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Background: Loneliness is more common in older adults and those who face structural vulnerabilities, including homelessness. The homeless population is aging in the United States; now, 48% of single homeless adults are 50 and older. We know little about loneliness among older adults who have experienced homelessness. We aimed to describe the loneliness experience among homeless-experienced older adults with cognitive and functional impairments and the individual, social, and structural conditions that shaped these loneliness experiences., Methods: We purposively sampled 22 older adults from the HOPE HOME study, a longitudinal cohort study among adults aged 50 years or older experiencing homelessness in Oakland, California. We conducted in-depth interviews about participants perceived social support and social isolation. We conducted qualitative content analysis., Results: Twenty participants discussed loneliness experience, who had a median age of 57 and were mostly Black (80%) and men (65%). We developed a typology of participants' loneliness experience and explored the individual, social, and structural conditions under which each loneliness experience occurred. We categorized the loneliness experience into four groups: (1) "lonely- distressed", characterized by physical impairment and severe isolation; (2) "lonely- rather be isolated", reflecting deliberate social isolation as a result of trauma, marginalization and aging-related resignation; (3) "lonely- transient", as a result of aging, acceptance and grieving; and (4) "not lonely"- characterized by stability and connection despite having experienced homelessness., Conclusions: Loneliness is a complex and heterogenous social phenomenon, with homeless-experienced older adults with cognitive or functional impairments exhibiting diverse loneliness experiences based on their individual life circumstances and needs. While the most distressing loneliness experience occurred among those with physical impairment and mobility challenges, social and structural factors such as interpersonal and structural violence during homelessness shaped these experiences., (© 2024. The Author(s).)

Background: People with lived or living experiences of drug use and services have been increasingly incorporated into nonpeer-led mainstream organizational settings as a unique workforce. Despite the much discussed effectiveness of peer services in achieving measurable outcomes, limited attention has been given to the experiential aspects of peer work from the perspectives of peers, clients, or others involved. This systematic review synthesized qualitative evidence examining the experiences of peer work in nonpeer-led drug use service settings. It focused on the benefits of incorporating peers as a unique workforce, the challenges they face, and the organizational factors that influence their practices., Methods: A search of 15 databases identified 3,940 unique citations, 33 of which met inclusion criteria. Thematic analysis was utilized to synthesize their findings., Results: Foregrounding the uniqueness of peers' shared experience, studies have shown that incorporating peers into nonpeer-led settings can provide benefits at the client, organizational, and societal levels while promoting peers' personal and professional growth. The unique shared experience of peers can also present multidimensional challenges, such as triggering, boundary negotiation, and feelings of being trapped by their peer identity. To fully integrate peers into the system, organizations need to work with them to reconstruct organizational mission, culture, and structures in a way that recognizes and genuine commits to peers' unique values., Conclusion: This review highlights the significance of understanding peer uniqueness for organizations to create nourishing conditions for peer services and calls for future research exploring context- and setting-specific peer roles and organizational enablers and barriers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Despite increasing efforts to improve housing stability, research has largely defined housing stability in a narrow sense and heavily relied on objective measures, such as housing types and housing duration. The present study constructed a conceptual framework for a subjective housing stability definition from the perspectives of individuals with co-occurring mental health and substance use disorders and their behavioral health service providers. Methods: Following the principles of grounded theory, we collected and analyzed qualitative data through semistructured interviews with 24 individuals with serious mental illness and substance use problems and three focus groups with 22 behavioral health service providers. Results: We developed a conceptual framework with two domains of subjective housing stability: functional stability and experiential stability. The functional stability domain includes four theoretical concepts: meeting basic needs, housing quality, housing affordability, and housing permanence. The experiential stability domain includes four theoretical concepts: autonomy and independence, connectedness, safety, and supportiveness. Conclusions: The conceptual framework can inform future research, practices, and policies to move beyond focusing on merely providing housing to consider the diverse and underlying needs in improving housing stability and well-being among those experiencing or at risk of housing instability.

