Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Cloning and characterization of a gene encoding an immunoglobulin-binding receptor on the cell surface of some members of the family Trypanosomatidae

Several members of the Trypanosomatidae family, when freshly isolated from their mammalian hosts, have immunoglobulins adsorbed to their cell surfaces. However, a significant portion of these antibody molecules is not parasite specific, i.e., the immunoglobulins are bound to the parasite's cell surface molecules via noncognitive interactions. It has been proposed that this noncognitive adsorption of immunoglobulins to the parasite is mediated by an Fc-like receptor present in several members of the Trypanosomatidae family. However, the molecular identification of this receptor has never been defined. Here, we describe the cloning of a gene encoding a protein that might represent this molecule. The gene, named Lmsp1, was cloned by screening a Leishmania major cDNA expression library using a rabbit antiserum. Lmsp1 is present in both Leishmania and Trypanosoma and is expressed in all developmental stages of these parasites. The predicted protein has a molecular mass of 16.6 kDa and contains an RGD sequence starting at residue 104 and three cysteine residues at positions 55, 74, and 116. The purified recombinant protein strongly binds to normal immunoglobulins of various animal species (humans, rabbits, sheep, goats, guinea pigs, donkeys, rats, and mice) and the binding to human immunoglobulins appears to be immunoglobulin G (IgG) and IgM isotype specific. Moreover, Lmsp1 binds to both purified Fc and Fab fragments of IgG from both humans and rabbits. The mapping of the Lmsp1 epitopes that bind human IgG revealed that different sequences of the molecule bind to Fc or Fab. In addition, fluorescence-activated cell sorter analyses with a specific rabbit anti-Lmsp1 antiserum showed that Lmsp1 is associated with the parasite's cell surface. Finally, inhibition experiments point to an active role of this molecule in the immunoglobulin-mediated attachment and penetration of Trypanosoma cruzi in its macrophage host cells, thus suggesting that Lmsp1 is a putative Trypanosomatidae immunoglobulin receptor.     

Use of multiepitope polyproteins in serodiagnosis of active tuberculosis

Screening of genomic expression libraries from Mycobacterium tuberculosis with sera from tuberculosis (TB) patients or rabbit antiserum to M. tuberculosis led to the identification of novel antigens capable of detecting specific antibodies to M. tuberculosis. Three antigens, Mtb11 (also known as CFP-10), Mtb8, and Mtb48, were tested together with the previously reported 38-kDa protein, in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in TB patients. These four proteins were also produced as a genetically fused polyprotein, which was tested with two additional antigens, DPEP (also known as MPT32) and Mtb81. Sera from individuals with pulmonary and extrapulmonary TB, human immunodeficiency virus (HIV)-TB coinfections, and purified protein derivative (PPD)-positive and PPD-negative status with no evidence of disease were tested. In samples from HIV-negative individuals, the ELISA detected antibodies in >80% of smear-positive individuals and >60% smear-negative individuals, with a specificity of approximately 98%. For this group, smears detected 81.6% but a combination of smear and ELISA had a sensitivity of approximately 93%. The antigen combination detected a significant number of HIV-TB coinfections as well as antibodies in patients with extrapulmonary infections. Improved reactivity in the HIV-TB group was observed by including the antigen Mtb81 that was identified by proteomics. The data indicate that the use of multiple antigens, some of which are in a single polyprotein, can be used to facilitate the development of a highly sensitive test for M. tuberculosis antibody detection.     

Prediction of Ecofriendly Concrete Compressive Strength Using Gradient Boosting Regression Tree Combined with GridSearchCV Hyperparameter-Optimization Techniques

A crucial factor in the efficient design of concrete sustainable buildings is the compressive strength (Cs) of eco-friendly concrete. In this work, a hybrid model of Gradient Boosting Regression Tree (GBRT) with grid search cross-validation (GridSearchCV) optimization technique was used to predict the compressive strength, which allowed us to increase the precision of the prediction models. In addition, to build the proposed models, 164 experiments on eco-friendly concrete compressive strength were gathered for previous researches. The dataset included the water/binder ratio (W/B), curing time (age), the recycled aggregate percentage from the total aggregate in the mixture (RA%), ground granulated blast-furnace slag (GGBFS) material percentage from the total binder used in the mixture (GGBFS%), and superplasticizer (kg). The root mean square error (RMSE) and coefficient of determination (R²) between the observed and forecast strengths were used to evaluate the accuracy of the predictive models. The obtained results indicated that—when compared to the default GBRT model—the GridSearchCV approach can capture more hyperparameters for the GBRT prediction model. Furthermore, the robustness and generalization of the GSC-GBRT model produced notable results, with RMSE and R² values (for the testing phase) of 2.3214 and 0.9612, respectively. The outcomes proved that the suggested GSC-GBRT model is advantageous. Additionally, the significance and contribution of the input factors that affect the compressive strength were explained using the Shapley additive explanation (SHAP) approach.     

