Indefinite Causal Order in a Quantum Switch.

Quantum mechanics allows events to happen with no definite causal order: this can be verified by measuring a causal witness, in the same way that an entanglement witness verifies entanglement. Here, we realize a photonic quantum switch, where two operations A[over ^] and B[over ^] act in a quantum superposition of their two possible orders. The operations are on the transverse spatial mode of the photons; polarization coherently controls their order. Our implementation ensures that the operations cannot be distinguished by spatial or temporal position-further it allows qudit encoding in the target. We confirm our quantum switch has no definite causal order by constructing a causal witness and measuring its value to be 18 standard deviations beyond the definite-order bound.

Human filarial proteins attenuate chronic colitis in an experimental mouse model.

Encouraged by our earlier results of promising therapeutic effect of filarial recombinant proteins BmALT2, BmCys and WbL2 individually in the mouse model of acute ulcerative colitis, in this study, these proteins have been explored individually and in different combinations for their therapeutic potential in dextran sulphate sodium (DSS)-induced chronic colitis mice. These mice, treated with filarial proteins, showed reduced disease parameters including body weight loss, disease activity index, macroscopic and histopathological scores of colon and myeloperoxidase activity in colonic mucosa. Among various treatment schemes, rBmALT2 + rBmCys which showed most pronounced therapeutic implication was found to downregulate the mRNA expressions of IFN-γ and TNF-α and upregulate IL-10 and TGF-ß expression in the splenocytes. Also, increase in level of IgG1 and IgG2a isotypes in the sera of rBmALT2 + rBmCys-treated colitis mice was noted. Activated NF-κB level was found to be reduced in the colon of treated colitis mice compared to untreated one. In conclusion, filarial proteins in combination have been shown to improve the clinicopathologic status of chronic colitis through suppression of pro-inflammatory immune response most possibly in NF-κB-dependent manner. We propose this therapeutic strategy to be tested further to be considered as an effective option in chronic colitis.

Therapeutic potential of the immunomodulatory proteins Wuchereria bancrofti L2 and Brugia malayi abundant larval transcript 2 against streptozotocin-induced type 1 diabetes in mice.

Epidemiological and experimental evidence has supported the concept of using helminths as alternative bio-therapeutic agents in the treatment of type 1 diabetes (T1D). In the current study, two filarial proteins, recombinant Wuchereria bancrofti L2 (rWbL2) and Brugia malayi abundant larval transcript 2 (rBmALT-2) have been investigated, individually and in combination, for their therapeutic potential in streptozotocin (STZ)-induced T1D. The rWbL2 and rBmALT-2 proteins, when administered individually or in combination, have resulted in lowering of the blood glucose levels and reducing the incidence of T1D in mice. In addition, these proteins have led to reduced lymphocytic infiltration and decreased islet damage and inflammation. The curative effect was found to be associated with the suppression of release of tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and increased production of interleukin (IL)-4, IL-5 and IL-10 cytokines by the splenocytes of the diabetic mice. Insulin-specific IgG1 and antigen-specific IgE antibodies were found to be elevated in the sera of mice treated with rWbL2 and rBmALT-2 proteins. From the findings in this study, it can be envisaged that both of these filarial immunomodulatory proteins have the potential to ameliorate T1D by altering the regulatory immune responses.

Status of Serum Calcium, Vitamin D and Parathyroid Hormone and Hematological Indices Among Lead Exposed Jewelry Workers in Dhaka, Bangladesh.

Jewelry utilizes lead either directly or as a base metal. Costume jewelry requires lead before molding and plating the product with valuable metals. Therefore, such ornaments have a great potential to release heavy metals having health hazards. Also, jewelry makers engaged in preparing German silver, an alloy, apply lead in smelting, alloying, rolling and milling silver wires and pieces. The metal is taken up by blood, soft tissues and bone. The biological effects of lead are dependent upon the level and duration of exposure. Lead inhibits three enzymes of heme biosynthesis- δ-amino-levulinic-acid dehydratase (ALAD), coproporphyrin oxidase, and ferrochelatase, impairing heme synthesis and depressing serum level of erythropoietin resulting in decreased hemoglobin synthesis. Lead exposure also affects calcium metabolism and impair the synthesis of Calcitriol. In the present study, jewelry makers from Dhaka, Bangladesh, were shown to have significantly high levels of lead, protein, albumin, and parathormone in their blood, and significantly high amount of zinc-protoporphyrin and δ-amino-levulinic-acid in their urine. The control group, on the other hand showed significantly higher amounts of calcium (both total and ionized form) Vitamin D3 and non-activated erythrocyte ALAD in their blood, along with hemoglobin. It might be due to inhibition of 1-α-hydroxylase enzyme in renal tubules. Lead causes nephro-toxicity and inhibits 1-α- hydroxylase enzyme leading to decreased calcitriol synthesis resulting in impaired calcium absorption across gastro-intestinal tract and renal tubules. Low Vitamin D3 and significantly increased Parathyroid hormone (PTH) in study group has been found.

