Magnetic resonance (MR) evaluation of deep venous thrombosis of 338 discharged viral pneumonia patients.

Background: Viral pneumonia (VP) often leads to the development of deep vein thrombosis (DVT) in hospitalized patients. The aim of the study was to investigate the incidence of DVT in discharged patients with VP, and whether new and old DVT differ in transverse relaxation time. Methods: In this prospective cohort study in Wuhan, China, 338 consecutive discharged VP patients from February 2021 to March 2023 who underwent T2 weighted Sampling Perfection with Application Optimized Contrast Evolution (SPACE) were recruited to detect DVT. T2 mapping and T2* mapping were performed for the patients with DVT detected by magnetic resonance imaging (MRI). The minimum, maximum, mean of T2 time and T2* time of DVT were recorded as T2min, T2max, T2mean, T2*min, T2*max, and T2*mean, respectively. Clinical data and laboratory findings were compared between new and old DVT cases, which were defined based on the examination results before and after discharge. A Mann-Whitney test was used to compare transverse relaxation time parameters between new and old DVT. Results: Twelve percent of VP patients (40/338) developed new DVT after discharge. Thirty-three out of 104 DVTs did not resolve after discharge. Compared with patients with new DVT, patients with old DVT were older (67 vs. 59 years, P=0.003); and had a higher proportion of bedridden time >72 hours (72.7% vs. 37.0%, P<0.001). Patients with old DVT had a lower lymphocyte count (0.67×109/L vs. 0.97×109/L, P=0.01), higher C-reactive protein (59 vs. 35 mg/L, P=0.019), and higher levels of D-dimer (6.7 vs. 0.9 µg/mL, P<0.001) than patients with new DVT. Patients with old DVT received more invasive mechanical ventilation (30.3% vs. 7.4%, P<0.001) and had a higher proportion of acute respiratory distress syndrome (75.8% vs. 51.9%, P<0.001), and a higher proportion of cardiac injury (39.4% vs. 14.8%, P=0.033) than patients with new DVT. T2min, T2max, T2mean, and T2*max of new DVT were significantly greater than old DVT (17.6±10.4 vs. 13.2±5.9 ms, 94.9±44.9 vs. 42.3±23.6 ms, 46.8±24.0 vs. 25.0±12.6 ms, 22.5±12.4 vs. 10.7±3.5 ms, P<0.05 for all). There was no significant difference in T2*min or T2*mean between new and old DVT (3.2±0.4 vs. 3.1±0.4 ms, 8.2±4.9 vs. 5.5±1.5 ms, P>0.05 for both). Conclusions: T2 weighted SPACE magnetic resonance (MR) is valuable in the follow-up of thrombosis of discharged VP patients. T2 mapping distinguishes between new and old DVT.

Paired comparisons of venetoclax concentration in cerebrospinal fluid, bone marrow, and plasma in acute leukemia patients.

Venetoclax, a small molecule inhibitor of BCL-2, has demonstrated efficacy in treating acute leukemias and has been recommended as one of the first-line anti-leukemia therapies. Although venetoclax has been suggested to probably possess the ability to penetrate the central nervous system (CNS), current data to elucidate the characteristics of venetoclax in cerebrospinal fluid (CSF), bone marrow (BM), and plasma are still lacking. This study investigated the real-world characteristics of venetoclax concentrations in CSF, BM, and plasma in acute leukemia patients. Thirteen acute leukemia patients treated with venetoclax were included, with paired samples of CSF, BM, and plasma collected and venetoclax concentrations measured using LC-MS/MS. With the results, the median venetoclax concentrations were 2030 ng/mL in plasma, 16.7 ng/mL in CSF, and 1390 ng/mL in BM. The percentages of CSF/plasma and BM/plasma were 0.74% and 70.37%, respectively. While no direct correlation was observed between CSF and plasma venetoclax levels, there was a trend toward an improved CSF/plasma percentage over time following the last administration of venetoclax. In contrast, a strong correlation was found between BM and plasma levels. This study demonstrated that venetoclax could reach its effective concentration in most patients, suggesting its potential clinical utility in the management of CNS involvement in acute leukemia.

