A cost-effective digital forensic investigation model

Computers operate at discrete points in time and hence digital traces are discrete events in temporal logic that re°ect the occurrence of computer processes. From the perspective of a digital investigation, it is the duty of digital investigators or forensic examiners to retrieve digital traces so as to prove or to refute the alleged computer acts. Given the resource constraints of most organizations and the limited time-frame available for the examination, it is not always feasible or indeed necessary for forensic examiners to retrieve all the related digital traces and to conduct a thorough digital forensic analysis. It is therefore the aim of this paper to propose a model that can o®er swift and practical digital examination in a cost-effective manner.postprin

Concordance between side-stream end-tidal carbon dioxide and arterial carbon dioxide partial pressure in respiratory service setting

OBJECTIVE: To explore the correlation and concordance between end-tidal carbon dioxide and arterial carbon dioxide partial pressure, and confirm the experience of the general consensus among service environments. DESIGN: A prospective cross-sectional analysis. SETTING: Two respiratory service units in Hong Kong. PARTICIPANTS: Two hundred respiratory patients were recruited, in whom 219 sets of observations were recorded. Patients deemed to require arterial blood gas determination also had their end-tidal carbon dioxide partial pressure measured at that time, using two LifeSense LS1-9R Capnometers. MAIN OUTCOME MEASURES: The agreement of end-tidal carbon dioxide partial pressure and arterial carbon dioxide partial pressure was studied by correlation coefficients, mean and standard deviation of their difference, and the Bland-Altman plot. RESULTS: Overall, the correlation was low and insignificant (r=0.1185, P=0.0801). The mean of the difference was 7.2 torr (95% confidence interval, 5.5-8.9) and significant (P<0.001). The limits of agreement by Bland-Altman analysis were -18.1 to 32.5 torr, which were too large to be acceptable. In the sub-group on room air, the mean difference was reduced to 2.26 torr, the correlation between end-tidal carbon dioxide partial pressure and arterial carbon dioxide partial pressure was 0.2194 (P=0.0068), though statistically significant, the extent of correlation was still low. CONCLUSION: End-tidal carbon dioxide partial pressure did not show significant correlation or concordance with arterial carbon dioxide partial pressure, especially when supplemental oxygen was used. End-tidal carbon dioxide partial pressure currently cannot replace arterial blood gas measurement as a tool for monitoring arterial carbon dioxide partial pressure. Possible reasons for the discrepancy with previous studies include small sample size in previous studies, lack of research facilities in service settings, and publication bias against negative studies.published_or_final_versio

Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133

This journal suppl. entitled: Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CATumor relapse after therapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive initial treatment. We have previously identified a CSC population derived from HCC that is characterized by the expression of the transmembrane glycoprotein, CD133. Despite our growing knowledge of the importance of a functional CD133+ liver CSC subset in driving HCC, the regulatory mechanism of CD133 is not known. Epigenetic changes are believed to be essential in the control of cancer and stem cells. We report here the dynamic epigenetic regulation of the functional liver CSC marker CD133 by promoter methylation and miR-142-3p regulation. Unlike in other tumor types, we found DNA methylation to only play a minor role in the control of CD133 expression in HCC. More importantly, our results revealed that miR-142-3p plays an integral part in the direct targeting of ...postprin

Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity

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Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133

Tumor relapse after therapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive treatment. We have previously identified a CSC population derived from HCC that is characterized by CD133. Despite our growing knowledge of the importance of this subset of cells in driving HCC, the regulatory mechanism of CD133 is not known. Epigenetic changes are believed to be essential in the control of cancer and stem cells. Here, we report the epigenetic regulation of CD133 by miR-142-3p. The interaction between CD133 and miR-142-3p was identified by in silico prediction and substantiated by luciferase reporter analysis. Expression of CD133 was found to be inversely correlated with miR-142-3p in HCC clinical samples as well as in cell lines. Importantly, lower miR-142-3p expression in HCC was significantly associated with worst survival. Functional studies with miR-142-3p stably transduced in HCC cells demonstrated a diminished ability to self-renew, initiate tumor growth, invade, migrate, induce angiogenesis and resist chemotherapy. Rescue experiments whereby CD133 and miR-142-3p is simultaneously overexpressed compensated the deregulated ability of the cells to confer these features. Thus, miR-142-3p directly targets CD133 to regulate its ability to confer cancer and stem cell-like features in HCC.published_or_final_versio

