Objectives
To explore the association between orthostatic hypotension (OH) and frailty for hospitalized older patients and their vulnerable subgroups.
Design
A prospective, observational ...cross-sectional study.
Participants
693 older patients admitted to a geriatric evaluation and management unit.
Measurements
Barthel Index, Lawton’s instrumental activities of daily living, clinical frailty scale, mini-mental state examination, geriatric depression scale, mini-nutritional assessment, and polypharmacy.
Results
Overall, the prevalence of OH and frailty was 26% and 36%, respectively. Subjects with OH were older, thinner, more commonly to have weakness, slowness, poorer physical function and higher levels of frailty. The prevalence of OH was substantially increased as higher levels of CFS (p for trend <0.001). Multivariate logistic regression showed significant association between OH and frailty (OR: 1.8, 95% CI: 1.2-2.7), but the association attenuated after adjustment for physical function. (OR: 1.4, 95% CI: 0.7-2.6). Nevertheless, associations between OH and frailty remained significant among vulnerable subgroups like women, subjects having weakness, slowness, poor cognitive function, polypharmacy or any IADL limitation.
Conclusions
OH in hospitalized older patients was associated with frailty and multiple complex care needs, especially in the vulnerable subgroups. Further study is needed to clarify the roles of OH in clinical practice.
Aim
3‐Phenyllactic acid (3‐PLA) has been widely used in food and material industries. Three Lactobacillus crustorum strains have shown greater 3‐PLA production ability in our previous study. The ...objectives of this study were to further improve 3‐PLA yields in batch and continuous fermentation systems using of free‐whole‐cells of the three L. crustorum strains.
Materials and Results
The fermentation conditions of free‐whole‐cells of the three L. crustorum strains for 3‐PLA production were optimized. Among these strains, L. crustorum NWAFU 1078 showed excellent reusability and significantly (P < 0·05) greater 3‐PLA production ability than the other strains after 10th recycle. The strain possesses three l‐lactate dehydrogenase and three d‐lactate dehydrogenase catalysing 3‐PLA production from phenylpyruvic acid (PPA). Under the optimal conditions, the strain produced 15·2 mmol l−1 3‐PLA (76% PPA conversion rate) in a batch fermentation system and 6·5 mmol l−1 h−1 3‐PLA (55% PPA conversion rate) in a continuous fermentation system using a 0·6 dilution rate.
Conclusions
Free‐whole‐cells of L. crustorum NWAFU 1078 showed excellent reusability and higher 3‐PLA yields under optimal biotransformation conditions in both batch and continuous fermentation systems.
Significance and Impact of the Study
This study provides the possibility to use the free‐whole‐cells of L. crustorum NWAFU 1078 as a biocatalyst for effective production of 3‐PLA.
Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the ...mechanistic underpinnings remain incompletely understood.
PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication. LC-MS/MS proteomic profiling and Dual-Luciferase analyses identified YAP1 as the direct target of miR-141. Human cytokine profiling, ChIP, luciferase reporter assays, and subcellular fractionation analyses confirmed YAP1 in modulating GROα production. A series of in vitro tumorigenic assays, an ex vivo model and Yap1 stromal conditional knockout (cKO) mouse model demonstrated the roles of miR-141/YAP1/GROα/CXCR1/2 signaling cascade. RNAi, CRISPR/Cas9 and CRISPRi systems were used for gene silencing. Blood sera, OvCa tumor tissue samples, and tissue array were included for clinical correlations.
Hsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted YAP1, a critical effector of the Hippo pathway, reducing the nuclear YAP1/TAZ ratio and enhancing GROα production from stromal fibroblasts. Stromal-specific knockout (cKO) of Yap1 in murine models shaped the GROα-enriched microenvironment, facilitating in vivo tumor colonization, but this effect was reversed after Cxcr1/2 depletion in OvCa cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers.
This study uncovers miR-141 as an OvCa-derived exosomal microRNA mediating the tumor-stroma interactions and the formation of tumor-promoting stromal niche through activating YAP1/GROα/CXCRs signaling cascade, providing new insight into therapy for OvCa patients with peritoneal metastases.