Brugia malayi soluble and excretory-secretory proteins attenuate development of streptozotocin-induced type 1 diabetes in mice.

Understanding the modulation of the host-immune system by pathogens-like filarial parasites offers an alternate approach to prevent autoimmune diseases. In this study, we have shown that treatment with filarial proteins prior to or after the clinical onset of streptozotocin-induced type-1 diabetes (T1D) can ameliorate the severity of disease in BALB/c mice. Pre-treatment with Brugia malayi adult soluble (Bm A S) or microfilarial excretory-secretory (Bm mf ES) or microfilarial soluble (Bm mf S) antigens followed by induction of diabetes led to lowering of fasting blood glucose levels with as many as 57.5-62.5% of mice remaining nondiabetic. These proteins were more effective when they were used to treat the mice with established T1D as 62.5-71.5% of the mice turned to be nondiabetic. Histopathological examination of pancreas of treated mice showed minor inflammatory changes in pancreatic islet cell architecture. The therapeutic effect was found to be associated with the decreased production of cytokines TNF-α & IFN-γ and increased production of IL-10 in the culture supernatants of splenocytes of treated mice. A switch in the production of anti-insulin antibodies from IgG2a to IgG1 isotype was also seen. Together these results provide a proof towards utilizing the filarial derived proteins as novel anti-diabetic therapeutics.

UV-cured, platinum-free, soft poly(dimethylsiloxane) networks.

To overcome the drawbacks exhibited by platinum-catalyzed curing of silicones, photoinitiated thiol-ene cross-linking of high-molecular-weight poly(dimethylsiloxane) (PDMS) prepolymers has been investigated as a pathway to novel soft PDMS networks, based on commercially available starting materials was developed. Through a fast and efficient two-step cross-linking reaction highly flexible PDMS elastomers were prepared.

Influence of alcohol on condom use pattern during non-spousal sexual encounter in male migrant workers in north India.

CONTEXT: Migrant workers constitute an important risk group for Human Immunodeficiency Virus/Acquired Immuno-Deficiency Syndrome transmission in India. Alcohol consumption before sexual intercourse has been postulated to influence condom use practices. This study aimed to assess this association with regard to non-spousal sexual encounters among male migrant workers in northern India. MATERIALS AND METHODS: A cross-sectional facility-based survey was conducted in 2011. Male migrant workers aged ≥18 years, who were born outside Haryana, who had moved to the current location after 15 years of age,had worked in the current factory for at least 1 year, who were willing to participate and were able to give written, informed consent were included in the study. A consecutive sampling was performed. Descriptive, bivariate and multiple logistic regression analyses were carried out. RESULTS: A total of 162 participants reported having experienced non-spousal sexual encounters in the last 1 year. The proportion of men who reported not having used a condom at their last non-spousal sexual encounter was 59.3%, and 78.4% of the men reported having consumed alcohol in the last 1 year. About 48.1% of men reported having consumed alcohol before their last non-spousal sexual encounter. Men who consumed alcohol were three times more likely to not use a condom at their last non-spousal sexual encounter (OR = 3.1, 95% CI: 1.5-6.4). This association persisted even after adjusting for relevant confounders. CONCLUSION: Alcohol consumption had a negative influence on condom use during non-spousal sexual encounter among male migrant workers. An integrated approach to promote condom use and reduce alcohol consumption among migrant men needs to be undertaken through targeted intervention strategies.

Congenital lead poisoning: an unusual presentation.

Lead poisoning presents a common acquired as well as congenital environmental threat to children's health today. An unusual case of severe lead poisoning in breast fed male infant is presented here. The objective of the study is to describe a patient who developed clinical lead intoxication with an uncommon source of poisoning. A 6 months old male baby presented with gradual loss of weight, not feeding well and persistent vomiting. Laboratory investigation revealed that he was having anemia (Hb level 5.4 gm/dl), abnormal liver enzymes (including elevated transaminase activity) and high blood lead value (83 µg/dl). RBC morphology showed basophilic stippling with cabot ring, suggestive of a case of lead poisoning. A course of chelation treatment using calcium versenate (EDTACaNa2) was prescribed following which a radical solution for mobilization of lead from his systems was observed.

