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1. This paper discusses the application of cognitive behavioural therapy (CBT) in the treatment of clients with schizophrenia and the implications for mental health nursing practice. 2. The literature shows that CBT has positive effects for clients in improving mental state and reducing relapse rate. 3. Because of their direct client contact, mental health nurses are in the best position to assess, address and manage clients' psychotic symptoms and problems. 4. A nursing care plan is used to illustrate how the principles of CBT could be incorporated into nursing care. 5. Education and training are important to equip nurses with the necessary knowledge and skills to implement the therapy. 6. Nurses have to take into account cultural issues related to the use of CBT. 7. Culturally sensitive research needs to be conducted to assess the outcome of the therapy. [ABSTRACT FROM AUTHOR]

This paper reports the preliminary results of a study on the implementation of case management in the community psychiatric nursing service (CPNS). The purpose of the study is to compare the outcome of case management service with the conventional practice of CPNS in the care of chronic schizophrenic clients. The impact of case management service on clients' clinical status, functional level and satisfaction was measured. A matched, pre-post, case-control group design was used to compare case management and conventional care groups. A specific case management model based on the practice at Carondelet Saint Mary's Hospital and Health Centre in Tucson has been developed to care for the schizophrenic clients in the community. Subjects in the experimental group were cared for by CPNs using this case management model. Subjects in the control group were cared for by CPNs based on current practices in the CPNS. Pre- and post-measures were taken upon recruitment and at 5 months later. Findings showed that the experimental group had better outcome in terms of their mental status and functional level when compared with the control group. They were generally more satisfied with the service. When comparing case managers' role with that of conventional CPNs, case managers performed more in areas such as assessment, liaison, case discussion and life skills training. This study demonstrates that this particular model of case management can be effective in caring for clients with long-term mental health problems in Hong Kong. [ABSTRACT FROM AUTHOR]

Background: Gaming Disorder was included as an addictive disorder in the latest version of the International Classification of Diseases (ICD-11), published in 2022. The present study aimed to develop a screening tool for Gaming Disorder, the Gaming Disorder Identification Test (GADIT), based on the four ICD-11 diagnostic criteria: impaired control, increasing priority, continued gaming despite harm, and functional impairment., Method: We reviewed 297 questionnaire items from 48 existing gaming addiction scales and selected 68 items based on content validity. Two datasets were collected: 1) an online panel (N = 803) from Australia, United States, United Kingdom and Canada, split into a development set (N = 589) and a validation dataset (N = 214); and 2) a university sample (N = 408) from Australia. Item response theory and confirmatory factor analyses were conducted to select eight items to form the GADIT. Validity was established by regressing the GADIT against known correlates of Gaming Disorder., Results: Confirmatory factor analyses of the GADIT showed good model fit (RMSEA=<0.001-0.108; CFI = 0.98-1.00), and internal consistency was excellent (Cronbach's alphas = 0.77-0.92). GADIT scores were strongly associated with the Internet Gaming Disorder Test (IGDT-10), and significantly associated with gaming intensity, eye fatigue, hand pain, wrist pain, back or neck pain, and excessive in-game purchases, in both the validation and the university sample datasets., Conclusion: The GADIT has strong psychometric properties in two independent samples from four English-speaking countries collected through different channels, and shown validity against existing scales and variables that are associated with Gaming Disorder. A cut-off of 5 is tentatively recommended for screening for Gaming Disorder.

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs) 1 , sources of high-frequency gravitational waves (GWs) 2 and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (the r-process) 3 . Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers 4-6 and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs.  7-12 ). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic mass A = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe., (© 2023. The Author(s).)

Subcellular partitioning of therapeutic agents is highly relevant to their interactions with target molecules and drug efficacy, but studying subcellular partitioning is an enormous challenge. Here, we describe the application of nanoscale secondary ion mass spectrometry (NanoSIMS) analysis to define the subcellular pharmacokinetics of a cytotoxic chemotherapy drug, arsenic trioxide (ATO). We reasoned that defining the partitioning of ATO would yield valuable insights into the mechanisms underlying ATO efficacy. NanoSIMS imaging made it possible to define the intracellular fate of ATO in a label-free manner─and with high resolution and high sensitivity. Our studies of ATO-treated cells revealed that arsenic accumulates in the nucleolus. After prolonged ATO exposure, ∼40 nm arsenic- and sulfur-rich protein aggregates appeared in the cell nucleolus, nucleus, and membrane-free compartments in the cytoplasm, and our studies suggested that the partitioning of nanoscale aggregates could be relevant to cell survival. All-trans retinoic acid increased intracellular ATO levels and accelerated the nanoscale aggregate formation in the nucleolus. This study yielded fresh insights into the subcellular pharmacokinetics of an important cancer therapeutic agent and the potential impact of drug partitioning and pharmacokinetics on drug activity.

