Interplay of mitochondria-associated membrane proteins and autophagy: Implications in neurodegeneration.

Since the discovery of membrane contact sites between ER and mitochondria called mitochondria-associated membranes (MAMs), several pieces of evidence identified their role in the regulation of different cellular processes such as Ca2+ signalling, mitochondrial transport, and dynamics, ER stress, inflammation, glucose homeostasis, and autophagy. The integrity of these membranes was found to be essential for the maintenance of these cellular functions. Accumulating pieces of evidence suggest that MAMs serve as a platform for autophagosome formation. However, the alteration within MAMs structure is associated with the progression of neurodegenerative diseases. Dysregulated autophagy is a hallmark of neurodegeneration. Here, in this review, we highlight the present knowledge on MAMs, their structural composition, and their roles in different cellular functions. We also discuss the association of MAMs proteins with impaired autophagy and their involvement in the progression of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

Riverine connectivity influences the phytoplankton ecology in the open floodplain wetland of the lower river Ganga.

The river Ganga has several floodplain wetlands that support its ecology and ecosystem. Phytoplankton is an important component of the aquatic ecosystem, which plays an important role as a bioindicator for the assessment of aquatic health. The present study was conducted between 2018 and 2019 to understand the seasonal variation in the phytoplankton diversity of the Charaganga wetland and, parallelly, in the river Ganga in Nabadweep, India. The study explains how riverine connectivity affects the structure of the algal community in the wetland ecosystem. In the study, it has been observed that in the wetland, maximum mean phytoplankton density was noticed during pre-monsoon, i.e., 4079 unit l-1 followed by post-monsoon 3812 unit l-1 and monsoon 550 unit l-1, respectively. In the river system, the phytoplankton density varied from 78 unit l-1 to 653 unit l-1 seasonally, i.e., highest during monsoon and lowest during pre-monsoon. In both the ecosystems, i.e., wetland and river, the supreme influential group was Cyanophyceae followed by diatoms. One-way ANOVA showed a significant variation (p > 0.05) of three algal groups of phytoplankton (Bacillariophyceae, Coscinodiscophyceae, Chlorophyceae) in the river, while in the wetland, no significant variation (p > 0.05) was found among the other algal groups. The observed higher Shannon and Margalef's species richness value in the wetland was observed than in the river defines the significance and importance of the wetland ecosystem, which may support the growth and conservation of various aquatic organisms as well. The study highlighted that the influencing abiotic factors like water temperature, dissolved oxygen, pH, and nutrients have affected the phytoplankton community in both the water bodies, i.e., wetland and river. We concluded that river connectivity is required to restore the biotic flora of the wetland ecosystem.

Association of Higher Intake of Plant-Based Foods and Protein With Slower Kidney Function Decline in Women With HIV.

BACKGROUND: We investigated whether there exists an association between dietary acid load and kidney function decline in women living with HIV (WLWH) receiving antiretroviral therapy (ART). SETTING: One thousand six hundred eight WLWH receiving ART in the WIHS cohort with available diet data and a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/minute/1.73 m2. METHODS: A brief dietary instrument conducted from 2013 to 2016 under the Food Insecurity Sub-Study was used for assessing fruits and vegetables (FV) and protein intake. A mixed-effects model with random intercept and slope was used to estimate subjects' annual decline rate in eGFR and the association between FV intake and eGFR decline, adjusting for sociodemographics, serum albumin, comorbidities, time on ART, ART drugs, HIV markers, and baseline eGFR. We evaluated whether markers of inflammation mediated the effect of FV intake on decline in eGFR, using causal mediation analysis. RESULTS: We found a dose-response relationship for the association of FV intake and eGFR decline, with lesser annual decline in eGFR in the middle and highest tertiles of FV intake. An increase of 5 servings of FV intake per day was associated with a lower annual eGFR decline (-1.18 [-1.43, -0.94]). On average, 39% of the association between higher FV intake and slower eGFR decline was explained by decreased levels of inflammation. CONCLUSIONS: Plant-rich diet was associated with slower decline in kidney function. Inflammation is a potential path through which diet may affect kidney function. The findings support an emerging body of literature on the potential benefits of plant-rich diets for prevention of chronic kidney disease.

Ameliorative effect of natural floating island as fish aggregating devices on heavy metals distribution in a freshwater wetland.