Distinct pathway activities are associated with prognosis and response to bortezomib-containing treatment in MCL1-M based molecular subtypes of multiple myeloma.

Multiple myeloma (MM) is the second most prevalent hematological malignancy and remains incurable with remarkable heterogeneity in prognosis and treatment response across the patients. Clinical diagnosis and the existing molecular classification systems are inadequate for predicting treatment responses. Based on the convergence between plasma cell development and MM pathogenesis, we identified a gene co-expression module centered on the plasma cell survival regulator MCL1 (MCL1 module, MCL1-M) in the transcriptomes of pre-treated MM, which enabled stratification of MM patients into MCL1-M high and MCL1-M low molecular subtypes with subtype-specific prognosis and response to bortezomib-containing treatment. Here, we aimed to examine the mechanism underlying the disparate prognosis and treatment responses between the two molecular subtypes. Our findings reveal that MCL1-M high MM displays significant activation of pathways associated with cell proliferation, while MCL1-M low MM exhibits activation of immune-related signaling pathways. The relative enrichment of immune cells within the bone marrow microenvironment of MCL1-M low MM, particularly plasmacytoid dendritic cells, likely contributes to the activation of immune-related signaling pathways in this subset of myeloma cells. Using phase III trial data, we show that responses to bortezomib-containing treatment are associated with the extent of unfolded protein response (UPR) signaling activity. Further, bortezomib-mediated killing of MM cells could be enhanced or inhibited by in vitro manipulation of UPR activities in representative cell lines. In conclusion, MCL1-M based molecular subtypes of MM are characterized by distinct signaling activities from both malignant cells and bone marrow microenvironment, which may drive distinct prognosis and treatment responses.

TLR7/8 Activation in Immune Cells and Muscle by RNA-Containing Immune Complexes: Role in Inflammation and the Pathogenesis of Myositis.

OBJECTIVE: Activation of endosomal toll-like receptors (TLRs) is one possible driver of inflammation in idiopathic inflammatory myopathies (IIM). We investigated the potential contribution of TLR7 and TLR8 to IIM pathogenesis. METHODS: Activation of TLR7/8 in healthy donor peripheral blood mononuclear cells (PBMCs) by immune complexes from patients with IIM and lupus was tested. Autoantibody profiling of patient IgG samples was performed using a 1581-antigen array. TLR7 and/or TLR8 activation by RNA molecules associated with autoantibodies was assessed. Gene expression in human myoblasts and satellite cells following treatment with supernatants from TLR7/8-activated PBMCs was evaluated by NanoString. C57BL/6 mice were dosed intramuscularly with the TLR7/8 agonist R848 and single-cell RNA-sequencing was performed on the muscle to ascertain the cell types responding to TLR7/8 activation and the downstream effects. RESULTS: Overall, 69 patients with IIM were included with representation of dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM) subsets. Immune complexes from patients with IIM, as well as autoantibody-associated RNAs His-tRNA, Y1, Y4 and U1, activated PBMCs to produce IFN-α and IL-6 via TLR7/8. Several canonical (Ro60, Ro52, HIST1H4A) and novel (IL-36RN) autoreactivities correlated highly with TLR7/8 activation. Supernatants from TLR7/8-activated PBMCs had a negative impact on human myoblasts and satellite cells. Endothelial cells were activated by R848 in mouse muscle in vivo, in addition to immune cells such as monocytes and macrophages. CONCLUSION: Our results suggest that patients with IIM have autoantibodies in their blood causing TLR7/8 activation, which leads to inflammation in muscles with potential deleterious effects.

A PIKfyve modulator combined with an integrated stress response inhibitor to treat lysosomal storage diseases.

