Unraveling the Complex Interactions: Machine Learning Approaches to Predict Bacterial Survival against ZnO and Lanthanum-Doped ZnO Nanoparticles.

The rise in antibiotic-resistant bacteria is a global health challenge. Due to their unique properties, metal oxide nanoparticles show promise in addressing this issue. However, optimizing these properties requires a deep understanding of complex interactions. This study incorporated data-driven machine learning to predict bacterial survival against lanthanum-doped ZnO nanoparticles. The effect of incorporation of lanthanum ions on ZnO was analyzed. Even with high lanthanum concentration, no significant variations in structural, morphological, and optical properties were observed. The antibacterial activity of La-doped ZnO nanoparticles against Gram-positive and Gram-negative bacteria was qualitatively and quantitatively evaluated. Nanoparticles induce 60%, 95%, and 55% bacterial death against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, respectively. Algorithms such as Multilayer Perceptron, K-Nearest Neighbors, Gradient Boosting, and Extremely Random Trees were used to predict the bacterial survival percentage. Extremely Random Trees performed the best among these models with 95.08% accuracy. A feature relevance analysis extracted the most significant attributes to predict the bacterial survival percentage. Lanthanum content and particle size were irrelevant, despite what can be assumed. This approach offers a promising avenue for developing effective and tailored strategies to reduce the time and cost of developing antimicrobial nanoparticles.

Cardiovascular disease in Alpha 1 antitrypsin deficiency: an observational study assessing the role of neutrophil proteinase activity and the suitability of validated screening tools.

BACKGROUND: Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD. This study had three aims. To compare CVD risk in never-augmented AATD patients to non-AATD COPD and healthy controls (HC). To assess relationships between CVD risk and lung physiology. To determine if neutrophil proteinase activity was associated with CVD risk in AATD. Cardiovascular risk was assessed by QRISK2® score and aortic stiffness measurements using carotid-femoral (aortic) pulse wave velocity (aPWV). Medical history, computed tomography scans and post-bronchodilator lung function parameters were reviewed. Systemic proteinase 3 activity was measured. Patients were followed for 4 years, to assess CVD development. RESULTS: 228 patients with AATD, 50 with non-AATD COPD and 51 healthy controls were recruited. In all COPD and HC participants, QRISK2® and aPWV gave concordant results (with both measures either high or in the normal range). This was not the case in AATD. Once aPWV was adjusted for age and smoking history, aPWV was highest and QRISK2® lowest in AATD patients compared to the COPD or HC participants. Higher aPWV was associated with impairments in lung physiology, the presence of emphysema on CT scan and proteinase 3 activity following adjustment for age, smoking status and traditional CVD risk factors (using QRISK2® scores) in AATD. There were no such relationships with QRISK2® in AATD. AATD patients with confirmed CVD at four-year follow up had a higher aPWV but not QRISK2® at baseline assessment. CONCLUSION: aPWV measured CVD risk is elevated in AATD. This risk is not captured by QRISK2®. There is a relationship between aPWV, lung disease and proteinase-3 activity. Proteinase-driven breakdown of elastin fibres in large arteries and lungs is a putative mechanism and forms a potential therapeutic target for CVD in AATD.

Enhancing antioxidant properties of CeO2 nanoparticles with Nd3+ doping: structural, biological, and machine learning insights.

The antioxidant capabilities of nanoparticles are contingent upon various factors, including their shape, size, and chemical composition. Herein, novel Nd-doped CeO2 nanoparticles were synthesized and the neodymium content was varied to investigate the synergistic impact on the antioxidant properties of CeO2 nanoparticles. Incorporating Nd3+ induced changes in lattice parameters and significantly altered the morphology from nanoparticles to nanorods. The biological activity of Nd-doped CeO2 was examined against pathogenic bacterial strains, breast cancer cell lines, and antioxidant models. The antibacterial and anticancer activities of nanoparticles were not observed, which could be associated with the Ce3+/Ce4+ ratio. Notably, the incorporation of neodymium improved the antioxidant capacity of CeO2. Machine learning techniques were employed to forecast the antioxidant activity to enhance understanding and predictive capabilities. Among these models, the random forest model exhibited the highest accuracy at 96.35%, establishing it as a robust computational tool for elucidating the biological behavior of Nd-doped CeO2 nanoparticles. This study presents the first exploration of the influence of Nd3+ on the structural, optical, and biological attributes of CeO2, contributing valuable insights and extending the application of machine learning in predicting the therapeutic efficacy of inorganic nanomaterials.