Chronic exposure to lead: a cause of oxidative stress and altered liver function in plastic industry workers in kolkata, India.

It is well known that chronic exposure of lead leads to adverse health effects. Workers for plastic industry are generally exposed to high concentration of lead as fume, dust, and additive that protect PVC. This study was done on them to find out the detrimental effects of chronic lead exposure on hepatic and hematological toxicity. Blood and 24 h urine sample was collected from 47 plastic industry workers and matched against 42 controls for various parameters. The study group shows significant increase in blood (p < 0.0001) and urinary level of lead (p < 0.0001). Hemoglobin levels were significantly decreased (p < 0.0001), and the liver enzymes like ALP, ALT, AST and y-GT were significantly increased (p < 0.0001) in all cases exposed for >10 years. Serum lipid peroxide by quantitative assay of thiobarbituric acid reactive substances was also found increased in the study group (p < 0.0001). The observations point towards the acute health risk faced by plastic industry workers, in whom chronic exposure to lead increases the absorption and accumulation, over a period of time, of this highly toxic element in their body. This increases oxidative stress, causes metabolic damage to RBC and cell membranes, and also suggests necrosis of liver cell, hepatocellular injury and presence of space occupying lesions. Considering the data immediate health and hygiene monitoring and proper rehabilitation for the suffering population seem to be of paramount need in plastic industry to minimize occupational hazards.

Exploration of 2, 4-diaminopyrimidine and 2, 4-diamino-s-triazine derivatives as potential antifilarial agents.

In view of the mandate from the World Health Organization (WHO) for developing novel drug candidates against human lymphatic filariasis, dihydrofolate reductase (DHFR) inhibitors are explored as potential antifilarial agents. The in vitro biological evaluation of an in-house library of 12 diverse antifolate compounds with 2,4-diaminopyrimidine and 2,4-diamino-s-triazine structural features against Brugia malayi is reported. To confirm the DHFR inhibitory potential of these compounds, reversal studies using folic acid and folinic acid were undertaken. Inhibition of DHFR can induce apoptosis; in this light, preliminary evidence of apoptosis by test compounds was detected using ethidium bromide-acridine orange staining and the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition assay. Among the evaluated compounds, 3 showed significant activity against both microfilariae and adult worms. The effects of 2 of these compounds were mostly reversed by folic acid, validating DHFR inhibitory activity. Partial reversal of the effect of 2 compounds by folinic acid and non-reversal of the effect of the third compound both by folic and folinic acids are discussed. This study opens new avenues for the discovery of lead molecules by exploiting the folate pathway against one of the major neglected tropical diseases, filariasis.

Eye cosmetic 'surma': hidden threats of lead poisoning.

Traditional eye cosmetics 'Surma' use is a popular practice. A total 34 'Surma' samples of black, brown, orange, grey and white were collected and analysed for the presence of lead. High lead levels were detected in all samples except white colour 'Surma'. Blood lead concentrations were measured in 93 children, of whom 69 used 'Surma' regularly. The mean blood lead concentration of 'Surma' users was found to be 29.6 ± 10.2 µg/100 ml; where as non user's value was 4.9 ± 0.8 µg/100 ml. Also, the low haemoglobin levels were observed in the users (10.2 ± 1.4 g/100 ml). In conclusion, the use of 'Surma' is associated with high blood lead concentration with significant reduction of haemoglobin levels. For better quality of life, the use of lead free 'Surma' is suggested.

Interdistrict variations in child health status and health services utilization: lessons for health sector priority setting and planning from a cross-sectional survey in rural India.

