Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

Integrated Hepatitis C-Opioid Use Disorder Care Through Facilitated Telemedicine: A Randomized Trial.

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, Setting, and Participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main Outcomes and Measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and Relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial Registration: ClinicalTrials.gov Identifier: NCT02933970.

Aicardi-Goutières syndrome: A monogenic type I interferonopathy.

Aicardi-Goutières syndrome (AGS) is a rare monogenic autoimmune disease that primarily affects the brains of children patients. Its main clinical features include encephalatrophy, basal ganglia calcification, leukoencephalopathy, lymphocytosis and increased interferon-α (IFN-α) levels in the patient's cerebrospinal fluid (CSF) and serum. AGS may be caused by mutations in any one of nine genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, IFIH1, LSM11 and RNU7-1) that result in accumulation of self-nucleic acids in the cytoplasm or aberrant sensing of self-nucleic acids. This triggers overproduction of type I interferons (IFNs) and subsequently causes AGS, the prototype of type I interferonopathies. This review describes the discovery history of AGS with various genotypes and provides the latest knowledge of clinical manifestations and causative genes of AGS. The relationship between AGS and type I interferonopathy and potential therapeutic methods for AGS are also discussed in this review.

Epigenetic Up-Regulation of ADAMTS4 in Sympathetic Ganglia is Involved in the Maintenance of Neuropathic Pain Following Nerve Injury.

Sympathetic axonal sprouting into dorsal root ganglia is a major phenomenon implicated in neuropathic pain, and sympathetic ganglia blockage may relieve some intractable chronic pain in animal pain models and clinical conditions. These suggest that sympathetic ganglia participated in the maintenance of chronic pain. However, the molecular mechanism underlying sympathetic ganglia-mediated chronic pain is not clear. Here, we found that spared nerve injury treatment upregulated the expression of ADAMTS4 and AP-2α protein and mRNA in the noradrenergic neurons of sympathetic ganglia during neuropathic pain maintenance. Knockdown the ADAMTS4 or AP-2α by injecting specific retro scAAV-TH (Tyrosine Hydroxylase)-shRNA ameliorated the mechanical allodynia induced by spared nerve injury on day 21 and 28. Furthermore, chromatin immunoprecipitation and coimmunoprecipitation assays found that spared nerve injury increased the recruitment of AP-2α to the ADAMTS4 gene promoter, the interaction between AP-2α and histone acetyltransferase p300 and the histone H4 acetylation on day 28. Finally, knockdown the AP-2α reduced the acetylation of H4 on the promoter region of ADAMTS4 gene and suppressed the increase of ADAMTS4 expression induced by spared nerve injury. Together, these results suggested that the enhanced interaction between AP-2α and p300 mediated the epigenetic upregulation of ADAMTS4 in sympathetic ganglia noradrenergic neurons, which contributed to the maintenance of spared nerve injury induced neuropathic pain.

Associations between Visual Acuity and Cognitive Decline in Older Adulthood: A 9-Year Longitudinal Study.

OBJECTIVE: Emerging evidence suggests low vision may be a modifiable risk factor for cognitive decline. We examined effects of baseline visual acuity (VA) on level of, and change in, cognitive test performance over 9 years. METHOD: A population-based sample of 1,621 participants (average age 77 years) completed a comprehensive neuropsychological evaluation and VA testing at baseline and reassessed at nine subsequent annual visits. Linear regression modeled the association between baseline VA and concurrent cognitive test performance. Joint modeling of a longitudinal sub-model and a survival sub-model to adjust for attrition were used to examine associations between baseline VA and repeated cognitive test performance over time. RESULTS: Better baseline VA was associated cross-sectionally with younger age, male sex, greater than high school education, and higher baseline neuropsychological test scores on both vision-dependent (B coefficient range -0.163 to -0.375, p = .006 to <.001) and vision-independent tests (-0.187 to -0.215, p = .003 to .002). In longitudinal modeling, better baseline VA was associated with slower decline in vision-dependent tests (B coefficient range -0.092 to 0.111, p = .005 to <.001) and vision-independent tests (-0.107 to 0.067, p = .007 to <.001). CONCLUSIONS: Higher VA is associated with higher concurrent cognitive abilities and slower rates of decline over 9 years in both vision-dependent and vision-independent tests of memory, language, and executive functioning. Findings are consistent with emerging literature supporting vision impairment in aging as a potentially modifiable risk factor for cognitive decline. Clinicians should encourage patient utilization of vision assessment and correction with the added aim of protecting cognition.

