total net cost of care for an individual with dementia was 175% more than a person without dementia 1 . With an aging population and increasing rates of dementia in the U.S., improved etiology of cognitive decline is pertinent to establishing preventative measures, and therefore slowing increasing rates. The aim of this study was to determine the association between domains of Adverse Childhood Experiences (ACEs), and subjective cognitive decline (SCD) in a representative sample of the US adult population.Methods: Data was obtained from the 2019 and 2020 Behavioral Risk Factor Surveillance Survey (N=18,096; > 45 years). ACEs were summed and categorized into 0, 1-2, and 3+ for ACE accumulation analysis. Among individuals reporting one ACE, domains of adversity (Family Mental Illness, Family Substance Abuse, Family Incarceration, Parental Divorce, Intimate Partner Violence, Emotional Abuse, Physical Abuse, and Sexual Abuse) were compared to those reporting 0 ACEs. We estimated prevalence of ACEs among individuals responding to the SCD questions within BRFSS and used multivariate logistic regression to determine the association between ACE domains and SCD.Results: Our sample included 178,441 respondents representing a population estimate of 38,215,839. Among respondents aged 45 and over, 10.14% (n = 18,096; N = 3,960,992) reported experiencing cognitive decline. Mean ACE scores among participants reporting cognitive decline were 2.61 compared to an ACE score 1.44 in participants not reporting cognitive decline, a statistically significant difference (P<.001).Compared to individuals reporting 0 ACEs, individuals reporting 1-2 ACEs were more likely to report frequently experiencing memory (OR: 1.59; 95%CI 1.43-1.76) and even greater among those reporting 3 or more ACEs (OR: 3.58; 95%CI: 3.23-3.96). Individuals reporting 3 or more ACEs were also significantly more likely to report frequent difficulties with ADLs, needing assistance with ADLs, and experiencing social limitations due to cognitive decline compared to individuals with no ACEs. Further, those with higher ACEs scores were significantly less likely to have spoken with a healthcare provider about their cognitive decline. Among individuals reporting 1 ACE of family mental illness, family substance abuse, family incarceration, emotional abuse, and physical abuse had significantly greater odds of reporting memory loss compared to individuals with no ACEs. Individuals with 1 ACE of parental divorce were less likely to get help with ADLs when needed, and individuals reporting 1 ACE of sexual abuse were significantly less likely to experience social limitations compared to those with no ACEs.Conclusions: Having multiple ACEs was significantly associated with higher odds of cognitive decline and associated limitation of social activity and inversely associated with getting help when it is needed. Further, many ACE domains were associated with SCD—a novel addition to the literature and the methodology used herein. Interventions focused on improving cognitive health and preventing cognitive decline should consider the potential role of ACEs among affected population