Background: A novel autosomal recessive skeletal dysplasia resulting from pathogenic variants in membrane-bound transcription factor peptidase, site 1 ( MBTPS1 ) has been recently delineated. To date, only three patients have been reported., Methods: In this study, we reported the clinical and molecular features of a Chinese boy who was diagnosed with spondyloepiphyseal dysplasia. The effects of variants on mRNA splicing were analyzed through transcript analysis in vivo and minigene splice assay in vitro ., Results: The proband mainly showed short stature, special facial features, cataract, hernias, and serious sleep apnea syndrome. Growth hormone stimulation tests suggested the boy had growth hormone deficiency. Imaging examinations suggested abnormal thoracolumbar vertebrae and severely decreased bone mineral density. Genetic analysis of MBTPS1 gene revealed two novel heterozygous variants, a nonsense mutation c.2656C > T (p.Q886*, 167) in exon 20 and a synonymous variant c.774C > T (p.A258=) in exon 6. The transcript analysis in vivo exhibited that the synonymous variant c.774C > T caused exon 6 skipping. The minigene splice assay in vitro confirmed the alteration of MBTPS1 mRNA splicing and the exon skipping was partially restored by an antisense oligonucleotide (ASO) treatment., Conclusion: Notably, we report a Chinese rare case of spondyloepiphyseal dysplasia and validate its pathogenic synonymous variant in the MBTPS1 gene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yuan, Zhou, Wang, Zhou, Gu and Zheng.)

Critical Time Intervention (CTI) is designed to reduce the risk of homelessness and other adverse outcomes by providing support to individuals during challenging life course transitions. While several narrative reviews suggest the benefit of CTI, the evidence on the model's effectiveness has not been systematically reviewed. This article systematically reviews studies of CTI applied to a variety of populations and transition types. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis for protocols (PRISMA-P) guidelines, we reviewed 13 eligible experimental and quasi-experimental studies. Findings were summarized by individual outcome domains, including housing, service engagement use, hospitalization or emergency services, mental health, substance use, family and social support, and quality of life. CTI had a consistent positive impact on two primary outcomes-reduced homelessness and increased service engagement use-among different populations and contexts. Despite the effectiveness of CTI, the specific mechanisms of the model's positive impacts remain unclear. Implications for practice, policy and research are addressed., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Tumor glycolysis is a critical event for tumor progression. Docetaxel is widely used as a first-line drug for chemotherapy and shown to have a survival advantage. However, the role of docetaxel in tumor glycolysis remained poorly understood., Methods: The effect of Docetaxel in tumor glycolysis and proliferation were performed by CCK-8, Western blotting, real-time PCR, glucose, and lactate detection and IHC. ChIP and luciferase assay were used to analyze the mechanism of Docetaxel on Smad3-mediated HIF-1α transactivity., Results: In this study, we showed that docetaxel treatment led to a significant inhibition of cell proliferation in prostate cancer cells through PFKP-mediated glycolysis. Addition of lactate, a production of glycolysis, could reverse the inhibitory effect of docetaxel on cell proliferation. Further analysis has demonstrated that phosphorylation of Smad3 (Ser213) was drastically decreased in response to docetaxel stimulation, leading to reduce Smad3 nuclear translocation. Luciferase and Chromatin immunoprecipitation (ChIP) analysis revealed that docetaxel treatment inhibited the binding of Smad3 to the promoter of the HIF-1α gene, suppressing transcriptional activation of HIF-1α. Moreover, ectopic expression of Smad3 in prostate cancer cells could overcome the decreased HIF-1α expression and its target gene PFKP caused by docetaxel treatment. Most importantly, endogenous Smad3 regulated and interacted with HIF-1α, and this interaction was destroyed in response to docetaxel treatment. What's more, both HIF-1α and PFKP expression were significantly reduced in prostate cancer received docetaxel treatment in vivo., Conclusion: These findings extended the essential role of docetaxel and revealed that docetaxel inhibited cell proliferation by targeting Smad3/HIF-1α signaling-mediated tumor Warburg in prostate cancer cells. Video Abstract., (© 2022. The Author(s).)