BACKGROUND: There are limited data on interdistrict variations in child health status and health services utilization within the states of India. We conducted this study to identify and understand district-wise variations in child morbidity, mortality, healthcare seeking, and the status of health facilities in India. METHODS: A cross-sectional population-based cluster survey was conducted from April to July 2007 in 16 districts of eight states in India. Two districts with similar demographic profile and health criteria were selected from each study state. RESULTS: A total of 216 794 households and 24 812 under-5 children were surveyed. There were wide interdistrict variations in the health status of children within the same state and between different states across India. Interdistrict difference of >5 points/1000 live-births was found for infant mortality rate and under-5 mortality rate in all eight study states, while in six out of eight states this difference was >10 points/1000 live-births. Four states had a difference of >10 points/1000 live-births between respective districts for neonatal mortality rate. The interdistrict differences were also noted in childhood morbidity and health-seeking behaviour. Analysis of proportion of health facilities conforming to Indian public health standards revealed that the difference was m10% for availability of vaccines in five states, emergency services in three, laboratory services and logistics in four each, and referral facility in three of the eight study states. CONCLUSION: This study underscores an important information gap in the country where planners seem to rely heavily on a few selected national-level databases that may not be adequate at the micro level. The current process of sporadic health surveys also appears inadequate and inappropriate. There is a need for district-specific data for planning, improving quality of service and generating demand for health service utilization to improve child survival in India. The findings of this study may prove useful for child health programme planning in India.

Distribution and solid-phase speciation of toxic heavy metals of bed sediments of Bharali tributary of Brahmaputra River.

Heavy metal (Fe, Mn, Zn, Cu, Ni, Pb, and Cd) concentrations and their chemical speciations were investigated for the first time in bed sediments of Bharali River, a major tributary of the Brahmaputra River of the Eastern Himalayas. Levels of Fe, Mn, Pb, and Cd in the bed sediments were much below the average Indian rivers; however, Cu and Zn exhibit levels on the higher side. Enrichment factors (EF) of all metals was greater than 1 and a higher trend of EF was seen in the abandoned channel for most metals. Pb showed maximum EF of 32 at site near an urban center. The geoaccumulation indices indicate that Bharali river is moderately polluted. The metals speciations, done by a sequential extraction regime, show that Cd, Cu, and Pb exhibit considerable presence in the exchangeable and carbonate fraction, thereby showing higher mobility and bioavailability. On the other hand, Ni, Mn, and Fe exhibit greater presence in the residual fraction and Zn was dominant in the Fe-Mn oxide phase. Inter-species correlations at three sites did not show similar trends for metal pairs indicating potential variations in the contributing sources.

Role of Glutathione in Chalcone Derivative Induced Apoptosis of Brugia malayi and its Possible Therapeutic Implication.

PURPOSE: Oxidative stress is an essential component of innate response against microbes. The oxidative impact has a very subtle connection with apoptosis. Our previous work indicated presumptive evidence of apoptosis by the chalcone derivatives against the human lymphatic filarial parasite. Evidence suggests the involvement of glutathione-S-transferase (GST) in the mechanism of action of chalcone drugs. In the present study, we explored the implications of redox status in apoptosis of the parasite by this drug. RESULTS: Treatment with the representative drug, 4t, significantly decreased GSH level and increased GST activity in the Brugia malayi microfilariae (Mf) in comparison to Mf without 4t treatment. Drug-induced loss of motility of the parasites was reversed by the treatment with GSH (41%) and NAC (19%). A significant fall in rGST activity was observed due to drug addition, which could be reversed by the addition of GSH co-substrate, but not with the re-addition of rGST, indicating a vital role of GSH. In silico study demonstrated a favorable drug-GST enzyme interaction. Oxidative stress was reflected by increased protein carbonylation and intracellular reactive oxygen species level, in the drug-treated parasite. Mitochondrial oxygen consumption was reduced by the drug, which was reversed on the addition of GSH. Mitochondrial dysfunction was confirmed by MTT and cytochrome c assay. Apoptosis was confirmed by the inhibition in PARP activity. CONCLUSION: We conclude that the depletion of GSH by chalcone with concomitant mitochondrial dysfunction revealed a novel rationale of apoptosis in the parasite. Such a mechanism might have wide therapeutic implications.

Cardiological Society of India: Document on acute MI care during COVID-19.

The unprecedented and rapidly spreading Coronavirus Disease-19 (COVID-19) pandemic has challenged public health care systems globally. Based on worldwide experience, India has initiated a nationwide lockdown to prevent the exponential surge of cases. During COVID-19, management of cardiovascular emergencies like acute Myocardial Infarction (MI) may be compromised. Cardiological Society of India (CSI) has ventured in this moment of crisis to evolve a consensus document for care of acute MI. However, this care should be individualized, based on local expertise and governmental advisories.

T-cell assay conversions and reversions among household contacts of tuberculosis patients in rural India.