Growing human population and climate change are leading reasons for water quality deterioration globally; and ecologically important waterbodies including freshwater wetlands are in a vulnerable state due to increasing concentrations of pollutants like heavy metals. Given the declining health of these valuable resources, the present study was conducted to evaluate the effect of natural floating island in the form of fish aggregating devices (FADs) made of native weed mass on the distribution of heavy metals in the abiotic and bio compartments of a freshwater wetland. Lower concentrations of surface water heavy metals were observed inside the FADs with a reduction of 73.91%, 65.22% and 40.57-49.16% for Cd, Pb and other metals (viz. Co, Cr, Cu, Ni and Zn), respectively as compared to outside FAD. These led to 14.72-55.39% reduction in the heavy metal pollution indices inside the FAD surface water. The fish species inside the FADs were also found less contaminated (24.07-25.07% reduction) with lower health risk indices. The study signifies the valuable contribution of natural floating island as FADs in ameliorating the effect of heavy metals pollution emphasizing the tremendous role of the natural floating islands in sustainable maintenance of freshwater wetlands for better human health and livelihood.

DNA Methylation-Mediated Mfn2 Gene Regulation in the Brain: A Role in Brain Trauma-Induced Mitochondrial Dysfunction and Memory Deficits.

Repeated mild traumatic brain injuries (rMTBI) affect mitochondrial homeostasis in the brain. However, mechanisms of long-lasting neurobehavioral effects of rMTBI are largely unknown. Mitofusin 2 (Mfn2) is a critical component of tethering complexes in mitochondria-associated membranes (MAMs) and thereby plays a pivotal role in mitochondrial functions. Herein, we investigated the implications of DNA methylation in the Mfn2 gene regulation, and its consequences on mitochondrial dysfunction in the hippocampus after rMTBI. rMTBI dramatically reduced the mitochondrial mass, which was concomitant with decrease in Mfn2 mRNA and protein levels. DNA hypermethylation at the Mfn2 gene promoter was observed post 30 days of rMTBI. The treatment of 5-Azacytidine, a pan DNA methyltransferase inhibitor, normalized DNA methylation levels at Mfn2 promoter, which further resulted into restoration of Mfn2 function. The normalization of Mfn2 function was well correlated with recovery in memory deficits in rMTBI-exposed rats. Since, glutamate excitotoxicity serves as a primary insult after TBI, we employed in vitro model of glutamate excitotoxicity in human neuronal cell line SH-SY5Y to investigate the causal epigenetic mechanisms of Mfn2 gene regulation. The glutamate excitotoxicity reduced Mfn2 levels via DNA hypermethylation at Mfn2 promoter. Loss of Mfn2 caused significant surge in cellular and mitochondrial ROS levels with lowered mitochondrial membrane potential in cultured SH-SY5Y cells. Like rMTBI, these consequences of glutamate excitotoxicity were also prevented by 5-AzaC pre-treatment. Therefore, DNA methylation serves as a vital epigenetic mechanism involved in Mfn2 expression in the brain; and this Mfn2 gene regulation may play a pivotal role in rMTBI-induced persistent cognitive deficits. Closed head weight drop injury method was employed to induce repeated mild traumatic brain (rMTBI) in jury in adult, male Wistar rats. rMTBI causes hyper DNA methylation at the Mfn2 promoter and lowers the Mfn2 expression triggering mitochondrial dysfunction. However, the treatment of 5-azacytidine normalizes DNA methylation at the Mfn2 promoter and restores mitochondrial function.

Mechanistic Insight into the role of Vitamin D and Zinc in Modulating Immunity Against COVID-19: A View from an Immunological Standpoint.

The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune cells, followed by necrosis. Consequently, these pathophysiological changes may lead to a life-threatening decline in perfusion due to hyperplasia of the lungs, instigating severe pneumonia, and causing fatalities. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause mortality due to viral septic shock, resulting from unrestrained and backfiring immune reactions to the pathogen. Sepsis can cause premature organ failure in COVID-19 patients, as well. Notably, vitamin D and its derivatives and minerals, such as zinc and magnesium, have been reported to improve the immune system against respiratory illnesses. This comprehensive review aims to provide updated mechanistic details of vitamin D and zinc as immunomodulators. Additionally, this review also focuses on their role in respiratory illnesses, while specifically delineating the plausibility of employing them as a preventive and therapeutic agent against current and future pandemics from an immunological perspective. Furthermore, this comprehensive review will attract the attention of health professionals, nutritionists, pharmaceuticals, and scientific communities, as it encourages the use of such micronutrients for therapeutic purposes, as well as promoting their health benefits for a healthy lifestyle and wellbeing.