Backgrounds: This study aimed to determine whether the Mayo adhesive probability score (MAP), which evaluated adherent perinephric fat (APF), is useful in evaluating the difficulty of retroperitoneal laparoscopic adrenalectomy (RLA), and to analyse the correlation between MAP and perioperative parameters., Methods: Clinical data of 104 patients with adrenal adenoma who underwent RLA were collected for retrospective analysis. According to the CT images obtained before surgery, patients were divided into two groups: High MAP group (2-5 points) and Low MAP group (0-1 points). Comparison of the general clinical characteristics and the perioperative data between the two groups was made., Results: There were more male patients (73.7% versus 34.3%), more patients with a smoking history (24.3% versus 7.5%), higher BMI (25.7 versus 23.2, kg/m 2 ), and bigger (23.8 versus 18.5, mm) neoplasm in the high MAP group (P < 0.05). Significant difference was observed in operative time (128.8 versus 102.3, min), estimated blood loss (47.2 versus 25.2, ml) and drainage tube removal time (4.0 versus 3.2, d) between the two groups (P < 0.05). A high MAP score (P < 0.001) and the size of tumour (P = 0.024) were independent risk factors for extended operative time. A higher BMI (OR = 1.525, P < 0.001) and larger tumour size (OR = 2.862, P = 0.004) were independent risk factors for a high MAP score., Conclusions: MAP score was associated with the perioperative outcomes of RLA. BMI and tumour size were better indicators of MAP score, which can influence the difficulty of RLA., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Osteocalcin is a bone-derived hormone that plays an important role in the crosstalk between bone and energy metabolism. Previous studies have found that treatment with uncarboxylated osteocalcin can protect mice from high-fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the potential mechanisms remain unclear. Although the G protein-coupled receptor family C group 6 subtype A (GPRC6A) is the putative receptor of osteocalcin, there is no direct evidence showing that GPRC6A mediates the effects of uncarboxylated osteocalcin in alleviating NAFLD in mice. We aimed to figure out this using liver-specific GPRC6A knockout (GPRC6A LKO ) mice. Consistent with previous studies, uncarboxylated osteocalcin significantly protected high-fat diet-fed wild-type mice from obesity and NAFLD, while it did not protect high-fat diet-fed GPRC6A LKO mice from NAFLD. Differential mRNA expression of lipogenesis and lipolysis between GPRC6A LKO mice and control mice revealed that GPRC6A mediated the effects of osteocalcin in alleviating NAFLD through inhibiting lipid synthesis and promoting lipolysis. In conclusion, this study found that uncarboxylated osteocalcin alleviates NAFLD in mice through the GPRC6A signaling pathway. Our study suggests that liver GPRC6A may be a potential target for treating NAFLD., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Mingliang Zhang et al.)

Prostate cancer (PCa) is a major serious malignant tumor and is commonly diagnosed in older men. Identification of novel cancer-related genes in PCa is important for understanding its tumorigenesis mechanism and developing new therapies against PCa. Here, we used RNA sequencing to identify the specific genes, which are upregulated in PCa cell lines and tissues. The cell division cycle associated protein (CDCA) family, which plays a critical role in cell division and proliferation, is upregulated in the PCa cell lines of our RNA-Sequencing data. Moreover, we found that CDCA2 is overexpressed, and its protein level positively correlates with its histological grade, clinical stage, and Gleason Score. CDCA2 was further found to be upregulated and correlated with poor prognosis and patient survival in multiple cancer types in The Cancer Genome Atlas (TCGA) dataset. The functional study suggests that inhibition of CDCA2 will lead to apoptosis and lower proliferation in vitro . Silencing of CDCA2 also repressed tumor growth in vivo . Loss of CDCA2 affects several oncogenic pathways, including MAPK signaling. In addition, we further demonstrated that CDCA2 was induced in hypoxia and directly regulated by the HIF-1α/Smad3 complex. Thus, our data indicate that CDCA2 could act as an oncogene and is regulated by hypoxia and the HIF-1αpathway. CDCA2 may be a useful prognostic biomarker and potential therapeutic target for PCa., (Copyright © 2020 Zhang, Cheng, Zhang, Bai, Jin, Guo, Huang, Li, Wang, Shu, Yuan and Ying.)

Anomalous epidermal growth factor receptor (EGFR) signaling plays an important role in the progression of prostate cancer (PCa) and the transformation to castration-resistant PCa (CRPC). A novel tumor suppressor CKLF-like MARVEL transmembrane domain-containing member 5(CMTM5) has a MARVEL domain and may regulate transmembrane signaling. Thus, we postulated that CMTM5 could regulate EGFR and its downstream molecules to affect the biological behaviors of PCa cells. In this study, we found that CMTM5 was expressed in benign prostatic hyperplasia (BPH) tissues but was undetectable in PCa cells. However, the EGFR was upregulated in PCa cells, especially in two metastatic CRPC cell lines, PC3 and DU145. Furthermore, ectopic expression of CMTM5-v1 suppressed cell proliferation and migration and p-EGFR levels. Further investigation revealed that restoration of CMTM5-v1 inhibited not only EGF-mediated proliferation but also chemotactic migration by EGF in PC3 and DU145 cells. Moreover, mechanistic studies showed that CMTM5-v1 attenuated EGF-induced receptor signaling by repressing EGFR and Akt phosphorylation in PCa cells, which were essential for malignant features. Finally, CMTM5-v1can promote the sensitivity of PC3 cells to Gefetinib, a tyrosine kinase inhibitor (TKI) targeting the EGFR. These observations indicate that CMTM5-v1 suppressed PCa cells through EGFR signaling. The loss of CMTM5 may participate in the progression of PCa resulting from deregulated EGFR, and CMTM5 might be associated with the efficacy of TKIs in terms of their potent inhibition of EGFR and human epidermal growth factor-2 (HER2) activation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

