Understanding the Transepithelial Transport and Transbilayer Diffusion of the Antihypertensive Peptide Asn-Cys-Trp: Insights from Caco-2 Cell Monolayers and the DPPC Model Membrane.

Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10-7 and (6.63 ± 2.31) × 10-7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.

Body mass index, waist circumference, and mortality in subjects older than 80 years: a Mendelian randomization study.

BACKGROUND AND AIMS: Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. METHODS: A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS: During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. CONCLUSIONS: Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.

Methodological quality of systematic reviews on atopic dermatitis treatments: a cross-sectional study.

BACKGROUND: Systematic reviews (SRs) could offer the best evidence supporting interventions, but methodological flaws limit their trustworthiness in decision-making. This cross-sectional study appraised the methodological quality of SRs on atopic dermatitis (AD) treatments. METHODS: We searched MEDLINE, EMBASE, PsycINFO, and Cochrane Database for SRs on AD treatments published in 2019-2022. We extracted SRs' bibliographical data and appraised SRs' methodological quality with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We explored associations between methodological quality and bibliographical characteristics. RESULTS: Among the 52 appraised SRs, only one (1.9%) had high methodological quality, while 45 (86.5%) critically low. For critical domains, only five (9.6%) employed comprehensive search strategy, seven (13.5%) provided list of excluded studies, 17 (32.7%) considered risk of bias in primary studies, 21 (40.4%) contained registered protocol, and 24 (46.2%) investigated publication bias. Cochrane reviews, SR updates, SRs with European corresponding authors, and SRs funded by European institutions had better overall quality. Impact factor and author number positively associated with overall quality. CONCLUSIONS: Methodological quality of SRs on AD treatments is unsatisfactory. Future reviewers should improve the above critical methodological aspects. Resources should be devolved into upscaling evidence synthesis infrastructure and improving critical appraisal skills of evidence users.

A Refined Thin-Film Model for Drug Dissolution Considering Radial Diffusion - Simulating Powder Dissolution.

PURPOSE: We aim to present a refined thin-film model describing the drug particle dissolution considering radial diffusion in spherical boundary layer, and to demonstrate the ability of the model to describe the dissolution behavior of bulk drug powders. METHODS: The dissolution model introduced in this study was refined from a radial diffusion-based model previously published by our laboratory (So et al. in Pharm Res. 39:907-17, 2022). The refined model was created to simulate the dissolution of bulk powders, and to account for the evolution of particle size and diffusion layer thickness during dissolution. In vitro dissolution testing, using fractionated hydrochlorothiazide powders, was employed to assess the performance of the model. RESULTS: Overall, there was a good agreement between the experimental dissolution data and the predicted dissolution profiles using the proposed model across all size fractions of hydrochlorothiazide. The model over-predicted the dissolution rate when the particles became smaller. Notably, the classic Nernst-Brunner formalism led to an under-estimation of the dissolution rate. Additionally, calculation based on the equivalent particle size derived from the specific surface area substantially over-predicted the dissolution rate. CONCLUSION: The study demonstrated the potential of the radial diffusion-based model to describe dissolution of drug powders. In contrast, the classic Nernst-Brunner equation could under-estimate drug dissolution rate, largely due to the underlying assumption of translational diffusion. Moreover, the study indicated that not all surfaces on a drug particle contribute to dissolution. Therefore, relying on the experimentally-determined specific surface area for predicting drug dissolution is not advisable.

Network analysis of posttraumatic stress and posttraumatic growth symptoms among women in subsequent pregnancies following pregnancy loss.