Lysosomal degradation pathways coordinate the clearance of superfluous and damaged cellular components. Compromised lysosomal degradation is a hallmark of many degenerative diseases, including lysosomal storage diseases (LSDs), which are caused by loss-of-function mutations within both alleles of a lysosomal hydrolase, leading to lysosomal substrate accumulation. Gaucher's disease, characterized by <15% of normal glucocerebrosidase function, is the most common LSD and is a prominent risk factor for developing Parkinson's disease. Here, we show that either of two structurally distinct small molecules that modulate PIKfyve activity, identified in a high-throughput cellular lipid droplet clearance screen, can improve glucocerebrosidase function in Gaucher patient-derived fibroblasts through an MiT/TFE transcription factor that promotes lysosomal gene translation. An integrated stress response (ISR) antagonist used in combination with a PIKfyve modulator further improves cellular glucocerebrosidase activity, likely because ISR signaling appears to also be slightly activated by treatment by either small molecule at the higher doses employed. This strategy of combining a PIKfyve modulator with an ISR inhibitor improves mutant lysosomal hydrolase function in cellular models of additional LSD.

Research on a Method for Classifying Bolt Corrosion Based on an Acoustic Emission Sensor System.

High-strength bolts play a crucial role in ultra-high-pressure equipment such as bridges and railway tracks. Effective monitoring of bolt conditions is of paramount importance for common fault repair and accident prevention. This paper aims to detect and classify bolt corrosion levels accurately. We design and implement a bolt corrosion classification system based on a Wireless Acoustic Emission Sensor Network (WASN). Initially, WASN nodes collect high-speed acoustic emission (AE) signals from bolts. Then, the ReliefF feature selection algorithm is applied to identify the optimal feature combination. Subsequently, the Extreme Learning Machine (ELM) model is utilized for bolt corrosion classification. Additionally, to achieve high prediction accuracy, an improved goose algorithm (GOOSE) is employed to ensure the most suitable parameter combination for the ELM model. Experimental measurements were conducted on five classes of bolt corrosion levels: 0%, 25%, 50%, 75%, and 100%. The classification accuracy obtained using the proposed method was at least 98.04%. Compared to state-of-the-art classification diagnostic models, our approach exhibits superior AE signal recognition performance and stronger generalization ability to adapt to variations in working conditions.

Physical Activity Levels in Persons With Patellofemoral Pain: A Systematic Review and Meta-analysis.

CONTEXT: Pain and symptoms of patellofemoral pain (PFP) are often exacerbated during daily activities, which may result in reduced overall physical activity levels. OBJECTIVE: To summarize the evidence for physical activity levels among persons with PFP compared with pain-free controls. DATA SOURCES: PubMed, Embase, CINHAL, Cochrane Library, and SPORTDiscus were searched from January 1, 2000 to February 22, 2024. STUDY SELECTION: Peer-reviewed studies published in English that measured physical activity subjectively or objectively in persons with PFP and pain-free controls. STUDY DESIGN: Systematic review with meta-analysis. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: Standardized mean difference (SMD) with 95% CI are reported based on Hedges' g effect sizes. RESULTS: From 23,745 records, 41 studies met the eligibility criteria. There was high-to-moderate-certainty evidence that persons with PFP reported higher physical activity levels compared with pain-free controls using the International Physical Activity Questionnaire (SMD, 0.27; 95% CI 0.03, 0.51), whereas lower physical activity levels compared with pain-free controls using the Tegner Activity Scale (SMD, -0.31; 95% CI -0.57, -0.04). There was low-to-moderate-certainty evidence that there was no group difference in physical activity levels using the Baecke Physical Activity Questionnaire (SMD, 0.17; 95% CI -0.09, 0.44) or self-reported sports participation duration (SMD, -0.46; 95% CI -0.98, 0.05). There was high-certainty evidence that runners with PFP reported shorter running distances compared with pain-free runners (SMD, -0.36, 95% CI -0.57, -0.14). No data pooling was possible for objectively measured physical activity levels due to device heterogeneity (ie, different algorithms used to quantify the intensity of physical activity). CONCLUSION: Self-reported physical activity levels among persons with PFP were inconsistent depending on the physical activity measurement tool used or which specific physical activity was measured. Clinicians should integrate multiple physical activity assessment tools to determine the extent to which PFP influences physical activity levels. TRIAL REGISTRATION: PROSPERO #CRD42022314598.