Background: The ageing population and the emergence of chronic diseases continue to pose immense challenges to the healthcare system. This study aims to explore how likely middle-aged citizens could be encouraged to attend health checkups by well-defined healthcare vouchers, and to explore potential factors associated with the uptake of health checkups. Methods: A cross-sectional survey with self-administered structured questionnaires was conducted among Hong Kong residents aged 45-59. The questionnaire consisted of 25 items, including attitudes toward healthcare vouchers and checkups, utilisation patterns of healthcare services, and socio-demographics. Results: We received 278 responses between June and September 2021. Among the study participants, 62.6% (174) attended regular checkups currently, and a total of 252 (90.6%) indicated that it was likely for them to undertake health checkups with well-defined vouchers. This proportion showed an increase of 44.8% after introducing vouchers (78 of 174) when compared with the proportion currently attending regular health checkups. Multiple logistic regression analysis revealed that the perceived barrier of health checkup uptake included financial cost (AOR 0.367, 95% CI 0.162-0.832, p = 0.016), whilst the government's recommendation (AOR 1.685, 95% CI 1.052-2.698, p = 0.030) and full support by the employer-purchased insurance (AOR 2.395, 95% CI 1.036-5.523, p = 0.041) were positively associated with uptakes. Conclusions: Financial cost is a significant barrier to health promotion and disease prevention. Well-defined vouchers, as a demand-side financial tool, were widely accepted by our participants as incentives to undergo health checkups. Our findings indicate that the voucher scheme could be extended to individuals aged 45-59 for health checkups by easing the financial barrier, and show the importance of involving government recommendations and employer-purchased insurance.

Reactive oxygen species (ROS) at the right concentration promote cell proliferation in cell culture, stem cells, and model organisms. However, the mystery of how ROS signaling is coordinated with cell cycle progression and integrated into the cell cycle control machinery on the molecular level remains unsolved. Here, we report increasing levels of mitochondrial ROS during the cell cycle in human cell lines that target cyclin-dependent kinase 2 (CDK2). Chemical and metabolic interferences with ROS production decrease T-loop phosphorylation on CDK2 and so impede its full activation and thus its efficient DNA replication. ROS regulate CDK2 activity through the oxidation of a conserved cysteine residue near the T-loop, which prevents the binding of the T-loop phosphatase KAP. Together, our data reveal how mitochondrial metabolism is coupled with DNA replication and cell cycle progression via ROS, thereby demonstrating how KAP activity toward CDKs can be cell cycle regulated., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Refugee children are at risk for mental/behavioral health problems but may not receive timely diagnosis or care. Parental experiences and perspectives about resources in the US may help guide interventions to improve mental/behavioral health care. In a community-academic partnership, we performed a qualitative study of recently-arrived Afghan refugee parents, using in-depth, semi-structured interviews to characterize experiences with parenting, education, and health care services. A four-person coding team identified, described, and refined themes. We interviewed 19 parents from ten families, with a median residence in the US of 24 months. Four themes emerged; parents described: (1) shifting focus as safety needs changed, (2) acculturation stress, (3) adjustment to an emerging US support system, and (4) appreciation of an engaged health care system. Health and educational providers' appreciation for the process of acculturation among newly-arrived refugee Afghan families may facilitate screening, diagnostic, and intervention strategies to improve care., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Myelin, the structure that surrounds and insulates neuronal axons, is an important component of the central nervous system. The visualization of the myelinated fibers in brain tissues can largely facilitate the diagnosis of myelin-related diseases and understand how the brain functions. However, the most widely used fluorescent probes for myelin visualization, such as Vybrant DiD and FluoroMyelin, have strong background staining, low-staining contrast, and low brightness. These drawbacks may originate from their self-quenching properties and greatly limit their applications in three-dimensional (3D) imaging and myelin tracing. Chemical probes for the fluorescence imaging of myelin in 3D, especially in optically cleared tissue, are highly desirable but rarely reported. We herein developed a near-infrared aggregation-induced emission (AIE)-active probe, PM-ML, for high-performance myelin imaging. PM-ML is plasma membrane targeting with good photostability. It could specifically label myelinated fibers in teased sciatic nerves and mouse brain tissues with a high-signal-to-background ratio. PM-ML could be used for 3D visualization of myelin sheaths, myelinated fibers, and fascicles with high-penetration depth. The staining is compatible with different brain tissue-clearing methods, such as Clear T and Clear T2 The utility of PM-ML staining in demyelinating disease studies was demonstrated using the mouse model of multiple sclerosis. Together, this work provides an important tool for high-quality myelin visualization across scales, which may greatly contribute to the study of myelin-related diseases., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background & Aims: Recently, a group of hepatologists proposed to rename non-alcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) with modified diagnostic criteria. We aimed to study the impact of the new definition on the epidemiology of fatty liver disease., Methods: We randomly selected 1013 adults from the Hong Kong census database for clinical assessment, proton-magnetic resonance spectroscopy, and transient elastography. Five hundred sixty-five subjects without fatty liver at baseline underwent follow-up assessment. MAFLD was diagnosed as intrahepatic triglyceride content (IHTG) ≥5% and the presence of overweight/obesity, diabetes, or two other metabolic risk factors, with and without concomitant liver diseases. The diagnosis of NAFLD required the exclusion of concomitant liver diseases; metabolic factors were not considered., Results: The population prevalence of MAFLD and NAFLD was 25.9% (95% CI 23.2-28.7%) and 25.7% (95% CI 23.1-28.5%), respectively. Among 277 subjects with IHTG ≥5%, 247 (89.2%) fulfilled both the definitions of MAFLD and NAFLD. Fourteen subjects (5.1%) had IHTG ≥5% but did not meet the metabolic criteria of MAFLD. The incidence of MAFLD was 2.8 per 100 person-years at a median interval of 47 months (range 34-60 months). Among 78 subjects with incident NAFLD, 59 (75.6%) met the criteria of MAFLD; only one of the latter, a regular drinker, had liver stiffness ≥10 kPa., Conclusions: The new definition of MAFLD does not significantly change the prevalence compared with NAFLD, but it may reduce the incidence by 25%. People with hepatic steatosis but not fulfilling the definition of MAFLD unlikely have significant liver disease., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in global social and economic disruption, putting the world economy to the largest global recession since the Great Depression. To control the spread of COVID-19, cutting off the transmission route is a critical step. In this work, the efficient inactivation of human coronavirus with photodynamic therapy (PDT) by employing photosensitizers with aggregation-induced emission characteristics (DTTPB) is reported. DTTPB is designed to bear a hydrophilic head and two hydrophobic tails, mimicking the structure of phospholipids on biological membranes. DTTPB demonstrates a broad absorption band covering the whole visible light range and high molar absorptivity, as well as excellent reactive oxygen species sensitizing ability, making it an excellent candidate for PDT. Besides, DTTPB can target membrane structure, and bind to the envelope of human coronaviruses. Upon light irradiation, DTTPB demonstrates highly effective antiviral behavior: human coronavirus treated with DTTPB and white-light irradiation can be efficiently inactivated with complete loss of infectivity, as revealed by the significant decrease of virus RNA and proteins in host cells. Thus, DTTPB sensitized PDT can efficiently prevent the infection and the spread of human coronavirus, which provides a new avenue for photodynamic combating of COVID-19., (© 2021 The Authors. Small published by Wiley-VCH GmbH.)

