Classification of Atrial Fibrillation using Random Forest Algorithm

The electrocardiogram is indicates the electrical activity of the heart and it can be used to detect cardiac arrhythmias. In the present work, we exhibited a methodology to classify Atrial Fibrillation (AF), Normal rhythm, and Other abnormal ECG rhythms using a machine learning algorithm by analyzing single-lead ECG signals of short duration. First, the events of ECG signals will be detected, after that morphological features and HRV features are extracted. Finally, these features are applied to the Random Forest classifier to perform classification. The Physionet challenge 2017 dataset with more than 8500 ECG recordings is used to train our model. The proposed methodology yields an F1 score of 0.86, 0.97, and 0.83 respectively in classifying AF, normal, other rhythms, and an accuracy of 0.91 after performing a 5-fold cross-validation

Malpositioned dialysis catheters: A case series

Hemodialysis catheters (HDC) are the commonly used vascular access for hemodialysis. Functioning access is essential for adequate dialysis. Dialysis catheter insertion under ultrasound guidance is now standard practice and has reduced the incidence of mechanical complications during catheter insertion. However, complications such as tip misplacement and puncture of the mediastinum cannot be prevented by ultrasound-guided procedures alone. We report four cases of abnormal positioning of HDC insertion and emphasize the importance of fluoroscopy or radiography after the procedure to verify the position of the cathete

A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model

Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5

Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease

The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage disorders for which there are no effective therapies. A potential approach is substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide and related glycosphingolipids that accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the visceral organs and CNS. As expected, oral administration of the drug inhibited hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels. The increase in brain glucosylceramide levels might be due to concurrent inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless delayed the loss of motor function and coordination and extended the lifespan of the Sandhoff mice. These results suggest that the CNS benefits observed in the Sandhoff mice might not necessarily be due to substrate reduction therapy but rather to off-target effects

Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells)

In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described

Clinical analysis of ectopic pregnancies in a tertiary care centre

Background: An ectopic pregnancy occurs when a fertilized egg grows outside of the uterus.Almost all ectopic pregnancies more than 90% occur in a fallopian tube.As the pregnancy grows, it can cause the tube to rupture. A rupture can cause major internal bleeding. Objectives: to determine the incidence, clinical features, risk factors, treatment and outcomes associated with ectopic pregnancy in a tertiary level teaching hospital. Methods: The data was collected from the medical records section of the hospital. There were 162 cases of ectopic pregnancy diagnosed and treated in the hospital in the study period. Results: 40 patients with history of previous miscarriage had ectopic pregnancies (24.69%). Past history of undergoing lower segment caesarean section was observed in 35 patients (21.60%). Eight (4.9%) out of 162 patients had prior history of ectopic pregnancy. Prior history of tubectomy was seen in 21 (12.9%) patients. The triad of symptoms i.e. amenorrhoea, pain abdomen and per vaginal bleeding was found in only 53 patients (32.7%). The most common site of ectopic pregnancy was ampullary 110 (67.9%) followed by isthmic in 33 (20.3). Other rare sites of ectopic pregnancy noted in our study were 3 (1.8%) cases of caesarean scar pregnancy, one (0.6%) case of cervical pregnancy and 3 (1.8%) cases of ovarian pregnancies. 142 patients (87.65%) were primarily treated with various surgical procedures. Of these, 80 patients (49.38%) were treated with various open procedures, and 62 patients (38.2%) were treated with laparoscopic procedures. Of the 20 patients (12.34%) treated medically, 10 patients (6.17%) failed to respond to the treatment and had to undergo surgical procedure later. Anaemia was the most common complication and was seen in 57 patients (35.1%). Conclusion: Prevention of ectopic pregnancy is difficult because only few of the risk factors are modifiable. Tubal pathology carries the highest risks and pelvic inflammatory diseases plays a major role in tubal adhesions and obstruction. Physicians and patients awareness about the possibility and risk of extra and intra uterine gestation following all methods of sterilization is necessary

Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease

Vitiligo is an autoimmune disease of the skin that results in the destruction of melanocytes and the clinical appearance of white spots. Disease pathogenesis depends on IFN-gamma and IFN-gamma-induced chemokines to promote T-cell recruitment to the epidermis where melanocytes reside. The skin is a complex organ, with a variety of resident cell types. We sought to better define the microenvironment and distinct cellular contributions during autoimmunity in vitiligo, and we found that the epidermis is a chemokine-high niche in both a mouse model and human vitiligo. Analysis of chemokine expression in mouse skin showed that CXCL9 and CXCL10 expression strongly correlate with disease activity, whereas CXCL10 alone correlates with severity, supporting them as potential biomarkers for following disease progression. Further studies in both our mouse model and human patients showed that keratinocytes were the major chemokine producers throughout the course of disease, and functional studies using a conditional signal transducer and activator of transcription (STAT)-1 knockout mouse showed that IFN-gamma signaling in keratinocytes was critical for disease progression and proper autoreactive T-cell homing to the epidermis. In contrast, epidermal immune cell populations including endogenous T cells, Langerhans cells, and gammadelta T cells were not required. These results have important clinical implications, because topical therapies that target IFN-gamma signaling in keratinocytes could be safe and effective new treatments, and skin expression of these chemokines could be used to monitor disease activity and treatment responses