Identification of KIFC1 as a putative vulnerability in lung cancers with centrosome amplification.

Centrosome amplification (CA), an abnormal increase in the number of centrosomes in the cell, is a recurrent phenomenon in lung and other malignancies. Although CA promotes tumor development and progression by inducing genomic instability (GIN), it also induces mitotic stress that jeopardizes cellular integrity. CA leads to the formation of multipolar mitotic spindles that can cause lethal chromosome segregation errors. To sustain the benefits of CA by mitigating its consequences, malignant cells are dependent on adaptive mechanisms that represent therapeutic vulnerabilities. We aimed to discover genetic dependencies associated with CA in lung cancer. Combining a CRISPR/Cas9 functional genomics screen with tumor genomic analyses, we identified the motor protein KIFC1, also known as HSET, as a putative vulnerability specifically in lung adenocarcinoma (LUAD) with CA. KIFC1 expression was positively correlated with CA in LUAD and associated with worse patient outcomes, smoking history, and indicators of GIN. KIFC1 loss-of-function sensitized LUAD cells with high basal KIFC1 expression to potentiation of CA, which was associated with a diminished ability to cluster extra centrosomes into pseudo-bipolar mitotic spindles. Our work suggests that KIFC1 inhibition represents a novel approach for potentiating GIN to lethal levels in LUAD with CA by forcing cells to divide with multipolar spindles, rationalizing further studies to investigate its therapeutic potential.

Short- medium- and long-term effects of botulinum toxin on upper limb spasticity in children with cerebral palsy: A meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin (BTX) is an effective management method for spasticity in children with cerebral palsy (CP), but the short- medium- and long-term effects remain unclear. OBJECTIVE: The primary objective was to quantify the effects of BTX injections on upper limb spasticity over time in children with CP. The secondary objective was to evaluate efficacy according to the International Classification of Functioning, Disability, and Health-Children & Youth version framework. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that included control/comparison groups treated with a placebo or other treatments. We searched CINAHL, Embase, PubMed, Scopus, Web of Science, and PsycINFO from their inception to April 2024. The pooled mean difference (MD) or standard mean difference (SMD) with 95 % CI was calculated using a random effects model at the short-term (up to 3 months), medium-term (3 to 6 months), and long-term (over 6 months). RESULTS: A total of 658 children with CP aged 1.8 to 19 years old in 12 eligible trials were involved. The primary outcome of the Melbourne Assessment percentile showed a significant increase in the medium- (MD = 2.63, 95 % CI 0.22 to 5.04, I² = 0 %) and long-term (MD = 4.72, 95 % CI 0.93 to 8.51, I² = 0 %) in favor of BTX. Pooled effects also showed that BTX significantly improved Modified Ashworth Scale scores in the short- (MD = -0.44, 95 % CI -0.88 to -0.01, I² = 88 %) and medium-term (MD = -0.20, 95 % CI -0.28 to -0.13, I² = 0 %), and individual goals and bimanual performance up to 6-months. No significantly higher risk of adverse events was observed with BTX. CONCLUSIONS AND IMPLICATIONS: BTX injections sustainably improved the quality of affected upper limb function and temporarily improved individual goals and bimanual performance in children with CP. Our findings cautiously support a time interval of 3 to 6 months between BTX injections in the upper limbs of children with CP. TRIAL REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Registration ID: CRD42022323672).

The influence of vigorous physical exertion on cardiac demand under conditions of daily living among firefighters with elevated blood pressure.