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM. The role of APN in AD has not been elucidated. In this study, we aim to examine if adiponectin deficiency would lead to cerebral insulin resistance, cognitive decline and Alzheimer's-like pathology in mice. METHODS: To study the role of adiponectin in cognitive functions, we employed adiponectin-knockout (APN-KO) mice and demonstrated chronic APN deficiency in their CNS. Behavioral tests were performed to study the cognitions of male APN-KO mice. Brains and tissue lysates were collected to study the pathophysiological and molecular changes in the brain of APN-KO mice. SH-SY5Y neuroblastoma cell line was used to study the molecular mechanism upon APN and insulin treatment. RESULTS: Aged APN-deficient mice displayed spatial memory and learning impairments, fear-conditioned memory deficit as well as anxiety. These mice also developed AD pathologies including increased cerebral Aβ42 level, Aβ deposition, hyperphosphorylated Tau proteins, microgliosis and astrogliosis with increased cerebral IL-1β and TNFα levels that associated with increased neuronal apoptosis and reduced synaptic proteins levels, suggesting APN deficiency may lead to neuronal and synaptic loss in the brain. AD pathologies-associated APN-KO mice displayed attenuated AMPK phosphorylation and impaired insulin signaling including decreased Akt induction and increased GSK3β activation in the hippocampus and frontal cortex. Aged APN-KO mice developed hippocampal insulin resistance with reduced pAkt induction upon intracerebral insulin injection. Consistently, APN treatment in SH-SY5Y cells with insulin resistance and overexpressing Aβ induce higher pAkt levels through AdipoR1 upon insulin treatment whereas the induction was blocked by compound C, indicating APN can enhance neuronal insulin sensitivity through AMPK activation. CONCLUSION: Our results indicated that chronic APN deficiency inactivated AMPK causing insulin desensitization and elicited AD-like pathogenesis in aged mice which also developed significant cognitive impairments and psychiatric symptoms.published_or_final_versio

The use of functional performance tests and simple anthropomorphic measures to screen for comorbidity in primary care

This is an accepted manuscript of an article published by Wiley in International Journal of Older People Nursing on 07/07/2020, available online: https://onlinelibrary.wiley.com/doi/abs/10.1111/opn.12333 The accepted version of the publication may differ from the final published version.Background Many older adults are unaware that they have comorbid diseases. Increased adiposity and reduced muscle mass are identified as key contributors to many chronic diseases in older adults. Understanding the role they play in the development of comorbidities in older populations is of prime importance. Objectives To identify the optimal body shape associated with three common functional performance tests and to determine which anthropometric and functional performance test best explains comorbidity in a sample of older adults in Hong Kong. Methods A total of 432 older adults participated in this cross‐sectional study. Researchers assessed their body height, body mass index, waist circumference, waist‐to‐hip ratio, handgrip strength (kg), functional reach (cm) and results in the timed‐up‐and‐go (TUG) test (seconds). The Charlson Comorbidity Index was used to assess comorbidity. Results Allometric modelling indicated that the optimal body shape associated with all functional performance tests would have required the participants to be taller and leaner. The only variable that predicted comorbidity was the TUG test. The inclusion of body size/shape variables did not improve the prediction model. Conclusion Performance in the TUG test alone was found to be capable of identifying participants at risk of developing comorbidities. The TUG test has potential as a screening tool for the early detection of chronic diseases in older adults. Implications for Practice Many older people are unaware of their own co‐existing illnesses when they consult physicians for a medical condition. TUG can be a quick and useful screening measure to alert nurses in primary care to the need to proceed with more detailed assessments. It is an especially useful screening measure in settings with high patient volumes and fiscal constraints. TUG is low cost and easy to learn and is therefore also relevant for nurses and health workers in low‐resource, low‐income countries.School of Nursing, The Hong Kong Polytechnic UniversityPublished onlin

TRPA1 Mediates Mechanical Currents in the Plasma Membrane of Mouse Sensory Neurons

Mechanosensitive channels serve as essential sensors for cells to interact with their environment. The identity of mechanosensitive channels that underlie somatosensory touch transduction is still a mystery. One promising mechanotransduction candidate is the Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel. To determine the role of TRPA1 in the generation of mechanically-sensitive currents, we used dorsal root ganglion (DRG) neuron cultures from adult mice and applied rapid focal mechanical stimulation (indentation) to the soma membrane. Small neurons (diameter <27 µm) were studied because TRPA1 is functionally present in these neurons which largely give rise to C-fiber afferents in vivo. Small neurons were classified by isolectin B4 binding

Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine

The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens. This study compared the neutralization susceptibility of serum specimens collected from 49 individuals of <18 years old, including 34 adolescent BNT162b2 (Pfizer-BioNTech) vaccine recipients, and 15 recovered COVID-19 patients aged between 2 and 17. We demonstrated that only 38.2% of BNT162b2 vaccine recipients and 26.7% of recovered COVID-19 patients had their serum neutralization titre at or above the detection threshold in our live virus microneutralization assay. Furthermore, the neutralizing antibody titer against the Omicron variant was substantially lower than those against the ancestral virus or the Beta variant. Our results suggest that vaccine recipients and COVID-19 patients in the pediatric age group will likely be more susceptible to vaccine breakthrough infections or reinfections due to the Omicron variant than previous variants

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis