Longitudinal Outcomes of the top 20 Utilizers of VA Connecticut's Psychiatric Emergency Services Between 2010 and 2020.

Frequent utilizers of emergency services represent a clinically important cohort with potentially unmet health care needs despite demanding a high volume of costly services. However, not much is known about their longitudinal course. This study identified the top 20 utilizers of VA Connecticut's psychiatric emergency services and conducted a chart review of their longitudinal outcomes during an 11-year period between 2010 and 2020, including their visit diagnoses, medical and psychiatric comorbidities, and types and frequency of other medical services and supports received. At the index visit, 19 of the 20 patients had substance use disorder and 14 patients had at least one non-substance psychiatric diagnosis. Despite all patients receiving primary care and other services, such as residential treatments, outpatient therapy, and social work consults, 11 of the 12 patients remaining alive and residing in the state continued to utilize psychiatric emergency services in 2020, revealing a pattern of persistent use.

Comparison of screening strategies for prevalent vertebral fractures in South Korea: vertebral fracture assessment vs. spine radiography.

BACKGROUND: Vertebral Fracture Assessment (VFA) is a useful tool to detect the vertebral fracture (VF) with low cost and radiation exposure. We aimed to compare screening strategies including VFA and spine radiography (X-ray) for detecting VF in terms of clinical effectiveness, cost and radiation exposure. METHODS: Three screening strategies: 1) X-ray following VFA, 2) VFA only, and 3) X-ray only were compared using a Markov model based on administrative data from South Korea in a population aged ≥50 years. We compared the incidence of new VFs, cost-effectiveness of reducing new VFs and radiation exposure in each strategy. RESULTS: The incidence of new VFs was reduced in all screening strategies compared to no screening: 29.4% for women and 12.5% for men in both X-ray following the VFA and VFA only strategies and 35% for women and 17.5% for men in the X-ray only strategy. The X-ray following VFA strategy had the lowest cost, followed by the X-ray only, and VFA only strategies. The radiation doses for X-ray only were 2,647-2,989 µSv and 3,253-3,398 µSv higher than in the X-ray following VFA and VFA only strategies. The new VF prevention effect was greater in women, and more prominent in older people (women ≥ 70, men ≥ 80) than people ≥ 50 years. CONCLUSIONS: The X-ray following VFA strategy is a cost-effective option for screening prevalent VF to prevent new VF in people aged ≥50 years due to its high effectiveness, lowest cost, and least radiation exposure.

Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies.

BACKGROUND: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemical antibodies in TNBC. METHODS: Interpretation of all three PD-L1 antibodies showed good concordance among three readers (kappa value >0.610) in both cancer cells and immune cells. Using a tissue microarray (TMA) constructed from 218 cases of TNBC, we performed immunohistochemical staining using three of the most popular commercially used PD-L1 monoclonal antibodies (clones 28-8, E1L3N and SP142) in cancer cells and immune cells. RESULTS: Using various cut-off values of previous studies (1, 5, 10 and 50 %), the expression rates in cancer cells were: PD-L1 (E1L3N) (14.7, 14.7, 11.0, 2.3 %), PD-L1 (28-8) (13.3, 12.4, 10.1, 1.8 %), and PD-L1 (SP142) (11.5, 11.0, 6.9, 0.5 %), respectively. At the 5 % cut-off value, the discordance rate among the three antibodies was 6.0-10.6 % and was highest between PD-L1 (SP142) and the other two antibodies. The expression rates in immune cells were PD-L1 (E1L3N) (37.6 %), PD-L1 (28-8) (36.7 %), and PD-L1 (SP142) (19.3 %), and the discordance rate among the three antibodies ranged from 13.8 to 24.8 % and was also highest between PD-L1 (SP142) and the other two antibodies. Among stromal histologic types, higher PD-L1 expression in cancer cells and immune cells was measured in inflammatory-type (p < 0.05). The absence of PD-L1 (28-8) staining in immune cells was associated with shorter disease free survival (DFS) and overall survival (OS) (p = 0.043, and p = 0.021) in univariate analyses, and with shorter OS in multivariate Cox analysis (hazard ratio: 5.429, 95 % CI 1.214-24.28, p = 0.027). CONCLUSIONS: PD-L1 detection in cancer cells and immune cells varied by antibody clone. The greatest amount of staining occurred with PD-L1 (E1L3N), followed by PD-L1 (28-8) and PD-L1 (SP142). The concordance rate among monoclonal PD-L1 antibodies was higher between PD-L1 (28-8) and PD-L1 (E1L3N). To determine the gold standard antibody and the most appropriate cut-off value, further study of the clinical trial group treated with PD-L1 inhibitor is necessary.