BACKGROUND: Firefighters have a high prevalence of cardiovascular disease. The poor heart health of firefighters is implicated in their increased risk of sudden cardiac death (SCD). Exercise may be protective against SCD partially due to the immediate blood pressure (BP) reductions of 5-8 mmHg following exercise, termed postexercise hypotension (PEH) OBJECTIVES: To examine PEH under ambulatory conditions after a maximal cardiopulmonary exercise test (CPET) among career firefighters METHODS: Firefighters (n = 19) completed a maximal CPET and non-exercise control (CONTROL) in random order on separate non-workdays and left the laboratory instrumented to an ambulatory BP (ABP) monitor. Ambulatory systolic BP (ASBP), diastolic BP (ADBP), and heart rate (AHR) were recorded at hourly intervals over 19hr. The ambulatory rate pressure product (ARPP) was calculated as ASBPxAHRx10-3 at each hourly interval. Repeated measures ANCOVA tested if the ABP, AHR, and ARPP responses differed after CPET vs CONTROL over 19hr RESULTS: Firefighters were middle-aged (39.5 ± 8.9 yr), overweight (29.2 ± 4.0 kg/m2) men with elevated BP (123.1 ± 9.6/79.8 ± 10.4 mmHg), while resting HR (67.7 ± 11.3 bpm) and RPP (8.4 ± 1.7mmHg*bpm*10-3) were in normal ranges. ASBP (16.6 ± 5.7 mmHg) and ADBP (3.1 ± 4.6 mmHg) increased after the CPET vs CONTROL over 19hr (ps<0.01), as did AHR (9.4 ± 7.9 bpm, p = 0.02) and ARPP (2.5 ± 1.1mmHg*bpm*10-3, p < 0.01). CONCLUSIONS: Unexpectedly, the firefighters exhibited postexercise hypertension rather than PEH. The increases in ABP and AHR we observed indicated a sustained increase in cardiac demand. Further investigation is needed to confirm our findings and determine whether the adverse hemodynamic responses we observed contribute to the high prevalence of SCD that firefighters experience on the job.

Dysregulated Wnt/ß-catenin signaling confers resistance to cuproptosis in cancer cells.

Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/ß-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/ß-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/ß-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the ß-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. Knockdown of TCF4 or pharmacological Wnt/ß-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/ß-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.

Opportunistic use of chest low-dose computed tomography (LDCT) imaging for low bone mineral density and osteoporosis screening: cutoff thresholds for the attenuation values of the lower thoracic and upper lumbar vertebrae.

Background: Osteoporosis remains substantially underdiagnosed and undertreated worldwide. Chest low-dose computed tomography (LDCT) may provide a valuable and popular opportunity for osteoporosis screening. This study sought to evaluate the feasibility of the screening of low bone mineral density (BMD) and osteoporosis with mean attenuation values of the lower thoracic compared to upper lumbar vertebrae. The cutoff thresholds of the mean attenuation values in Hounsfield units (HU) were derived to facilitate implementation of opportunistic screening using chest LDCT. Methods: The participants aged 30 years or older who underwent chest LDCT and quantitative computed tomography (QCT) examinations from August 2018 to October 2020 in our hospital were consecutively included in this retrospective study. A region of interest (ROI) was placed in the trabecular bone of each vertebral body to measure the HU values. The correlations of mean HU values of lower thoracic (T11-T12) and upper lumbar (L1-L2) vertebrae with age and lumbar BMD obtained with QCT were performed using the Pearson correlation coefficient, respectively. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve was generated to determine the cutoff thresholds for distinguishing low BMD from normal and osteoporosis from non-osteoporosis. Results: A total of 1,112 participants were included in the final study cohort (743 men and 369 women, mean age 58.2±8.9 years; range, 32-88 years). The mean HU values of T11-T12 and L1-L2 were significantly different among 3 QCT-defined BMD categories of osteoporosis, osteopenia, and normal (P<0.001). The differences in HU values between T11-T12 and L1-L2 in each category of bone status were statistically significant (P<0.001). The mean HU values of T11-T12 (r=-0.453, P<0.001) and L1-L2 (r=-0.498, P<0.001) had negative correlations with age. Positive correlations were observed between the mean HU values of T11-T12 (r=0.872, P<0.001) and L1-L2 (r=0.899, P<0.001) with BMD. The optimal cutoff thresholds for distinguishing low BMD from normal were average T11-T12 ≤157 HU [AUC =0.941, 95% confidence interval (CI): 0.925-0.954, P<0.001] and L1-L2 ≤138 HU (AUC =0.950, 95% CI: 0.935-0.962, P<0.001), as well as distinguishing osteoporosis from non-osteoporosis were average T11-T12 ≤125 HU (AUC =0.960, 95% CI: 0.947-0.971, P<0.001) and L1-L2 ≤107 HU (AUC =0.961, 95% CI: 0.948-0.972, P<0.001). There was no significant difference between the AUC values of T11-T12 and L1-L2 for low BMD (P=0.07) and osteoporosis (P=0.92) screening. Conclusions: We have conducted a study on low BMD and osteoporosis screening using mean attenuation values of lower thoracic and upper lumbar vertebrae. Assessment of mean attenuation values of T11-T12 and L1-L2 can be used interchangeably for low BMD and osteoporosis screening using chest LDCT, and their cutoff thresholds were established.