Association of Diet-dependent Systemic Acid Load, Renal Function, and Serum Albumin Concentration.

OBJECTIVE: Inflammation may be present with chronic kidney disease CKD and diet composition high in protein intake and fats may affect inflammation thereby impacting kidney health. We investigated whether acid load estimated from urine measures is associated with kidney function decline and whether the effect of acid load on an inflammatory marker, serum albumin, is a pathway to this association. METHODS: We studied 188 postmenopausal women in a randomized clinical trial of potassium bicarbonate treatment for up to 36 months. Twenty-four-hour urine and arterialized blood collections were done at baseline and at subsequent follow-up visits at 3 months interval. Acid load was estimated from potential renal acid load calculated using urinary measures of chloride, phosphate, sodium, potassium, calcium, and magnesium (UPRAL). Mixed effects model with random-intercept and slope was used to estimate subjects' annual decline rate in creatinine clearance (CrCl), and the association between (i) UPRAL and serum albumin and (ii) serum albumin and CrCl, adjusting for age, body mass index, systolic BP, and glucose. A Cox proportional regression model was used to study the relative hazard (RH) for rapid progression of kidney function decline (defined as loss of ≥5 mL/min CrCl/yr based on the last CrCl in the rolling window) with UPRAL, adjusting for the potential covariates and baseline CrCl. RESULTS: A 25 mEq/day increase in UPRAL was inversely associated with serum albumin (Adjusted ß[95% CI]: -0.02[-0.09;-0.001). During a mean follow-up of 28 months, 19 women (10%) had a rapid decline in kidney function. For each 25 mEq/day increase in UPRAL, the risk of a rapid decline in CrCl increased by 17% (95% CI: 1.06-1.28). On adjustment for potential confounders, the risk attenuated to 5% (1.02-1.14). Mediation analysis indicated that of the total effect of the association between UPRAL and CrCl, the proportion mediated by serum albumin increased to 0.346 (i.e. 34.6%). CONCLUSION: Higher UPRAL was associated with lower serum albumin as well as greater kidney function decline in postmenopausal women. Our findings suggest inflammatory response may exert a modulatory effect on the association of UPRAL and kidney function and might be a potential pathway explaining the effects of systemic acid load on progression of kidney failure.

Mitofusin-2: Functional switch between mitochondrial function and neurodegeneration.

Mitochondria are highly dynamic organelles known to play role in the regulation of several cellular biological processes. However, their dynamics such as number, shape, and biological functions are regulated by mitochondrial fusion and fission process. The balance between the fusion and fission process is most important for the maintenance of mitochondrial structure as well as cellular functions. The alterations within mitochondrial dynamic processes were found to be associated with the progression of neurodegenerative diseases. In recent years, mitofusin-2 (Mfn2), a GTPase has emerged as a multifunctional protein which not only is found to regulate the mitochondrial fusion-fission process but also known to regulate several cellular functions such as mitochondrial metabolism, cellular biogenesis, signalling, and apoptosis via maintaining the ER-mitochondria contact sites. In this review, we summarize the current knowledge of the structural and functional properties of the Mfn2, its transcriptional regulation and their roles in several cellular functions with a focus on current advances in the pathogenesis of neurodegenerative diseases.

Proinflammatory Diets and Risk of ESKD in US Adults with CKD.