Sensitive detection of synthetic cannabinoids in human blood using magnetic polydopamine molecularly imprinted polymer nanocomposites.

Synthetic cannabinoids (SCs) are a series of artificial chemical substances with pharmacological properties similar to those of natural cannabinoids and their abuse poses a great risk to social security and human health. However, the highly sensitive detection of low concentrations of SCs in human serum remains a great challenge. In this work, we developed a highly sensitive, rapid and highly selective method for the detection of SCs in human serum. Magnetic molecularly imprinted polymer (MIP) nanocomposites were prepared through self-polymerization of dopamine and template molecules on the surfaces of magnetic beads. 9H-Carbazole-9-hexanol (9CH) was used as a template molecule because of its long chain structure shared with six synthetic cannabinoids and its ability to provide specific recognition sites. With these magnetic MIP nanoparticles, six SCs could be rapidly and effectively extracted from human blood. The concentrations of six SCs could be accurately determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. The limits of detection were in the range of 0.1-0.3 ng mL-1. The proposed method is characterized by high sensitivity and selectivity, and has great potential for application in the analysis of practical samples.

The potent analgesia of intrathecal 2R, 6R-HNK via TRPA1 inhibition in LF-PENS-induced chronic primary pain model.

BACKGROUND: Chronic primary pain (CPP) is an intractable pain of unknown cause with significant emotional distress and/or dysfunction that is a leading factor of disability globally. The lack of a suitable animal model that mimic CPP in humans has frustrated efforts to curb disease progression. 2R, 6R-hydroxynorketamine (2R, 6R-HNK) is the major antidepressant metabolite of ketamine and also exerts antinociceptive action. However, the analgesic mechanism and whether it is effective for CPP are still unknown. METHODS: Based on nociplastic pain is evoked by long-term potentiation (LTP)-inducible high- or low-frequency electrical stimulation (HFS/LFS), we wanted to develop a novel CPP mouse model with mood and cognitive comorbidities by noninvasive low-frequency percutaneous electrical nerve stimulation (LF-PENS). Single/repeated 2R, 6R-HNK or other drug was intraperitoneally (i.p.) or intrathecally (i.t.) injected into naïve or CPP mice to investigate their analgesic effect in CPP model. A variety of behavioral tests were used to detect the changes in pain, mood and memory. Immunofluorescent staining, western blot, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and calcium imaging of in cultured dorsal root ganglia (DRG) neurons by Fluo-8-AM were used to elucidate the role and mechanisms of 2R, 6R-HNK in vivo or in vitro. RESULTS: Intrathecal 2R, 6R-HNK, rather than intraperitoneal 2R, 6R-HNK or intrathecal S-Ketamine, successfully mitigated HFS-induced pain. Importantly, intrathecal 2R, 6R-HNK displayed effective relief of bilateral pain hypersensitivity and depressive and cognitive comorbidities in a dose-dependent manner in LF-PENS-induced CPP model. Mechanically, 2R, 6R-HNK markedly attenuated neuronal hyperexcitability and the upregulation of calcitonin gene-related peptide (CGRP), transient receptor potential ankyrin 1 (TRPA1) or vanilloid-1 (TRPV1), and vesicular glutamate transporter-2 (VGLUT2) in peripheral nociceptive pathway. In addition, 2R, 6R-HNK suppressed calcium responses and CGRP overexpression in cultured DRG neurons elicited by the agonists of TRPA1 or/and TRPV1. Strikingly, the inhibitory effects of 2R, 6R-HNK on these pain-related molecules and mechanical allodynia were substantially occluded by TRPA1 antagonist menthol. CONCLUSIONS: In the newly designed CPP model, our findings highlighted the potential utility of intrathecal 2R, 6R-HNK for preventing and therapeutic modality of CPP. TRPA1-mediated uprgulation of CGRP and neuronal hyperexcitability in nociceptive pathways may undertake both unique characteristics and solving process of CPP.

On the use of the likelihood ratio test methodology in pharmacovigilance.