Little evidence that androstadienone affects social distance-dependent prosocial behaviour: a pre-registered study.

In navigating the complexities of social life, humans have evolved to interpret invisible odorous chemical cues, with profound behavioural impacts often unbeknown to the conscious mind. The manifestation of this in humans is evident in the scent of androstadienone (androsta-4,16-dien-3-one), an odorous compound which is considered a putative human pheromone. The current study investigated the effect of androstadienone on social distance-dependent prosocial behaviour measured by a social discounting task, in which participants chose between selfish and generous options. Based on our pre-registration, we predicted a sex-specific effect, with males exposed to androstadienone exhibiting increased generosity, while females would choose more selfishly. Employing a double-blind, placebo-controlled, between-subject design, we recruited 170 participants who were randomly assigned to either the androstadienone or control condition. Olfactory stimuli were administered while participants completed the social discounting task. Inconsistent with our hypothesis, inhaling androstadienone did not impact social distance-dependent prosocial behaviour. This finding was supported by multiple estimates of prosociality, including model-free, model-based and maximum likelihood estimation. Further analyses indicated that androstadienone administration did not influence perceived social distance or bias participants towards being generous or selfish. Thus, our empirical findings provide no support for the hypothesis that androstadienone modulates generosity.

Synergistic ferrate(VI) and chlorine for reclaimed water disinfection: Microbial control and chlorine decay mitigation.

Chlorination is the most widely used disinfection technology due to its simplicity and continuous disinfection ability. However, the drawbacks of disinfection by-products and chlorine-resistant bacteria have gained increasing attention. Nowadays, ferrate (Fe(VI)) is a multifunctional and environmentally friendly agent which has great potential in wastewater reclamation and reuse. This study investigated synergistic Fe(VI) and chlorine technology for reclaimed water disinfection in terms of microbial control and chlorine decay mitigation. Specifically, synergistic disinfection significantly improved the inactivation efficiency on total coliform, Escherichia coli and heterotrophic bacteria compared to sole chlorination. Synergistic disinfection also exhibited superior performance on controlling the relative abundance of chlorine-resistant bacteria and pathogenic bacteria. In addition, the decay rate of residual chlorine was relatively lower after Fe(VI) pretreatment, which was beneficial for microbial control during the reclaimed water distribution process. Technical and economic analyses revealed that synergistic Fe(VI) and chlorine disinfection was suitable and feasible. Results of this study are believed to provide useful information and alternative options on the optimization of reclaimed water disinfection.

Depression prevalence of the Geriatric Depression Scale-15 was compared to Structured Clinical Interview for DSM using individual participant data meta-analysis.

