S gene drop-out predicts super spreader H69del/V70del mutated SARS-CoV-2 virus

正Emergence of newer SARS-CoV-2 variants, especially strain B.1.1.7/SARS-CoV-2 VUI 202012/01, discovered in the United Kingdom with H69del/V70del mutation in spike S gene was reported with higher transmissibility of up to 70%[1]. Identification of this variant was sparsely done in India because performing routine diagnosis as well as genomic surveillance using a single kit is the hour of need. To our knowledge, two publications identified the aforesaid mutation by phenomena called S gene drop-out using Applied Biosystems Taq Path COVID-19 Combo kit(Thermo Fisher Scientific, Waltham, USA)[2-4].     

Diagnosing pulmonary arteriovenous malformations in the presence of atrial septal defect and anomalous pulmonary venous drainage—An imaging challenge

Saline contrast echocardiography is a simple and effective method to diagnose the presence and type of right-to-left shunt in patients with unexplained cyanosis. It is considered a very sensitive test to diagnose pulmonary arteriovenous malformations. Our patient presented with unexplained cyanosis and transthoracic echocardiography showed an atrial septal defect and anomalous pulmonary venous drainage of the right and left upper pulmonary veins to the superior venacava. We describe how we used saline contrast echocardiography to demonstrate the presence of pulmonary arteriovenous malformations even in the presence of atrial septal defect and anomalous pulmonary venous drainage.     

A complex component modulating immune-deficient cells in leprosy patients leading to loss of viability of Mycobacterium leprae--a possible vaccine.

Macrophages from peripheral blood of leprosy patients, both multi-bacillary and paucibacillary are unable to kill phagocytosed Mycobacterium leprae due to their inability to produce superoxide (O2-) and hydroxyl radicals (OH.). The macrophages from healthy individuals are able to kill M. leprae along with release of O2- and OH. radicals. The deficiency in the macrophages of both types of leprosy patients is removed by activation of these cells when exposed to a culture supernatant obtained after stimulation of peripheral blood mononuclear cells from the same patients with delipidified cell components of M. leprae which are most likely cell wall proteins. The activation of macrophages also leads to recognition of whole live M. leprae as an antigen by cells from lepromatous patients. This activation of the phagocytes by delipidified cell components is blocked by cyclosporin A, indicating the possible role of several steps involved in immune activation of cells. The observations thus indicate the significant ability of delipidified cell components to eliminate the deficiencies in the macrophages from leprosy patients and restore them to behave like the cells from healthy individuals. Considering all these, it is suggested that delipidified cell components could be potential modulators, and are probably capable of functioning as a vaccine for leprosy.     

In vivo evidence for serotonin 5-HT2C receptor-mediated long-lasting excitability of lumbar spinal reflex and its functional interaction with 5-HT1A receptor in the mammalian spinal cord

The purpose of the present study was to investigate the 5-HT(2C) receptor-mediated effects on the spinal monosynaptic mass reflex activities and also its functional interactions with 5-HT(1A) receptors in anesthetized, acutely spinalized mammalian adult spinal cord in vivo. Intravenous administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) (0.1 mg/kg), an agonist of 5-HT(2A/2C) receptors, significantly increased the excitability of spinal motoneurons as reflected by an increase in the spinal monosynaptic mass reflex amplitude to 150-200% of the control. 5-HT(2A/2C) receptor-induced motoneuron excitability was slow, persistent and long-lasting for more than 2h that was significantly inhibited by 5-HT(2C) receptor specific antagonist SB 242084 administered 10 min prior to DOI. Simultaneous administration of DOI (0.1 mg/kg, i.v.) along with (+/-)-8-hydroxy dipropylaminotetraline hydrobromide (8-OH-DPAT) (0.1 mg/kg, i.v.) completely inhibited DOI-induced spinal monosynaptic mass reflex facilitation. In another separate study, administration of 8-OH-DPAT (0.1 mg/kg, i.v.) at the maximum response of DOI also inhibited the motoneuron's excitability; however, the inhibition lasted only for a period of 40-60 min after administration of 8-OH-DPAT, after which the spinal monosynaptic mass reflex amplitude reached its maximum level. These findings suggest that the 5-HT(2C) receptor is primarily involved in the mediation of the long-lasting excitability of spinal motoneurons and possibly interacts with its functional counterpart, 5-HT(1A) receptors in the mammalian adult spinal cord.     