Therapies for lethal castration-resistant prostate cancer (CRPC) are an unmet medical need. One mechanism underlying CRPC and resistance to hormonal therapies is the expression of constitutively active splice variant(s) of androgen receptor (AR-Vs) that lack its C-terminus ligand-binding domain. Transcriptional activities of AR-Vs and full-length AR reside in its N-terminal domain (NTD). Ralaniten is the only drug proven to bind AR NTD, and it showed promise of efficacy in Phase 1 trials. The peptidyl-prolyl isomerase Pin1 is frequently overexpressed in prostate cancer. Here we show that Pin1 interacted with AR NTD. The inhibition of Pin1 expression or its activity selectively reduced the transcriptional activities of full-length AR and AR-V7. Combination of Pin1 inhibitor with ralaniten promoted cell cycle arrest and had improved antitumor activity against CRPC xenografts in vivo compared to individual monotherapies. These findings support the rationale for therapy that combines a Pin1 inhibitor with ralaniten for treating CRPC.

The androgen receptor (AR) is a validated therapeutic target for prostate cancer and has been a focus for drug development for more than six decades. Currently approved therapies that inhibit AR signaling, such as enzalutamide, rely solely on targeting the AR ligand-binding domain and, therefore, have limited efficacy on prostate cancer cells that express truncated, constitutively active AR splice variants (AR-Vs). The LNCaP95 cell line is a human prostate cancer cell line that expresses both functional full-length AR and AR-V7. LNCaP95 is a heterogeneous cell population that is resistant to enzalutamide, with its proliferation dependent on transcriptionally active AR-V7. The purpose of this study was to identify a LNCaP95 clone that would be useful for evaluating therapies for their effectiveness against enzalutamide-resistant prostate cancer cells. Seven clones from the LNCaP95 cell line were isolated and characterized using morphology, in vitro growth rate, and response to ralaniten (AR N-terminal domain inhibitor) and enzalutamide (antiandrogen). In vivo growth of the clones as subcutaneous xenografts was evaluated in castrated immunodeficient mice. All of the clones maintained the expression of full-length AR and AR-V7. Cell proliferation of the clones was insensitive to androgen and enzalutamide but importantly was inhibited by ralaniten, which is consistent with AR-Vs driving the proliferation of parental LNCaP95 cells. In castrated immunodeficient animals, the growth of subcutaneous xenografts of the D3 clone was the most reproducible compared to the parental cell line and other clones. These data support that the enzalutamide-resistant LNCaP95-D3 subline may be suitable as a xenograft tumor model for preclinical drug development with improved reproducibility.

Background and Aims: Type 2 diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis. Current international guidelines recommend the use of noninvasive tests as initial assessments for NAFLD, but the role of noninvasive tests as monitoring tools has not been established. We aimed to study the role of transient elastography as a monitoring tool in patients with type 2 diabetes., Approach and Results: We recruited patients with type 2 diabetes without viral hepatitis or excessive alcohol intake from a complication screening facility in Hong Kong in 2013-2014 and repeated the assessments in 2016-2018. The primary endpoint was an increase of liver stiffness measurement (LSM) to ≥10 kPa. The secondary endpoint was the change in the controlled attenuation parameter (CAP). A total of 611 patients with type 2 diabetes and a valid LSM (mean age, 57.7 ± 10.9 years; 342 men [56.0%]) were included in this study (568 also had a valid CAP). Overall, there was moderate correlation between the baseline and follow-up LSM (r = 0.689, P < 0.001). Among 487 patients with a baseline LSM <10 kPa, 21 (4.3%) had a follow-up LSM ≥10 kPa. Baseline body mass index, alanine aminotransferase (ALT), and ∆ALT were independent factors associated with LSM increase. Among 124 patients with a baseline LSM ≥10 kPa, 70 (56.5%) had a follow-up LSM <10 kPa. Among 198 patients with a CAP <248 dB/m at baseline, 103 (52.0%) had a CAP increased to ≥248 dB/m., Conclusions: The prevalence and incidence of NAFLD in patients with type 2 diabetes are high. Although advanced fibrosis is common in this population, few patients progress to advanced fibrosis in 3 years. Future studies should define the optimal surveillance interval in patients with diabetes., (© 2020 by the American Association for the Study of Liver Diseases.)