Depression questionnaire cutoffs are calibrated for screening accuracy and not to assess prevalence, but the Geriatric Depression Scale (GDS-15) is often used to estimate diagnostic prevalence among older adults, most commonly with scores of ≥ 5. We conducted an individual participant data meta-analysis to compare depression prevalence based on GDS-15 ≥ 5 to Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) diagnoses and assessed whether an alternative cutoff could be more accurate. We used generalized linear mixed models to estimate prevalence. Data from 14 studies (3602 participants, 434 SCID major depression) were included. Pooled GDS-15 ≥ 5 prevalence was 34.2% (95% confidence interval [CI] 27.5-41.6%), and pooled SCID prevalence was 14.8% (95% CI 10.0-21.5%; difference of 17.6%, 95% CI 11.6-23.6%). GDS-15 ≥ 8 provided the closest estimate to SCID with mean difference of - 0.3% (95% prediction interval - 17.0-16.5%). Prevalence estimate differences were not associated with study or participant characteristics. In sum, GDS-15 ≥ 5 substantially overestimated depression prevalence. A cutoff of ≥ 8 was accurate overall, but heterogeneity was too high for implementation in practice. Validated diagnostic interviews should be used to estimate major depression prevalence among older adults.

Disinfection-residual bacteria (DRB) after chlorine dioxide treatment: Microbial community structure, regrowth potential, and secretion characteristics.

This study investigates the effects of chlorine dioxide (ClO2) disinfection on the community structure, regrowth potential, and metabolic product secretion of disinfection-residual bacteria (DRB) in secondary effluent (SE), denitrification filter effluent (DFE), and ultrafiltration effluent (UE). Results show that ClO2 effectively reduces bacteria in SE and UE, achieving log removal values exceeding 3 at 1 mg/L within 30 min. A salient positive correlation (R2 > 0.95) exists between changes in total fluorescence intensity and disinfection efficacy. Post-treatment, Acinetobacter abundance increased in SE, while Pseudomonas decreased in DFE and UE. At lower ClO2 concentrations, Staphylococcus, Mycobacterium, Aeromonas, and Lactobacillus increased in DFE, but decreased at higher concentrations. After storage, bacterial counts in disinfected samples exceeded those in the control group, surpassing 105 CFU/mL. Despite an initial decline, species richness and evenness partially recovered but remained lower than control levels. Culturing DRB for 72 h showed elevated extracellular polymeric substances (EPS) secretion, quantified as total organic carbon (TOC), ranging from 5 to 27 mg/L, with significantly higher EPS in the disinfection group. Parallel factor analysis with self-organizing maps (PARAFAC-SOM) effectively differentiated water sample types and EPS fluorescent substances, underscoring the potential of three-dimensional fluorescence as an indirect measure of ClO2 disinfection efficacy.

Development and validation of dietary depression index in Chinese adults.

Objective: Previous studies have suggested diet was associated with depressive symptoms. We aimed to develop and validate Dietary Depression Index (DDI) based on dietary prediction of depression in a large Chinese cancer screening cohort.Methods: In the training set (n = 2729), we developed DDI by using intake of 20 food groups derived from a food frequency questionnaire to predict depression as assessed by Patient Health Questionnaire-9 based on the reduced rank regression method. Sensitivity, specificity, positive predictive value, and negative predictive value were used to assess the performance of DDI in evaluating depression in the validation dataset (n = 1176).Results: Receiver operating characteristic analysis was constructed to determine the best cut-off value of DDI in predicting depression. In the study population, the DDI ranged from -3.126 to 1.810. The discriminative ability of DDI in predicting depression was good with the AUC of 0.799 overall, 0.794 in males and 0.808 in females. The best cut-off values of DDI for depression prediction were 0.204 overall, 0.330 in males and 0.034 in females. DDI was a validated method to assess the effects of diet on depression.Conclusion: Among individual food components in DDI, fermented vegetables, fresh vegetables, whole grains and onions were inversely associated, whereas legumes, pickled vegetables and rice were positively associated with depressive symptoms.

Polystyrene microplastics facilitate renal fibrosis through accelerating tubular epithelial cell senescence.

