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.

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

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

Sleep and circadian rhythm disruption alters the lung transcriptome to predispose to viral infection

Sleep and circadian rhythm disruption (SCRD), as encountered during shift work, increases the risk of respiratory viral infection including SARS-CoV-2. However, the mechanism(s) underpinning higher rates of respiratory viral infection following SCRD remain poorly characterised. To address this, we investigated the effects of acute sleep deprivation on the mouse lung transcriptome. Here we show that sleep deprivation profoundly alters the transcriptional landscape of the lung, causing the suppression of both innate and adaptive immune systems, disrupting the circadian clock, and activating genes implicated in SARS-CoV-2 replication, thereby generating a lung environment that could promote viral infection and associated disease pathogenesis. Our study provides a mechanistic explanation of how SCRD increases the risk of respiratory viral infections including SARS-CoV-2 and highlights possible therapeutic avenues for the prevention and treatment of respiratory viral infection

Patient fibroblast circadian rhythms predict lithium sensitivity in bipolar disorder.

Bipolar disorder is a chronic neuropsychiatric condition associated with mood instability, where patients present significant sleep and circadian rhythm abnormalities. Currently, the pathophysiology of bipolar disorder remains elusive, but treatment with lithium continues as the benchmark pharmacotherapy, functioning as a potent mood stabilizer in most, but not all patients. Lithium is well documented to induce period lengthening and amplitude enhancement of the circadian clock. Based on this, we sought to investigate whether lithium differentially impacts circadian rhythms in bipolar patient cell lines and crucially if lithium's effect on the clock is fundamental to its mood-stabilizing effects. We analyzed the circadian rhythms of bipolar patient-derived fibroblasts (n = 39) and their responses to lithium and three further chronomodulators. Here we show, relative to controls (n = 23), patients exhibited a wider distribution of circadian period (p < 0.05), and that patients with longer periods were medicated with a wider range of drugs, suggesting lower effectiveness of lithium. In agreement, patient fibroblasts with longer periods displayed muted circadian responses to lithium as well as to other chronomodulators that phenocopy lithium. These results show that lithium differentially impacts the circadian system in a patient-specific manner and its effect is dependent on the patient's circadian phenotype. We also found that lithium-induced behavioral changes in mice were phenocopied by modulation of the circadian system with drugs that target the clock, and that a dysfunctional clock ablates this response. Thus, chronomodulatory compounds offer a promising route to a novel treatment paradigm. These findings, upon larger-scale validation, could facilitate the implementation of a personalized approach for mood stabilization

Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice

Abstract: The accumulation of adenosine is strongly correlated with the need for sleep and the detection of sleep pressure is antagonised by caffeine. Caffeine also affects the circadian timing system directly and independently of sleep physiology, but how caffeine mediates these effects upon the circadian clock is unclear. Here we identify an adenosine-based regulatory mechanism that allows sleep and circadian processes to interact for the optimisation of sleep/wake timing in mice. Adenosine encodes sleep history and this signal modulates circadian entrainment by light. Pharmacological and genetic approaches demonstrate that adenosine acts upon the circadian clockwork via adenosine A1/A2A receptor signalling through the activation of the Ca2+ -ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes Per1 and Per2. We show that these signalling pathways converge upon and inhibit the same pathways activated by light. Thus, circadian entrainment by light is systematically modulated on a daily basis by sleep history. These findings contribute to our understanding of how adenosine integrates signalling from both light and sleep to regulate circadian timing in mice