Photosensitizers (PSs), a critical drug administered for successful photodynamic therapy (PDT), have been well researched regarding their anticancer or bactericidal capability with high precision and low invasiveness. Although traditional PSs have been explored either in photodynamic anticancer or in antibiosis, they usually require synthesis with multiple steps, harsh synthetic conditions, and a complicated purification process for a single targeted product. Therefore, developing new multifunctional PSs with a simple synthesis and reactant flexibility which combine mitochondrial and bacterial imaging, efficient photodynamic anticancer and antibacterial effects is of the utmost urgency and of great importance for clinical applications. Herein, a large structural investigation of isoquinolinium-based PSs synthesized by a simple Rh-catalysed annulation reaction with high yields is presented. These lipophilic cationic PSs have a tunable photophysical property. LIQ-6 was found to perform not only as an ideal mitochondria targeting probe but also an effective cancer cell killing PS, and moreover, a tracker for bacterial imaging and ablation. LIQ-6 can be used to image a wide range of cancer cells and to monitor the photo-induced cell apoptosis, and simultaneously, it can also image and be a photodynamic germicide for both Gram-positive and Gram-negative bacteria. Furthermore, LIQ-6 shows great effectiveness in the wound healing process, showing its ability to be an ideal PS in vivo as well. This contribution is believed to offer a new platform for the construction of a theragnostic system for future practical applications in biology and biomedicine.

Blocking androgen receptor (AR) transcriptional activity by androgen deprivation therapy (ADT) improves the response to radiotherapy for intermediate and high risk prostate cancer. Unfortunately, ADT, antiandrogens, and abiraterone increase expression of constitutively active splice variants of AR (AR-Vs) which regulate DNA damage repair leading to resistance to radiotherapy. Here we investigate whether blocking the transcriptional activities of full-length AR and AR-Vs with ralaniten leads to enhanced sensitivity to radiotherapy. Combination therapies using ralaniten with ionizing radiation were evaluated for effects on proliferation, colony formation, cell cycle, DNA damage, and Western blot analyses in human prostate cancer cells that express both full-length AR and AR-Vs. Ralaniten and a potent next-generation analog (EPI-7170) decreased expression of DNA repair genes whereas enzalutamide had no effect. FACS analysis revealed a dose-dependent decrease of BrdU incorporation with increased accumulation of γH2AX with a combination of ionizing radiation with ralaniten. An additive inhibitory effect on proliferation of enzalutamide-resistant cells was achieved with a combination of ralaniten compounds with ionizing radiation. Ralaniten and EPI-7170 sensitized prostate cancer cells that express full-length AR and AR-Vs to radiotherapy whereas enzalutamide had no added benefit.

The chromosome periphery (CP) is a complex network that covers the outer surface of chromosomes. It acts as a carrier of nucleolar components, helps maintain chromosome structure, and plays an important role in mitosis. Current methods for fluorescence imaging of CP largely rely on immunostaining. We herein report a small-molecule fluorescent probe, ID-IQ, which possesses aggregation-induced emission (AIE) property, for CP imaging. By labelling the CP, ID-IQ sharply highlighted the chromosome boundaries, which enabled rapid segmentation of touching and overlapping chromosomes, direct identification of the centromere, and clear visualization of chromosome morphology. ID-IQ staining was also compatible with fluorescence in situ hybridization and could assist the precise location of the gene in designated chromosome. Altogether, this study provides a versatile cytogenetic tool for improved chromosome analysis, which greatly benefits the clinical diagnostic testing and genomic research., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

An aggregation-enhanced emission mitochondrial probe, LIQ-3, was developed for ultrafast labeling within one minute and for distinguishing cancer cells from normal cells. Furthermore, the probe revealed high-fidelity tracking of mitochondria in a three-dimensional localization with advantages that include a specific targeting capacity and a high signal-to-noise ratio.

Cancer is a global health issue and a leading cause of death. The discrimination of cancer cells from normal cells is of significant importance for the early diagnosis of cancers. As one of the useful biomarkers for developing cancer diagnosis and chemotherapy resistance systems, biothiols not only play an essential role in physiological and pathological processes but also exhibit cytoprotective effects in the susceptibility to carcinogenesis. It would be highly desirable to explore near-infrared biothiol-specific fluorescent probes for cancer diagnosis with outstanding specificity. In this study, a novel near-infrared fluorescent probe BPO-THAZ decorated with thiazole as a recognition site was presented for sensitive and selective detection of endogenous biothiols. BPO-THAZ can be used to not only evaluate the biothiol level in living HeLa cells upon treatment with H2O2 or anti-cancer drugs but also assess endogenous biothiols in stem cells. Furthermore, BPO-THAZ was successfully utilized to discriminate cancer cells from normal cells showing great promise for cancer diagnosis.