Abstract Background Which surgical strategy is the best one for intertrochanteric fractures remains a controversial issue. Dynamic hip screw (DHS) and Gamma nail were commonly used but often ...associated with some complications, such as fixation failure and implant-related fractures. Meanwhile, proximal femoral nail anti-rotation (PFNA) fixation has recently been developed for minimally invasive surgery to reduce the complications rate. To facilitate the clinical decision-making, we conducted an updated meta-analysis to discuss the optimal treatment of intertrochanteric fractures aiming to determine which implant gives the lower rates of blood loss, complications (peri-implant fracture, fixation failure, infection, thromboembolic), reoperation, and mortality, as well as the minimal duration related to surgery (fluoroscopic exposure, surgery and hospital stay). Patients and methods Seven electronic databases were searched for randomized controlled trials (including OVID, Springer, Google Scholar, PubMed, Cochrane library, Embase, and Web of Science). Fourteen studies with 1983 patients were included. The modified Jadad Scale was used to assess the methodological quality of these studies. Risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool. Comparison among the three groups was based on twelve indicators, including operative time, fluoroscopy time, operative blood loss, length of hospital stays, wound infection or hematoma, pneumonia, thromboembolic complications, fixation failure, operative fracture of femur, later fracture of femur, reoperation, and mortality. Results (1) PFNA group versus DHS group: PFNA was associated with less blood loss (mean difference (MD) –253.86, 95% CI –270.25 to 237.47; P < 0.00001) and lower rate of fixation failure (MD 0.20, 95% CI 0.07 to 0.59; P = 0.004), but led to more fluoroscopy time (MD 2.11, 95% CI 1.78 to 2.43; P < 0.00001). (2) PFNA group versus Gamma nail group: PFNA led to less blood loss (MD –55.30, 95% CI –60.07 to –50.53; P < 0.00001), shorter fluoroscopy time (MD –0.50, 95% CI –0.55 to –0.45; P < 0.00001) and length of hospital stay (MD –0.20, 95% CI –0.27 to –0.13; P < 0.00001). (3) DHS group versus Gamma nail group: DHS was associated with lower rate of operative fracture of femur (MD 0.31, 95% CI 0.11 to 0.89; P = 0.03), later fracture of femur (MD 0.16, 95% CI 0.06 to 0.43; P = 0.0004), and reoperation (MD 0.49, 95% CI 0.27 to 0.88; P = 0.02), but caused more blood loss (MD 29.49, 95% CI 8.27 to 50.70; P = 0.006). In contrast, there was no difference regarding operative time, infection hematoma, pneumonia, thromboembolic events, and mortality. Discussion PFNA should be a priority choice for treatment of intertrochanteric fractures with minimal rate of fixation failure, less blood loss and shorter length of hospital stay. DHS has distinct advantages over Gamma nail with lower rate of plant-related complications and should be preferred device for intertrochanteric fractures. However, owing to the low quality evidence currently available, more high-quality RCTs are needed to confirm these findings. Level of evidence Level II.
Systemic characterisation of the human faecal microbiome provides the opportunity to develop non-invasive approaches in the diagnosis of a major human disease. However, shared microbial signatures ...across different diseases make accurate diagnosis challenging in single-disease models. Herein, we present a machine-learning multi-class model using faecal metagenomic dataset of 2,320 individuals with nine well-characterised phenotypes, including colorectal cancer, colorectal adenomas, Crohn's disease, ulcerative colitis, irritable bowel syndrome, obesity, cardiovascular disease, post-acute COVID-19 syndrome and healthy individuals. Our processed data covers 325 microbial species derived from 14.3 terabytes of sequence. The trained model achieves an area under the receiver operating characteristic curve (AUROC) of 0.90 to 0.99 (Interquartile range, IQR, 0.91-0.94) in predicting different diseases in the independent test set, with a sensitivity of 0.81 to 0.95 (IQR, 0.87-0.93) at a specificity of 0.76 to 0.98 (IQR 0.83-0.95). Metagenomic analysis from public datasets of 1,597 samples across different populations observes comparable predictions with AUROC of 0.69 to 0.91 (IQR 0.79-0.87). Correlation of the top 50 microbial species with disease phenotypes identifies 363 significant associations (FDR < 0.05). This microbiome-based multi-disease model has potential clinical application in disease diagnostics and treatment response monitoring and warrants further exploration.
