Secure telemedicine system for home health care

This thesis describes a low-cost telemedicine system that provides home based patient care by linking patients with skilled nurses at the home care agency. The system employs compact vital signs sensors and a two-way real-time video conference over telephone lines. It stores the patient\u27s medical records, still images and enforces clinical pathways during the televisits. Physicians, paramedics, and nurses can then have access to these records from anywhere, securely, through a Web browser.;This document discusses the underlying technologies, the features implemented in the prototype, and the methodologies used in developing the software. The prototype uses the Enterprise Java Bean [EJB] architecture and emphasizes security and scalability. Preliminary experience of its use is presented. A performance analysis of the system\u27s behavior if it were scaled up has also been done

Middle third clavicle fractures are the most common fractures in head injuries: a biomechanical and epidemiological study in 1000 patients

A consecutive series of 1000 cases of head injury, out of which 385 patients presented with fractures. In the 385 patients with fractures, 179 patients presented with clavicle fractures, among that, 127 are middle third fractures. Out of the 189 patients who had clavicle fractures, 90% of them had direct blow to shoulders and 10% had fallen on the outstretched hand. This variation with the mechanism of injury was further investigated by biomechanical analysis of the forces involved in clavicular fractures.

The regulation of circadian entrainment in mice by the adenosine the A2A/A1 receptor antagonist CT1500

Circadian entrainment in mice relies primarily on photic cues that trigger the transcription of the core clock genes Period1/2 in the suprachiasmatic nucleus (SCN), thus aligning the phase of the clock with the dawn/dusk cycle. It has been shown previously that this pathway is directly regulated by adenosine signalling and that adenosine A2A/A1 receptor antagonists can both enhance photic entrainment and phase shift circadian rhythms of wheel-running behaviour in mice. In this study, we tested the ability of CT1500, a clinically safe adenosine A2A/A1 receptor antagonist to effect circadian entrainment. We show that CT1500 lengthens circadian period in SCN ex vivo preparations. Furthermore, we show in vivo that a single dose of CT1500 enhances re-entrainment to a shifted light dark cycle in a dose-dependent manner in mice and also phase shifts the circadian clock under constant dark with a clear time-of-day related pattern. The phase response curve shows CT1500 causes phase advances during the day and phase delays at dusk. Finally, we show that daily timed administration of CT1500 can entrain the circadian clock to a 24 h rhythm in free-running mice. Collectively, these data support the use of CT1500 in the treatment of disorders of circadian entrainment

Inhibition of salt inducible kinases reduces rhythmic HIV-1 replication and reactivation from latency

Human immunodeficiency virus type 1 (HIV-1) causes a major burden on global health, and eradication of latent virus infection is one of the biggest challenges in the field. The circadian clock is an endogenous timing system that oscillates with a ~24 h period regulating multiple physiological processes and cellular functions, and we recently reported that the cell intrinsic clock regulates rhythmic HIV-1 replication. Salt inducible kinases (SIK) contribute to circadian regulatory networks, however, there is limited evidence for SIKs regulating HIV-1 infection. Here, we show that pharmacological inhibition of SIKs perturbed the cellular clock and reduced rhythmic HIV-1 replication in circadian synchronised cells. Further, SIK inhibitors or genetic silencing of Sik expression inhibited viral replication in primary cells and in a latency model, respectively. Overall, this study demonstrates a role for salt inducible kinases in regulating HIV-1 replication and latency reactivation, which can provide innovative routes to better understand and target latent HIV-1 infection

TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses

The suprachiasmatic nucleus (SCN) is a complex structure dependent upon multiple mechanisms to ensure rhythmic electrical activity that varies between day and night, to determine circadian adaptation and behaviours. SCN neurons are exposed to glutamate from multiple sources including from the retino-hypothalamic tract and from astrocytes. However, the mechanism preventing inappropriate post-synaptic glutamatergic effects is unexplored and unknown. Unexpectedly we discovered that TRESK, a calcium regulated two-pore potassium channel, plays a crucial role in this system. We propose that glutamate activates TRESK through NMDA and AMPA mediated calcium influx and calcineurin activation to then oppose further membrane depolarisation and rising intracellular calcium. Hence, in the absence of TRESK, glutamatergic activity is unregulated leading to membrane depolarisation, increased nocturnal SCN firing, inverted basal calcium levels and impaired sensitivity in light induced phase delays. Our data reveals TRESK plays an essential part in SCN regulatory mechanisms and light induced adaptive behaviours

