High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay

Viruses are extremely heterogeneous entities; the size and the nature of their genetic information, as well as the strategies employed to amplify and propagate their genomes, are highly variable. However, as obligatory intracellular parasites, replication of all viruses relies on the host cell. Having co-evolved with their host for several million years, viruses have developed very sophisticated strategies to hijack cellular factors that promote virus uptake, replication, and spread. Identification of host cell factors (HCFs) required for these processes is a major challenge for researchers, but it enables the identification of new, highly selective targets for anti viral therapeutics. To this end, the establishment of platforms enabling genome-wide high-throughput RNA interference (HT-RNAi) screens has led to the identification of several key factors involved in the viral life cycle. A number of genome-wide HT-RNAi screens have been performed for major human pathogens. These studies enable first inter-viral comparisons related to HCF requirements. Although several cellular functions appear to be uniformly required for the life cycle of most viruses tested (such as the proteasome and the Golgi-mediated secretory pathways), some factors, like the lipid kinase Phosphatidylinositol 4-kinase IIIα in the case of hepatitis C virus, are selectively required for individual viruses. However, despite the amount of data available, we are still far away from a comprehensive understanding of the interplay between viruses and host factors. Major limitations towards this goal are the low sensitivity and specificity of such screens, resulting in limited overlap between different screens performed with the same virus. This review focuses on how statistical and bioinformatic analysis methods applied to HT-RNAi screens can help overcoming these issues thus increasing the reliability and impact of such studies.     

Assessment scales for delirium: A review

Over the years many scales have been designed for screening, diagnosis and assessing the severity of delirium. In this paper we review the various instruments available to screen the patients for delirium, instruments available to diagnose delirium, assess the severity, cognitive functions, motoric subtypes, etiology and associated distress. Among the various screening instruments, NEECHAM confusion scale and delirium observation scale appear to be most suitable screening instrument for patients' in general medical and surgical wards, depending on the type of rater(physician or nurse). In general, the instruments which are used for diagnosis [i.e., confusion assessment method(CAM), CAM for intensive care unit(CAM-ICU), Delirium Rating Scale-revised version(DRS-R-98), memorial selirium assessment scale, etc. ] are based on various Diagnostic and Statistical Manual criteria and have good to excellent reliability and fair to good validity. Among the various diagnostic instruments, CAM is considered to be most useful instrument because of its accuracy, brevity, and ease of use by clinicians and lay interviewers. In contrast, DRS-R-98 appears to be a comprehensive instrument useful for diagnosis, severity rating and is sensitive to change and hence can be used for monitoring patients over a period. In the ICU setting, evidence suggests that CAM-ICU and Nursing Delirium Screening Scale had comparable sensitivities, but CAM-ICU has higher specificity. With regard to assessment of delirium in pediatric age group, certain instruments like Pediatric Anesthesia Emergence Delirium scale and pediatric CAM-ICU has been designed and have been found to be useful.     

Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1: A Placebo-Controlled Randomized Clinical Trial

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Neem oil poisoning

We report an unusual case of neem oil poisoning in a previously normal 5 year old child. The child presented with refractory seizures and was having metabolic acidosis. Late neurological sequelae in the form of auditory and visual disturbances, and ataxia were present.     

Chronic urticaria

Chronic urticaria (CU) is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the 'idiopathic' forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented.