Developing a Mental Health Screening Questionnaire in an Asian Children's Hospital Emergency Setting.

INTRODUCTION: Mental health concerns among adolescents are increasingly prevalent, yet underrecognized. Adolescents with psychological distress often present to the emergency department (ED) with somatic symptoms. Due to inadequate time for rapport building and lack of familiarity of ED clinicians with psychosocial evaluation, these concerns often get missed. We describe the development and implementation of the Youth Well Being (YWB) questionnaire, a self-administered psychosocial screening tool that aims to overcome the communication barriers to psychosocial evaluation. METHODS: A multidisciplinary team used a Delphi-like approach to develop the questionnaire, using the home, education, activities/peers, drugs/alcohol, suicidality, emotions/behavior, discharge resources (HEADS-ED) questionnaire as the main reference. Modifications were made based on panel members' clinical experience and adapted to suit local sociocultural context. The YWB questionnaire is administered to adolescents aged 10 to 19 years presenting to the KK Women's and Children's Hospital ED with possible psychosomatic symptoms and behavioral or mental health issues. Positive findings prompt further targeted face-to-face interviews by the clinicians to facilitate appropriate psychosocial referral. RESULTS: The 9 domains in the YWB questionnaire explore potential psychosocial difficulties that affect the adolescent's well-being and aim to uncover potential issues that could account for the adolescent's symptoms. We discuss the rationale behind the questions and response options in the YWB questionnaire. CONCLUSIONS: The YWB questionnaire is the first initiative in Singapore to enable efficient psychosocial screening of at-risk adolescents in the ED. This communication tool can potentially be used in other health care settings to enable early recognition and intervention for adolescents distressed by psychosocial problems.

Colonial rodent control in Tanganyika and the application of ecological frameworks.

ABSTRACTAt the end of the 1920s, Tanganyika Territory experienced several serious rodent outbreaks that threatened cotton and other grain production. At the same time, regular reports of pneumonic and bubonic plague occurred in the northern areas of Tanganyika. These events led the British colonial administration to dispatch several studies into rodent taxonomy and ecology in 1931 to determine the causes of rodent outbreaks and plague disease, and to control future outbreaks. The application of ecological frameworks to the control of rodent outbreaks and plague disease transmission in colonial Tanganyika Territory gradually moved from a view that prioritised 'ecological interrelations' among rodents, fleas and people to one where those interrelations required studies into population dynamics, endemicity and social organisation in order to mitigate pests and pestilence. This shift in Tanganyika anticipated later population ecology approaches on the African continent. Drawing on sources from the Tanzania National Archives, this article offers an important case study of the application of ecological frameworks in a colonial setting that anticipated later global scientific interest in studies of rodent populations and rodent-borne disease ecologies.

Right siting of complex acute wound management---preliminary study of teleconsultation wound services between acute and primary care in Singapore.

This study aimed to provide preliminary evidence on feasibility of the inaugural use of teleconsultation between acute hospitals and primary care for acute wound management in Singapore. Post-surgical patients with carbuncle wounds, perianal abscess wounds or surgical abdominal dehiscence wounds were recruited from an acute hospital. Instead of receiving their follow up care at the acute care tertiary hospital, patients were given the option to receive their care at primary care facilities instead, supported by teleconsultation wound services provided by wound care nurses from the hospital. The following outcome measures were collected: number of care sessions required (until wound healed), readmissions or referrals back to hospital, cost (patient's and healthcare provider's perspective), patients' and nurses' satisfaction. In total, 18 patients were recruited and completed the study (teleconsult group = 5; tertiary care clinic group = 13). The mean age (SD) of patients were 63.2 (SD 11.5) years old in the teleconsult group and 47.9 years old (SD 11.5) in the tertiary care clinic group. There were 7 female (54%), and 6 male (46%) in the tertiary care clinic group whereas teleconsult group consisted of male only (n = 5). Most had carbuncle wounds (teleconsult group: n = 4; 80%); tertiary care clinic group: (n = 10; 77%). For patients with carbuncle wounds, the average number of care sessions required were 21 and 33 for the tertiary care clinic and teleconsult respectively. None of the patients in the teleconsult group were referred back to the tertiary care hospital. All 16 nurses (n = 6 from acute care hospital, n = 10 from polyclinics) who participated in the feedback survey cited convenience, ease of tracking wound sizes, and closer collaboration between the acute care and primary care nurses as advantages of the service. Wound teleconsultation is feasible and potentially cost savings for patients with acute complex wounds.

A Near-Infrared Probe Tracks and Treats Lung Tumor Initiating Cells by Targeting HMOX2.