The safety of medical products due to adverse events (AE) from drugs, therapeutic biologics, and medical devices is a major public health concern worldwide. Likelihood ratio test (LRT) approaches to pharmacovigilance constitute a class of rigorous statistical tools that permit objective identification of AEs of a specific drug and/or a class of drugs cataloged in spontaneous reporting system databases. However, the existing LRT approaches encounter certain theoretical and computational challenges when an underlying Poisson model assumption is violated, including in cases of zero-inflated data. We briefly review existing LRT approaches and propose a novel class of (pseudo-) LRT methods to address these challenges. Our approach uses an alternative parametrization to formulate a unified framework with a common test statistic that can handle both Poisson and zero-inflated Poisson (ZIP) models. The proposed framework is computationally efficient, and it reveals deeper insights into the comparative behaviors of the Poisson and the ZIP models for handling AE data. Our extensive simulation studies document notably superior performances of the proposed methods over existing approaches particularly under zero-inflation, both in terms of statistical (eg, much better control of the nominal level and false discovery rate with substantially enhanced power) and computational ( ∼ $$ \sim $$ 100-500-fold gains in average running times) performance metrics. An application of our method on the statin drug class from the FDA FAERS database reveals interesting insights on potential AEs. An R package, pvLRT, implementing our methods has been released in the public domain.

Association of body composition with risk of overall and site-specific cancers: A population-based prospective cohort study.

Although excess adiposity has been linked with various cancers, association between body composition and some cancers remains unclear, like lung and prostate cancers. We investigated associations of body composition with risk of overall cancer and major site-specific cancers in a prospective cohort of 454 079 cancer-free participants from UK-Biobank. Body composition was measured with bioimpedance analysis. We evaluated hazard ratio (HR) and 95% confidence interval (CI) with multivariate Cox linear and nonlinear models in men and women separately. We identified 27 794 cancers over 7.6 years of follow-up. Multivariable adjusted models including fat-free mass (FFM) and fat mass (FM) showed that FFM was positively associated with overall cancer risk in men and women (HR 1.03, 95% CI 1.01-1.04 and 1.07, 1.04-1.10, respectively); while the association between FM and overall cancer disappeared after adjusting for FFM. FFM was associated with higher risks of obesity-related cancers combined, stomach (women only), malignant melanoma, postmenopausal breast, corpus uteri, prostate, kidney (men only), and blood cancers and lower risk of lung cancer. FM was associated with higher risks of obesity-related cancers combined, esophageal, colon, lung (men only), postmenopausal breast (at the lower end of FM range), and corpus uteri cancers and lower risks of rectal, malignant melanoma (women only), prostate and blood cancers. FFM and FM seemed to have different effects on cancer risk, and the effects varied substantially by cancer type, in both direction and size. Higher FM/FFM ratio was also associated with some cancers risk, and might be a useful predictor of cancer risk.

Metabolic syndrome and its component traits present gender-specific association with liver cancer risk: a prospective cohort study.

BACKGROUND & AIMS: Little is known on the gender-specific effect and potential role of non-linear associations between metabolic syndrome (MetS) components and liver cancer risk. We evaluated these associations based on the UK Biobank cohort. METHODS: We included 474,929 individuals without previous cancer based on the UK Biobank cohort. Gender-specific hazard ratios (HRs) and 95% confidence interval (CIs) were calculated by Cox proportional hazards regression, adjusting for potential confounders. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method. RESULTS: Over a median follow-up of 6.6 years, we observed 276 cases of liver cancer (175 men, 101 women). MetS [HR 1.48, 95% CI 1.27-1.72] and central obesity [HR 1.65, 95% CI 1.18-2.31] were associated with higher risk of liver cancer in men but not in women. Participants with hyperglycaemia has higher risk of liver cancer. High waist circumference and blood glucose were dose-dependently associated with increased liver cancer risk in both genders. For high density lipoprotein (HDL) cholesterol (both genders) and blood pressure (women), U-shaped associations were observed. Low HDL cholesterol (< 1.35 mmol/L) in men and high HDL cholesterol in women (> 1.52 mmol/L) were associated with increased liver cancer risk. CONCLUSIONS: MetS components showed gender-specific linear or U- shaped associations with the risk of liver cancer. Our study might provide evidence for individualized management of MetS for preventing liver cancer.

Exercise and the Risk of Mild Cognitive Impairment: Does the Effect Depend on Vascular Factors?