Background: Inflammation may affect long-term kidney function. Diet may play a role in chronic inflammation. We hypothesized that proinflammatory diets increase the risk of progression to kidney failure with replacement therapy (KFRT), and systemic inflammation is a mediator of the effect of diet on progression to KFRT. Methods: In the 1988-1994 National Health and Nutrition Examination Survey linked to the national ESKD registry, in adults with CKD (eGFR 15-59 ml/min per 1.73 m2), aged ≥20 years, we calculated the Adapted Dietary Inflammatory Index (ADII) at baseline from a 24-hour dietary recall and an inflammation score (IS) using average of z scores of four inflammation biomarkers. We explored the association of the ADII and IS with risk of incident KFRT using Cox proportional model, adjusting for sociodemographics, physical activity, Framingham risk score, eGFR, and urinary ACR. We evaluated whether, and to what extent, IS mediated the effect of the ADII on KFRT incidence, using causal mediation analysis. Results: Of 1084 adults with CKD, 109 (10%) developed KFRT. The ADII was associated with increased risk of KFRT (relative hazard [RH] per SD increase (2.56): 1.4 [1.04-1.78]). IS was also associated with KFRT (RH: 1.12; 95% CI, 1.02 to 1.25). Approximately 36% of the association between the ADII and KFRT was explained by IS. Conclusions: Among adults with CKD, a proinflammatory diet was associated with risk of KFRT, and that association was partially explained by an increase in inflammatory markers. Dietary interventions that reduce inflammation may offer an approach for preventing KFRT.

Dietary Contributions to Metabolic Acidosis.

Eating a net acid-producing diet can produce an "acid stress" of severity proportional to the diet net acid load, as indexed by the steady-state renal net acid excretion rate. Depending on how much acid or base is ingested or produced from endogenous metabolic processes and how well our homeostatic mechanisms can buffer or eliminate the additional acids or bases, we can alter our systemic acid-base balance. With increasing age, the kidney's ability to excrete daily net acid loads declines (a condition similar to that of mild CKD), invoking increased utilization of potential base stores (eg, bone, skeletal muscle) on a daily basis to mitigate the acid accumulation, thereby contributing to development of osteoporosis, loss of muscle mass, and age-related renal insufficiency. Patients suffering from more advanced CKD often present with more severe acid stress or metabolic acidosis, as the kidney can no longer excrete the entire acid load. Alkaline diets based on fruits and vegetables may have a positive effect on long-term preservation of renal function while maintaining nutritional status. This chapter discusses the biochemistry of dietary precursors that affect acid or base production.

Design of a Realtime Photoplethysmogram Signal Quality Checker for Wearables and Edge Computing.

Photoplethysmogram (PPG) signal is extensively used for deducing health parameters of patients in order to infer about physiological conditions of heart, blood pressure, respiratory patterns, and so on. Such analysis and estimations can be done accurately only on high quality PPG signals with very minimal artifacts. PPG signals collected from fitness grade and smart phone scenarios are prone to muscle artifacts and hence there is a need to assess the signal quality before using the signal. Although there are approaches available in the realm of machine learning and deep learning, they are computationally expensive and may not be suitable for a wearable or edge computing scenario. In this paper, we propose the design of a quality checker to check the quality of the signal that can be directly implemented on edge devices like smartwatch. The algorithm is tested on PPG data collected from wearable, ICU and medical grade devices. In the wearable scenario where the noise levels are very high, our algorithm has performed significantly better with a Fscore of over 0.92. Further we show that by applying the proposed quality checker, the accuracy of the computed heart rate from a smart phone PPG-application significantly improves.

In-Hospital and 1-Year Mortality Trends in a National Cohort of US Veterans with Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: AKI, a frequent complication among hospitalized patients, confers excess short- and long-term mortality. We sought to determine trends in in-hospital and 1-year mortality associated with AKI as defined by Kidney Disease Improving Global Outcomes consensus criteria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study used data from the national Veterans Health Administration on all patients hospitalized from October 1, 2008 to September 31, 2017. AKI was defined by Kidney Disease Improving Global Outcomes serum creatinine criteria. In-hospital and 1-year mortality trends were analyzed in patients with and without AKI using Cox regression with year as a continuous variable. RESULTS: We identified 1,688,457 patients and 2,689,093 hospitalizations across the study period. Among patients with AKI, 6% died in hospital, and 28% died within 1 year. In contrast, in-hospital and 1-year mortality rates were 0.8% and 14%, respectively, among non-AKI hospitalizations. During the study period, there was a slight decline in crude in-hospital AKI-associated mortality (hazard ratio, 0.98 per year; 95% confidence interval, 0.98 to 0.99) that was attenuated after accounting for patient demographics, comorbid conditions, and acute hospitalization characteristics (adjusted hazard ratio, 0.99 per year; 95% confidence interval, 0.99 to 1.00). This stable temporal trend in mortality persisted at 1 year (adjusted hazard ratio, 1.00 per year; 95% confidence interval, 0.99 to 1.00). CONCLUSIONS: AKI associated mortality remains high, as greater than one in four patients with AKI died within 1 year of hospitalization. Over the past decade, there seems to have been no significant progress toward improving in-hospital or long-term AKI survivorship.