Tumor initiating cells (TIC) are resistant to conventional anticancer therapy and associated with metastasis and relapse in cancer. Although various TIC markers and their antibodies have been proposed, it is limited to the use of antibodies for in vivo imaging or treatment of TIC. In this study, we discovered heme oxygenase 2 (HMOX2) as a novel biomarker for TIC and developed a selective small molecule probe TiNIR (tumor initiating cell probe with near infrared). TiNIR detects and enriches the functionally active TIC in human lung tumors, and through the photoacoustic property, TiNIR also visualizes lung TIC in the patient-derived xenograft (PDX) model. Furthermore, we demonstrate that TiNIR inhibits tumor growth by blocking the function of HMOX2, resulting in significantly increased survival rates of the cancer model mice. The novel therapeutic target HMOX2 and its fluorescent ligand TiNIR will open a new path for the molecular level of lung TIC diagnosis and treatment.

AAV-mediated gene delivery of the calreticulin anti-angiogenic domain inhibits ocular neovascularization.

Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. The expression of CAD180 and CAD112 was elevated in human umbilical vein endothelial cells transduced with scAAV2-CAD180 or scAAV2-CAD112, respectively, and both inhibited angiogenic activity in vitro. Intravitreal gene delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly inhibited ischemia-induced retinal neovascularization in rat eyes (CAD180: 52.7% reduction; CAD112: 49.2% reduction) compared to scAAV2-mCherry, as measured in retinal flatmounts stained with isolectin B4. Moreover, the retinal structure and function were unaffected by scAAV2-CAD180 or scAAV2-CAD112, as measured by optical coherence tomography and electroretinography. Moreover, subretinal delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly attenuated laser-induced choroidal neovascularization in mouse eyes compared to scAAV2-mCherry, as measured by fundus fluorescein angiography (CAD180: 62.4% reduction; CAD112: 57.5% reduction) and choroidal flatmounts (CAD180: 40.21% reduction; CAD112: 43.03% reduction). Gene delivery using scAAV2-CAD180 or scAAV2-CAD112 has significant potential as a therapeutic option for the management of ocular neovascularization.

A chemical-inducible CRISPR-Cas9 system for rapid control of genome editing.

CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human cells with 4-hydroxytamoxifen (4-HT) by fusing the Cas9 enzyme with the hormone-binding domain of the estrogen receptor (ERT2). The final optimized variant, termed iCas, showed low endonuclease activity without 4-HT but high editing efficiency at multiple loci with the chemical. We also tuned the duration and concentration of 4-HT treatment to reduce off-target genome modification. Additionally, we benchmarked iCas against other chemical-inducible methods and found that it had the fastest on rate and that its activity could be toggled on and off repeatedly. Collectively, these results highlight the utility of iCas for rapid and reversible control of genome-editing function.

Identification of Tumor Initiating Cells with a Small-Molecule Fluorescent Probe by Using Vimentin as a Biomarker.

Tumor initiating cells (TICs) have been implicated in clinical relapse and metastasis of a variety of epithelial cancers, including lung cancer. While efforts toward the development of specific probes for TIC detection and targeting are ongoing, a universal TIC probe has yet to be developed. We report the first TIC-specific fluorescent chemical probe, TiY, with identification of the molecular target as vimentin, a marker for epithelial-to-mesenchymal transition (EMT). TiY selectively stains TICs over differentiated tumor cells or normal cells, and facilitates the visualization and enrichment of functionally active TICs from patient tumors. At high concentration, TiY also shows anti-TIC activity with low toxicity to non-TICs. With the unexplored target vimentin, TiY shows potential as a first universal probe for TIC detection in different cancers.

Low-dose Nicotine Exposure Induced the Oxidative Damage of Reproductive Organs and Altered the Sperm Characteristics of Adolescent Male Rats.

BACKGROUND: Nicotine is a major toxic and hazardous component of cigarette smoke, and it has been widely used in nicotine replacement therapy (NRT). This study was aimed to investigate the effects of chronic low-dose nicotine on sperm characteristics and reproductive organ integrity in adolescent male Sprague-Dawley rats. METHODS: Twelve rats were equally divided into two groups. Group I received normal saline, and group II received 0.6 mg/kg body weight nicotine intraperitoneally for 28 consecutive days. At the end of the experimental period, sperm was collected for sperm characteristic evaluation, and the testes and prostate were isolated for biochemical and morphological analysis. The effects of nicotine on the body and reproductive organ weights of the animals were evaluated. RESULTS: Chronic nicotine treatment significantly (P < 0.05) altered the sperm count, motility, viability, and morphology, and remarkably increased the malondialdehyde (P < 0.001) and advanced oxidation protein product (P < 0.05) levels in the testes and prostate of nicotine-treated group compared to control group. Moreover, nicotine caused a significant decrease (P < 0.05) in the superoxide dismutase activity of the testes. No significant differences were observed in the reduced glutathione level in both of the testes and prostate of nicotine group compared with control group. Nicotine also induced histopathological alteration in the testes. CONCLUSION: A low-dose nicotine exposure at 0.6 mg/kg caused detrimental effects on sperm characteristics and induced oxidative stress in the testes and prostate.