Lanthanide-Doped ZnO Nanoparticles: Unraveling Their Role in Cytotoxicity, Antioxidant Capacity, and Nanotoxicology.

This study used a sonochemical synthesis method to prepare (La, Sm)-doped ZnO nanoparticles (NPs). The effect of incorporating these lanthanide elements on the structural, optical, and morphological properties of ZnO-NPs was analyzed. The cytotoxicity and the reactive oxygen species (ROS) generation capacity of ZnO-NPs were evaluated against breast (MCF7) and colon (HT29) cancer cell lines. Their antioxidant activity was analyzed using a DPPH assay, and their toxicity towards Artemia salina nauplii was also evaluated. The results revealed that treatment with NPs resulted in the death of 10.559-42.546% and 18.230-38.643% of MCF7 and HT29 cells, respectively. This effect was attributed to the ability of NPs to downregulate ROS formation within the two cell lines in a dose-dependent manner. In the DPPH assay, treatment with (La, Sm)-doped ZnO-NPs inhibited the generation of free radicals at IC50 values ranging from 3.898 to 126.948 µg/mL. Against A. salina nauplii, the synthesized NPs did not cause death nor induce morphological changes at the tested concentrations. A series of machine learning (ML) models were used to predict the biological performance of (La, Sm)-doped ZnO-NPs. Among the designed ML models, the gradient boosting model resulted in the greatest mean absolute error (MAE) (MAE 9.027, R2 = 0.86). The data generated in this work provide innovative insights into the influence of La and Sm on the structural arrangement and chemical features of ZnO-NPs, together with their cytotoxicity, antioxidant activity, and in vivo toxicity.

Frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico.

Background: Between 29% and 67% of neuromyelitis optica spectrum disorder patients have cognitive alterations. Objective: To assess the frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico using the Brief International Cognitive Assessment for Multiple Sclerosis. Methods: We evaluated 40 neuromyelitis optica spectrum disorder patients and 40 healthy controls from Mexico. Results: 28 (70.0%) patients with neuromyelitis optica spectrum disorder had cognitive impairment in two or more cognitive domains. Student´s T test showed statistically poor performance by neuromyelitis optica spectrum disorder patients compared to healthy controls on all three neuropsychological test scores. This significant difference was observed on the Symbols Digit Modalities Test (t = 8.875; p ≤ 0.001); California Verbal Learning Test-II memory (t = 10.418; p ≤ 0.001); and Brief Visuospatial Memory Test Revised (t = 6.123; p ≤ 0.001). Conclusions: This study showed that 70% of neuromyelitis optica spectrum disorder patients exhibited cognitive impairment in two or more cognitive domains. Determining the frequency of cognitive impairment will guide the decision of Neuropsychologists in planning cognitive rehabilitation across various domains.

An in vitro agent-based modelling approach to optimization of culture medium for generating muscle cells.

Methodologies for culturing muscle tissue are currently lacking in terms of quality and quantity of mature cells produced. We analyse images from in vitro experiments to quantify the effects of culture media composition on mouse-derived myoblast behaviour and myotube quality. Metrics of early indicators of cell quality were defined. Images of muscle cell differentiation reveal that altering culture media significantly affects quality indicators and myoblast migratory behaviours. To study the effects of early-stage cell behaviours on mature cell quality, metrics drawn from experimental images or inferred by approximate Bayesian computation (ABC) were applied as inputs to an agent-based model (ABM) of skeletal muscle cell differentiation with quality indicator metrics as outputs. Computational modelling was used to inform further in vitro experiments to predict the optimum media composition for culturing muscle cells. Our results suggest that myonuclei production in myotubes is inversely related to early-stage nuclei fusion index and that myonuclei density and spatial distribution are correlated with residence time of fusing myoblasts, the age at which myotube-myotube fusion ends and the repulsion force between myonuclei. Culture media with 5% serum was found to produce the optimum cell quality and to make muscle cells cultured in a neuron differentiation medium viable.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in individuals with multiple sclerosis from Mexico.

BACKGROUND: Cognitive impairment is observed in 43-70 % of Multiple sclerosis (MS) patients. One of the most widely used batteries for cognitive assessment in this population is the Brief International Cognitive Assessment for MS (BICAMS). The objective of this study was to validate and assess the reliability of the BICAMS in a Mexican population with MS and to obtain and provide regression-based norms. METHODS: One hundred healthy controls (HCs) and 100 patients with multiple sclerosis participated in the present study, and groups were matched for age, years of education and sex. Subjects completed all three tests of the BICAMS. Test-retest measures were obtained from 30 patients to test reliability. RESULTS: The sample´s average age was 43.39 ± 6.03 years old, and the average years of education was 12.55 ± 2.52 years. Approximately 63 % of the participants were female. The groups did not differ in age, years of education, or sex. The MS group performed significantly worse than the HCs group on all three neuropsychological tests. A significant difference was observed for the SDMT (t = 10.166; p=<0.001), CVLT-II (t = 10.949; p=<0.001), and BVMT-R (t = 2.636; p = 0.009). For all comparisons, the effect size (d) for each test was calculated as follows: SDMT= 0.58 and CVLT-II= 0.61. The test-retest coefficients for each test were as follows: SDMT: r = 0.95; CVLT-II: r = 0.84; and BVMT-R = 0.81. CONCLUSION: The BICAMS can provide information on cognitive impairment in MS patients, and this information can be used by neuropsychologists for cognitive rehabilitation in different domains.

Survey response rates in health sciences education research: A 10-year meta-analysis.

Growth in the online survey market may be increasing response burden and possibly jeopardizing higher response rates. This meta-analysis evaluated survey trends over one decade (2011-2020) to determine: (1) changes in survey publication rates over time, (2) changes in response rates over time, (3) typical response rates within health sciences education research, (4) the factors influencing survey completion levels, and (5) common gaps in survey methods and outcomes reporting. Study I estimated survey publication trends between 2011 and 2020 using articles published in the top three health sciences education research journals. Study II searched the anatomical sciences education literature across six databases and extracted study/survey features and survey response rates. Time plots and a proportional meta-analysis were performed. Per 2926 research articles, the annual estimated proportion of studies with survey methodologies has remained constant, with no linear trend (p > 0.050) over time (Study I). Study II reported a pooled absolute response rate of 67% (95% CI = 63.9-69.0) across 360 studies (k), totaling 115,526 distributed surveys. Despite response rate oscillations over time, no significant linear trend (p = 0.995) was detected. Neither survey length, incentives, sponsorship, nor population type affected absolute response rates (p ≥ 0.070). Only 35% (120 of 339) of studies utilizing a Likert scale reported evidence of survey validity. Survey response rates and the prevalence of studies with survey methodologies have remained stable with no linear trends over time. We recommend researchers strive for a typical absolute response rate of 67% or higher and clearly document evidence of survey validity for empirical studies.

Adaptive changes in the DNA damage response during skeletal muscle cell differentiation.

DNA double-strand breaks (DSBs) trigger specialized cellular mechanisms that collectively form the DNA damage response (DDR). In proliferating cells, the DDR serves the function of mending DNA breaks and satisfying the cell-cycle checkpoints. Distinct goals exist in differentiated cells that are postmitotic and do not face cell-cycle checkpoints. Nonetheless, the distinctive requirements and mechanistic details of the DDR in differentiated cells are still poorly understood. In this study, we set an in vitro differentiation model of human skeletal muscle myoblasts into multinucleated myotubes that allowed monitoring DDR dynamics during cell differentiation. Our results demonstrate that myotubes have a prolonged DDR, which is nonetheless competent to repair DSBs and render them significantly more resistant to cell death than their progenitors. Using live-cell microscopy and single-molecule kinetic measurements of transcriptional activity, we observed that myotubes respond to DNA damage by rapidly and transiently suppressing global gene expression and rewiring the epigenetic landscape of the damaged nucleus. Our findings provide novel insights into the DDR dynamics during cellular differentiation and shed light on the strategy employed by human skeletal muscle to preserve the integrity of the genetic information and sustain long-term organ function after DNA damage.

Independent and joint associations of cardiorespiratory fitness and lower-limb muscle strength with cardiometabolic risk in older adults.

The aim of this study was to investigate the independent and joint associations of low cardiorespiratory fitness and lower-limb muscle strength with cardiometabolic risk in older adults. A total of 360 community-dwelling older adults aged 60-80 years participated in this cross-sectional study. Cardiometabolic risk was based on the diagnosis of Metabolic Syndrome and poor Ideal Cardiovascular Health according to the American Heart Association guidelines. Cardiorespiratory fitness and lower-limb muscle strength were estimated using the six-minute walk and the 30-second chair stand tests, respectively. Participants in the 20th percentile were defined as having low cardiorespiratory fitness and lower-limb muscle strength. Poisson's regression was used to determine the prevalence ratio (PR) and 95% confidence intervals (CI) of Metabolic Syndrome and poor Ideal Cardiovascular Health. Participants with low cardiorespiratory fitness alone and combined with low lower-limb muscle strength were similarly associated with a higher risk for Metabolic Syndrome (PR 1.27, 95% CI 1.09-1.48, and PR 1.32, 95% CI 1.10-1.58, respectively), and poor Ideal Cardiovascular Health (PR 1.76, 95% CI 1.25-2.47, and PR 1.65, 95% CI 1.19-2.28, respectively). Low lower-limb muscle strength alone was not associated with a higher risk for either Metabolic Syndrome or poor Ideal Cardiovascular Health (PR 1.23, 95% CI 0.81-1.87, and PR 1.11, 95% CI 0.89-1.37, respectively). Low cardiorespiratory fitness alone or combined with low lower-limb muscle strength, but not low lower-limb muscle strength alone, was associated with a higher cardiometabolic risk in older adults. The assessment of physical fitness may be a "window of opportunity" to identify youngest-old adults with a high cardiovascular disease risk.

Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease: An Individual Participant Meta-Analysis.

Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension. Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension. Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments. Data Extraction and Synthesis: Individual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach. Main Outcomes and Measures: Main outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less. Results: The 9 trials included 29 235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P = .68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P = .16 for interaction of treatment with baseline standing hypotension). Conclusions and Relevance: In this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension.

Development and Evaluation of Zinc and Iron Nanoparticles Functionalized with Plant Growth-Promoting Rhizobacteria (PGPR) and Microalgae for Their Application as Bio-Nanofertilizers.

Micronutrient deficiencies are widespread and growing global concerns. Nanoscale nutrients present higher absorption rates and improved nutrient availability and nutrient use efficiency. Co-application of nanofertilizers (NFs) with biological agents or organic compounds increases NF biocompatibility, stability, and efficacy. This study aimed to develop and evaluate zinc and iron bio-nanofertilizers formulated with plant growth-promoting rhizobacteria (PGPR) and microalgae. Nanoparticles (NPs) were synthesized with the co-precipitation method and functionalized with Pseudomonas species and Spirulina platensis preparation. NPs were characterized and evaluated on seed germination, soil microbial growth, and early plant response under seedbed conditions. NPs corresponded to zinc oxide (ZnO; 77 nm) and maghemite (γ-Fe2O3; 68 nm). Functionalized nanoparticles showed larger sizes, around 145-233 nm. The seedling vigor index of tomato and maize was significantly increased (32.9-46.1%) by bacteria-functionalized ZnO- and γ-Fe2O3-NPs at 75 ppm. NFs at 250 and 75 ppm significantly increased bacterial growth. NFs also improved early plant growth by increasing plant height (14-44%), leaf diameter (22-47%), and fresh weight (46-119%) in broccoli and radish, which were mainly influenced by bacteria capped ZnO- and γ-Fe2O3-NPs at 250 ppm. Beneficial effects on plant growth can be attributed to the synergistic interaction of the biological components and the zinc and iron NPs in the bio-nanofertilizers.

Biological Activities and Chemical Profiles of Kalanchoe fedtschenkoi Extracts.

In this study, the leaves of Kalanchoe fedtschenkoi were consecutively macerated with hexane, chloroform, and methanol. These extracts were used to assess the bioactivities of the plant. The antimicrobial activity was tested against a panel of Gram-positive and -negative pathogenic bacterial and fungal strains using the microdilution method. The cytotoxicity of K. fedtschenkoi extracts was investigated using human-derived macrophage THP-1 cells through the MTT assay. Finally, the anti-inflammatory activity of extracts was studied using the same cell line by measuring the secretion of IL-10 and IL-6. The phytoconstituents of hexane and chloroform extracts were evaluated using gas chromatography-mass spectrometry (GC/MS). In addition, high-performance liquid chromatography (HPLC) was used to study the phytochemical content of methanol extract. The total flavonoid content (TFC) of methanol extract is also reported. The chemical composition of K. fedtschenkoi extracts was evaluated using Fourier-transform infrared spectroscopy (FTIR). Results revealed that the chloroform extract inhibited the growth of Pseudomonas aeruginosa at 150 µg/mL. At the same concentration, methanol extract inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA). Regarding their cytotoxicity, the three extracts were highly cytotoxic against the tested cell line at IC50 < 3 µg/mL. In addition, the chloroform extract significantly stimulated the secretion of IL-10 at 50 µg/mL (p < 0.01). GC/MS analyses revealed that hexane and chloroform extracts contain fatty acids, sterols, vitamin E, and triterpenes. The HPLC analysis demonstrated that methanol extract was constituted by quercetin and kaempferol derivatives. This is the first report in which the bioactivities and chemical profiles of K. fedtschenkoi are assessed for non-polar and polar extracts.

Genetically encoded discovery of perfluoroaryl macrocycles that bind to albumin and exhibit extended circulation in vivo.

Peptide-based therapeutics have gained attention as promising therapeutic modalities, however, their prevalent drawback is poor circulation half-life in vivo. In this paper, we report the selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine SNAr chemistry, with decafluoro-diphenylsulfone (DFS). Testing of the binding of the selected peptides to albumin identified SICRFFC as the lead sequence. We replaced DFS with isosteric pentafluorophenyl sulfide (PFS) and the PFS-SICRFFCGG exhibited KD = 4-6 µM towards human serum albumin. When injected in mice, the concentration of the PFS-SICRFFCGG in plasma was indistinguishable from the reference peptide, SA-21. More importantly, a conjugate of PFS-SICRFFCGG and peptide apelin-17 analogue (N3-PEG6-NMe17A2) showed retention in circulation similar to SA-21; in contrast, apelin-17 analogue was cleared from the circulation after 2 min. The PFS-SICRFFC is the smallest known peptide macrocycle with a significant affinity for human albumin and substantial in vivo circulation half-life. It is a productive starting point for future development of compact macrocycles with extended half-life in vivo.

Antimicrobial, Cytotoxic, and Anti-Inflammatory Activities of Tigridia vanhouttei Extracts.

In this work, bulb extracts of Tigridia vanhouttei were obtained by maceration with solvents of increasing polarity. The extracts were evaluated against a panel of pathogenic bacterial and fungal strains using the minimal inhibitory concentration (MIC) assay. The cytotoxicity of the extracts was tested against two cell lines (THP-1 and A549) using the MTT assay. The anti-inflammatory activity of the extracts was evaluated in THP-1 cells by measuring the secretion of pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines by ELISA. The chemical composition of the extracts was recorded by FTIR spectroscopy, and their chemical profiles were evaluated using GC-MS. The results revealed that only hexane extract inhibited the growth of the clinical isolate of Pseudomonas aeruginosa at 200 µg/mL. Against THP-1 cells, hexane and chloroform extracts were moderately cytotoxic, as they exhibited LC50 values of 90.16, and 46.42 µg/mL, respectively. Treatment with methanol extract was weakly cytotoxic at LC50 443.12 µg/mL against the same cell line. Against the A549 cell line, hexane, chloroform, and methanol extracts were weakly cytotoxic because of their LC50 values: 294.77, 1472.37, and 843.12 µg/mL. The FTIR analysis suggested the presence of natural products were confirmed by carboxylic acids, ketones, hydroxyl groups, or esters. The GC-MS profile of extracts revealed the presence of phytosterols, tetracyclic triterpenes, multiple fatty acids, and sugars. This report confirms the antimicrobial, cytotoxic, and anti-inflammatory activities of T. vanhouttei.