Understanding the role of nACE2 in neurogenic hypertension among COVID-19 patients.

Currently, the third and fourth waves of the coronavirus disease -19 (COVID-19) pandemic are creating havoc in many parts of the world. Although vaccination programs have been launched in most countries, emerging new strains of the virus along with geographical variations are leading to varying success rates of the available vaccines. The presence of comorbidities such as diabetes, cardiovascular diseases and hypertension is responsible for increasing the severity of COVID-19 and, thus, the COVID-19 mortality rate. Angiotensin-converting enzyme 2 (ACE2), which is utilized by SARS-CoV-2 for entry into host cells, is widely expressed in the lungs, kidneys, testes, gut, adipose tissue, and brain. Infection within host cells mediates RAS overactivation, which leads to a decrease in the ACE2/ACE ratio, AT2R/AT1R ratio, and MasR/AT1R ratio. Such imbalances lead to the development of heightened inflammatory responses, such as cytokine storms, leading to post-COVID-19 complications and mortality. As the association of SARS-CoV-2 infection and hypertension remains unclear, this report provides an overview of the effects of SARS-CoV-2 infection on patients with hypertension. We discuss here the interaction of ACE2 with SARS-CoV-2, focusing on neuronal ACE2 (nACE2), and further shed light on the possible involvement of nACE2 in hypertension. SARS-CoV-2 enters the brain through neuronal ACE2 and spreads in various regions of the brain. The effect of viral binding to neuronal ACE2 in areas of the brain that regulate salt/water balance and blood pressure is also discussed in light of the neural regulation of hypertension in COVID-19.

Diet-dependent acid load is associated with mean arterial pressure in a cohort of non-obese, non-black, postmenopausal women.

Higher sodium (Na+) intake is associated with higher blood pressure (BP). Whether this relationship is stronger with diet-dependent acid load (DAL) and in patients diagnosed with hypertension or normal BP is not well determined. We studied 170 postmenopausal women randomized to receive potassium bicarbonate or placebo for 36 months, after which 24-hour urine and arterialized blood samples were collected. We investigated the association between DAL estimated as urinary potential renal acid load (UPRAL) and mean arterial pressure (MAP) using a mixed-effects model, adjusting for age, anthropometrics, creatinine clearance, and treatment. Adjusted regression estimates for changes in Na+ and UPRAL on MAP after 12 months of follow-up were calculated, and further adjustments were made for changes in potassium (K+) and body mass index (BMI). MAP was inversely associated with UPRAL (ß [95% confidence interval]: -0.11 [-0.25, -0.001]). There was an effect modification by hypertension (p-interaction = 0.04); MAP decreased significantly in normotensives, but the association was not significant in hypertensives. A decrease of 0.70 mm Hg in MAP [0.13, 1.69] per 50 mmol/24 hour reduction in Na+ was noted when the model was adjusted for change in K+. Our results with UPRAL exhibited a stronger dose-response for MAP, which remained significant after adjusting for BMI. UPRAL was independently associated with MAP even after adjusting for potential confounders, and the data showed that this association was more pronounced in normotensive patients. Novelty: First longitudinal study on the association of UPRAL and MAP. Association was a more robust relationship than that between U [Na+/K+] ratio and MAP. UPRAL may play a significant role in the pathogenesis of primary hypertension.

An in silico scientific basis for LL-37 as a therapeutic for Covid-19.

A multi-pronged approach with help in all forms possible is essential to completely overcome the Covid-19 pandemic. There is a requirement to research as many new and different types of approaches as possible to cater to the entire world population, complementing the vaccines with promising results. The need is also because SARS-CoV-2 has several unknown or variable facets which get revealed from time to time. In this work, in silico scientific findings are presented, which are indicative of the potential for the use of the LL-37 human anti-microbial peptide as a therapeutic against SARS-CoV-2. This indication is based on the high structural similarity of LL-37 to the N-terminal helix, with which the virus interacts, of the receptor for SARS-CoV-2, Angiotensin Converting Enzyme 2. Moreover, there is positive prediction of binding of LL-37 to the receptor-binding domain of SARS-CoV-2; this is the first study to have described this interaction. In silico data on the safety of LL-37 are also reported. As Vitamin D is known to upregulate the expression of LL-37, the vitamin is a candidate preventive molecule. This work provides the possible basis for an inverse correlation between Vitamin D levels in the body and the severity of or susceptibility to Covid-19, as widely reported in literature. With the scientific link put forth herein, Vitamin D could be used at an effective, medically prescribed, safe dose as a preventive. The information in this report would be valuable in bolstering the worldwide efforts to eliminate the pandemic as early as possible.