Proteome analysis of adrenal cortical tumors.

INTRODUCTION: Adrenal tumor is a relatively common tumor. The discrimination between adrenal cortical adenoma (ACA) and adrenal cortical carcinoma (ACC) is crucial as these two diseases have distinct prognosis. ACA is a benign tumor curable by surgical excision, while the prognosis of ACC is extremely poor, with a 5-year mortality of 75-90%. Therefore, previous proteomic studies focused on markers allowing the differentiation between ACA and ACC. AREAS COVERED: Several proteomic approaches based on the analysis of various samples such as human tissues, urine, and cell lines. In this review, we focused on proteomic studies performed to improve adrenal tumor diagnosis and identify ACC therapeutic targets. Expert commentary: The rapid development of cancer genomics provided a lot of information, which affects functional proteomics. In practice, differentially expressed proteins between ACA and ACC have been suggested in several proteomic studies and had a biologic implication in ACC.

Expression of cancer-associated fibroblast-related proteins in adipose stroma of breast cancer.

Cancer-associated fibroblasts (CAFs) play key roles in tumor microenvironment; they are thought to originate from adipocytes. This study aimed to evaluate CAF-related protein expression and its implications in breast cancer. Of the 939 enrolled breast cancer patients, 642 had fibrous and 297 had adipose stroma. The status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER-2), Ki-67, podoplanin, prolyl 4-hydroxylase, fibroblast activation protein α (FAPα), S100A4, platelet-derived growth factor receptor α (PDGFRα), PDGFRß, and chondroitin sulfate proteoglycan (NG2) was evaluated via tissue microarrays. Tumors were divided into luminal A, luminal B, HER-2, or triple-negative breast cancer subtypes according to their molecular status. Luminal A subtype was more prevalent in breast cancer of adipose stroma type, whereas other molecular subtypes were more common in fibrous stroma type (p < 0.001). Tumor cell expression of podoplanin and FAPα was higher in adipose stroma type, while higher expression of prolyl 4-hydroxylase and PDGFRα was observed in fibrous stroma type. Furthermore, adipose stroma type exhibited higher stromal expression of podoplanin, FAPα, PDGFRß, and NG2, whereas fibrous stroma type had higher prolyl 4-hydroxylase and S100A4 expression. In adipose stroma type, tumor positivity (p = 0.034) and stromal positivity (p = 0.005) of prolyl 4-hydroxylase were associated with shorter disease-free survival, and stromal prolyl 4-hydroxylase positivity was with shorter overall survival (p < 0.001). In conclusion, expression of CAF-related proteins was observed in breast cancer, with different profiles between adipose and fibrous stroma types. Prolyl 4-hydrolase status might be of prognostic value in adipose stroma type.

Effect of chitosan coating on a bacteria-based alginate microrobot.

To develop an efficient bacteria-based microrobot, first, therapeutic bacteria should be encapsulated into microbeads using biodegradable and biocompatible materials; second, the releasing rate of the encapsulated bacteria for theragnostic function should be regulated; and finally, flagellated bacteria should be attached on the microbeads to ensure the motility of the microrobot. For the therapeutic bacteria encapsulation, an alginate can be a promising candidate as a biodegradable and biocompatible material. Owing to the non-regulated releasing rate of the encapsulated bacteria in alginate microbeads and the weak attachment of flagellated bacteria on the surface of alginate microbeads, however, the alginate microbeads cannot be used as effective cargo for a bacteria-based microrobot. In this paper, to enhance the stability of the bacteria encapsulation and the adhesion of flagellated bacteria in alginate microbeads, we performed a surface modification of alginate microbeads using chitosan coating. The bacteria-encapsulated alginate microbeads with 1% chitosan coating maintained their structural integrity up to 72 h, whereas the control alginate microbead group without chitosan coating showed severe degradations after 24 h. The chitosan coating in alginate microbeads shows the enhanced attachment of flagellated bacteria on the surface of alginate microbeads. The bacteria-actuated microrobot with the enhanced flagellated bacteria attachment could show approximately 4.2 times higher average velocities than the control bacteria-actuated microrobot without chitosan coating. Consequently, the surface modification using chitosan coating enhanced the structural stability and the motility of the bacteria-based alginate microrobots.

Usefulness of 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Monitoring Adhesive Capsulitis After Breast Cancer Treatment.

OBJECTIVES: We aimed to assess the usefulness of F-fluorodeoxyglucose (F-FDG) positron emission tomography-computed tomography (PET/CT) in the monitoring of adhesive capsulitis (AC), a joint problem commonly observed in the upper arm after breast cancer treatment. METHODS: This retrospective study included 230 patients who underwent F-FDG PET/CT before and after modified radical mastectomy of whom 22 patients were identified as having AC and categorized into 2 groups: with severely and mildly limited range of motion in the shoulder joint. The F-FDG uptake patterns and mean and maximum standardized uptake values (SUVs) were analyzed. RESULTS: The overall incidence of AC after MRM was 9.57%. The SUVs were significantly higher in patients with severely limited range of motion compared with the other group. There was no association between the SUV and radiotherapy. The F-FDG uptake pattern differed between the groups. CONCLUSIONS: F-fluorodeoxyglucose PET/CT is useful in evaluating AC after breast cancer treatment.

Motility analysis of bacteria-based microrobot (bacteriobot) using chemical gradient microchamber.

A bacteria-based microrobot (bacteriobot) was proposed and investigated as a new type of active drug delivery system because of its useful advantages, such as active tumor targeting, bacteria-mediated tumor diagnosis, and therapy. In this study, we fabricated a bacteriobot with enhanced motility by selective attachment of flagellar bacteria (Salmonella typhimurium). Through selective bovine serum albumin (BSA) pattering on hydrophobic polystyrene (PS) microbeads, many S. typhimurium could be selectively attached only on the unpatterned surface of PS microbead. For the evaluation of the chemotactic motility of the bacteriobot, we developed a microfluidic chamber which can generate a stable concentration gradient of bacterial chemotactic chemicals. Prior to the evaluation of the bacteriobot, we first evaluated the directional chemotactic motility of S. typhimurium using the proposed microfluidic chamber, which contained a bacterial chemo-attractant (L-aspartic acid) and a chemo-repellent (NiSO4 ), respectively. Compared to density of the control group in the microfluidic chamber without any chemical gradient, S. typhimurium increased by about 16% in the L-aspartic acid gradient region and decreased by about 22% in the NiSO4 gradient region. Second, we evaluated the bacteriobot's directional motility by using this microfluidic chamber. The chemotactic directional motility of the bacteriobot increased by 14% and decreased by 13% in the concentration gradients of L-aspartic acid and NiSO4 , respectively. These results confirm that the bacteriobot with selectively patterned S. typhimurium shows chemotaxis motility very similar to that of S. typhimurium. Moreover, the directional motilities of the bacteria and bacteriobot could be demonstrated quantitatively through the proposed microfluidic chamber.

Evaluation of cadmium-induced nephrotoxicity using urinary metabolomic profiles in sprague-dawley male rats.

The aim of this study was to investigate urinary metabolomic profiles associated with cadmium (Cd)-induced nephrotoxicity and their potential mechanisms. Metabolomic profiles were measured by high-resolution (1)H-nuclear magnetic resonance (NMR) spectroscopy in the urine of rats after oral exposure to CdCl2 (1, 5, or 25 mg/kg) for 6 wk. The spectral data were further analyzed by a multivariate analysis to identify specific urinary metabolites. Urinary excretion levels of protein biomarkers were also measured and CdCl2 accumulated dose-dependently in the kidney. High-dose (25 mg/kg) CdCl2 exposure significantly increased serum blood urea nitrogen (BUN), but serum creatinine (sCr) levels were unchanged. High-dose CdCl2 (25 mg/kg) exposure also significantly elevated protein-based urinary biomarkers including osteopontin, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecules-1 (Kim-1), and selenium-binding protein 1 (SBP1) in rat urine. Under these conditions, six urinary metabolites (citrate, serine, 3-hydroxyisovalerate, 4-hydroxyphenyllactate, dimethylamine, and betaine) were involved in mitochondrial energy metabolism. In addition, a few number of amino acids such as glycine, glutamate, tyrosine, proline, or phenylalanine and carbohydrate (glucose) were altered in urine after CdCl2 exposure. In particular, the metabolites involved in the glutathione biosynthesis pathway, including cysteine, serine, methionine, and glutamate, were markedly decreased compared to the control. Thus, these metabolites are potential biomarkers for detection of Cd-induced nephrotoxicity. Our results further indicate that redox metabolomics pathways may be associated with Cd-mediated chronic kidney injury. These findings provide a biochemical pathway for better understanding of cellular mechanism underlying Cd-induced renal injury in humans.