Phagocytosis of bacteria is an important biological process. Gaining insight into this process may greatly benefit related pathological studies and further contribute to development of therapies for infectious diseases. Tools for studying these internalization processes, however, are limited. Herein, we demonstrate the feasibility of employing an environmentally sensitive aggregation-induced emission (AIE) probe for bacteria labeling and imaging. By tracking the fluorescence variation of the stained bacteria, the pH changes of its microenvironment can be monitored. In this way, the phagocytic entry of these bacteria into the macrophage cells and the intravacuolar acidification can be visualized in real-time., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Aim: The Baveno VI Consensus recommends repeating examination in patients with high liver stiffness measurement (LSM) by transient elastography to reduce false-positive diagnosis of advanced liver disease. We tested whether repeating transient elastography can increase the overall diagnostic accuracy., Methods: Ninety-seven patients with non-alcoholic fatty liver disease who underwent two FibroScan examinations within 6 months prior to liver biopsy were evaluated. An LSM cut-off of 7.9 kPa was used to exclude F3-4 fibrosis., Results: Seventy-eight patients had high LSM at baseline, among whom 27 had low LSM on repeated testing; only four had F3 and none had cirrhosis. In contrast, 31 of 51 patients with high LSM at both examinations had F3-4. Nineteen patients had low LSM at baseline; none of them had F3-4 regardless of the second LSM results. If we took LSM <7.9 kPa at either examination as sufficient to exclude F3-4, the negative predictive value remained high at 91%. The positive predictive value for F3-4 increased from 45% in patients with high LSM at baseline to 61% in those with high LSM at both examinations. Sensitivity analysis using different cut-offs yielded similar results, with 76% of patients with LSM >12 kPa at both examinations having F3-4., Conclusions: Transient elastography is a highly sensitive screening test to exclude F3-4 fibrosis in non-alcoholic fatty liver disease patients. One-third of patients with high LSM may have normal results on repeated examination. By repeating examination in cases with high LSM, one may spare patients from unnecessary liver biopsy., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background & Aims: Around 10-20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese patients with NAFLD and to identify factors that predict treatment response., Methods: A total of 154 community NAFLD patients were randomised to a 12-month lifestyle intervention programme involving regular exercise, or to standard care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed until Year 6. The Asian body mass index (BMI) cut-off of 25 kg/m 2 was used to define non-obese NAFLD., Results: Patients were assigned to the intervention (n = 77) and control (n = 77) groups (39 and 38 in each group had baseline BMI <25 and ≥25 kg/m 2 , respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs. 18%, p <0.001; obese: 61% vs. 21%, p <0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3-5% weight reduction; the same could only be achieved in obese patients with 7-10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalisation than the control group., Conclusions: Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population., Lay Summary: Some patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3-10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Compact neutron generators can provide high flux of neutrons with energies ranging from thermal (0.025 eV) to 14 MeV. Recent measurements demonstrated high neutron yields from the D- 7 Li fusion reaction at an interaction energy of 500 keV. Using the D- 7 Li reaction and applying new advancements in high flux neutron generator technology along with the commercial availability of high voltage DC power supplies enables the production of useful quantities of radioisotopes for medical applications. Using the known neutron reaction cross-sections, it has been estimated that hundreds-to-thousands MBq (or tens-to-hundreds mCi) of 99 Mo, 225 Ac, 64 Cu and 67 Cu can be obtained from a compact high flux neutron generator., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hyperbaric oxygen therapy is widely accepted as life-saving treatment for decompression illness. Yet its use in acute carbon monoxide poisoning has remained controversial because of inconsistent findings in clinical trials. Hyperbaric oxygen therapy has an adjunctive role in managing gas gangrene, necrotising soft-tissue infection, and crush injury, as supported by case series. Several cases have been reported in the literature detailing the use of hyperbaric oxygen therapy in patients with severe anaemia in whom blood transfusion is not possible. Today, use of hyperbaric oxygen therapy in Hong Kong is limited by low awareness among physicians and patients, a lack of service access, and inadequate hospital and critical care support for the existing non-hospital facility. The recent introduction of a hospital-based facility is expected to benefit more patients for whom hyperbaric oxygen therapy is appropriate. This article reviews the mechanistic basis of and emerging scientific evidence to support the use of hyperbaric oxygen therapy in a number of acute medical emergencies, as well as the past and future development of hyperbaric oxygen therapy in Hong Kong.

Purpose: Resilience, coping with uncertainty and learning from mistakes are vital characteristics for all medical disciplines - particularly rural practice. Levels of coping constructs were examined in medical students with and without a rural background or an interest in rural practice., Methods: Cross-sectional surveys identified two personality profiles, and their association with levels of Tolerance of Ambiguity, Resilience, Perfectionism-High Standards and Concern over mistakes as constructs indicative of coping. Medical students (N = 797) were stratified by rural background and degree of rural interest. Mediation analysis tested the effect of personality profile on levels of the coping constructs., Results: More (72%) rural background students had Profile 1 which was associated with higher levels of Tolerance of Ambiguity, High standards, and Resilience, but lower Concern over mistakes. Non-rural background students reporting a strong rural interest also had Profile 1 (64%) and similar levels of coping constructs. Personality profile mediated the association between rural interest and levels of coping constructs regardless of background., Conclusions: Having a rural background or strong rural interest are associated with a personality profile that indicates a better capacity for coping. Personality may play a part in an individual's interest in rural practice. Rural workforce initiatives through education should encourage and nurture students with a genuine interest in rural practice - regardless of background.

