The identification of mitochondrial DNA variants in glioblastoma multiforme

Background: Mitochondrial DNA (mtDNA) encodes key proteins of the electron transfer chain (ETC), which produces ATP through oxidative phosphorylation (OXPHOS) and is essential for cells to perform specialised functions. Tumor-initiating cells use aerobic glycolysis, a combination of glycolysis and low levels of OXPHOS, to promote rapid cell proliferation and tumor growth. Glioblastoma multiforme (GBM) is an aggressively malignant brain tumor and mitochondria have been proposed to play a vital role in GBM tumorigenesis. Results: Using next generation sequencing and high resolution melt analysis, we identified a large number of mtDNA variants within coding and non-coding regions of GBM cell lines and predicted their disease-causing potential through in silico modeling. The frequency of variants was greatest in the D-loop and origin of light strand replication in non-coding regions. ND6 was the most susceptible coding gene to mutation whilst ND4 had the highest frequency of mutation. Both genes encode subunits of complex I of the ETC. These variants were not detected in unaffected brain samples and many have not been previously reported. Depletion of HSR-GBM1 cells to varying degrees of their mtDNA followed by transplantation into immunedeficient mice resulted in the repopulation of the same variants during tumorigenesis. Likewise, de novo variants identified in other GBM cell lines were also incorporated. Nevertheless, ND4 and ND6 were still the most affected genes. We confirmed the presence of these variants in high grade gliomas. Conclusions: These novel variants contribute to GBM by rendering the ETC. partially dysfunctional. This restricts metabolism to anaerobic glycolysis and promotes cell proliferation

The lift industry in Hong Kong : regulatory action and capacity building

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Parenting approaches, family functionality, and internet addiction among Hong Kong adolescents

© 2016 Wu et al. Background: Internet addiction (IA) among adolescents has become a global health problem, and public awareness of it is increasing. Many IA risk factors relate to parents and the family environment. This study examined the relationship between IA and parenting approaches and family functionality. Methods: A cross-sectional study was conducted with 2021 secondary students to identify the prevalence of IA and to explore the association between adolescent IA and familial variables, including parents' marital status, family income, family conflict, family functionality, and parenting approaches. Results: The results revealed that 25.3 % of the adolescent respondents exhibited IA, and logistic regression positively predicted the IA of adolescents from divorced families, low-income families, families in which family conflict existed, and severely dysfunctional families. Interestingly, adolescents with restricted Internet use were almost 1.9 times more likely to have IA than those whose use was not restricted. Conclusions: Internet addiction is common among Chinese adolescents in Hong Kong, and family-based prevention strategies should be aligned with the risk factors of IA.Link_to_subscribed_fulltex

A report on an exploratory study on visual conditions of older people living in public housing

HOPE worldwide (HWW) has been a chartered charity organization in Hong Kong since 1993, with its focus on organizing service programmes in China and Hong Kong. Volunteers for Seniors Day (formerly Hope for Seniors Day) is one of the many programmes initiated by HWW to meet the urgent needs of the growing ageing population in Hong Kong. Starting in 1996, volunteers from corporations and social organizations have been recruited for Volunteers for Seniors Days on an annual basis. Since 2000, the programme has been jointly organized with the Housing Authority to provide cleaning and painting services to single elderly tenants living in public housing estates. It also helps to build relationships between the volunteers and the elderly people in the community. Over the past nine years, the programme has served over 5,300 single elderly people and mobilized more than 20,000 volunteers to participate. In the survey conducted by HWW during Volunteers for Seniors Day 2004, we found that there were up to 40.1% and 49.6% of the single elderly living in public housing estates suffering from various kinds of eye diseases and poor eyesight respectively. The prevalence of eye diseases and poor eyesight would result in a high percentage of falls and thereby affect their functional activities of daily living (ADL). In fact, most of the eye diseases are curable with early detection and treatment, and elderly people with poor eyesight may need minor home adaptation e.g. handrails or night lights to prevent home accidents. According to a study by the Department of Orthopaedics & Traumatology of Chinese University, exercise is important to the elderly and can strengthen their low-limb and upper-limb muscles, which in turn prevents falls at home or on the street. Due to the above findings, HWW cooperated with Housing Authority to initiate a pilot programme to help identify the eye diseases as well as provide public health education to the elderly in 30 public estates in the second half of 2004. Health care professionals provided training to 150 volunteers on eye care knowledge and simple eye screening tests that could be carried out in road shows in shopping arcades of public housing estates. In addition, experienced ophthalmologists or optometrists were present to answer elderly participants’ inquiries on eye health and delivered health information during the kick-off ceremony and road shows in the shopping arcades. The programme had the following objectives: To enhance the awareness of eye health and eye diseases of the elderly through 30 public eye screenings at public housing arcades; To carry out a survey on the visual conditions of elderly living in public housing; and To foster partnership between government, NGO and business sectors in promoting the health of the elderly in the community

