Aim
Hong Kong's existing mental health services are inadequate in addressing young people's needs. The LevelMind@JC project established an early intervention platform of community‐based ...youth‐specific mental health centres involving youth workers, cross‐disciplinary professionals, and young people. The project intends to (1) pilot a community platform that incorporates a youth‐friendly early screening tool with preventative intervention capabilities, (2) set up a state‐of‐the‐art training system for youth mental health workers, (3) establish a community clinical support team and (4) develop a timely evaluation system to monitor the service and evaluate its outcome and cost‐effectiveness against generic youth services.
Methods
Six hundred LevelMind@JC service users will be assessed alongside 600 young people visiting generic youth centres and 100 young people in the community. Participants will be matched according to age, gender, years of education, socioeconomic status, and level of distress. Assessments, administered at baseline and at 3, 6 and 12 months, will cover demographic characteristics, psychological distress, quality of life, depressive and anxiety symptoms, functioning, physical health and lifestyle, personality and social measures, cognitive measures and health economics. Mixed‐model ANOVAs will be used to indicate interactions between services and between time points.
Conclusion
Built upon a community‐based support model, LevelMind@JC aims to promote positive mental health in young people through the collaboration of cross‐disciplinary mental health professionals. If efficacy and cost‐effectiveness are established, the project could be scaled up, implicating a wider reach of care. We anticipate its success to be critical in combatting mental health issues stemming from both personal and population‐level stressors.
Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but ...K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3-/- mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3-/- bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3-/- epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3+/- mice ( approximately 18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Runx3+/- mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma.
We report two microlensing events, KMT-2017-BLG-1038 and KMT-2017-BLG-1146, that are caused by planetary systems. These events were discovered by Korea Microlensing Telescope Network survey ...observations from the 2017 bulge season. The discovered systems consist of a planet and host star with mass ratios of and , respectively. Based on a Bayesian analysis assuming a Galactic model without stellar remnant hosts, we find that the planet KMT-2017-BLG-1038Lb is a super-Jupiter-mass planet ( ) orbiting a mid-M dwarf host ( ) that is located at kpc toward the Galactic bulge. The other planet, KMT-2017-BLG-1146Lb, is a sub-Jupiter-mass planet ( ) orbiting a mid-M dwarf host ( ) at a distance of kpc toward the Galactic bulge. Both are potentially gaseous planets that are beyond their hosts' snow lines. These typical microlensing planets will be routinely discovered by second-generation microlensing surveys, rapidly increasing the number of detections.
MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from ...the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.
Background Previous reports have indicated that statins could prevent bone loss in ovariectomized (OVX) rats and increase the expressions of osteogenic genes in cultured osteoblasts. In this study, ...we hypothesized that simvastatin might increase osteoblast number and protein expressions of osteogenic markers localized in bones in concomitance with the prevention of bone loss in OVX rats.
Materials and methods Fifty‐four 3‐month‐old OVX and sham‐operated (SHAM) female Sprague–Dawley rats were used. Simvastatin (10–20 mg kg−1 day−1) was administrated orally for 6 weeks. Trabecular volume, osteoblast number and osteogenic proteins including BMP2, collagen type I and osteocalcin on bone sections obtained from lumbar vertebral body, distal femur and proximal tibia were measured.
Results The results showed that SHAM rats had significantly less trabecular bone volume and osteoblast number than that of OVX rats 6 weeks after operation. Oral simvastatin treatment (10–20 mg kg−1 day−1) increased bone volume and osteoblast number in the distal femurs, proximal tibiae and vertebrae of OVX rats. Furthermore, the osteoblastic cells with immuno‐stained BMP2, collagen type I and osteocalcin in vertebral bones were significantly increased by simvastatin treatment (20 mg kg−1 day−1) in OVX rats.
Conclusions This study demonstrates that simvastatin enhances the production of osteogenic proteins in bone and this effect may contribute to the prevention of bone loss in OVX rats.
Aims To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and ...methods Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of ≥100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results After a median follow-up of 26.7 ± 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and ≥100 ng/ml, respectively ( p = 0.003). In the 58 patients with a baseline AFP of ≥100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively ( p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 ( p = 0.009), non-optimal AFP response ( p = 0.023), and creatinine >1.5 mg/dl ( p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively ( p < 0.001). Multivariate analysis demonstrated platelet count ≤105 /mm3 ( p = 0.048), tumour size >2 cm ( p = 0.027), and non-optimal AFP response ( p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.
Aim
To evaluate the effect of 2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐D‐glucoside (THSG) on cell proliferation and examine the mechanisms of THSG‐enhanced proliferative potential in human dental pulp ...stem cells (hDPSC).
Methodology
After treatment with THSG, hDPSC were collected. Cell viability was determined by MTS assay, while messenger RNA (mRNA) expressions of proliferation and stem cell markers were analyzed using real‐time PCR. Flow cytometry was also conducted to analysis protein expression of stem cell markers. A colony‐forming unit assay of hDPSC was carried out. Cellular telomerase activity was also identified using real‐time PCR. In addition, proliferation‐related proteins involved in the effects of THSG on hDPSC were analyzed by Western blotting. Data were analyzed using one‐way analysis of variance and two‐tailed Student's t‐test.