WHAT IS KNOWN ON THE SUBJECT?: Understanding what strategies individuals use to cope with serious mental illness is vital for enhancing their quality of life, mental well-being and recovery, and effective use of services; An episode of homelessness can be a profoundly disruptive event that often leads to chronic stress, social isolation, a negative belief about oneself and restricted access to care, among other adverse experiences; WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: In contrast to existing reviews of qualitative research focusing on escaping homelessness, managing problem substance use and growing resilience, the current review offers an in-depth, interpretive account of coping with serious mental illness during an episode of homelessness; This paper integrates evidence showing the diverse and intricate processes via which homelessness can impede an individual's ability to successfully cope with life stressors and with chronic mental illness; Despite experiencing severe social disadvantage, many individuals demonstrate positive adaptation and coping, and even personal growth; WHAT ARE THE IMPLICATIONS FOR PRACTICE?: It is important to be aware of the many ways in which coping with serious mental illness can be influenced by adverse environmental factors such as poverty, homelessness, traumatic life experiences and institutional discrimination; Nursing practice should recognize that coping efforts by individuals facing multiple forms of social disadvantage may be shaped by acute adverse life events and institutional interactions, as well as by the stresses and strains of living on the streets; Nursing practice should focus not only on reducing clients' mental illness symptoms and facilitating positive coping behaviours, but also on helping create the conditions that aid clients in leveraging inner resources for personal growth and constructive meaning-making. Abstract Introduction An evidence gap persists concerning the impact of extreme socio-structural disadvantage, such as homelessness, on the nature and effectiveness of coping with severe mental illness (SMI). While existing reviews of qualitative research into homelessness have focused on processes such as escaping homelessness and managing concurrent problem substance use, as well as on the experiences of specific vulnerable groups such as women and youth, no analogical review has been dedicated to understanding the management of SMI during an episode of homelessness. Aim/Question A qualitative metasynthesis of first-person accounts was conducted to understand how individuals cope with SMI when experiencing homelessness. Method The systematic search strategy yielded 481 potentially eligible sources. Following the team-based full-text screening and the two-tiered quality appraisal, 14 studies involving 377 participants with lived experience were synthesized following Noblit and Hare's metaethnographic method. Results Seven third-order concepts were derived capturing the complex nature and processual character of coping, as well as the web of contextual influences upon coping strategies. The resultant line-of-argument synthesis reveals the dialectical relationship between the two higher-order constructs-"the continuum of coping" and "the assemblage of disadvantage." Discussion Despite the profoundly adverse impacts of biographical and socio-structural conditions, many individuals mobilized internal and external resources to enable various coping processes. Coping in the context of multiple disadvantage is not a monolith but rather a multidimensional, contingent and fluid phenomenon. Implications for practice Nursing practice should espouse a humanizing, structurally competent, and strength- and meaning-oriented approach in order to meet the complex and multifaceted needs of such multiply disadvantaged persons., (© 2019 John Wiley & Sons Ltd.)

MicroRNAs (miRNAs) are endogenous non-coding RNAs that negatively regulate the expression of downstream targeted mRNAs. Increasing evidence has suggested that miRNAs act as tumor suppressors or oncogenes to interfere the progression of cancers. Here, we showed that miR-204-3p was decreased in bladder cancer tissues and cell lines. Down-regulation of miR-204-3p was significantly associated with a poor prognosis in bladder cancer patients. Overexpression of miR-204-3p inhibited proliferation and induced apoptosis in bladder cancer cells. Furthermore, miR-204-3p was found to bind to the 3'-untranslated region (UTR) of the lactate dehydrogenase (LDHA), which consequently reduced the expression of both mRNA and protein of LDHA. Interestingly, overexpression of miR-204-3p decreased glucose consumption and lactate production of bladder cancer cells. Overexpression of LDHA relieved the growth inhibition and cell apoptosis enhancement by miR-204-3p in bladder cancer cells. These results demonstrated that miR-204-3p negatively modulated the proliferation of bladder cancer cells via targeting LDHA-mediated glycolysis. MiR-204-3p might be a promising candidate for designing anticancer medication., (Copyright © 2019 Guo, Zhao, Liu, Li, Yuan, Zhang, Yu, Fang and Xiao.)

This report explores the nature and quality of social ties of formerly homeless individuals in recovery from serious mental illness and substance abuse and how these ties relate to experiences of community. Using grounded theory and cross-case analysis techniques, we analyzed 34 qualitative interviews conducted with predominantly racial/ethnic minority individuals receiving mental health services. Participants described a range of involvement and experiences in the mental health service and mainstream communities indicating a combination of weak or strong ties in these communities. Across participants, two broad themes emerged: ties that bind and obstacles that "get in the way" of forming social ties. Salient subthemes included those related to family, cultural spaces, employment, substance abuse, stigma and mental health service providers and peers. The current study integrates our understanding of positive and negative aspects of social ties and provides a theoretical framework highlighting the complexity of social ties within mainstream and mental health service communities.