Effects of 17α-ethynylestradiol-induced cholestasis on the pharmacokinetics of doxorubicin in rats: reduced biliary excretion and hepatic metabolism of doxorubicin.

1. Since the prevalent hormonal combination therapy with estrogen analogues in cancer patients has frequency and possibility to induce the cholestasis, the frequent combination therapy with 17α-ethynylestradiol (EE, an oral contraceptive) and doxorubicin (an anticancer drug) might be monitored in aspect of efficacy and safety. Doxorubicin is mainly excreted into the bile via P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily. Also the hepatic Mrp2 (not P-gp) and CYP3A subfamily levels were reduced in EE-induced cholestatic (EEC) rats. Thus, we herein report the pharmacokinetic changes of doxorubicin with respect to the changes in its biliary excretion and hepatic metabolism in EEC rats. 2. The pharmacokinetic study of doxorubicin after intravenous administration of its hydrochloride was conducted along with the investigation of bile flow rate and hepatobiliary excretion of doxorubicin in control and EEC rats. 3. The significantly greater AUC (58.7% increase) of doxorubicin in EEC rats was due to the slower CL (32.9% decrease). The slower CL was due to the reduction of hepatic biliary excretion (67.0% decrease) and hepatic CYP3A subfamily-mediated metabolism (21.9% decrease) of doxorubicin. These results might have broader implications to understand the altered pharmacokinetics and/or pharmacologic effects of doxorubicin via biliary excretion and hepatic metabolism in experimental and clinical estrogen-induced cholestasis.

Pharmacokinetics of isoliquiritigenin and its metabolites in rats: low bioavailability is primarily due to the hepatic and intestinal metabolism.

Isoliquiritigenin, a chalcone found in licorice has shown a variety of biological activities including antioxidative, anti-inflammatory, estrogenic, chemopreventive and antitumor effects. Thus, pharmacokinetics of isoliquiritigenin and its metabolites [liquiritigenin, glucuronidated isoliquiritigenin (M1), and glucuronidated liquiritigenin (M2)] after intravenous and oral administration of isoliquiritigenin was evaluated in rats. The pharmacokinetics of isoliquiritigenin, liquiritigenin, M1, and M2 showed no dose dependence after both intravenous and oral administration of isoliquiritigenin. Although approximately 92.0 % of the oral isoliquiritigenin was absorbed, the extent of the absolute bioavailability value was only 11.8 % of the oral dose. The low absolute bioavailability value of isoliquiritigenin might be due to the considerable metabolism of isoliquiritigenin in the small intestine and liver. This was supported by the facts that the ratios of AUC(M1)/AUC(isoLQ) and AUC(M2)/AUC(isoLQ) were high (over 0.25), isoliquiritigenin disappeared, and M1 and M2 were formed mainly in S9 fractions of the liver and small intestine. The affinities of liquiritigenin, isoliquiritigenin, M1, and M2 were high in the liver, small intestine, large intestine, and/or kidney.

Opioid use disorder: current trends and potential treatments.