INTRODUCTION: Although exercise is associated with a lower risk for mild cognitive impairment (MCI), it is unclear whether its protective effect depends on the presence or absence of vascular factors. METHODS: In an exploratory study of data from a population-based cohort, 1254 participants aged 65+ years were followed for 10 years for incident MCI. The main effect of baseline total minutes of exercise per week (0 vs. 1 to 149 vs. 150+), and its interaction with several vascular factors, on risk for incident MCI was examined using Cox proportional hazards regression models, adjusting for demographics. RESULTS: Compared with no exercise, 1 to 149 minutes [hazard ratio (HR)=0.90; 95% confidence interval (95% CI), 0.69-1.16] and 150 or more minutes per week (HR=0.84; 95% CI, 0.66-1.07) of exercise lowered risk for incident MCI in a dose-dependent manner. The majority of interactions were not statistically significant, but risk reduction effect sizes of <0.75 suggested that exercise may have stronger effects among those without high cholesterol, never smoking, and not currently consuming alcohol; also, those with arrhythmia, coronary artery disease, and heart failure. Overall, there was a pattern of exercise being associated with lower MCI risk among those without vascular factors. CONCLUSIONS: Spending more time engaging in exercise each week may offer protection against MCI in late life, with some variation among those with different vascular conditions and risk factors. Our findings may help target subgroups for exercise recommendations and interventions, and also generate hypotheses to test regarding underlying mechanisms.

A novel missense pathogenic variant in NEFH causing rare Charcot-Marie-Tooth neuropathy type 2CC.

The purpose of this research is to explore the underlying genes of Charcot-Marie-Tooth (CMT). Technologies such as electrophysiological testing and gene sequencing have been applied. We identified a novel variant NEFH c.2215C>T(p.P739S)(HGNC:7737) in a heterozygous state, which was considered to be pathogenic for CMT2CC(OMIM:616924).The proband and his brothers presented with muscle atrophy of hand and calf and moderately decreased conduction velocities. By whole exome sequencing analysis, we found the novel missense pathogenic variant in the proband, his brother and mother. This report broadened current knowledge about intermediate CMT and the phenotypic spectrum of defects associated with NEFH. In addition, the proband carried other five variants {HSPD1c.695C>A (p.S232X), FLNCc.1073A>G (p.N358S), GUSBc.323C>A (p.P108Q), ACY1 c.1063-1G>A and APTX c.484-2A>T}, which have not been reported until now. The NEFH c.2215C>T (p.P739S) give us a new understanding of CMT, which might provide new therapeutic targets in the future.

Predictors of attrition in a longitudinal population-based study of aging.

BACKGROUND: Longitudinal studies predictably experience non-random attrition over time. Among older adults, risk factors for attrition may be similar to risk factors for outcomes such as cognitive decline and dementia, potentially biasing study results. OBJECTIVE: To characterize participants lost to follow-up which can be useful in the study design and interpretation of results. METHODS: In a longitudinal aging population study with 10 years of annual follow-up, we characterized the attrited participants (77%) compared to those who remained in the study. We used multivariable logistic regression models to identify attrition predictors. We then implemented four machine learning approaches to predict attrition status from one wave to the next and compared the results of all five approaches. RESULTS: Multivariable logistic regression identified those more likely to drop out as older, male, not living with another study participant, having lower cognitive test scores and higher clinical dementia ratings, lower functional ability, fewer subjective memory complaints, no physical activity, reported hobbies, or engagement in social activities, worse self-rated health, and leaving the house less often. The four machine learning approaches using areas under the receiver operating characteristic curves produced similar discrimination results to the multivariable logistic regression model. CONCLUSIONS: Attrition was most likely to occur in participants who were older, male, inactive, socially isolated, and cognitively impaired. Ignoring attrition would bias study results especially when the missing data might be related to the outcome (e.g. cognitive impairment or dementia). We discuss possible solutions including oversampling and other statistical modeling approaches.

Metabolic syndrome and risk of pancreatic cancer: A population-based prospective cohort study.

Metabolic syndrome (MetS) and its components may link to pancreatic cancer risk; however, current epidemiological evidence is limited, and the potential mechanisms underlying the associations remain unclear. To investigate this, we carried out this prospective cohort study of 474 929 participants without a diagnosis of cancer based on UK Biobank dataset. MetS was defined according to the International Diabetes Federation criteria and pancreatic cancer was identified through linkage to UK cancer registries (median follow-up time: 6.6 years). We evaluated hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demography and lifestyle factors. Restricted cubic spline was performed for each MetS component to investigate their possible nonlinear associations with risk of pancreatic cancer. During 3 112 566 person-years of follow-up, 565 cases of pancreatic cancer were identified. Individuals with MetS (HR = 1.31, 95% CI, 1.09-1.56), central obesity (HR = 1.24, 95% CI, 1.02-1.50) and hyperglycemia (HR = 1.60, 95% CI, 1.31-1.97) had increased risk of pancreatic cancer. Higher waist circumference (WC) and blood glucose were independently associated with pancreatic cancer, with no evidence against nonlinearity. Although elevated CRP (≥1.00 mg/dL) showed a positive association with the risk for pancreatic cancer, the effect was substantially increased only in participants with MetS and CRP ≥1.00 mg/dL. Our study demonstrated a positive association between MetS and increased risk of pancreatic cancer, with two of the MetS components, WC and blood glucose, showing independent associations in linear manner. Our study also suggested a potential joint effect of MetS and CRP in pancreas tumorigenesis.