Effect of artificial mixtures of environmental polycyclic aromatic hydrocarbons present in coal tar, urban dust, and diesel exhaust particulates on MCF-7 cells in culture

Human exposure to polycyclic aromatic hydrocarbons (PAHs) occurs through complex mixtures. The National Institute of Standards and Technology has established standard reference materials (SRMs) for selected PAH mixtures that are composed of carcinogenic, noncarcinogenic, and weakly carcinogenic compounds, such as those derived from coal tar (SRM 1597), atmospheric particulate matter (SRM 1649), and diesel particulate matter (SRM 1650). To study the effects of PAHs with different carcinogenic potential in complex mixtures, and to investigate the metabolic activation of noncarcinogenic and weakly carcinogenic PAHs to DNA-binding derivatives, artificial mixtures (1597H, 1649H, and 1650H) were prepared in the laboratory. These artificial mixtures contained the same relative ratios of noncarcinogenic and weakly carcinogenic PAHs present in SRM 1597, SRM 1649, and SRM 1650. The human mammary carcinoma-derived cell line MCF-7 was treated with these artificial mixtures and analyzed for PAH-DNA adduct formation and the induction of cytochrome P450 (CYP) enzymes. We found that the artificial mixtures formed lower but detectable levels of DNA adducts 24 and 48 hr after treatment than benzo[a]pyrene. Induction of CYP enzyme activity was measured by the ethoxyresorufin-O-deethylase assay, and the expression of CYP1A1 and CYP1B1 was confirmed by immunoblots. Both noncarcinogenic and weakly carcinogenic PAHs present in the artificial mixtures have the ability to induce CYP1A1 and CYP1B1 in MCF-7 cells and contribute to DNA binding. Therefore, it is necessary to take into account the noncarcinogenic and weakly carcinogenic PAHs present in environmental mixtures in assessing the potential risk associated with human exposure.     

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study

Background:

Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world.

Objectives:

The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years.

Materials and Methods:

In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded.

Results:

The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI.

Conclusions:

Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.     

Absence of age-related changes in nigral dopaminergic neurons of Asian Indians: Relevance to lower incidence of Parkinson's disease

Age-related loss of melanized nigral neurons reported in the British Caucasians is not observed in Asian Indian, American and French adults. In the Americans, loss of dopaminergic phenotype occurs from midlife, without frank neurodegeneration. Here, we investigated whether nigral dopaminergic neurons in Asian Indians are lost with age or undergo morphological or biochemical dysfunction. Using unbiased stereology we estimated volume, number of melanized, borderline/non-melanized (n=34, 28 gestational weeks to 80 years) and tyrosine hydroxylase (TH)–Nurr1 co-labeled neurons (n=32, 28 gestational weeks to 80 years) in substantia nigra pars compacta. We quantified Nurr1 and TH proteins by immunoblotting (n=18, 28 gestational weeks to 69 years) and apoptotic neurons by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Nuclear and soma size was estimated by morphometry. There was no age-related decline in volume, neuronal density, neuronal numbers and TH-Nurr1 co-labeled neurons. TH and Nurr1 protein expression remained stable. Lack of TUNEL-TH co-labeled cells confirmed absence of neuronal apoptosis. The neuronal size remained unaltered. Our findings of preserved nigral dopaminergic neurons suggest no age-related loss of nigral function in Asian Indians, unlike the Americans. This may explain the lower incidence of Parkinson's disease in Asian Indians.