A decoy strategy to activate the immune system.

An approach comprising a novel fusion protein and inactivated virus, as a more efficacious vaccine against invading viruses is presented, using SARS-CoV-2 as a most prominent example. The fusion protein consists of the Hepatitis B surface antigen (HBsAg) conjugated to the N-terminal helix (NTH) of Angiotensin-Converting Enzyme 2 (ACE2), which is the receptor for SARS-CoV-2. For vaccination, this fusion protein is to be administered together with the whole killed virus. The NTH would bind to the Receptor Binding Domain (RBD) of the Spike protein of the killed virus. Due to HBsAg acting as a decoy, immune responses would be mounted. Neutralizing antibodies (NAbs) pre-existing in people already vaccinated with the recombinant Hepatitis B vaccine, fresh production of NAbs, and NAbs produced by memory B cells would bind to the HBsAg. This would lead to "presentation" of the killed virus to elements of the immune system at close range. Also, there would be enhanced opsonization and effective antigen presentation. This two-component vaccine could be a platform strategy, wherein HBsAg could be linked to the part of the cellular receptor that any new intractable virus binds to, and is administered together with whole inactivated virus. Now, the same fusion protein, administered by itself to persons with infection, would have therapeutic action, yet by harnessing elements of the immune system. NAbs would bind to the fusion protein as above, the NTH of which would bind to the RBDs of the infecting virus, which, in effect would be neutralized.

Dietary Factors and Prevention: Risk of End-Stage Kidney Disease by Fruit and Vegetable Consumption.

BACKGROUND: The association between fruit and vegetable (FV) intake and the risk of end-stage kidney disease (ESKD) has not been examined in the general population and fully explored in chronic kidney disease (CKD). We prospectively evaluated this relationship in US representative sample of adults and evaluated consistency by the presence or absence, and severity, of CKD. METHODS: We used data from the Third National Health and Nutrition Examination Survey (1988-1994) linked with the US Renal Data System, including 14,725 adults aged ≥20 years and with follow-up for ESKD through 2008. Daily FV intake was ascertained using a food frequency questionnaire. We examined the association between selected categories of FV intake and ESKD using a Fine Gray competing risk model adjusting for sociodemographics, lifestyle, clinical and nutritional factors, estimated glomerular filtration rate, and albuminuria. We evaluated whether risk varied in individuals with severe versus any CKD. RESULTS: 230 participants (1.5%) developed ESKD during follow-up. In the adjusted model, compared to highest intake, those in lowest categories of FV intake had a higher risk of ESKD, for <2 times/day (1.45 [1.24-1.68], 2 to <3 times/day (1.40 [1.18-1.61]), 3 to <4 times/day (1.25 [1.04-1.46]), and 4 to <6 times/day (1.14 [0.97-1.31]). There was suggestion of heterogeneity (p for interaction = 0.03) with possible stronger inverse association in patients with CKD than those without CKD. After stratification, we obtained similar strong inverse association when we examined ESKD incidence across intake of FVs in participants with CKD stages 1-4 (n = 5,346) and specifically in those with CKD stages 3-4 (n = 1,084). CONCLUSIONS: Low intake of FVs was associated with higher risk of ESKD in US adults with and without CKD, supporting an emerging body of literature on the potential benefits of plant-rich diets for prevention of ESKD.

Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use Among Hypertensive US Adults With Albuminuria.