Background: Schizophrenia is a leading cause of disability, and a shift from facility- to community-based care has been proposed to meet the resource challenges of mental healthcare in low- and middle-income countries. We hypothesized that the addition of mobile texting would improve schizophrenia care in a resource-poor community setting compared with a community-based free-medicine program alone., Methods and Findings: In this 2-arm randomized controlled trial, 278 community-dwelling villagers (patient participants) were randomly selected from people with schizophrenia from 9 townships of Hunan, China, and were randomized 1:1 into 2 groups. The program participants were recruited between May 1, 2015, and August 31, 2015, and the intervention and follow-up took place between December 15, 2015, and July 1, 2016. Baseline characteristics of the 2 groups were similar. The patients were on average 46 years of age, had 7 years of education, had a duration of schizophrenia of 18 years with minimal to mild symptoms and nearly one-fifth loss of functioning, and were mostly living with family (95%) and had low incomes. Both the intervention and the control groups received a nationwide community-based mental health program that provided free antipsychotic medications. The patient participants in the intervention group also received LEAN (Lay health supporters, E-platform, Award, and iNtegration), a program that featured recruitment of a lay health supporter and text messages for medication reminders, health education, monitoring of early signs of relapses, and facilitated linkage to primary healthcare. The primary outcome was medication adherence (proportion of dosages taken) assessed by 2 unannounced home-based pill counts 30 days apart at the 6-month endpoint. The secondary and other outcomes included patient symptoms, functioning, relapses, re-hospitalizations, death for any reason, wandering away without notifying anyone, violence against others, damaging goods, and suicide. Intent-to-treat analysis was used. Missing data were handled with multiple imputations. In total, 271 out of 278 patient participants were successfully followed up for outcome assessment. Medication adherence was 0.48 in the control group and 0.61 in the intervention group (adjusted mean difference [AMD] 0.12 [95% CI 0.03 to 0.22]; p = 0.013; effect size 0.38). Among secondary and other outcomes we noted substantial reduction in the risk of relapse (26 [21.7%] of 120 interventional participants versus 40 [34.2%] of 117 controls; relative risk 0.63 [95% CI 0.42 to 0.97]; number needed to treat [NNT] 8.0) and re-hospitalization (9 [7.3%] of 123 interventional participants versus 25 [20.5%] of 122 controls; relative risk 0.36 [95% CI 0.17 to 0.73]; NNT 7.6). The program showed no statistical difference in all other outcomes. During the course of the program, 2 participants in the intervention group and 1 in the control group died. The limitations of the study include its lack of a full economic analysis, lack of individual tailoring of the text messages, the relatively short 6-month follow-up, and the generalizability constraint of the Chinese context., Conclusions: The addition of texting to patients and their lay health supporters in a resource-poor community setting was more effective than a free-medicine program alone in improving medication adherence and reducing relapses and re-hospitalizations. Future studies may test the effectiveness of customization of the texting to individual patients., Trial Registration: Chinese Clinical Trial Registry ChiCTR-ICR-15006053., Competing Interests: The authors have declared that no competing interests exist.

Background: The prognostic role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with prostate cancer (PCa) remains inconsistent. Here we quantify the prognostic impact of these biomarkers and assess their consistency in PCa., Materials and Methods: We systematically searched PubMed, Web of Science, and Embase for eligible studies embracing multivariate results. The Newcastle-Ottawa Scale were used to assess the study quality. Pooled hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated., Results: A total of 7228 patients from 18 studies were included in the meta-analysis. Overall, elevated pretreatment NLR was associated with poor overall survival (OS, HR 1.58, 95% CI 1.41-1.78, P < 0.001), progression-free survival (PFS, HR 1.95, 95% CI 1.53-2.49, P < 0.001) and biochemical recurrence-free survival (BRFS, HR 1.37, 95% CI 1.07-1.75, P = 0.011). And high pretreatment PLR was correlated with more inferior PFS (HR 1.62, 95% CI 1.20-2.19, P = 0.002), OS (HR 1.70, 95% CI 1.34-2.15, P < 0.001) and cancer-specific survival (CSS, HR 2.02, 95% CI 1.24-3.29, P = 0.005). Moreover, the subgroup analyses did not alter the direction of results for OS and PFS., Conclusion: Based on these findings, elevated NLR and PLR was associated with poor oncologic outcomes, and they can serve as prognostic factors in PCa patients., (Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: Individuals with mental health and/or substance abuse problems experience disparities in health care utilization. While previous studies have focused on individual and social determinants of health care use in these populations, few have investigated the role of residential stability, especially in relation to different types of service use (i.e., inpatient vs. outpatient treatment). The present study examined the relationship between residential mobility, defined as the number of residential relocations in the past year, and past-year use of four types of behavioral services (i.e., inpatient and outpatient mental health services, inpatient and outpatient substance abuse services) among a national sample of adults with mental health and/or substance abuse problems., Methods: Data were drawn from the 2011-2014 National Survey of Drug Use and Health (unweighted N = 43,411). Based on prior literature and theory, we hypothesized that individuals who frequently relocate are more likely to use inpatient services and are less likely to use outpatient services. Logistic regression analyses were conducted and all models controlled for predisposing, need, and enabling factors., Results: Compared to individuals who did not move in the past year, those who moved three or more times were more likely to report using inpatient mental health and substance abuse services. The relationship between residential mobility and outpatient mental health and substance use service use is not significant., Conclusions: The findings highlight the importance of understanding housing stability as a predictor factor of service use and access. Future research is needed to shed light on the pathway through which residential mobility affects behavioral health service utilization.