Opioid use disorder (OUD) is a major public health threat, contributing to morbidity and mortality from addiction, overdose, and related medical conditions. Despite our increasing knowledge about the pathophysiology and existing medical treatments of OUD, it has remained a relapsing and remitting disorder for decades, with rising deaths from overdoses, rather than declining. The COVID-19 pandemic has accelerated the increase in overall substance use and interrupted access to treatment. If increased naloxone access, more buprenorphine prescribers, greater access to treatment, enhanced reimbursement, less stigma and various harm reduction strategies were effective for OUD, overdose deaths would not be at an all-time high. Different prevention and treatment approaches are needed to reverse the concerning trend in OUD. This article will review the recent trends and limitations on existing medications for OUD and briefly review novel approaches to treatment that have the potential to be more durable and effective than existing medications. The focus will be on promising interventional treatments, psychedelics, neuroimmune, neutraceutical, and electromagnetic therapies. At different phases of investigation and FDA approval, these novel approaches have the potential to not just reduce overdoses and deaths, but attenuate OUD, as well as address existing comorbid disorders.

Sequential therapy with JX-594, a targeted oncolytic poxvirus, followed by sorafenib in hepatocellular carcinoma: preclinical and clinical demonstration of combination efficacy.

JX-594 is a targeted and granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. In a phase 1 trial, JX-594 injection into hepatocellular carcinoma (HCC) was well-tolerated and associated with viral replication, decreased tumor perfusion, and tumor necrosis. We hypothesized that JX-594 and sorafenib, a small molecule inhibitor of B-raf and vascular endothelial growth factor receptor (VEGFR) approved for HCC, would have clinical benefit in combination given their demonstrated efficacy in HCC patients and their complementary mechanisms-of-action. HCC cell lines were uniformly sensitive to JX-594. Anti-raf kinase effects of concurrent sorafenib inhibited JX-594 replication in vitro, whereas sequential therapy was superior to either agent alone in murine tumor models. We therefore explored pilot safety and efficacy of JX-594 followed by sorafenib in three HCC patients. In all three patients, sequential treatment was (i) well-tolerated, (ii) associated with significantly decreased tumor perfusion, and (iii) associated with objective tumor responses (Choi criteria; up to 100% necrosis). HCC historical control patients on sorafenib alone at the same institutions had no objective tumor responses (0 of 15). Treatment of HCC with JX-594 followed by sorafenib has antitumoral activity, and JX-594 may sensitize tumors to subsequent therapy with VEGF/VEGFR inhibitors.

Effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition.

Protein-calorie malnutrition (PCM) could occur frequently in cancer patients and alter the pharmacokinetics of drugs. Also cysteine shows anti-oxidative effect and changes the activities of drug metabolizing enzyme and/or transporters. Herein, we investigated the effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of tamoxifen were assessed using control, CC (control with cysteine), PCM, PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of tamoxifen were further investigated through in vitro transport studies using rat intestine. The AUCs of intravenous tamoxifen in PCM rats were significantly greater than control rats due to the decrease in the hepatic metabolism via CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels by oral cysteine supplement. The AUC of oral tamoxifen in PCM rats was significantly smaller than in control rats mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of tamoxifen probably via intestinal P-gp inhibition. The present study demonstrated that PCM state and/or oral cysteine supplement had a profound impact on the pharmacokinetics of tamoxifen in rats. If the present rat data are extrapolated to humans, the alterations in tamoxifen absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM and/or oral cysteine supplement.

Looking beyond the opioid receptor: A desperate need for new treatments for opioid use disorder.

The mainstay of treatment for opioid use disorder (OUD) is opioid agonist therapy (OAT), which modulates opioid receptors to reduce substance craving and use. OAT maintains dependence on opioids but helps reduce overdose and negative sequelae of substance abuse. Despite increasing availability of OAT, its effectiveness is limited by difficulty in initiating and maintaining patients on treatment. With the worsening opioid epidemic in the United States and rising overdose deaths, a more durable and effective treatment for OUD is necessary. This paper reviews novel treatments being investigated for OUD, including neuromodulatory interventions, psychedelic drugs, and other novel approaches. Neuromodulatory interventions can stimulate the addiction neural circuitry involving the dorsolateral prefrontal cortex and deeper mesolimbic structures to curb craving and reduce use, and multiple clinical trials for interventional treatment for OUD are currently conducted. Similarly, psychedelic agents are being investigated for efficacy in OUD specifically. There is a resurgence of interest in psychedelic agents' therapeutic potential, with evidence of improving mood symptoms and decreased substance use even after just one dose. Exact mechanism of their anti-addictive effect is not fully elucidated, but psychedelic agents do not maintain opioid dependence and some may even be helpful in abating symptoms of withdrawal. Other potential approaches for OUD include targeting different parts of the dopamine-dependent addiction pathway, identifying susceptible genes and modulating gene products, as well as utilizing vaccines as immunotherapy to blunt the addictive effects of substances. Much more clinical data are needed to support efficacy and safety of these therapies in OUD, but these proposed novel treatments look beyond the opioid receptor to offer hope for a more durably effective OUD treatment.

An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes.

Importance: Certain psychiatric and immune-related disorders are reciprocal risk factors. However, the nature of these associations is unclear. Objective: To characterize the pleiotropy between psychiatric and immune-related traits, as well as risk factors of hypothesized relevance. Design, Setting, and Participants: This genetic association study was conducted from July 10, 2020, to January 15, 2022. Analyses used genome-wide association (GWA) statistics related to 14 psychiatric traits; 13 immune-related phenotypes, ie, allergic, autoimmune, and inflammatory disorders; and 15 risk factors related to health-related behaviors, social determinants of health, and stress response. Genetically correlated psychiatric-immune pairs were assessed using 2-sample mendelian randomization (MR) with sensitivity analyses and multivariable adjustment for genetic associations of third variables. False discovery rate correction (Q value < .05) was applied for each analysis. Exposures: Genetic associations. Main Outcomes and Measures: Genetic correlations and MR association estimates with SEs and P values. A data-driven approach was used that did not test a priori planned hypotheses. Results: A total of 44 genetically correlated psychiatric-immune pairs were identified, including 31 positive correlations (most consistently involving asthma, Crohn disease, hypothyroidism, and ulcerative colitis) and 13 negative correlations (most consistently involving allergic rhinitis and type 1 diabetes). Correlations with third variables were especially strong for psychiatric phenotypes. MR identified 7 associations of psychiatric phenotypes on immune-related phenotypes that were robust to multivariable adjustment, including the positive association of (1) the psychiatric cross-disorder phenotype with asthma (odds ratio [OR], 1.04; 95% CI, 1.02-1.06), Crohn disease (OR, 1.09; 95% CI, 1.05-1.14), and ulcerative colitis (OR, 1.09; 95% CI, 1.05-1.14); (2) major depression with asthma (OR, 1.25; 95% CI, 1.13-1.37); (3) schizophrenia with Crohn disease (OR, 1.12; 95% CI, 1.05-1.18) and ulcerative colitis (OR, 1.14; 95% CI, 1.07-1.21); and a negative association of risk tolerance with allergic rhinitis (OR, 0.77; 95% CI, 0.67-0.92). Conclusions and Relevance: Results of this genetic association study suggest that genetic liability for psychiatric disorders was associated with liability for several immune disorders, suggesting that vertical pleiotropy related to behavioral traits (or correlated third variables) contributes to clinical associations observed in population-scale data.

Perceived dementia risk and advance care planning among older adults.

BACKGROUND: Although advance care planning (ACP) is beneficial if dementia develops, and virtually all older adults are at risk for this disease, older adults do not consistently engage in ACP. Health behavior models have highlighted the importance of perceived susceptibility to medical conditions in motivating behavior. Following these models, we sought to determine how often older adults believe they are not at risk of developing dementia and to examine the association between perceived dementia risk and ACP participation. METHODS: We performed a cross-sectional study of community-dwelling adults without cognitive impairment, aged ≥65 years, who were interviewed for the Health and Retirement Study in 2016 and asked about their perceived dementia risk (n = 711). Perceived dementia risk was ascertained with this question: "on a scale of 0 to 100, what is the percent chance that you will develop dementia sometime in the future?" We used multivariable-adjusted logistic regression to evaluate the association between perceived risk (0% versus >0%) and completion of a living will, appointment of a durable power of attorney for healthcare decisions, and discussion of treatment preferences. RESULTS: Among respondents, 10.5% reported a perceived dementia risk of 0%. Perceived risk of 0% was associated with lower odds of completing a living will (OR 0.53; 95% CI, 0.30-0.93) and discussing treatment preferences (OR 0.51; 95% CI, 0.28-0.93) but not appointment of a durable power of attorney (OR 0.77; 95% CI, 0.42-1.39). Many respondents with perceived dementia risk >0% had not completed ACP activities, including a substantial minority of those with perceived risk >50%. CONCLUSIONS: Older adults with no perceived dementia risk are less likely to participate in several forms of ACP, but the fact that many older adults with high levels of perceived risk had not completed ACP activities suggests that efforts beyond raising risk awareness are needed to increase engagement.