Results
Cell viability, colony‐forming rates and telomerase activities of hDPSCs were enhanced after THSG treatment. mRNA expressions of proliferation markers (including expressions of NAD+‐dependent histone deacetylase sirtuin 1 (SIRT1), proliferating cell nuclear antigen (PCNA), cyclin D1 and ribonucleotide reductase subunit M2 (RRM2)) increased significantly after THSG treatment (P < 0.05). Treatment with THSG for 3 h significantly augmented SIRT1 protein expression (P < 0.05). Furthermore, activities of proliferation‐related proteins (including AMP‐activated protein kinase (AMPK) and extracellular signal‐regulated kinase (ERK) had also significantly increased at 3 h (P < 0.05). After THSG treatment, increased gene and protein expressions of pluripotent‐like stem cell markers (including NANOG, OCT4, and SOX2) were observed.
Conclusions
2,3,5,4′‐Tetrahydroxystilbene‐2‐O‐β‐glucoside treatment enhanced the renewal ability and proliferative potential of hDPSCs via the AMPK/ERK/SIRT1 axis, which may provide a novel autogenic cell‐based therapeutic strategy in regenerative dentistry.
The Korea Invisible Mass Search (KIMS) collaboration has developed low-background NaI(Tl) crystals that are suitable for the direct detection of WIMP dark matter. Building on experience accumulated ...during the KIMS-CsI programs, the KIMS-NaI experiment will consist of a 200 kg NaI(Tl) crystal array surrounded by layers of shielding structures and will be operated at the Yangyang underground laboratory. The goal is to provide an unambiguous test of the DAMA/LIBRA annual modulation signature. Measurements of six prototype crystals show progress in the reduction of internal contamination from radioisotopes. Based on our understanding of these measurements, we expect to achieve a background level in the final detector configuration that is less than 1 count/day/keV/kg for recoil energies around 2 keV. The annual modulation sensitivity for the KIMS-NaI experiment shows that an unambiguous 7
σ
test of the DAMA/LIBRA signature would be possible with a 600 kg year exposure with this system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
To investigate the effects of LY2405319, an analogue of fibroblast growth factor 21 (FGF21), on glucose homeostasis in streptozotocin (STZ)‐induced insulin‐deficient mice (STZ mice).
Methods
...Nine‐week‐old male C57BL/6J mice were administered a single intraperitoneal injection of STZ (150 mg/kg). One week later, after confirmation of hyperglycaemia, saline or LY2405319 (5 mg/kg) was injected subcutaneously daily for 4 weeks. Changes in glucose homeostasis, energy metabolism and brown adipose tissue (BAT) function were assessed.
Results
The STZ mice had elevated blood glucose and reduced plasma FGF21 levels, impaired glucose uptake in the BAT, and BAT mitochondria with absent or swollen cristae and fewer lipid vacuoles. LY2405319 significantly reduced blood glucose levels and this was associated with increased BAT glucose uptake and changes in gene expression and morphology, indicating improved mitochondrial lipid metabolism in the BAT. Importantly, the ability of LY2405319 to lower blood glucose in STZ mice was compromised after removing interscapular BAT.
Conclusions
Our results show that LY2405319 reduces blood glucose levels in insulin‐deficient diabetes by improving BAT metabolism. Additional studies investigating the therapeutic potential of FGF21 for the treatment of type 1 diabetes are warranted.
Background and purpose
The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after ...acute ischaemic stroke (AIS) in patients with non‐valvular atrial fibrillation (NVAF).
Methods
Patients were categorized on the basis of their BMI into underweight (BMI <18.5, n = 111), normal (18.5 ≤ BMI <25, n = 1036) and overweight to obese (BMI ≥25, n = 472) groups. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score and functional outcomes were assessed using the modified Rankin Scale score at discharge. The differences in stroke severity and functional outcomes were compared between groups using robust log‐linear regression with a Poisson distribution and binary logistic regression analysis.
Results
A total of 1619 AIS patients with NVAF from six hospitals were included. Compared with the NIHSS scores median 5, interquartile range (IQR) 2–14 of normal‐weight patients, the NIHSS scores (median 9, IQR 4–19) of underweight patients were more likely to be higher, whereas those of overweight to obese patients were lower (median 4, IQR 1–12) (P < 0.001). In terms of functional outcomes after stroke, underweight patients had a higher risk of poor functional outcomes (odds ratio 1.78, 95% confidence interval 1.09–2.56, P = 0.01) but overweight to obese patients had no significant difference in functional outcomes compared with normal‐weight patients.
Conclusion
An inverse association was found between BMI and stroke severity in AIS patients with NVAF. This suggests the presence of an obesity paradox for short‐term outcomes in patients with NVAF.
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