Characterization of Mouse and Human Astrocytes in Amyotrophic Lateral Sclerosis: Effects of Oxidative Stress and Blockade of the Metabotropic Glutamate Receptor 5

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to upper and lower motor neuron (MNs) death. Recognized as a non-cell-autonomous disease, ALS is also characterized by damage and degeneration of glial cells, such as astrocytes, microglia, and oligodendrocytes. Astrocytes acquire a reactive and toxic phenotype defined by an abnormal proliferation and by the release of neurotoxic factors. Recent studies reported that the uptake of [18F]-fluorodeoxyglucose (FDG) is increased in the spinal cord (SC) and decreased in the motor cortex (MC) of patients with ALS, suggesting that the disease might differently affect the two nervous districts with different time sequence or with different mechanisms. Here we show that MC and SC astrocytes harvested from newborn B6SJL-Tg (SOD1G93A) 1Gur (SOD1G93A) mice could play different roles in the pathogenesis of the disease. Spectrophotometric and cytofluorimetric analyses showed an increase in redox stress, a decrease in antioxidant capacity, and a relative mitochondria respiratory uncoupling in MC SOD1G93A astrocytes. By contrast, SC mutated cells showed a higher endurance against oxidative damage, through the increase in antioxidant defense and a preserved respiratory function. Thus, SOD1G93A mutation differently impaired MC and SC astrocyte biology in a very early stage of life. One major cause for MN degeneration in ALS is represented by glutamate-mediated excitotoxicity, due to the alteration of glutamate transmission mechanisms, including glutamate receptor function. In this context, the Group I metabotropic glutamate receptor 5 (mGluR5) has been proposed to play an important role in ALS, since it is largely overexpressed during disease progression and is involved in the altered neuronal and glial cellular processes. My research group previously demonstrated that mGluR5 produces abnormal glutamate release in the spinal cord of the SOD1G93A mouse model of ALS and that halving its expression has a positive impact on in-vivo disease progression, including motor neuron survival, astrogliosis, and microgliosis. They also investigated the consequences of reducing the mGluR5 expression in SOD1G93A mice on the reactive phenotype of spinal cord astrocytes cultured from late symptomatic (120 days old) SOD1G93A mice. Also in this model, reducing the mGluR5 expression ameliorated the astrocyte phenotype. UNIVERSITY OF GENOVA 8 Here, I translated this study to human astrocytes derived from healthy donors and ALS patients. We investigated the in-vitro pharmacological treatment effect of chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP), a negative allosteric modulator of mGluR5 on i-astrocytes differentiated from the inducible neural progenitor cells (iNPCs) obtained from the skin fibroblast (i-astrocytes) of two ALS patients and two healthy donors. The overexpression of anti-glial fibrillary acid protein (GFAP), S100 calcium-binding protein \u3b2 (S100\u3b2), and Complement component 3 (C3), three markers of astrogliosis, was reduced in CTEP-treated i-astrocytes. The same positive effect was obtained in the case of NLR family pyrin domain containing 3 (NLRP3) and nuclear factor erythroid 2-related factor 2 (NRF2), markers strictly related to inflammation and oxidative stress respectively, which are upregulated in ALS astrocytes. In-vitro pharmacological treatment with CTEP also reduced the expression of mGluR5 in mutated i-astrocytes. In addition, the CTEP treatment caused a decrement in antioxidant enzymatic activity such as malondialdehyde (MDA), glucose-6-phosphate dehydrogenase (G6PD), Glutathione reductase (GR), Glutathione peroxidase (GP), and catalase compared to the untreated samples, suggesting that the drug could cause a reduction of oxidative stress. Altogether, these results indicate that reduction of mGluR5 activation has a positive impact on i-astrocytes in ALS patients supporting the idea that the in-vivo amelioration of the disease progression, registered after mGluR5 genetical or pharmacological silencing, involve an astrocyte phenotype improvement also in humans. As a whole, mGluR5 may represent a potential therapeutic target to preserve MNs from death, also by modulating the reactive astroglial phenotype in ALS

Optimum Percentage of Sawdust and Brick Ballast in Light Weight Concrete

Construction industry relies heavily on conventional material such as cement, sand and gravel for the production of concrete The river sand and gravels which are most commonly used as fine aggregates and coarse aggregates respectively in the production of concrete, poses the problem of acute shortage in many areas, whose continued use has started posing serious problem with respect to its availability, cost and environmental impact. Attempt is being made in this project to use the locally available waste materials to replace the river sand and gravels to produce light weight and low cost concrete. Sawdust and Brick ballast are easily affordable at low costs, which are partially replaces with river sand and gravels respectively for making concrete. Natural sand and Gravels have been partially replaced (4% SD 8% BB, 4% SD 16% BB, 4% SD 24% BB, 8% SD 8% BB, 8% SD 16% BB, 8% SD 24% BB, 12% SD 8% BB, 12% SD 16% BB and 12% SD 24% BB. by using M30 grade of concrete) with sawdust and broken brick ballast respectively. For this, thirty concrete cubes of size 150mm X 150mm X 150mm have been casted and water cement ratio of 0.42 has been used. Water reducing admixture is used to increase the workability. Slump test, Compacting factor test and compressive strength at (28 days) of specimens having above combinations have been compared with control specimens. The workability and compressive strength gradually decreases for the increasing the replacement percentages. The optimum mix found to produce M30 grade of concrete is 8% of sawdust and 16% of Brick ballast