An Algorithm for Modelling Escalator Fixed Loss Energy for PHM and sustainable energy usage

Prognostic Health Management (PHM) is designed to assess and monitor the health status of systems, anticipate the onset of potential failure, and prevent unplanned downtime. In recent decades, collecting massive amounts of real-time sensor data enabled condition monitoring (CM) and consequently, detection of abnormalities to support maintenance decision-making. Additionally, the utilization of PHM techniques can support energy sustainability efforts by optimizing energy usage and identifying opportunities for energy-saving measures. Escalators are efficient machines for transporting people and goods, and measuring energy consumption in time can facilitate PHM of escalators. Fixed loss energy, or no-load energy, of escalators denotes the energy consumption by an unloaded escalator. Fixed loss energy varies over time indicating varying operating conditions. In this paper, we propose to use escalators' fixed loss energy for PHM. We propose an approach to compute daily fixed loss energy based on energy consumption sensor data. The proposed approach is validated using a set of experimental data. The advantages and disadvantages of each approach are also presented, and recommendations are given. Finally, to illustrate PHM, we set up an EWMA chart for monitoring the fixed loss over time and demonstrate the potential in reducing energy costs associated with escalator operation

Remaining Useful Life Modelling with an Escalator Health Condition Analytic System

The refurbishment of an escalator is usually linked with its design life as recommended by the manufacturer. However, the actual useful life of an escalator should be determined by its operating condition which is affected by the runtime, workload, maintenance quality, vibration, etc., rather than age only. The objective of this project is to develop a comprehensive health condition analytic system for escalators to support refurbishment decisions. The analytic system consists of four parts: 1) online data gathering and processing; 2) a dashboard for condition monitoring; 3) a health index model; and 4) remaining useful life prediction. The results can be used for a) predicting the remaining useful life of the escalators, in order to support asset replacement planning and b) monitoring the real-time condition of escalators; including alerts when vibration exceeds the threshold and signal diagnosis, giving an indication of possible root cause (components) of the alert signal.Comment: 14 pages, 12 figures, 7 table

Satin associated lower cancer risk and related mortaity in patients with heart failure

Aims Patients with heart failure (HF) have an increased risk of incident cancer. Data relating to the association of statin use with cancer risk and cancer-related mortality among patients with HF are sparse. Methods and results Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (n = 87 102) from 2003 to 2015. Inverse probability of treatment weighting was used to balance baseline covariates between statin nonusers (n = 50 926) with statin users (n = 36 176). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of cancer and cancer-related mortality associated with statin use. Of all eligible subjects, the mean age was 76.5 +/- 12.8 years, and 47.8% was male. Over a median follow-up of 4.1 years (interquartile range: 1.6-6.8), 11 052 (12.7%) were diagnosed with cancer. Statin use (vs. none) was associated with a 16% lower risk of cancer incidence [multivariable adjusted subdistribution hazard ratio (SHR) = 0.84; 95% confidence interval (CI), 0.80-0.89]. This inverse association with risk of cancer was duration dependent; as compared with short-term statin use (3 months to = 6 years of use. Ten-year cancer-related mortality was 3.8% among statin users and 5.2% among nonusers (absolute risk difference, -1.4 percentage points [95% CI, -1.6% to -1.2%]; adjusted SHR= 0.74; 95% CI, 0.67-0.81). Conclusion Our study suggests that statin use is associated with a significantly lower risk of incident cancer and cancer-related mortality in HF, an association that appears to be duration dependent. [GRAPHICS]

Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Pneumonia and Septic Shock

CONTEXT: Individuals with type 2 diabetes mellitus (DM) have an increased risk of pneumonia and septic shock. Traditional glucose-lowering drugs have recently been found to be associated with a higher risk of infections. It remains unclear whether sodium-glucose cotransporter 2 inhibitors (SGLT2is), which have pleiotropic/anti-inflammatory effects, may reduce the risk of pneumonia and septic shock in DM. METHODS: MEDLINE, Embase, and ClinicalTrials.gov were searched from inception up to May 19, 2022, for randomized, placebo-controlled trials of SGLT2i that included patients with DM and reported outcomes of interest (pneumonia and/or septic shock). Study selection, data extraction, and quality assessment (using the Cochrane Risk of Bias Assessment Tool) were conducted by independent authors. A fixed-effects model was used to pool the relative risk (RRs) and 95% CI across trials. RESULTS: Out of 4568 citations, 26 trials with a total of 59 264 patients (1.9% developed pneumonia and 0.2% developed septic shock) were included. Compared with placebo, SGLT2is significantly reduced the risk of pneumonia (pooled RR 0.87, 95% CI 0.78-0.98) and septic shock (pooled RR 0.65, 95% CI 0.44-0.95). There was no significant heterogeneity of effect size among trials. Subgroup analyses according to the type of SGLT2i used, baseline comorbidities, glycemic control, duration of DM, and trial follow-up showed consistent results without evidence of significant treatment-by-subgroup heterogeneity (all P(heterogeneity) > .10). CONCLUSION: Among DM patients, SGLT2is reduced the risk of pneumonia and septic shock compared with placebo. Our findings should be viewed as hypothesis generating, with concepts requiring validation in future studies

Concomitant Hepatorenal Dysfunction and Malnutrition in Valvular Heart Surgery:Long-Term Prognostic Implications for Death and Heart Failure

BACKGROUND: Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. METHODS AND RESULTS: In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups in-curred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40–7.17] and HR, 9.30 [95% CI, 4.09– 21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14– 9.52] and subdistribution HR, 9.29 [95% CI, 3.09– 27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25– 3.55] and subdistribution HR, 3.55 [95% CI, 2.04– 6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25– 3.55] and HR, 3.55 [95% CI, 2.04– 6.16]). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, P<0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, P=0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without.  CONCLUSIONS: Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery

Embryonic Lethality in Mice Lacking the Nuclear Factor of Activated T Cells 5 Protein Due to Impaired Cardiac Development and Function

Nuclear factor of activated T cells 5 protein (NFAT5) is thought to be important for cellular adaptation to osmotic stress by regulating the transcription of genes responsible for the synthesis or transport of organic osmolytes. It is also thought to play a role in immune function, myogenesis and cancer invasion. To better understand the function of NFAT5, we developed NFAT5 gene knockout mice. Homozygous NFAT5 null (NFAT5−/−) mouse embryos failed to develop normally and died after 14.5 days of embryonic development (E14.5). The embryos showed peripheral edema, and abnormal heart development as indicated by thinner ventricular wall and reduced cell density at the compact and trabecular areas of myocardium. This is associated with reduced level of proliferating cell nuclear antigen and increased caspase-3 in these tissues. Cardiomyocytes from E14.5 NFAT5−/− embryos showed a significant reduction of beating rate and abnormal Ca2+ signaling profile as a consequence of reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR) expressions. Expression of NFAT5 target genes, such as HSP 70 and SMIT were reduced in NFAT5−/− cardiomyocytes. Our findings demonstrated an essential role of NFAT5 in cardiac development and Ca2+ signaling. Cardiac failure is most likely responsible for the peripheral edema and death of NFAT5−/− embryos at E14.5 days