Newborn weight change and predictors of underweight in the neonatal period in Guinea‐Bissau,Nepal, Pakistan and Uganda

In low‐ and middle‐income countries (LMIC), growth impairment is common; however, the trajectory of growth over the course of the first month has not been well characterised. To describe newborn growth trajectory and predictors of growth impairment, we assessed growth frequently over the first 30 days among infants born ≥2000 g in Guinea‐Bissau, Nepal, Pakistan and Uganda. In this cohort of 741 infants, the mean birth weight was 3036 ± 424 g. For 721 (98%) infants, weight loss occurred for a median of 2 days (interquartile range, 1–4) following birth until weight nadir was reached 5.9 ± 4.3% below birth weight. At 30 days of age, the mean weight was 3934 ± 592 g. The prevalence of being underweight at 30 days ranged from 5% in Uganda to 31% in Pakistan. Of those underweight at 30 days of age, 56 (59%) had not been low birth weight (LBW), and 48 (50%) had reached weight nadir subsequent to 4 days of age. Male sex (relative risk [RR] 2.73 [1.58, 3.57]), LBW (RR 6.41 [4.67, 8.81]), maternal primiparity (1.74 [1.20, 2.51]) and reaching weight nadir subsequent to 4 days of age (RR 5.03 [3.46, 7.31]) were highly predictive of being underweight at 30 days of age. In this LMIC cohort, country of birth, male sex, LBW and maternal primiparity increased the risk of impaired growth, as did the modifiable factor of delayed initiation of growth. Interventions tailored to infants with modifiable risk factors could reduce the burden of growth impairment in LMIC.     

Paradigm shift in migraine management impacted by COVID-19 pandemic and the role of confounding factors inflicting the change

Objectives:To assess the impact of the COVID-19 pandemic on migraineur’s quality of life and confounding factors.Methods:This is an observational cohort study conducted in Rashid hospital, Dubai Health Authority, UAE. Study was plotted to assess migraine indices in pre-COVID period, pre-pandemic and pandemic periods and to evaluate the pandemic induced paradigm shift in migraine management.Results:Out of 840 migraineurs 201 patients were selected, with an obvious female predominance (78%). Migraine without Aura was found in 70% and Migraine with Aura in 29.9%. Mean MIDAS score during period I, II and II was 22.78, 18.58 and 17.92 respectively indicating certain degree of improvement rather than deterioration during pandemic (p=0.001). Interestingly significant reduction in both migraine frequency and severity from pre-COVID to COVID period was noticed (p=0.01). Parameters like headache days/month, use of abortive therapy and Emergency visits also declined. Chronic migraine (CM) showed more improvement than episodic migraine (EM). Confounding factors like distance working and lack of social/professional stress mainly rendered this change. A modified strategy to handle headache during any pandemic/crisis can ensure quality management of migraine.Conclusion:Migraine patients had a resilient behavior during the COVID pandemic and showed significant improvement of all indices. Confounding factors like distance working played the most favorable role.