Investigation of Environmental Pollutant-Induced Lung Inflammation and Injury in a 3D Coculture-Based Microfluidic Pulmonary Alveolus System.

The health impact of environmental pollution involving an increase in human diseases has been subject to extensive study in recent decades. The methodology in biomimetic investigation of these pathophysiologic events is still in progress to uncover the gaps in knowledge associated with pollution and its influences on health. Herein, we describe a comprehensive evaluation of environmental pollutant-caused lung inflammation and injury using a microfluidic pulmonary alveolus platform with alveolar-capillary interfaces. We performed a microfluidic three-dimensional coculture with physiological microenvironment simulation at microscale control and demonstrated a reliable reconstruction of tissue layers including alveolar epithelium and microvascular endothelium with typical mechanical, structural, and junctional integrity, as well as viability. On-chip detection and analysis of pulmonary alveolus responses focusing on various inflammatory and injurious dynamics to the respective pollutant stimulations were achieved in the coculture-based microfluidic pulmonary alveolus model, in comparison with common on-chip monoculture and off-chip culture tools. We confirmed the synergistic effects of the epithelial and endothelial interfaces on the stimuli resistance and verified the importance of creating complex tissue microenvironments in vitro to explore pollution-involved human pathology. We believe the microfluidic approach presents great promise in environmental monitoring, drug discovery, and tissue engineering.

Simvastatin Improves Behavioral Disorders and Hippocampal Inflammatory Reaction by NMDA-Mediated Anti-inflammatory Function in MPTP-Treated Mice.

The cognitive function impairment may be related to the inflammation of the hippocampus in Parkinson's disease. Simvastatin can play a positive role in Parkinson's disease. The purpose of this study was to investigate whether simvastatin could improve behavioral disorders, especially depression, anxiety and cognitive function in mouse PD models, and further explore the molecular mechanism. In the present study, C57BL-6 mice underwent intraperitoneal injection of MPTP (30 mg/kg) once a day for 5 consecutive days. At the same time, simvastatin (10 mg/kg) was pretreated for 2 days before the Parkinson's disease model was established, and then continued for 5 days, and the control group underwent intraperitoneal injection of MK801 (dizocilpine, 0.2 mg/kg) and saline solution. Depression status was tested by a tail suspension test and a sucrose splash test, followed by an open-field test and an elevated plus maze test to determine anxiety levels. Spatial behavior and muscle status were measured with a water maze and a rotarod test. The expression of RNA and protein of N-methyl-D-aspartate receptor subtype 2B (NMDAR2B), nerve growth factor IB (Nur77), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF) α were assayed by real-time polymerase chain reaction and Western blot. Our results showed that simvastatin can improve the cognitive function, anxiety, and depression of PD mice with MPTP injury. Simvastatin reversed the NMDAR2B increase, restored Nur77 downward, and reduced the expression of COX-2 and TNF-α in MPTP-treated mice. This role of simvastatin was consistent with MK801 in increasing the expression of Nur77 and inhibiting NMDAR2B and cytokines in MPTP-lesioned PD mice. These findings suggest that reversed the NMDAR2B increase, restored Nur77 downward, and reduced the expression of COX-2 and TNF-α in MPTP-treated mice may be one of the mechanisms that simvastatin improves cognitive functions, depression, and anxiety in MPTP-lesioned mice.

Depression Symptoms Declining Among Older Adults: Birth Cohort Analyses From the Rust Belt.