Background: In order to efficiently determine genotypic differences in rooting patterns of crops, novel hardware and software are needed simultaneously to characterize dynamics of root development., Results: We describe a prototype robotic monitoring platform-the RhizoChamber-Monitor for analyzing growth patterns of plant roots automatically. The RhizoChamber-Monitor comprises an automatic imaging system for acquiring sequential images of roots which grow on a cloth substrate in custom rhizoboxes, an automatic irrigation system and a flexible shading arrangement. A customized image processing software was developed to analyze the spatio-temporal dynamics of root growth from time-course images of multiple plants. This software can quantify overall growth of roots and extract detailed growth traits (e.g. dynamics of length and diameter) of primary roots and of individual lateral roots automatically. It can also identify local growth traits of lateral roots (pseudo-mean-length and pseudo-maximum-length) semi-automatically. Two cotton genotypes were used to test both the physical platform and the analysis software., Conclusions: The combination of hardware and software is expected to facilitate quantification of root geometry and its spatio-temporal growth patterns, and therefore to provide opportunities for high-throughput root phenotyping in support of crop breeding to optimize root architecture.

Purpose: This observational study investigated the association between serum osteocalcin level and blood pressure in a Chinese population., Materials and Methods: A total of 2241 subjects (909 men and 1,332 women; age, 24-78 years) from Shanghai communities were recruited. Subjects were divided into non-hypertensive and hypertensive groups according to diagnosis of hypertension based on the 1999 World Health Organization-International Society of Hypertension Guidelines. Serum osteocalcin levels were measured using an electrochemiluminescence immunoassay., Results: Men in the hypertensive group showed lower serum osteocalcin level compared with those in the non-hypertensive group, [16.37 (13.34-20.11) ng/mL versus 17.01 (14.23-20.79) ng/mL, p = .039]. No difference in serum osteocalcin level was found between the two groups of women (p = .675). An inverse association was observed between serum osteocalcin level and systolic blood pressure (SBP) in men (p = .004), but serum osteocalcin level was not associated with diastolic blood pressure (DBP) in men (p = .472). No associations were detected between serum osteocalcin level and SBP or DBP in women (SBP: p = .108; DBP: p = .575). A multiple stepwise regression analysis showed an inverse association between serum osteocalcin level and SBP in men after adjusting for age, smoking status, family history of hypertension, and lipid and C-reactive protein levels (standardized β = -0.074, p = .023), but the association disappeared after adjustment for body mass index, waist circumference, blood glucose, and homeostasis model assessment of insulin resistance (p = .327)., Conclusions: Serum osteocalcin level was not independently associated with blood pressure in a Chinese population.

Prostate cancer (PCa) is the second leading cause of death from cancer in men. The mechanism underlying tumorigenesis and development of PCa is largely unknown. Here, we identified Kinesin family member 14 (KIF14) as a novel candidate oncogene in PCa. We found that KIF14 was overexpressed in multiple PCa cell lines and primary PCa tissues. Knockdown of KIF14 in DU145 and PC3 prostate cancer cells suppressed cell proliferation, induced cell cycle arrest and apoptosis. Transcriptome analysis by RNA-sequencing demonstrated that KIF4 suppression led to transcriptional changes of genes involved in p53 and TGF-beta signaling pathway. In addition, upregulated expression of GADD45A, GADD45B, p21, PIDD and Shisa5, which contribute to growth arrest and apoptosis induction, and downregulated CCNB1 that promotes cell cycle progression were confirmed by quantitative real-time PCR after KIF4 knockdown. We further found that KIF14 protein level was positively correlated with T stage and Gleason Score. Patients with higher KIF14 expression had shorter overall survival time than those with lower KIF14 expression. Thus, our data indicate that KIF14 could act as a potential oncogene that contributes to tumor progression and poor prognosis in PCa, which may represent a novel and useful prognostic biomarker for PCa.