Microplastics (MPs), emerging contaminants, are easily transported and enriched in the kidney, suggesting the kidney is susceptible to the toxicity of MPs. In this study, we explored the toxicity of MPs, including unmodified polystyrene (PS), negative-charged PS-SO3H, and positive-charged PS-NH2 MPs, in mice models for 28 days at a human equivalent concentration. The results showed MPs significantly increased levels of UREA, urea nitrogen (BUN), creatinine (CREA), and uric acid (UA) levels in serum and white blood cells, protein, and microalbumin in urine. In the kidney, MPs triggered persistent inflammation and renal fibrosis, which was caused by the increased senescence of tubular epithelial cells. Moreover, we identified the critical role of the Klotho/Wnt/ß-catenin signaling pathway in the process of MPs induced senescence of tubular epithelial cells, promoting the epithelial-mesenchymal transformation of epithelial cells. MPs supported the secretion of TGF-ß1 by senescent epithelial cells and induced the activation of renal fibroblasts. On the contrary, restoring the function of Klotho can alleviate the senescence of epithelial cells and reverse the activation of fibroblasts. Thus, our study revealed new evidence between MPs and renal fibrosis, and adds an important piece to the whole picture of the plastic pollution on people's health.

COVID-19 vaccinations and infections among individuals with systemic sclerosis: A Scleroderma Patient-centered Intervention Network (SPIN) Cohort study.

BACKGROUND/PURPOSE: We previously surveyed adults with systemic sclerosis (SSc) regarding COVID-19 vaccination in April-May 2021. The objective of the present study was to update through June-July 2022 and assess self-reported (1) COVID-19 vaccination rates, including boosters; (2) vaccine-related adverse events; (3) peri­vaccination immunosuppressive medication management; (4) vaccine hesitancy; and (5) prevalence and severity of COVID-19 infections. METHODS: In April-May 2021 and June-July 2022, SPIN Cohort participants completed surveys on COVID-19 vaccination and infection. Primary vaccine series was defined according to the standard for each COVID-19 vaccine; additional vaccine administrations were considered booster doses. Fully vaccinated was defined as having completed a primary vaccine series and at least one booster dose. RESULTS: 544 participants completed the 2021 survey only, 101 the 2022 survey only, and 388 both surveys. Among 489 participants with 2022 data, 437 (89 %) had received both primary and booster vaccines. Among all 1,033 participants, 960 (93 %) received at least one dose. At least one adverse reaction was reported by 34 % (330 of 960 participants) following first, 48 % (314 of 657 participants) following second, and 34 % (147 of 437 participants) following booster vaccine doses (primarily sore arm and fatigue); no severe adverse reactions were reported. SSc symptom worsening was reported in 6 % (53 of 960) after the first, 6 % after the second (39 of 657), and 4 % (17 of 437) after the booster dose. Of participants taking methotrexate or mycophenolate (including Cellcept or Myfortic), 34 of 266 (13 %) reported that they temporarily stopped or decreased their medication at the first dose, 32 of 215 (15 %) at the second dose, and 28 of 148 (19 %) for booster vaccination. Of 52 individuals not fully vaccinated with primary and booster doses in 2022, 29 (56 %) reported worry about vaccine related SSc flares. 172 of 489 (35 %) 2022 participants reported a history of at least one COVID-19 infection; 114 (66 %) occurred after receiving at least a primary vaccine series. Among initial COVID-19 infections, 9 (5 %) were asymptomatic, 66 (38 %) involved mild symptoms, 82 (48 %) moderate symptoms, and 15 (9 %) required hospitalization. CONCLUSION: Most people with SSc in the study were fully vaccinated, and most continued their methotrexate or mycophenolate post-primary and booster vaccinations. Over half of vaccine-hesitant participants were concerned regarding risk of SSc flare; however, few vaccinated participants reported this. These data may be useful for counselling people with SSc regarding COVID-19 vaccine safety and outcomes.