The corrosion behaviour of a recently developed Al-Li-Cu-Mg alloy thick plate was investigated using correlative immersion testing in 3.5% NaCl solution with analytical electron and ion microscopy. ...Intergranular corrosion was observed along grain boundaries and the particle-matrix interface of Al7Cu2(Fe, Mn) and Al20Cu2Mn3 phases from 7 min of immersion. The Li-containing Al7Cu2(Fe, Mn) phases are electrochemically more active and susceptible to de-alloying than the Al20Cu2Mn3 phases. Intergranular T1 (Al2CuLi) precipitates are attacked via selective dissolution of Li and Al. In contrast to previous observation, the dissolution rates of T1 precipitates and the adjacent alloy matrix are almost the same.
•Clusters of Al7Cu2(Fe, Mn) phase act as preferred sites for corrosion initiation.•The Li-containing Al7Cu2(Fe, Mn) phases are more active than Al20Cu2Mn3 phases.•Corrosion along the particle-matrix interface is facilitated by galvanic coupling.•Intermetallic particles are de-alloyed via selective dissolution of Li and Al.•T1 (Al2CuLi) phases are dissolved at a similar rate as the adjacent alloy matrix.
The most heavily polluted white dwarfs often show excess infrared radiation from circumstellar dust disks, which are modeled as a result of tidal disruption of extrasolar minor planets. Interaction ...of dust, gas, and disintegrating objects can all contribute to the dynamical evolution of these dust disks. Here, we report two infrared variable dusty white dwarfs, SDSS J1228+1040 and G29-38. For SDSS J1228+1040, compared to the first measurements in 2007, the IRAC 3.6 and 4.5 fluxes decreased by 20% before 2014 to a level also seen in the recent 2018 observations. For G29-38, the infrared flux of the 10 m silicate emission feature became 10% stronger between 2004 and 2007, We explore several scenarios that could account for these changes, including tidal disruption events, perturbation from a companion, and runaway accretion. No satisfactory causes are found for the flux drop in SDSS J1228+1040 due to the limited time coverage. Continuous tidal disruption of small planetesimals could increase the mass of small grains and concurrently change the strength of the 10 m feature of G29-38. Dust disks around white dwarfs are actively evolving and we speculate that there could be different mechanisms responsible for the temporal changes of these disks.
Background
Cognitive frailty is a condition where physical frailty and mild cognitive impairment (MCI) co-exist. It is associated with increased risk of dementia and dependency. Previous studies ...reported that malnutrition and depression are associated with physical frailty and MCI; however, their relationships with cognitive frailty remained to be explored. The aims of this study were to examine the association of nutrition and depression with cognitive frailty, in comparison to having physical frailty or MCI alone.
Methods
This study employed a cross-sectional design. Data collection was conducted in the community settings on the older people without dementia. Dependent variables were cognitive frailty, physical frailty, and MCI. The independent variables were depression and nutrition. Multi-nominal regression was employed to examine the relationships between the dependent and independent variables. The associations were adjusted by four known co-variates, including age, gender, education and APOE ε4 carrier status.
Results
A total of 185 participants were recruited from four community centres and one elderly hostel and completed the data collection. Approximately 44.9% of the older people with physical frailty and 82.5% of elderly with MCI belonged to cognitive frailty. Multi-nominal regression models showed that depression is positively associated with cognitive frailty and with physical frailty, but not associated with solely MCI. Nutrition is negatively associated with cognitive frailty, but not associated with physical frailty or MCI alone.
Conclusion
Cognitive frailty is associated with malnutrition and depression. Therapeutic interventions managing depression and malnutrition may focus the older people with cognitive frailty to improve efficacy and cost-effectiveness.
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