Renal cell carcinoma (RCC) is one of the most malignant tumors in human. Here, we found that odd-skipped related transcription factor 1 (OSR1) was downregulated in 769-P and 786-O cells due to promoter CpG methylation. OSR1 expression could be restored by pharmacological demethylation treatment in silenced cell lines. Knockdown of OSR1 in two normal expressed cell lines- A498 and ACHN promoted cell invasion and cellular proliferation. RNA-Sequencing analysis showed that expression profile of genes involved in multiple cancer-related pathways was changed when OSR1 was downregulated. By quantitative real-time PCR, we confirmed that depletion of OSR1 repressed the expression of several tumor suppresor genes involved in p53 pathway, such as p53, p21, p27, p57 and RB in A498 and ACHN. Moreover, knockdown of OSR1 suppressed the transcriptional activity of p53. Of note, OSR1 depletion also led to increased expression of a few oncogenic genes. We further evaluated the clinical significance of OSR1 in primary human RCC specimens by immunohistochemical staining and found that OSR1 expression was downregulated in primary RCC and negatively correlated with histological grade. Thus, our data indicate that OSR1 is a novel tumor suppressor gene in RCC. Downregulation of OSR1 might represent a potentially prognostic marker and therapeutic target for RCC.

Although residential substance abuse treatment has been shown to improve substance use and other outcomes, relapse is common. This qualitative study explores factors that hinder and help individuals during the transition from long-term residential substance abuse treatment to the community. Semi-structured interviews were conducted with 32 individuals from residential substance abuse treatment. Based on the socio-ecological model, barriers and facilitators to transition were identified across five levels: individual, interpersonal, organizational, community, and policy. The major results indicate that primary areas of intervention needed to improve outcomes for these high-risk individuals include access to stable housing and employment, aftercare services and positive support networks; expanded discharge planning services and transitional assistance; and funding to address gaps in service delivery and to meet individuals' basic needs. This study contributes to the literature by identifying transition barriers and facilitators from the perspectives of individuals in residential treatment, and by using the socio-ecological model to understand the complexity of this transition at multiple levels. Findings identify potential targets for enhanced support post-discharge from residential treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

It is widely accepted that immunoglobulin (Ig), the classical immune molecule, is extensively expressed in many cell types other than B-cells (non-B-IgG), including some malignant cells. The expression of Ig in malignant cells has been associated with a poor prognosis. In the present study, immunohistochemical analysis detected strong positive staining of IgG in three bladder cancer cell lines, the cancer cells in 77 bladder cancer patient samples and the cells in 3 cystitis glandularis tissue samples, while negative staining was observed in 4 specimens of normal transitional epithelial tissues. Importantly, functional transcripts of IgG with unique V H DJ H rearrangement patterns were also found in bladder cancer cells. The knockdown of IgG in bladder cancer cell lines using small interfering RNA significantly inhibited the proliferation, migration and invasion of the cells. Notably, high IgG expression, as determined by immunostaining, was significantly correlated with a high histological grade and recurrence. The results of the present study suggested that IgG expression is involved in the malignant biological behavior and poor prognosis of bladder cancer. Therefore, IgG may serve as a novel target for bladder cancer therapy.

The GSTP1 gene plays an important role in detoxification of carcinogens. GSTP1 gene polymorphisms may alter the susceptibility of urinary system cancer. Numerous studies have been performed to investigate the association between GSTP1 Ile105Val (rs1695 A>G) polymorphism and urinary system cancer risk. Nevertheless, the results remain controversial and only prostate cancer and bladder cancer are covered. We identified eligible studies from PubMed, Elsevier, and three equivalent Chinese databases including the Chinese National Knowledge Infrastructure, Wanfang, and Weipu. Pooled odds ratios and 95% confidence intervals were used to assess the strength of the association between GSTP1 Ile105Val polymorphism and urinary system cancer risk. In total, 11,762 cases and 15,150 controls from 51 studies were included in the final meta-analysis. The pooled results from all included studies showed a statistically significant association between GSTP1 Ile105Val polymorphism and urinary system cancer. In the subgroup analyses, the GSTP1 Ile105Val polymorphism was found to be significantly associated with prostate cancer risk and also a risk factor for urinary system cancer among Asians. In conclusion, our meta-analysis indicated that GSTP1 Ile105Val polymorphism was associated with urinary system cancer susceptibility, which needs to be validated by more rigorous data from further large-scale population studies with different ethnicities.