Coronavirus disease 2019 (COVID-19) mainly exerts its effect by binding to receptors in the pulmonary epithelium and blood vessels with a special affinity to ACE2 receptors; release of inflammatory cytokines like IL-6 and TNFα; dysregulation of the immune response; dysregulation of the renin–angiotensin–aldosterone system (RAAS); thrombo-inflammation; and direct viral toxicity. ¹ Awareness of its clinical manifestations has developed over couple of years and thousands of researchers have reported their experiences to illuminate the world about this novel disease.A systemic review on neurological manifestations has shown up a wide spectrum of symptoms, including smell disorders (59%), taste disorder (56%), headache (20%), ischemic stroke (5%), encephalopathy (8.8%), intracerebral hemorrhage (0.45%), encephalitis/meningitis (1.4%), myelitis (1.2%), neuropathy (acute like Guillain-Barre-syndrome) (1.2%) and rhabdomyolysis. ² Headaches are encountered mainly in neurology clinics, reportedly these make 33% of neurology clinic visits. ³ With a serious concern, headaches are a major symptom reported during the COVID-19 pandemic. Headache-related issues can be segregated into 2 main categories: (i) already existing headaches that are affected by COVID or (ii) new headaches introduced by the infection itself or protective gadgets. For instance, frontline healthcare workers in all hospitals were mandated to wear personal protective equipment (PPE) while handling COVID-19 patients. Wearing the N95 mask during severe acute respiratory distress syndrome (SARS) epidemic in Singapore (2003) resulted in the occurrence of novel onset face-mask-associated headaches with a prevalence of 37.3%. ⁴ Similarly, amongst medical professionals using the N-95-mask and protective eyewear for an average of 5.7 hours/day, 81% reported de-novo PPE induced headaches and 91% stated aggravation in their pre-existing headaches. However, certain trigger factors, such as sleep deprivation (60.9%), physical stress (29.3%), emotional stress (13.0%), irregular mealtimes (15.2%), and inadequate hydration (39.1%) contributed too. ⁵ Of the primary headaches, migraine is highly prevalent and is the second leading cause of years-lost-to-disability worldwide. ⁶ Pandemic induced changes in the healthcare model impacted considerably on headaches and other chronic disorders. ⁷ Management protocols, patient consultancy, clinic visit frequency, emergency visit criteria, and all other management protocols were modified during the pandemic. Consequentially, individuals’ suffering from migraines intensified. Certain factors, such as stress, infection, fear of catching infection, isolation, limited options of recreation, altered sleep cycle, and wearing PPE, rendered notable changes in the frequency and severity of migraine. However, there were certain factors which positively impacted on migraineurs’ lives.Our objective in this study was to assess the impact of the COVID-19 pandemic on migraineur’s quality of life and confounding factors. Such studies can play a leading role in devising new protocols for migraine management during any crisis in future.     

Nomogram of peripapillary retinal nerve fiber layer thickness in myopic eyes of north Indian population

Purpose:To evaluate peripapillary-RNFL thickness in myopia by Cirrus OCT among north Indian population by spherical equivalent (SE), age, gender, and axial length (AL).Methods:This was a cross-sectional study held during 2019–2020. Patients aged 18–60 years underwent ophthalmic examination including retinoscopy, AL, and OCT RNFL thickness. Persons with previous ocular surgery or ocular ailment other than refractive error were excluded. The peripapillary-RNFL thickness was noted and compared by demographic determinants.Results:We examined 300 eyes of 300 persons (mean age: 30.75 ± 8.57 years; 144 males/156 females). Among them, 224 were myopes and 76 were emmetropes (EM). The mean SE was − 3.3 ± 0.4D (range: −11.0D to + 0.37D). The mean AL was 24.61 ± 1.92 mm (22.1–29.5). Overall temporal, nasal, superior, inferior, and mean peripapillary-RNFL thickness was 66.31 ± 7.58, 78.57 ± 16.00, 120.63 ± 11.69, 116.60 ± 15.80, and 95.50 ± 10.84 mm, respectively. Temporal, nasal, superior, inferior, and mean peripapillary-RNFL thickness was 73.97 ± 8.36, 94.84 ± 7.63, 127.96 ± 8.96, 136.89 ± 6.53, and 108.34 ± 6.28 mm, respectively, in EM eyes as compared to 63.71 ± 6.18, 73.05 ± 14.24, 118.21 ± 11.53, 109.71 ± 11.50, and 91.14 ± 8.31 mm, respectively, in myopic eyes (P < 0.001). Association of peripapillary-RNFL thickness with myopia and its different grades was P < 0.001. Association of mean peripapillary-RNFL thickness with age was P > 0.005 and gender was P = 0.168. Correlation between SE and RNFL thickness was positive and significant. Correlation between AL and RNFL thickness was negative but statistically significant. Association of AL with SE was P < 0.001.Conclusion:We provide normative peripapillary-RNFL thickness in the north Indian population in order to help in screening for myopia with comorbidity such as glaucoma based on RNFL thickness.