BACKGROUND: Pregnant women who have undergone pregnancy loss often display both posttraumatic stress (PTS) and posttraumatic growth (PTG). However, the precise relationship and structure of symptomatic levels of PTS and PTG have not been well understood. This study aimed to assess the associations between PTS and PTG symptoms in women during subsequent pregnancies following a previous pregnancy loss. METHODS: A total of 406 pregnant women with a history of pregnancy loss were included in this study. The Impact of Events Scale-6 (IES-6) and the Posttraumatic Growth Inventory Short Form (PTGI-SF) were used to assess symptoms of PTS and PTG, respectively. The Graphical Gaussian Model was employed to estimate the network model. Central symptoms and bridge symptoms were identified based on "expected influence" and "bridge expected influence" indices, respectively. The stability and accuracy of the network were examined using the case-dropping procedure and nonparametric bootstrapped procedure. RESULTS: The network analysis identified PTG3 ("Ability to do better things") as the most central symptom, followed by PTS3 ("Avoidance of thoughts") and PTG6 ("New path for life") in the sample. Additionally, PTS3 ("Avoidance of thoughts") and PTG9 ("Perception of greater personal strength") were bridge symptoms linking PTS and PTG clusters. The network structure was robust in stability and accuracy tests. CONCLUSIONS: Interventions targeting the central symptoms identified, along with key bridge symptoms, have the potential to alleviate the severity of PTS experienced by women with a history of pregnancy loss and promote their personal growth.

Systematic analyses of AISNPs screening and classification algorithms based on genome-wide data for forensic biogeographic ancestry inference.

Identifying the biogeographic ancestral origin of biological sample left at a crime scene can provide important evidence for judicial case, as well as clue for narrowing down suspect. Ancestry informative single nucleotide polymorphism (AISNP) has become one of the most important genetic markers in recent years for screening ancestry information loci and analyzing the population genetic background and structure due to their high number and wide distributions in the human genome. In this study, based on data from 26 populations in the 1000 Genomes Project Phase 3, a Random Forest classification model was constructed with one-vs-rest classification strategy for embedded feature selection in order to obtain a panel with a small number of efficient AISNPs. The research aim was to clarify differentiations of population genetic structures among continents and subregions of East Asia. ADMIXTURE results showed that based on the 58 AISNPs selected by the machine learning algorithm, the 26 populations involved in the study could be categorized into six intercontinental ancestry components: North East Asia, South East Asia, Africa, Europe, South Asia, and America. The 24 continental-specific AISNPs and 34 East Asian-specific AISNPs were finally obtained, and used to construct the ancestry prediction model using XGBoost algorithm, resulting in the Matthews correlation coefficients of 0.94 and 0.89, and accuracies of 0.94 and 0.92, respectively. The machine learning models that we constructed using population-specific AISNPs were able to accurately predict the ancestral origins of continental and intra-East Asian populations. To summarize, screening a set of high-perform AISNPs to infer biogeographical ancestral information using embedded feature selection has potential application in creating a layered inference system that accurately differentiates from intercontinental populations to local subpopulations.

Long-term air pollutants exposure and respiratory mortality: A large prospective cohort study.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Associations between pregnancy loss and common mental disorders in women: a large prospective cohort study.

Background: Increasing evidence suggests that pregnancy loss can lead to negative emotional outcomes, such as anxiety and depression, for women. However, limited knowledge exists regarding the long-term risk of mental disorders among individuals who have experienced pregnancy loss. Objective: To investigate the associations between pregnancy loss and the risk of common mental disorders. Methods: In the UK Biobank, a total of 218,990 women without any mental disorder at baseline were enrolled between 2006 and 2010 and followed until October 2022. Information on the history of pregnancy loss was obtained through self-reported questionnaires at baseline. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between pregnancy loss and common mental disorders. Results: During a median follow-up time of 13.36 years, there were 26,930 incident cases of common mental disorders. Incidence rates of common mental disorders were elevated among women with a history of stillbirth (HR 1.15, 95% CI: 1.07-1.23), miscarriage (HR 1.06, 95% CI: 1.02-1.10), or pregnancy termination (HR 1.21, 95% CI: 1.17-1.25) compared to those without such experiences. Furthermore, the risk of common mental disorders significantly increased in women with two or more miscarriages (HR 1.14, 95% CI: 1.08-1.19) or two or more pregnancy terminations (HR 1.39, 95% CI: 1.30-1.48). Conclusions: Pregnancy loss is associated with an increased risk of common mental disorders in women later in life. These findings may contribute to the enhancement of long-term monitoring and prevention of common mental disorders for women with such a history.

Study transport of hesperidin based on the DPPC lipid model and the BSA transport model.