Androgen receptor (AR) is a validated drug target for prostate cancer based on its role in proliferation, survival, and metastases of prostate cancer cells. Unfortunately, despite recent improvements to androgen deprivation therapy and the advent of better antiandrogens with a superior affinity for the AR ligand-binding domain (LBD), most patients with recurrent disease will eventually develop lethal metastatic castration-resistant prostate cancer (CRPC). Expression of constitutively active AR splice variants that lack the LBD contribute toward therapeutic resistance by bypassing androgen blockade and antiandrogens. In the canonical pathway, binding of androgen to AR LBD triggers the release of AR from molecular chaperones which enable conformational changes and protein-protein interactions to facilitate its nuclear translocation where it regulates the expression of target genes. However, preceding AR function in the nucleus, initial binding of androgen to AR LBD in the cytoplasm may already initiate signal transduction pathways to modulate cellular proliferation and migration. In this article, we review the significance of signal transduction pathways activated by rapid, non-genomic signaling of the AR during the progression to metastatic CRPC and put into perspective the implications for current and novel therapies that target different domains of AR.

Background: Skog's collectivity theory of alcohol consumption predicted that changes in alcohol consumption would synchronize across all types of drinkers in a population. The aim of this paper is examine this theory in the Australian context. We examined whether there was a collective change in alcohol use in Australia from 2001 to 2013, estimated alcohol consumption in non-high risk and high risk drinkers, and examined the trends in alcohol treatment episodes., Methods: Data from the 2001-2013 National Drug Strategy Household Surveys (N = 127,916) was used to estimate the prevalence and alcohol consumption of abstainers, high risk drinkers and frequent heavy episodic drinkers. Closed treatment episodes recorded in the Alcohol and Other Drug Treatment Services National Minimum Dataset (N = 608,367) from 2001 to 2013 were used to examine the trends of closed alcohol treatment episodes., Results: The prevalence of non-drinkers (abstainers) decreased to the lowest level in 2004 (15.3 %) and rebounded steadily thereafter (20.4 % in 2013; p < .001). Correspondingly, the per capita consumption of high risk drinkers (2 standard drinks or more on average per day) increased from 20.7 L in 2001 to peak in 2010 (21.5 L; p = .020). Non-high risk drinkers' consumption peaked in 2004 (2.9 L) and decreased to 2.8 L in 2013 (p < .05). There were decreases in alcohol treatment episodes across nearly all birth cohorts in recent years., Conclusion: These findings are partially consistent with and support Skog's collectivity theory. There has been a turnaround in alcohol consumption after a decade-long uptrend, as evident in the collective decreases in alcohol consumption among nearly all types of drinkers. There was also a turnaround in rate of treatment seeking, which peaked at 2007 and then decreased steadily. The timing of this turnaround differs with level of drinking, with non-high risk drinkers reaching its peak consumption in 2004 and high risk drinkers reaching its peak consumption in 2010.

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^{2}2θ&#95;{μe} are set over 6 orders of magnitude in the sterile mass-squared splitting Δm&#95;{41}^{2}. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Δm&#95;{41}^{2}<0.8  eV^{2} at 95%  CL&#95;{s}.

This Letter reports an improved search for light sterile neutrino mixing in the electron antineutrino disappearance channel with the full configuration of the Daya Bay Reactor Neutrino Experiment. With an additional 404 days of data collected in eight antineutrino detectors, this search benefits from 3.6 times the statistics available to the previous publication, as well as from improvements in energy calibration and background reduction. A relative comparison of the rate and energy spectrum of reactor antineutrinos in the three experimental halls yields no evidence of sterile neutrino mixing in the 2×10^{-4}≲|Δm&#95;{41}^{2}|≲0.3  eV^{2} mass range. The resulting limits on sin^{2}2θ&#95;{14} are improved by approx imately a factor of 2 over previous results and constitute the most stringent constraints to date in the |Δm&#95;{41}^{2}|≲0.2  eV^{2} region.

Background: Driving cessation in later life is associated with depression. This study examines if social support can buffer the negative effects of driving cessation on older women's mental health., Methods: Participants were drawn from the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health (ALSWH) and included 4,075 older women (aged 76-87 years) who drove at baseline, following them for three years to assess driving cessation. The outcome variable was mental health, measured by the mental health index (MHI) of the SF-36. The explanatory variables were social support factors, including social interaction, whether the women were living alone or with others, and engagement in social activities. Control variables included age, country of birth, area of residence, ability to manage on income, marital status, and general health., Results: Main effect results showed that poor mental health was predicted by driving cessation, low levels of social interaction, and non-engagement in social activities. There was a significant interaction effect of driving status by social activities engagement on mental health. Women who remained active in their engagement of social activities were able to maintain a good level of mental health despite driving cessation., Conclusion: Engagement and participation in social activities can help older women who stopped driving maintain a good level of mental health.