OBJECTIVES: To investigate potential birth cohort effects in depression symptoms in older adults. DESIGN: Population-based prospective cohort. SETTING: Small-town communities in Pennsylvania. PARTICIPANTS: Three thousand two hundred and twenty seven older adults (average baseline age = 71.6) born between 1902 and 1941. MEASUREMENTS: Four decade-long birth cohorts were the primary predictors in this study: 1902-1911, 1912-1921, 1922-1931, and 1932-1941. The outcome was symptoms of depression assessed at baseline and follow-up study visits using a modified Center for Epidemiologic Studies Depression Scale (mCES-D). The depression outcome was operationalized as: 1). A binary outcome of having greater than equal to 5 depression symptoms on the total mCES-D at any study visit, and 2). A continuous outcome of four factor-analyzed component scores of the mCES-D including depressed mood, anergia/hopelessness, withdrawal, and poor self-esteem. All analyses were jointly modeled with attrition and adjusted for age, sex, education, Mini Mental State Examination score, antidepressant medications, and total prescription medications. RESULTS: Participants from more recently born cohorts were significantly less likely to have a study visit in which they reported greater than or equal to 5 depression symptoms, controlling for attrition. Specifically, in comparison to the 1902-1911 referent cohort, the 1912-1921 birth cohort was 43% less likely (odds ratio [OR] = 0.566, 95% confidence interval [CI]: 0.341-0.939), the 1922-1931 birth cohort was 63% less likely (OR = 0.0369, 95% CI: 0.215-0.632), and the 1932-1941 cohort was 79% less likely (OR = 0.205, 95% CI: 0.106-0.399). The cohort effect was most evident in the depressed mood and anergia/hopelessness symptom composites. CONCLUSION: Reduced rates of depression symptoms observed in successive birth cohorts of older adults may reflect compression of morbidity or other secular trends.

Research Progress of Drug Treatment in Novel Coronavirus Pneumonia.

As of March 10, 2020, more than 100,000 novel coronavirus pneumonia cases have been confirmed globally. With the continuous spread of the new coronavirus pneumonia epidemic in even the world, prevention and treatment of the disease have become urgent tasks. The drugs currently being developed are not adequate to deal with this critical situation. In addition to being controlled through effective isolation, we need a rapid response from the healthcare and biotechnology industries to accelerate drug treatment research. By reviewing the currently available literature published at home and abroad, we summarize the current research progress of drug treatment during the epidemic period. At present, the drugs that can be used for treatment mainly include antiviral drugs, antimalarials, glucocorticoids, plasma therapy, biological agents, and traditional Chinese medicine. The effectiveness and safety of drug therapy need to be confirmed by more clinical studies.

Blood Pressure and Memory: Novel Approaches to Modeling Nonlinear Effects in Longitudinal Studies.

BACKGROUND: Linear models cannot capture nonlinear associations when the relationships between cognition and risk factors vary across risk levels. We demonstrate a method of modelling nonlinear associations using the example of blood pressure (BP) and memory. METHODS: We measured memory and BP (in mm Hg) annually for 10 years in a population-based cohort (N=1982) aged 65+. We evaluated the relationship between BP and memory at the same time points using both linear mixed models and generalized additive mixed models with smoothing splines, adjusting for relevant covariates. RESULTS: Linear mixed models found no significant associations. Generalized additive mixed models detected different associations between BP and memory across baseline BP categories (normotensive, hypertensive, hypotensive). Among normotensives, systolic blood pressure (SBP)/diastolic blood pressure (DBP) around 140/80 was associated with the highest, while SBP/DBP around 110/60 was associated with the lowest, predicted memory scores. Among hypertensives, SBP/DBP around 130/85 was associated with the highest, while SBP/DBP around 150/65 was associated with the lowest, predicted memory scores. Among hypotensives, no significant association was found. Among both normotensives and hypertensives, a DBP >75 was associated with better memory. CONCLUSIONS: By modelling nonlinear associations, we showed that the relationship between BP and memory performance varied by baseline BP among normotensives and hypertensives.

Boosting Gas Involved Reactions at Nanochannel Reactor with Joint Gas-Solid-Liquid Interfaces and Controlled Wettability.

The low solubility of gases in aqueous solution is the major kinetic limitation of reactions that involve gases. To address this challenge, we report a nanochannel reactor with joint gas-solid-liquid interfaces and controlled wettability. As a proof of concept, a porous anodic alumina (PAA) nanochannel membrane with different wettability is used for glucose oxidase (GOx) immobilization, which contacts with glucose aqueous solution on one side, while the other side gets in touch with the gas phase directly. Interestingly, it is observed that the O2 could participate in the enzymatic reaction directly from gas phase through the proposed nanochannels, and a hydrophobic interface is more favorable for the enzymatic reaction due to the rearrangement of GOx structure as well as the high gas adhesion. As a result, the catalytic efficiency of GOx in the proposed interface is increased up to 80-fold compared with that of the free state in traditional aqueous air-saturated electrolyte. This triphase interface with controlled wettability can be generally applied to immobilize enzymes or catalysts with gas substrates for high efficiency.