Human transcription factor YY1 could upregulate the HIV-1 gene expression.

Gene expression in HIV-1 is regulated by the promoters in 5' long-terminal repeat (LTR) element, which contain multiple DNA regulatory elements that serve as binding sites for cellular transcription factors. YY1 could repress HIV-1 gene expression and latent infection. Here, however, we observed that virus production can be increased by YY1 over-expression and decreased under YY1 depleted condition by siRNA treatment. To identify functional domain(s) of YY1 activation, we constructed a number of YY1 truncated mutants. Our data show that full-length YY1 enhances the viral transcription both through U3 and U3RU5 promoters. Moreover, the C-terminal region (296-414 residues) of YY1 is responsible for the transcriptional upregulation, which could be enhanced further in the presence of the viral Tat protein. The central domain of YY1 (155-295 residues) does not affect LTR activity but has a negative effect on HIV-1 gene expression. Taken together, our study shows that YY1 could act as a transcriptional activator in HIV-1 replication, at least in the early stages of infection. [BMB Reports 2020; 53(5): 248-253].

Benefit of Adjuvant Traditional Herbal Medicine With Chemotherapy for Resectable Gastric Cancer.

INTRODUCTION: Stomach cancer, historically, has a low survival rate advances in curative resection procedures. OBJECTIVES: To assess the potential benefits of traditional herbal medicines in conjunction with chemotherapy in postoperative gastric cancer patients in terms of overall survival and disease-free survival. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, a Chinese database (CNKI), a Korean database, a Japanese database, AMED, and CINAHL up to September 2016. We summarized survival data from all RCTs. STUDY SELECTION: All RCTs of oral traditional medicines for resectable gastric cancer compared with chemotherapy alone were eligible. DATA EXTRACTION: Thirteen eligible trials with survival data (1075 patients) were deemed eligible for inclusion. RESULTS: There were 217 documented deaths of the 574 patients assigned to adjuvant traditional medicines groups and 319 documented deaths of the 501 patients assigned to the chemotherapy-only groups. Adjuvant traditional medicines were associated with a statistically significant benefit in terms of overall survival rate (hazard ratio = 0.56; 95% confidence interval = 0.47-0.66; P < .00001) and disease-free survival (hazard ratio = 0.54; 95% confidence interval = 0.43-0.66; P < .00001). CONCLUSION: Among the RCTs included, the inclusion of postoperative adjuvant traditional medicines was associated with reduced risk of death in gastric cancer patients, when survival rates were compared with the group of patients who received chemotherapy alone. However, most of the included studies utilized are thought to be of low quality, so it would certainly appear that more trials are both advisable and necessary to arrive at correct and convincing conclusions.

Distinct regulations of ARF1 by two Aplysia Sec7 isoforms.

Sec7 protein is a guanine nucleotide exchange factor in the ADP-ribosylation factor (ARF) family of small GTP-binding proteins. Aplysia Sec7 proteins (ApSec7s) play many roles in neurite outgrowth and synaptic facilitation in Aplysia neurons. However, the binding property of Aplysia ARF1 by ApSec7 isoforms has not been examined. In this study, we found that the cloned Aplysia ARF1 (ApARF1) protein only localized to the Golgi complex when it was expressed alone in HEK293T cells; however, if ApARF1 was co-expressed with plasma membrane-targeted ApSec7, it localized to both the plasma membrane and the Golgi complex via association with the Sec7 domain of ApSec7. Moreover, in HEK293T cells expressing both ApARF1 and another Sec7 isoform, ApSec7(VPKIS), the pleckstrin homology domain of ApSec7(VPKIS) associated with ApARF1, resulting in its localization to the Golgi complex. Overall, we propose a model in which ApSec7(VPKIS) activates ApARF1 in the Golgi complex, while ApSec7 recruits ApARF1 to the plasma membrane where it activates ApARF1/6 downstream signaling.