Constitutively active splice variants of androgen receptor (AR-Vs) lacking ligand-binding domain (LBD) are a mechanism of resistance to androgen receptor LBD-targeted (AR LBD-targeted) therapies for metastatic castration-resistant prostate cancer (CRPC). There is a strong unmet clinical need to identify prostate cancer patients with AR-V-positive lesions to determine whether they will benefit from further AR LBD-targeting therapies or should receive taxanes or investigational drugs like EPI-506 or galeterone. Both EPI-506 (NCT02606123) and galeterone (NCT02438007) are in clinical trials and are proposed to have efficacy against lesions that are positive for AR-Vs. AR activation function-1 (AF-1) is common to the N-terminal domains of full-length AR and AR-Vs. Here, we provide proof of concept for developing imaging compounds that directly bind AR AF-1 to detect both AR-Vs and full-length AR. 123 I-EPI-002 had specific binding to AR AF-1, which enabled direct visualization of CRPC xenografts that express full-length AR and AR-Vs. Our findings highlight the potential of 123 I-EPI-002 as an imaging agent for the detection of full-length AR and AR-Vs in CRPC.

Purpose: The PI3K/Akt/mTOR pathway is activated in most castration-resistant prostate cancers (CRPC). Transcriptionally active androgen receptor (AR) plays a role in the majority of CRPCs. Therefore, cotargeting full-length (FL) AR and PI3K/Akt/mTOR signaling has been proposed as a possible, more effective therapeutic approach for CRPC. However, truncated AR-splice variants (AR-V) that are constitutively active and dominant over FL-AR are associated with tumor progression and resistance mechanisms in CRPC. It is currently unknown how blocking the PI3K/Akt/mTOR pathway impacts prostate cancer driven by AR-Vs. Here, we evaluated the efficacy and mechanism of combination therapy to block mTOR activity together with EPI-002, an AR N-terminal domain (NTD) antagonist that blocks the transcriptional activities of FL-AR and AR-Vs in models of CRPC., Experimental Design: To determine the functional roles of FL-AR, AR-Vs, and PI3K/Akt/mTOR pathways, we employed EPI-002 or enzalutamide and BEZ235 (low dose) or everolimus in human prostate cancer cells that express FL-AR or FL-AR and AR-Vs (LNCaP95). Gene expression and efficacy were examined in vitro and in vivo, Results: EPI-002 had antitumor activity in enzalutamide-resistant LNCaP95 cells that was associated with decreased expression of AR-V target genes (e.g., UBE2C). Inhibition of mTOR provided additional blockade of UBE2C expression. A combination of EPI-002 and BEZ235 decreased the growth of LNCaP95 cells in vitro and in vivo, Conclusions: Cotargeting mTOR and AR-NTD to block transcriptional activities of FL-AR and AR-Vs provided maximum antitumor efficacy in PTEN-null, enzalutamide-resistant CRPC. Clin Cancer Res; 22(11); 2744-54. ©2015 AACR., (©2015 American Association for Cancer Research.)

This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18)  cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43)  cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.

We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW&#95;{th}  ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ&#95;{13} and |Δm&#95;{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ&#95;{13}=0.084±0.005 and |Δm&#95;{ee}^{2}|=(2.42±0.11)×10^{-3}  eV^{2} in the three-neutrino framework.

A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)<|Δm(41)(2) |< 0.3 eV(2) range. The relative spectral distortion due to the disappearance of electron antineutrinos was found to be consistent with that of the three-flavor oscillation model. The derived limits on sin(2) 2θ(14) cover the 10(-3) eV(2) ≲ |Δm(41)(2)| ≲ 0.1 eV(2) region, which was largely unexplored.

A measurement of the energy dependence of antineutrino disappearance at the Daya Bay reactor neutrino experiment is reported. Electron antineutrinos (ν¯(e)) from six 2.9  GW(th) reactors were detected with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls. Using 217 days of data, 41 589 (203 809 and 92 912) antineutrino candidates were detected in the far hall (near halls). An improved measurement of the oscillation amplitude sin(2)2θ(13)=0.090(-0.009)(+0.008) and the first direct measurement of the ν¯(e) mass-squared difference |Δm(ee)2|=(2.59(-0.20)(+0.19))×10(-3)  eV2 is obtained using the observed ν¯(e) rates and energy spectra in a three-neutrino framework. This value of |Δm(ee)2| is consistent with |Δm(μμ)2| measured by muon neutrino disappearance, supporting the three-flavor oscillation model.

Based on 106×10(6)ψ(3686) events collected with the BESIII detector at the BEPCII facility, a partial wave analysis of ψ(3686)→ppπ0 is performed. The branching fraction of this channel has been determined to be B(ψ(3686)→ppπ0)=(1.65±0.03±0.15)×10(-4). In this decay, 7 N* intermediate resonances are observed. Among these, two new resonances, N(2300) and N(2570) are significant, one 1/2+ resonance with a mass of 2300(-30-0)(+40+109)  MeV/c2 and width of 340(-30-58)(+30+110)  MeV/c2, and one 5/2- resonance with a mass of 2570(-10-10)(+19+34)  MeV/c2 and width of 250(-24-21)(+14+69)  MeV/c2. For the remaining 5 N* intermediate resonances [N(1440), N(1520), N(1535), N(1650) and N(1720)], the analysis yields mass and width values that are consistent with those from established resonances.