Hesperidin (HE), a significant flavonoid polyphenolic compound present in citrus plants, exhibits diverse pharmacological effects. Considering the crucial involvement of biological membranes and transporter proteins in the transportation and biological processes of HE, it becomes essential to comprehend the potential mechanisms through which HE interacts with membranes and transporter proteins. In order to simulate the process of active molecule transport, a cell membrane model consisting of 1,2-dipalmitoyl-n-glycero-3-phosphatidylcholine (DPPC) and a transporter protein model of bovine serum albumin (BSA) were employed for investigation. The present study aimed to investigate the mechanism of action of hesperidin (HE) in DPPC and BSA using fluorescence quenching, Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The localization and interaction of HE within liposomes were also elucidated. Furthermore, the binding of BSA and HE was analyzed through UV/Vis absorption spectroscopy, fluorescence spectroscopy, infrared spectroscopy, and computational biology techniques. Computational biology analysis revealed that the binding between HE and BSA primarily occurred via hydrogen bonding and hydrophobic interactions. This study aimed to investigate the role and mechanism of HE in the DPPC cell membrane model and the BSA transporter protein model, thereby offering novel insights into the action of HE in DPPC and BSA.

Association between leisure sedentary behaviors and hypertension risk: A prospective cohort study and two-sample Mendelian randomization analysis in Europeans.

OBJECTIVE: This study aimed to investigate the potential causal relationship between domain-specific sedentary behaviors (including television watching, computer use, and driving) and hypertension risk in European populations. METHODS: Initially, we conducted a multivariable Cox regression analysis to evaluate the associations between domain-specific sedentary behaviors and the risk of developing hypertension using data from 261,829 hypertension-free participants in the UK Biobank. To validate the findings of observational analysis, we employed two-sample univariable mendelian randomization (UVMR) analysis utilizing summary statistics from genome-wide association study conducted on European populations. We then performed multivariable mendelian randomization (MVMR) analysis to account for the influence of the risk factors for hypertension. RESULTS: In this prospective observational analysis, individuals who spent >3 h per day watching television had significantly higher risk of developing hypertension (HR = 1.24, 95% CI: 1.20-1.29, P < 0.001) compared to those who watched television for 0-1 h per day. The mendelian randomization analysis provided consistent evidence for a causal relationship between prolonged television watching time and hypertension risk (OR = 1.45, 95% CI: 1.25-1.69, P < 0.001; all PMVMR < 0.05) in both UVMR and MVMR results. No significant associations were found between computer use, driving behaviors and the risk of hypertension in either the observational or UVMR/MVMR analyses. CONCLUSIONS: These findings provide evidence for a causal effect specifically linking higher television watching time to an increased risk of hypertension and indicate the potential effectiveness of reducing television viewing time as a preventive measure to mitigate the risk of hypertension.

Marine Bioactive Peptides: Anti-Photoaging Mechanisms and Potential Skin Protective Effects.

Skin photoaging, resulting from prolonged exposure to ultraviolet radiation, is a form of exogenous aging that not only impacts the aesthetic aspect of the skin but also exhibits a strong correlation with the onset of skin cancer. Nonetheless, the safety profile of non-natural anti-photoaging medications and the underlying physiological alterations during the process of photoaging remain inadequately elucidated. Consequently, there exists a pressing necessity to devise more secure interventions involving anti-photoaging drugs. Multiple studies have demonstrated the noteworthy significance of marine biomolecules in addressing safety concerns related to anti-photoaging and safeguarding the skin. Notably, bioactive peptides have gained considerable attention in anti-photoaging research due to their capacity to mitigate the physiological alterations associated with photoaging, including oxidative stress; inflammatory response; the abnormal expression of matrix metalloproteinase, hyaluronidase, and elastase; and excessive melanin synthesis. This review provides a systematic description of the research progress on the anti-photoaging and skin protection mechanism of marine bioactive peptides. The focus is on the utilization of marine bioactive peptides as anti-photoaging agents, aiming to offer theoretical references for the development of novel anti-photoaging drugs and methodologies. Additionally, the future prospects of anti-aging drugs are discussed, providing an initial reference for further research in this field.

Association of healthy lifestyle behaviours with incident irritable bowel syndrome: a large population-based prospective cohort study.