BACKGROUND: Interferon-gamma assays (IGRAs) are alternatives to the tuberculin skin test (TST), but IGRA conversions and reversions are not well understood. In a pilot study, we determined conversions and reversions using QuantiFERON-TB Gold In-Tube((R)) (QFT) among household contacts of TB cases, and evaluated the effect of using various definitions and criteria for conversions. DESIGN: In a cohort of 250 contacts in India, 46% were TST-positive at baseline and 54% were QFT-positive. We re-tested this cohort after 12 months. Conversion rates were estimated using several definitions. RESULTS: Of the 250 contacts, 205 (82%) underwent repeat testing. Among 85 contacts with baseline TST-negative/QFT-negative results, TST conversion rates ranged between 7.5% and 13.8%, and QFT conversion rates ranged between 11.8% and 21.2%, depending on the definitions used. Among 109 contacts who were QFT-positive at baseline, seven (6.4%) had QFT reversions. QFT reversions were most likely when the baseline TST was negative and QFT results were just above the diagnostic cut-off. CONCLUSIONS: QFT conversions and reversions occurred among contacts of TB cases. Conversion rates seemed to vary, depending on the test and definitions used for conversions. These findings need to be verified in larger studies in various settings.

Glioblastoma invasion and NMDA receptors: A novel prospect.

PURPOSE: Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. MAIN METHODS: LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. RESULTS: We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. CONCLUSIONS: This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

2019 John Insall Award: Fructosamine is a better glycaemic marker compared with glycated haemoglobin (HbA1C) in predicting adverse outcomes following total knee arthroplasty: a prospective multicentre study.

AIMS: The best marker for assessing glycaemic control prior to total knee arthroplasty (TKA) remains unknown. The purpose of this study was to assess the utility of fructosamine compared with glycated haemoglobin (HbA1c) in predicting early complications following TKA, and to determine the threshold above which the risk of complications increased markedly. PATIENTS AND METHODS: This prospective multi-institutional study evaluated primary TKA patients from four academic institutions. Patients (both diabetics and non-diabetics) were assessed using fructosamine and HbA1c levels within 30 days of surgery. Complications were assessed for 12 weeks from surgery and included prosthetic joint infection (PJI), wound complication, re-admission, re-operation, and death. The Youden's index was used to determine the cut-off for fructosamine and HbA1c associated with complications. Two additional cut-offs for HbA1c were examined: 7% and 7.5% and compared with fructosamine as a predictor for complications. RESULTS: Overall, 1119 patients (441 men, 678 women) were included in the study. Fructosamine level of 293 µmol/l was identified as the optimal cut-off associated with complications. Patients with high fructosamine (> 293 µmol/l) were 11.2 times more likely to develop PJI compared with patients with low fructosamine (p = 0.001). Re-admission and re-operation rates were 4.2 and 4.5 times higher in patients with fructosamine above the threshold (p = 0.005 and p = 0.019, respectively). One patient (1.7%) from the elevated fructosamine group died compared with one patient (0.1%) in the normal fructosamine group (p = 0.10). These complications remained statistically significant in multiple regression analysis. Unlike fructosamine, all three cut-offs for HbA1c failed to show a significant association with complications. CONCLUSION: Fructosamine is a valid and an excellent predictor of complications following TKA. It better reflects the glycaemic control, has greater predictive power for adverse events, and responds quicker to treatment compared with HbA1c. These findings support the screening of all patients undergoing TKA using fructosamine and in those with a level above 293 µmol/l, the risk of surgery should be carefully weighed against its benefit. Cite this article: Bone Joint J 2019;101-B(7 Supple C):3-9.

Prevalence of hypertension among Indian adults: Results from the great India blood pressure survey.

OBJECTIVE: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. There is limited data on hypertension prevalence in India. This study was conducted to estimate the prevalence of hypertension among Indian adults. METHODS: A national level survey was conducted with fixed one-day blood pressure measurement camps across 24 states and union territories of India. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg or on treatment for hypertension. The prevalence was age- and gender-standardized according to the 2011 census population of India. RESULTS: Blood pressure was recorded for 180,335 participants (33.2% women; mean age 40.6 ± 14.9 years). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%), and 2,878 (1.6%) participants were of the age group 18-19, 20-44, 45-54, 55-64, 65-74, and ≥ 75 years, respectively. Overall prevalence of hypertension was 30.7% (95% confidence interval [CI]: 30.5, 30.9) and the prevalence among women was 23.7% (95% CI: 23.3, 24). Prevalence adjusted for 2011 census population and the WHO reference population was 29.7% and 32.8%, respectively. CONCLUSION: There is a high prevalence of hypertension, with almost one in every three Indian adult affected.