The two-photon transition ψ(3686)→γγJ/ψ is studied in a sample of 1.06×10(8) ψ(3686) decays collected by the BESIII detector. The branching fraction is measured to be (3.1±0.6(stat)(-1.0)(+0.8)(syst))×10(-4) using J/ψ→e(+)e(-) and J/ψ→μ(+)μ(-) decays, and its upper limit is estimated to be 4.5×10(-4) at the 90% confidence level. This work represents the first measurement of a two-photon transition among charmonium states. The orientation of the ψ(3686) decay plane and the J/ψ polarization in this decay are also studied. In addition, the product branching fractions of sequential E1 transitions ψ(3686)→γχ(cJ) and χ(cJ)→γJ/ψ(J=0,1,2) are reported.

Using a sample of 106×10(6) ψ(3686) events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium S-wave spin-triplet and the radially excited S-wave spin-singlet states: ψ(3686)→γη(c)(2S). Analyses of the processes ψ(3686)→γη(c)(2S) with η(c)(2S)→K(S)(0)K(±)π(∓) and K(+)K(-)π(0) give an η(c)(2S) signal with a statistical significance of greater than 10 standard deviations under a wide range of assumptions about the signal and background properties. The data are used to obtain measurements of the η(c)(2S) mass (M(η(c)(2S))=3637.6±2.9(stat)±1.6(syst) MeV/c(2)), width (Γ(η(c)(2S))=16.9±6.4(stat)±4.8(syst) MeV), and the product branching-fraction (B(ψ(3686)→γη(c)(2S))×B(η(c)(2S)→KKπ)=(1.30±0.20(stat)±0.30(syst))×10(-5)). Combining our result with a BABAR measurement of B(η(c)(2S)→KKπ), we find the branching fraction of the M1 transition to be B(ψ(3686)→γη(c)(2S))=(6.8±1.1(stat)±4.5(syst))×10(-4).

The mass and width of the lowest-lying S-wave spin singlet charmonium state, the η(c), are measured using a data sample of 1.06×10(8) ψ(3686) decays collected with the BESIII detector at the BEPCII storage ring. We use a model that incorporates full interference between the signal reaction, ψ(3686)→γη(c), and a nonresonant radiative background to describe the line shape of the η(c) successfully. We measure the η(c) mass to be 2984.3±0.6±0.6 MeV/c(2) and the total width to be 32.0±1.2±1.0 MeV, where the first errors are statistical and the second are systematic.

The decays J/ψ → γ π+ π- π0 and J/ψ → γ π0 π0 π0 are analyzed using a sample of 225×10(6) J/ψ events collected with the BESIII detector. The decay of η(1405) → f(0)(980)π0 with a large isospin violation is observed for the first time. The width of the f(0)(980) observed in the dipion mass spectra is anomalously narrower than the world average. Decay rates for three-pion decays of the η' are also measured precisely.

The Daya Bay Reactor Neutrino Experiment has measured a nonzero value for the neutrino mixing angle θ(13) with a significance of 5.2 standard deviations. Antineutrinos from six 2.9 GWth reactors were detected in six antineutrino detectors deployed in two near (flux-weighted baseline 470 m and 576 m) and one far (1648 m) underground experimental halls. With a 43,000 ton-GWth-day live-time exposure in 55 days, 10,416 (80,376) electron-antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to expected number of antineutrinos at the far hall is R=0.940±0.011(stat.)±0.004(syst.). A rate-only analysis finds sin(2)2θ(13)=0.092±0.016(stat.)±0.005(syst.) in a three-neutrino framework.

A partial wave analysis of the pp¯ mass-threshold enhancement in the reaction J/ψ→γpp¯ is used to determine its J(PC) quantum numbers to be 0(-+), its peak mass to be below threshold at M=1832(-5)(+19)(stat)(-17)(+18)(syst)±19(model) MeV/c(2), and its total width to be Γ<76 MeV/c(2) at the 90% C.L. The product of branching ratios is measured to be BR[J/ψ→γX(pp¯)]BR[X(pp¯)→pp¯]=[9.0(-1.1)(+0.4)(stat)(-5.0)(+1.5)(syst)±2.3(model)]×10(-5). A similar analysis performed on ψ(3686)→γpp¯ decays shows, for the first time, the presence of a corresponding enhancement with a production rate relative to that for J/ψ decays of R=[5.08(-0.45)(+0.71)(stat)(-3.58)(+0.67)(syst)±0.12(model)]%.

A novel symbiosis between scleractinians and hydroids (Zanclea spp.) was recently discovered using taxonomic approaches for hydroid species identification. In this study, we address the question whether this is a species-specific symbiosis or a cosmopolitan association between Zanclea and its coral hosts. Three molecular markers, including mitochondrial 16S and nuclear 28S ribosomal genes, and internal transcribed spacer (ITS), were utilized to examine the existence of Zanclea species from 14 Acropora species and 4 other Acroporidae genera including 142 coral samples collected from reefs in Kenting and the Penghu Islands, Taiwan, Togian Island, Indonesia, and Osprey Reef and Orpheus Island on the Great Barrier Reef, Australia. Molecular phylogenetic analyses of the 16S and 28S genes showed that Acropora-associated Zanclea was monophyletic, but the genus Zanclea was not. Analysis of the ITS, and 16S and 28S genes showed either identical or extremely low genetic diversity (with mean pairwise distances of 0.009 and 0.006 base substitutions per site for the 16S and 28S genes, respectively) among Zanclea spp. collected from diverse Acropora hosts in different geographic locations, suggesting that a cosmopolitan and probably genus-specific association occurs between Zanclea hydroids and their coral hosts.