OBJECTIVES: To evaluate the association between healthy lifestyle behaviours and the incidence of irritable bowel syndrome (IBS). DESIGN: Population-based prospective cohort study. SETTING: The UK Biobank. PARTICIPANTS: 64 268 adults aged 37 to 73 years who had no IBS diagnosis at baseline were enrolled between 2006 and 2010 and followed up to 2022. MAIN EXPOSURE: The five healthy lifestyle behaviours studied were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality and moderate alcohol intake. MAIN OUTCOME MEASURE: The incidence of IBS. RESULTS: During a mean follow-up of 12.6 years, 961 (1.5%) incident IBS cases were recorded. Among the 64 268 participants (mean age 55.9 years, 35 342 (55.0%) female, 7604 (11.8%) reported none of the five healthy lifestyle behaviours, 20 662 (32.1%) reported 1 behaviour, 21 901 (34.1%) reported 2 behaviours and 14 101 (21.9%) reported 3 to 5 behaviours at baseline. The multivariable adjusted hazard ratios associated with having 1, 2 and 3 to 5 behaviours for IBS incidence were 0.79 (95% confidence intervals 0.65 to 0.96), 0.64 (0.53 to 0.78) and 0.58 (0.46 to 0.72), respectively (P for trend <0.001). Never smoking (0.86, 0.76 to 0.98, P=0.02), high level of vigorous physical activity (0.83, 0.73 to 0.95, P=0.006) and optimal sleep (0.73, 0.60 to 0.88, P=0.001) demonstrated significant independent inverse associations with IBS incidence. No significant interactions were observed between these associations and age, sex, employment status, geographic location, gastrointestinal infection, endometriosis, family history of IBS or lifestyle behaviours. CONCLUSIONS: Adhering to a higher number of healthy lifestyle behaviours is significantly associated with a lower incidence of IBS in the general population. Our findings suggest the potential of lifestyle modifications as a primary prevention strategy for IBS.

Risks of Powder Flow Obstruction in Hopper and Bin Discharge in Solid Dosage Form Manufacture should be Predicted Under The Active Stress State.

Discharge of powder from a hopper or bin is a common operation in solid dosage form manufacture. Powder flow obstruction during hopper/bin discharge, such as arching or ratholing, remains an outstanding risk and cannot be reliably diagnosed using the existing flow function coefficient-based method. In this study, we showed that the major principal stress (σ1) at the bin outlet is required for an accurate prediction of powder flow obstruction risks. We noted that powder is susceptible to flow obstruction when the unconfined yield strength exceeds the stress facilitating powder failure. We presented a complete model to calculate the stress conditions and subsequently predict flow obstruction risks in hopper/bin discharge based on this criterion. The method was experimentally verified by hopper/bin discharge experiments encompassing 10 powder blends and 2 equipment systems. Importantly, we showed that the active stress state assumption should be employed for the powder flow obstruction prediction because σ1 is high and powder is more susceptible to flow obstruction. Prediction under the passive stress state can lead to significant under-estimation of flow obstruction risks. Therefore, the hopper design protocol, which assumes the passive stress state in arching prediction, should not be indiscriminately used toward pharmaceutical powder flow applications.

Methodological quality of systematic reviews on sepsis treatments: A cross-sectional study.

OBJECTIVE: Systematic reviews (SRs) offer updated evidence to support decision-making on sepsis treatments. However, the rigour of SRs may vary, and methodological flaws may limit their validity in guiding clinical practice. This cross-sectional study appraised the methodological quality of SRs on sepsis treatments. METHODS: We searched MEDLINE, EMBASE, and Cochrane Database for eligible SRs on randomised controlled trials on sepsis treatments with at least one meta-analysis published between 2018 and 2023. We extracted SRs' bibliographical characteristics with a pre-designed form and appraised their methodological quality using AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We applied logistic regressions to explore associations between bibliographical characteristics and methodological quality ratings. RESULTS: Among the 102 SRs, two (2.0%) had high overall quality, while respectively four (3.9%), seven (6.9%) and 89 (87.3%) were of moderate, low, and critically low quality. Performance in several critical methodological domains was poor, with only 32 (31.4%) considering the risk of bias in primary studies in result interpretation, 22 (21.6%) explaining excluded primary studies, and 16 (15.7%) applying comprehensive searching strategies. SRs published in higher impact factor journals (adjusted odds ratio: 1.19; 95% confidence interval: 1.05 to 1.36) was associated with higher methodological quality. CONCLUSIONS: The methodological quality of recent SRs on sepsis treatments is unsatisfactory. Future reviewers should address the above critical methodological aspects. More resources should also be allocated to support continuous training in critical appraisal among healthcare professionals and other evidence users.