Objective: To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis., Materials and Methods: By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines., Results: By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC., Conclusion: IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To elucidate the glycoprotein non-metastatic melanoma protein B(Gpnmb) expression in clear-cell renal cell carcinoma (ccRCC) and to determine its potential prognostic relevance., Methods: A total of 12 pairs of ccRCC tissue specimens were collected from patients undergoing surgery in our hospital from March 2009 to March 2012. Gpnmb expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for another 43 evaluable patients., Results: The expression level of Gpnmb was significantly higher in metastatic ccRCCs than that in matched primary samples ((6.36±4.01) vs (3.14±2.38) scores, P=0.036). The high expression of Gpnmb was not affected by age, gender, clinical stage and pathological grade (all P>0.05). Kaplan-Meier analysis disclosed significant differences in overall survival for patients with higher and lower average Gpnmb expression levels (P=0.020). Cox regression analysis revealed that a high Gpnmb protein expression level in the tumor cell could be identified as an independent poor prognostic marker of overall survival in ccRCC patients (P=0.049)., Conclusion: Over expression of Gpnmb in tumour cell predicts a poor prognosis of patients with ccRCC.

Current cancer therapies are largely reliant upon drugs and radiation that kill dividing cells or inhibit cell division in the primary tumor after radical surgery, whereas metastatic tumors should be more commonly the focus of targeted molecular therapies. Glycoprotein non‑metastatic melanoma protein B (Gpnmb) is expressed in various types of cancer, and promotes the migration, invasion and metastasis of tumor cells. Thus, it was hypothesized that a unique clear‑cell renal carcinoma (ccRCC) subclone expressing a high level of Gpnmb may metastasize more easily and thus be associated with poor prognosis. In the present study, the expression of Gpnmb was analyzed in primary and metastatic ccRCC samples, and the expression levels of Gpnmb were significantly higher in metastatic ccRCCs than in matched primary samples (P=0.036). Receiver operating characteristic (ROC) curve analysis was then performed to determine a cutoff score for Gpnmb expression in another 43 primary ccRCCs. For validation, the ROC‑derived cutoff score was subjected to an analysis of the association between Gpnmb expression and patient outcome/clinical characteristics. Kaplan‑Meier analysis demonstrated that elevated Gpnmb expression predicted a poorer overall survival (OS) in 43 cases of primary ccRCC. In addition, multivariate analyses revealed that Gpnmb expression served as an independent risk factor for ccRCC. Thus, the overexpression of Gpnmb identified patients at high risk and Gpnmb is a potential therapeutic molecular target for this type of tumor.

Integrin-linked kinase (ILK) localizes at focal adhesion sites, plays an important role in cell-matrix interactions and is involved in the regulation of tumor cell growth and migration. The aim of the present study was to clarify the functional characterization of ILK in prostate cancer (PCa) cells. ILK was shown to be overexpressed in 57.1% (36/63) of PCa samples and 18.2% (2/11) of benign prostatic hyperplasia (BPH) samples using immunohistochemical analysis. DU145 PCa cells knocked down for ILK were examined using western blot analysis, proliferation assay, flow cytometry and wound healing assay. Depletion of ILK significantly impaired cell growth and motility, induced apoptosis in vitro, and delayed xenograft tumor proliferation in nude mice, which were important for oncogenesis and tumor progression. Western blot analysis showed that Akt activity was attenuated in ILK‑depleted cells compared with the control cells. These results indicate that ILK knockdown attenuates the biological behavior of PCa cells by decreasing Akt activity, demonstrating that ILK is involved in the development and progression of PCa. Thus, ILK is suggested to serve as a potential therapeutic target for PCa.

An increased risk of renal cell carcinoma (RCC) has been linked with obesity and metabolic syndrome. However, the mechanisms by which lipid metabolic disorders affect the development of RCC remain unclear and highly controversial. Integrin-linked kinase (ILK) is a serine/threonine protein kinase involved in the regulation of tumor cell growth and angiogenesis. In the present study, the effect of free fatty acids in the promotion of RCC progression was investigated by upregulating ILK. Results of the MTT assay indicated that treatment of 786-O cells with oleic acid induced a concentration-dependent increase in cell viability. Flow cytometry analysis revealed that the effect of oleic acid on cell apoptosis was not significant. Following treatment with oleic acid, the expression of ILK, phospho-Akt and G protein-coupled receptor 40 (GPR40) was increased in 786-O cells. These effects were reversed when the expression of ILK was downregulated using specific small interfering RNA. These results indicate that free fatty acids are associated with the development of renal cell carcinoma via activation of the GPR40/ILK/Akt pathway, revealing a novel mechanism for the correlation between metabolic disturbance and renal carcinoma.