Since 2003, US hypertension guidelines have recommended ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) as first-line antihypertensive therapy in the presence of albuminuria (urine albumin/creatinine ratio ≥300 mg/g). To examine national trends in guideline-concordant ACE inhibitor/ARB utilization, we studied adults participating in the National Health and Nutrition Examination Surveys 2001 to 2018 with hypertension (defined by self-report of high blood pressure, systolic blood pressure ≥140 mm Hg or diastolic ≥90 mm Hg, or use of antihypertensive medications). Among 20 538 included adults, the prevalence of albuminuria ≥300 mg/g was 2.8% in 2001 to 2006, 2.8% in 2007 to 2012, and 3.2% in 2013 to 2018. Among those with albuminuria ≥300 mg/g, no consistent trends were observed for the proportion receiving ACE inhibitor/ARB treatment from 2001 to 2018 among persons with diabetes, without diabetes, or overall. In 2013 to 2018, ACE inhibitor/ARB usage in the setting of albuminuria ≥300 mg/g was 55.3% (95% CI, 46.8%-63.6%) among adults with diabetes and 33.4% (95% CI, 23.1%-45.5%) among those without diabetes. Based on US population counts, these estimates represent 1.6 million adults with albuminuria ≥300 mg/g currently not receiving ACE inhibitor/ARB therapy, nearly half of whom do not have diabetes. ACE inhibitor/ARB underutilization represents a significant gap in preventive care delivery for adults with hypertension and albuminuria that has not substantially changed over time.

Performance of Predictive Equations and Biochemical Measures Quantifying Net Endogenous Acid Production and the Potential Renal Acid Load.

INTRODUCTION: A limited number of studies have assessed the accuracy and precision of methods for determining the net endogenous acid production (NEAP) and its components. We aimed to investigate the performance of methods quantifying the diet dependent acid-base load. METHODS: Data from metabolic balance studies enabled calculations of NEAP according to the biochemical measures (of net acid excretion [NAE], urinary net endogenous acid production [UNEAP], and urinary potential renal acid load [UPRAL]) as well as estimative diet equations (by Frassetto et al., Remer and Manz, Sebastian et al., and Lemann) that were compared among themselves in healthy participants fed both acid and base forming diets for 6 days each. RESULTS: Seventeen participants (mean ± SD age, 60 ± 8 years; body mass index, 23 ± 2 kg/m2) provided 102 twenty-four-hour urine samples for analysis (NAE, 39 ± 38 mEq/d [range, -9 to 95 mEq/d]). Bland-Altman analysis comparing UNEAP to NAE showed good accuracy (bias, -2 mEq/d [95% confidence interval {CI}, -8 to 3]) and modest precision (limits of agreement, -32 to 28 mEq/d). Accurate diet equations included potential renal acid load (PRAL) by Sebastian et al. (bias, -4 mEq/d [95% CI, -8 to 0]) as well as NEAP by Lemann et al. (bias, 4 mEq/d [95% CI, -1 to 9]) and Remer and Manz (bias, -1 mEq/d [95% CI, -6 to 3]). CONCLUSIONS: Researchers are encouraged to collect measures of UPRAL and UNEAP; however, investigators drawing conclusions between the diet-dependent acid-base load and human health should consider the limitations within all methods.

Nanotized curcumin-benzothiophene conjugate: A potential combination for treatment of cerebral malaria.

The declining effectiveness of the available antimalarial drugs due to drug resistance requires a continued effort to develop new therapeutic approaches. In this context, combination therapies hold a great promise for developing effective first-line antimalarial treatments for reducing malaria mortality. The present study explores the antimalarial efficacy of nanotized formulation of curcumin in combination with benzothiophene compound 6 (3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide) with a view to achieve better efficacy at a very low dose in comparison to that accomplished with monotherapy alone. Herein, we formulated nanotized conjugate of curcumin and compound 6 (cur-compound 6) in the size range of 30-90 nm as observed via TEM, AFM and DLS analysis in the study. The nanotized preparation was found to be readily dispersible in water, physically and chemically stable and exhibited sustained release profile of both curcumin and compound 6 till 48 hr. Treatment of P. falciparum parasites with the nanotized conjugate for 24 hr resulted in rapid clearance of the parasites. Furthermore, P. berghei infected mice treated with nanotized conjugate formulation survived till 90 days with complete eradication of the parasites from RBC. This improved efficacy of the nanotized formulation was possible because of the increased absorption of the compounds via oral administration owing to enhanced dispersibility of the formulation in aqueous medium. Moreover, an improved oral bioavailability of the nanotized formulation lowered the dosage at which the pharmacological effect was achieved while avoiding any observable adverse harmful side effects.