Molecular components of the circadian clock regulate HIV-1 replication

Human immunodeficiency virus 1 (HIV-1) causes major health burdens worldwide and still lacks curative therapies and vaccines. Circadian rhythms are endogenous daily oscillations that coordinate an organism’s response to its environment and invading pathogens. Peripheral viral loads of HIV-1 infected patients show diurnal variation; however, the underlying mechanisms remain unknown. Here, we demonstrate a role for the cell-intrinsic clock to regulate rhythmic HIV-1 replication in circadian-synchronized systems. Silencing the circadian activator Bmal1 abolishes this phenotype, and we observe BMAL1 binding to the HIV-1 promoter. Importantly, we show differential binding of the nuclear receptors REV-ERB and ROR to the HIV-long terminal repeat at different circadian times, demonstrating a dynamic interplay in time-of-day regulation of HIV-1 transcription. Bioinformatic analysis shows circadian regulation of host factors that control HIV-1 replication, providing an additional mechanism for rhythmic viral replication. This study increases our understanding of the circadian regulation of HIV-1, which can ultimately inform new therapies

Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing

Rationale: Lithium remains the most effective treatment for bipolar disorder and also has important effects to lower suicidal behaviour, a property that may be linked to its ability to diminish impulsive, aggressive behaviour. The antioxidant drug, ebselen, has been proposed as a possible lithium-mimetic based on its ability in animals to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium. Objectives: The aim of the study was to determine whether treatment with ebselen altered emotional processing and diminished measures of risk-taking behaviour. Methods: We studied 20 healthy participants who were tested on two occasions receiving either ebselen (3600 mg over 24 h) or identical placebo in a double-blind, randomized, cross-over design. Three hours after the final dose of ebselen/placebo, participants completed the Cambridge Gambling Task (CGT) and a task that required the detection of emotional facial expressions (facial emotion recognition task (FERT)). Results: On the CGT, relative to placebo, ebselen reduced delay aversion while on the FERT, it increased the recognition of positive vs negative facial expressions. Conclusions: The study suggests that at the dosage used, ebselen can decrease impulsivity and produce a positive bias in emotional processing. These findings have implications for the possible use of ebselen in the disorders characterized by impulsive behaviour and dysphoric mood

Evaluation of High Resolution Melting analysis as an alternate tool to screen for risk alleles associated with small kidneys in Indian newborns

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) are the most common forms of sequence variations in the human genome. They contribute to the human phenotypic spectrum and are associated with variations in response to pathogens, drugs and vaccines. Recently, SNPs in three human genes involved in kidney development (<it>RET</it>, <it>PAX2 </it>and <it>ALDH1A2</it>) have been reported to be associated with variation in renal size and function. These known SNPs could potentially be used in the clinic as markers for identifying babies who may have smaller kidneys and permit close follow up for early detection of hypertension and acquired renal dysfunction. The aim of this study was to evaluate the use of High Resolution Melting technique (HRM) as a tool for detecting the known SNPs in these three genes in comparison to sequencing which is the gold standard.</p> <p>Methods</p> <p>High resolution melting analysis was performed on 75 DNA samples that were previously sequenced for the known polymorphisms in <it>RET </it>(rs1800860), <it>PAX2 </it>(rs11190688) and <it>ALDH1A2 </it>(rs7169289) genes. The SNPs were G > A transitions in <it>RET </it>and <it>PAX2 </it>and A > G in <it>ALDH1A2 </it>gene. A blinded assessment was performed on these samples for evaluation of the HRM technique as compared to sequencing.</p> <p>Results</p> <p>Each variant had a unique melt curve profile that was reproducible. The shift in melting temperature (Tm) allowed visual discrimination between the homozygous alleles (major and minor) in all three genes. The shape of the melting curve as compared to the major allele homozygous curve allowed the identification of the heterozygotes in each of the three SNPs. For validation, HRM was performed on 25 samples for each of the three SNPs. The results were compared with the sequencing results and 100% correct identification of the samples was obtained for <it>RET</it>, <it>PAX2</it>, and <it>ALDA1H2 </it>gene.</p> <p>Conclusion</p> <p>High Resolution Melting analysis is a simple, rapid and cost effective technique that could be used in a large population to identify babies with the risk alleles. These high risk children could be followed up for early detection of hypertension and acquired renal dysfunction.</p