Association between regular proton pump inhibitors use and cardiovascular outcomes: A large prospective cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) are widely prescribed for gastroesophageal reflux disease and peptic ulcer disease. However, the association between the regular PPIs use and the risk of cardiovascular disease (CVD) outcomes remains unclear. We aimed to determine whether regular proton pump inhibitors (PPIs) use is associated with an altered incidence of cardiovascular disease (CVD) in the general population. METHODS: This prospective cohort study included 459,207 participants (mean [SD] age, 56.2 [8.1] years) from the UK Biobank study without prevalent CVD who enrolled between 2006 and 2010 and were followed until 2018. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD and its components (coronary heart disease [CHD], stroke, heart failure, atrial fibrillation, and venous thromboembolism) were obtained using Cox proportional hazards models with adjustment for potential confounding factors, including demographic factors, lifestyle behaviors, prevalent comorbidities, and clinical indicators for PPIs use. RESULTS: During the follow-up period, we recorded 26,346 incident CVD events (including 13,749 CHD events, 4144 stroke events, 5812 atrial fibrillation events, 1159 heart failure events, and 4206 venous thromboembolism events). The fully adjusted HRs (and 95% CIs) associated with PPIs users compared to nonusers were 1.44 (95% CI 1.39-1.50) for incident CVD, 1.65 (95% CI 1.57-1.74) for CHD, 1.21 (95% CI 1.09-1.33) for stroke, 1.17 (95% CI 1.08-1.28) for atrial fibrillation, 1.61 (95% CI 1.37-1.89) for heart failure, and 1.36 (95% CI 1.24-1.50) for venous thromboembolism. CONCLUSIONS: Regular PPIs use was associated with higher risk of CVD outcomes. Clinicians should therefore exercise caution when prescribing PPIs.

Automatic MDSPE Combined with DART-HRMS for the Rapid Quantitation of 21 Synthetic Cathinones in Urine.

A new, rapid, and automated method for the quantitation of 21 synthetic cathinones in urine was established using magnetic dispersive solid-phase extraction (MDSPE) in combination with direct analysis in real time-high-resolution mass spectrometry (DART-HRMS). Sample preparation and quantitation were verified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methcathinone-D3, α-PVP-D8, and proadifen (SKF525A) were used as internal standards. Magnetic HLB extractant and NaH2PO4/NaOH buffer (0.2 M, pH 7) were used in automatic MDSPE. All 21 synthetic cathinones could be detected and analyzed by DART-HRMS in under 1 min. It was proven that the linearities of 21 synthetic cathinones were suitable (R2 > 0.99) in the concentration ranges of 0.5-100 ng/mL or 1-100 ng/mL. The precision and accuracy values were all within ±15%, and the samples were stable under various conditions. The average time of each sample from preprocessing to completion of detection was approximately 2 min, allowing for rapid sample analysis. The relative error (RE) of the concentrations obtained by DART-HRMS and LC-MS/MS were within ±13.61%, and the linear coefficient (R) was 0.9964. The results of DART-HRMS and LC-MS/MS provided equivalent values at the 95% confidence level. In summary, a simple, fast, and convenient quantitation method via DART-HRMS was established. This application can be utilized to reduce backlogs and promote rapid case processing.

Effect of Buffer pH and Concentration on the Dissolution Rates of Sodium Indomethacin-Copovidone and Indomethacin-Copovidone Amorphous Solid Dispersions.

The incorporation of counterions into amorphous solid dispersions (ASDs) has been proven to be effective for improving the dissolution rates of ionizable drugs in ASDs. In this work, the effect of dissolution buffer pH and concentration on the dissolution rate of indomethacin-copovidone 40:60 (IMC-PVPVA, w/w) ASD with or without incorporated sodium hydroxide (NaOH) was studied by surface area-normalized dissolution to provide further mechanistic understanding of this phenomenon. Buffer pH from 4.7 to 7.2 and concentration from 20 to 100 mM at pH 5.5 were investigated. As the buffer pH decreased, the IMC dissolution rate from both ASDs decreased. Compared to IMC-PVPVA ASD, the dissolution rate decrease from IMCNa-PVPVA ASD was more resistant to the decrease of buffer pH. In contrast, while buffer concentration had a negligible impact on the IMC dissolution rate from IMC-PVPVA ASD, the increase of buffer concentration significantly reduced the IMC dissolution rate from IMCNa-PVPVA ASD. Surrogate evaluation of microenvironment pH modification by the dissolution of IMCNa-PVPVA ASD demonstrated the successful elevation of buffer microenvironment pH and the suppression of such pH elevation by the increase of buffer concentration. These results are consistent with the hypothesis that the dissolution rate enhancement by the incorporation of counterions originates from the enhanced drug solubility by ionization and the modification of diffusion layer pH in favor of drug dissolution. At the studied drug loading (∼40%), relatively congruent release between IMC and PVPVA was observed when IMC was ionized in ASD or in solution, highlighting the importance of studying the ionization effect on the congruent release of ASDs, especially when drug ionization is expected in vivo. Overall, this work further supports the application of incorporating counterions into ASDs for improving the dissolution rates of ionizable drugs when enabling formulation development is needed.

Associations Between Specific Diets, Dietary Diversity, and Cognitive Frailty in Older Adults - China, 2002-2018.

What is already known about this topic?: The relationship between specific dietary patterns and dietary diversity with cognitive frailty continues to be a subject of ambiguity. What is added by this report?: This research revealed that regular consumption of fruit, meat, bean products, garlic, and tea was connected to a decreased risk of cognitive frailty. Compared to participants with dietary diversity score (DDS) ≤6 points, those with DDS of 9-10, 11-12, and ≥12 had a lower risk of cognitive frailty. What are the implications for public health practice?: The results of the study corroborate the relationship between the augmented consumption frequency of meat, fruit, bean products, garlic, and tea, in conjunction with an elevated DDS, and an increased risk of developing cognitive frailty.

Dietary Diversity Changes and Cognitive Frailty in Chinese Older Adults: A Prospective Community-Based Cohort Study.

Evidence for the effects of dietary diversity changes and cognitive frailty (CF) in the older adults is not clear. This study aimed to investigate the relationship between dietary diversity changes and CF in older adults Chinese. A total of 14,382 participants (mean age: 82.3 years) were enrolled. Dietary diversity scores (DDSs) were collected and calculated using a food frequency questionnaire. DDS changes between baseline and first follow-up were categorized into nine patterns. The associations between DDS changes and the incidence of CF were estimated using Cox proportional hazards models. During an 80,860 person-year follow-up, 3023 CF cases were identified. Groups with a decrease in DDS had increased CF risk compared with the high-to-high DDS group, with adjusted hazard ratios (HRs; 95% confidence intervals (Cis)) of 1.30 (1.06, 1.59), 2.04 (1.51, 2.74), and 1.81 (1.47, 2.22) for high-to-medium, high-to-low, and medium-to-low groups, respectively. Lower overall DDS groups were associated with greater CF risks, with HRs (95% CIs) of 1.49 (1.19, 1.86) for the low-to-medium group and 1.96 (1.53, 2.52) for the low-to-low group. Compared with the high-to-high group, significant associations with CF were found in other DDS change groups; HRs ranged from 1.38 to 3.12 for the plant-based DDS group and from 1.24 to 1.32 for the animal-based DDS group. Additionally, extreme and moderate declines in overall DDS increased CF risk compared with stable DDS, with HRs (95% CIs) of 1.67 (1.50, 1.86) and 1.13 (1.03, 1.24), respectively. In conclusion, among older adults, a declining or persistently low DDS and a moderately or extremely declining DDS were linked to higher incident CF. Plant-based DDS changes correlated more strongly with CF than animal-based DDS changes.