Laparoscopic Repair of Bochdalek Hernia: A Rare Presentation of Abdominal Pain in the Elderly.

Bochdalek hernias (BHs) are rare, and the presentation, diagnosis, and management of them can be complex. We present a 70-year-old man presenting with left flank pain who underwent a successful laparoscopic repair of BH with mesh placement.

Posterior cervical necrotising fasciitis: a multidisciplinary endeavour in surgery.

A 62-year-old male was diagnosed to the Emergency Department with 5-cm posterior neck carbuncle, and was subsequently discovered to have severe necrotising fasciitis intraoperatively during saucerization of the carbuncle. Subsequently, the patient was admitted to the intensive care unit and underwent combined debridement by the General Surgery, Neurosurgery and Plastic Surgery team. The large defect necessitated a trapezius flap reconstruction for coverage. Three months post-surgery, the patient had recovered well with the full range of movement of his neck.

Theranostics application of tumor-initiating cell probe TiY in non-small cell lung cancer.

Background: Tumor-initiating cells (TIC) often elude conventional cancer treatment, which results in metastasis and cancer relapse. Recently, studies have begun to focus on the TIC population in tumors to provide better therapeutic options. Previously, we have reported the successful development of a TIC-specific probe TiY with the binding target as vimentin. While a low concentration of TiY showed a TIC visualization, at a high concentration, TiY induced selective toxicity onto TIC in vitro. In this study, we aim to assess TiY's applicability in theranostics purposes, from in vivo visualization to therapeutic effect toward TIC, in cancer mouse models. Methods: We performed cell experiments with the TIC line model derived from resected primary non-small cell lung cancer (NSCLC) patient tumor. The animal model studies were conducted in mice of NSCLC patient-derived xenograft (PDX). TiY was intravenously delivered into the mice models at different concentrations to assess its in vivo TIC-selective staining and therapeutic effect. Results: We demonstrated the TIC-selective identification and therapeutic effect of TiY in animal models. TiY treatment induced a significant ablation of the TIC population in the tumor, and further molecular study elucidated that the mechanism of TiY is through vimentin dynamics in TIC. Conclusion: The results underscore the applicability of TiY for cancer treatment by selectively targeting soluble vimentin in TIC.

Perforated viscus as first presentation of Crohn's disease: a case report.

Bowel perforation as the first presentation of inflammatory bowel disease is rare and unusual in young patients. A previously asymptomatic 21-year-old Asian male presented with perforated small bowel secondary to previously undiagnosed Crohn's disease. He underwent an exploratory laparotomy and subsequent small bowel resection and was commenced on mesalazine post-operation. He recovered well with subsequent regular follow-up with gastroenterology. The main management of Crohn's disease is multidisciplinary in nature, and collaboration between different disciplines is inherent with the aim of reducing symptoms and maximizing patient quality of life.

Gene therapy for visual loss: Opportunities and concerns.

Many clinical trials using gene therapy have shown significant therapeutic benefits and exceptional safety records. Increasing evidence is verifying the long sought-after promise that gene therapy will genetically 'cure' some severely disabling diseases. In particular, the first gene therapy bioproduct for RPE65-associated Leber's congenital amaurosis, which was approved by the US Food and Drug Administration in 2017, has provided tremendous encouragement to the field of gene therapy. Recent developments in genome editing technologies have significantly advanced our capability to precisely engineer genomes in eukaryotic cells. Programmable nucleases, particularly the CRISPR/Cas system, have been widely adopted in studies applying genome engineering therapy to ocular diseases with the hope of managing these diseases. In this review article, we summarize the current approaches that have been developed in the area of gene therapy for ocular disease. We also discuss the challenges and opportunities facing gene therapy for ocular diseases, as well as its prospects.

Methionine is a metabolic dependency of tumor-initiating cells.