Effects of the DASH diet and losartan on serum urate among adults with hypertension: Results of a randomized trial.

Serum urate is a risk factor for hypertension and gout. The DASH diet and losartan independently lower blood pressure (BP); however, their effects on serum urate are understudied. We performed a post-hoc analysis of the DASH-losartan trial, which randomized participants with hypertension in parallel fashion to the DASH diet or a standard American diet (control) and in crossover fashion to 4-week losartan or placebo. Serum urate was measured at baseline and after each 4-week period. Diets were designed to maintain weight constant. We examined the effects of DASH (vs control) and/or losartan (vs placebo) on serum urate, overall and among those with baseline serum urate ≥6 mg/dL, using generalized estimating equations. Of 55 participants (mean age 52 years, 58% women, 64% Black), mean (±SD) baseline ambulatory SBP/DBP was 146±12/91±9 and mean (±SD) serum urate was 5.2±1.2 mg/dL. The DASH diet did not significantly reduce urate levels overall (mean difference -0.05 mg/dL; 95%CI: -0.39, 0.28), but did decrease levels among participants with baseline hyperuricemia (-0.33 mg/dL; 95%CI: -0.87, 0.21; P-interaction=0.007 across hyperuricemia groups). Losartan significantly decreased serum urate (-0.23 mg/dL; 95%CI: -0.40, -0.05) with greater effects on serum urate among adults <60 years old versus adults ≥60 years old (-0.33 mg/dL vs 0.16 mg/dL, P interaction = 0.003). In summary, the DASH diet significantly decreased serum urate among participants with higher urate at baseline, while losartan significantly reduced serum urate, especially among younger adults. Future research should examine the effects of these interventions in patients with hyperuricemia or gout.

Timing of orthostatic hypotension and its relationship with falls in older adults.

BACKGROUND: There is inconsistent evidence on the optimal time after standing to assess for orthostatic hypotension. We determined the prevalence of orthostatic hypotension at different time points after standing in a population of older adults, as well as fall risk and symptoms associated with orthostatic hypotension. METHODS: We performed a secondary analysis of the Study to Understand Fall Reduction and Vitamin D in You (STURDY), a randomized clinical trial funded by the National Institute on Aging, testing the effect of differing vitamin D3 doses on fall risk in older adults. STURDY occurred between July 2015 and May 2019. Secondary analysis occurred in 2022. Participants were community-dwelling adults, 70 years or older. In the orthostatic hypotension assessment, participants stood upright from supine position and underwent six standing blood pressure measurements (M1-M6) in two clusters of three measurements (immediately and 3 min after standing). Cox proportional hazard models were used to examine the relationship between orthostatic hypotension at each measurement and subsequent falls. Participants were followed until the earlier of their 24-month visit or study completion. RESULTS: Orthostatic hypotension occurred in 32% of assessments at M1, and only 16% at M5 and M6. Orthostatic hypotension from average immediate (M1-3) and average delayed (M4-6) measurements, respectively, predicted higher fall risk (M1-3 = 1.65 [1.08, 2.52]; M4-6 = 1.73 [1.03, 2.91]) (hazard ratio [95% confidence interval]). However, among individual measurements, only orthostatic hypotension at M5 (1.84 [1.16, 2.93]) and M6 (1.85 [1.17, 2.91]) predicted higher fall risk. Participants with orthostatic hypotension at M1 (3.07 [1.48, 6.38]) and M2 (3.72 [1.72, 8.03]) were more likely to have reported orthostatic symptoms. CONCLUSIONS: Orthostatic hypotension was most prevalent and symptomatic immediately within 1-2 min after standing, but more informative for fall risk after 4.5 min. Clinicians may consider both intervals when assessing for orthostatic hypotension.