Understanding cellular metabolism holds immense potential for developing new classes of therapeutics that target metabolic pathways in cancer. Metabolic pathways are altered in bulk neoplastic cells in comparison to normal tissues. However, carcinoma cells within tumors are heterogeneous, and tumor-initiating cells (TICs) are important therapeutic targets that have remained metabolically uncharacterized. To understand their metabolic alterations, we performed metabolomics and metabolite tracing analyses, which revealed that TICs have highly elevated methionine cycle activity and transmethylation rates that are driven by MAT2A. High methionine cycle activity causes methionine consumption to far outstrip its regeneration, leading to addiction to exogenous methionine. Pharmacological inhibition of the methionine cycle, even transiently, is sufficient to cripple the tumor-initiating capability of these cells. Methionine cycle flux specifically influences the epigenetic state of cancer cells and drives tumor initiation. Methionine cycle enzymes are also enriched in other tumor types, and MAT2A expression impinges upon the sensitivity of certain cancer cells to therapeutic inhibition.

Publisher Correction: Methionine is a metabolic dependency of tumor-initiating cells.

In the version of this article originally published, there is an error in Fig. 5a. Originally, 'MAT2A' appeared between 'Methionine' and 'Homocysteine'. 'MAT2A' should have been 'MTR'. The error has been corrected in the PDF and HTML versions of this article.

Barriers to Accessing Testing and Treatment for Chronic Hepatitis B in Afghan, Rohingyan, and South Sudanese Populations in Australia.

The burden of chronic Hepatitis B (CHB) infection and associated complications such as hepatocellular carcinoma is growing significantly in Australia due to increased migration from countries with a high prevalence of CHB. Significant barriers to screening and engagement with healthcare persist due to stigma and perceptions associated with CHB within these communities. Our study was a pilot intervention aimed at engaging Afghan, Rohingyan, and Sudanese populations into CHB care through an initial needs assessment. Twenty six patients from Afghan, Rohingyan, and Sudanese communities, identified in the Monash Health CHB database, participated in a combination of survey questionnaires and semi-structured interviews. Language and cultural barriers, lack of HBV knowledge, housing and family reunification priorities associated with new settlement, as well as previous experiences of healthcare engagement were all identified as obstacles to accessing CHB care. Healthcare and health promotion workers should be sensitive to the additional health barriers associated with seeking asylum, as these barriers can take priority over the often asymptomatic and chronic nature of CHB. Communities with high prevalence of CHB require culturally relevant education tools delivered at a community level in order to improve their knowledge.

Engaging new refugee in Australian communities at risk for chronic hepatitis B infection into care: A peer-educator intervention.

Chronic Hepatitis B (CHB) infection and subsequent liver complications are rising in prevalence in Australia due to increased migration from endemic regions. Nearly 50% of all those living with CHB in Australia are undiagnosed, leading to missed opportunities for liver cancer and cirrhosis prevention. Health literacy around CHB among refugee communities such as Afghan, Rohingyan, and Sudanese populations (all with a high prevalence of CHB) is low, partly due to a paucity of targeted health promotion programmes; despite the release of the Victorian Hepatitis B Strategy (2016-2020). We developed a peer-education intervention in these three communities to deliver CHB focused radio programmes and community forums in their own language, following a needs assessment consisting of semistructured interviews and surveys. Effectiveness of this intervention was measured through paired comparison of disease-knowledge assessment pre and post forum. Community forums were held between 2015 and 2016, with 25 attendees at the Rohingyan forum (68% male), 10 attendees at the Afghan forum (90% male) and 0 attendees at the Sudanese forum. Participants demonstrated a significant improvement in CHB knowledge between pre- and post-forum surveys (p-value < 0.05). A peer-educator approach was a cost-effective health promotion strategy in building CHB knowledge and dispelling misconceptions within the Afghan and Rohingya communities. There were significant barriers in the engagement of the South Sudanese community, which will inform future strategies for health promotion.

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma.

Self-renewing tumor-initiating cells (TICs) are thought to be responsible for tumor recurrence and chemo-resistance. Glycine decarboxylase, encoded by the GLDC gene, is reported to be overexpressed in TIC-enriched primary non-small-cell lung carcinoma (NSCLC). GLDC is a component of the mitochondrial glycine cleavage system, and its high expression is required for growth and tumorigenic capacity. Currently, there are no therapeutic agents against GLDC. As a therapeutic strategy, we have designed and tested splicing-modulating steric hindrance antisense oligonucleotides (shAONs) that efficiently induce exon skipping (half maximal inhibitory concentration [IC50] at 3.5-7 nM), disrupt the open reading frame (ORF) of GLDC transcript (predisposing it for nonsense-mediated decay), halt cell proliferation, and prevent colony formation in both A549 cells and TIC-enriched NSCLC tumor sphere cells (TS32). One candidate shAON causes 60% inhibition of tumor growth in mice transplanted with TS32. Thus, our shAONs candidates can effectively inhibit the expression of NSCLC-associated metabolic enzyme GLDC and may have promising therapeutic implications.