Healthcare Expenditure on Childbirth in India: Two Part Model Analysis

The aim of the study is to estimate the extent and determinants of healthcare expenditure of inpatients on childbirth in India. The study is based on sample of 14510 women who gave birth to a child (whether live or still-birth, vaginal or caesarean). To estimate the determinants two-part models has been utilised. The results indicate that women spent on average around INR 9103 per childbirth in hospitals. There are also wide variations in the spending pattern of women on childbirth. Household size, economic status, occupation, religion, and caste impact the expenditure on childbirth in hospitals. There are also wide variations in the spending of women belonging to different geo-graphical locations of India. Surgeries/caesarean or utilisation of facilities like special room and diagnostic tests etc. also significantly increase the expenditure. Women opting for public health facilities or having insurance spend less as compared to others. Government of India should increase investment in health to strengthen its current infrastructure. There is dire need to improve the quality of public health facilities, to reduce the regional imbalances in health facilities, to improve the coverage of health insurance in India for equitable and pro-people health facilities

Bird fancier’s lung: clinical-radiological presentation in 15 cases

Wstęp: Płuco hodowców ptaków (BLF, bird fancier lung) jest chorobą śródmiąższową rozwijającą się u chorych w odpowiedzi na kontakt wziewny z alergenami ptaków (białka ptasich piór i odchodów). Rozpoznanie ustala się na podstawie charakterystycznego wywiadu, obrazu klinicznego oraz wyniku biopsji płuca. Celem obecnej pracy była analiza przypadków BFL w materiale własnym.Materiał i metody: Poddano retrospektywnej analizie przypadki BFL rozpoznane w Vallabhbhai Patel Institute w okresie dwóch lat: 2013 i 2014. Rozpoznanie BFL ustalono zgodnie z kryteriami ustanowionymi przez Marka Schuylera i Yvon Cormier.Wyniki: W omawianym przedziale czasu rozpoznanie BFL ustalono u 15 chorych, dwunastu kobiet i trzech mężczyzn, w średnim wieku 54,93 ±14,21 roku. Wszyscy chorzy zgłaszali narażenie na kontakt z gołębiami, były to osoby niepalące. Czas od początku objawów choroby do ustalenia rozpoznania wynosił 1−8 lat. Głównymi objawami zgłaszanymi przez chorych były duszność wysiłkowa i kaszel. W badaniach radiologicznych stwierdzano rozproszone guzki śródzrazikowe, obszary matowej szyby, dominujące w płatach górnych, włóknienie, niekiedy z obecnością rozstrzeni z pociągania, zmiany o typie plastra miodu oraz powiększenie węzłów chłonnych śródpiersia. W materiale z biopsji płuca pobranej przez bronchofiberoskop stwierdzano słabo uformowane ziarniniaki oraz cechy przewlekłego śródmiąższowego zapalenia.Wnioski: Płuco hodowców ptaków może powodować szeroką gamę obrazów radiologicznych, dlatego u każdego chorego na śródmiąższową chorobę płuc należy zwrócić uwagę na historię ekspozycji na alergeny wywołujące BLF.Introduction: Bird fancier’s lung (BFL) is a type of hypersensitivity pneumonitis occurring in response to avian antigens (usually inhaled proteins in bird feathers and droppings). The diagnosis is based on a combination of clinical, radiological, and biopsy characteristics. The present study was planned to highlight the clinico-radiological presentation in cases of BFL.Material and methods: The present study is a retrospective analysis of cases of bird fancier’s lung diagnosed in a unit of Vallabhbhai Patel Chest Institute over a period of two years, from 2013−2014. The clinico-radiological features of the subjects were analysed. The diagnosis of BFL was made as per criteria laid down by Mark Schuyler and Yvon Cormier.Results: There were a total of fifteen cases diagnosed with BFL during the study period, comprising twelve females and three males with a mean age of 54.93 ± 14.21 years. All the studied subjects gave significant history of exposure to pigeons and were non-smokers. The period of symptoms prior to presentation varied from one to eight years. The main symptoms on presentation were exertional breathlessness and cough. Radiologically, diffuse centrilobular nodules, ground glassing — diffuse or patchy predominant in upper lobes, fibrosis with or without traction bronchiectasis, honeycombing, and mediastinal lymphadenopathy were seen. Bronchoscopy showed ill-defined granulomas and chronic interstitial inflammation.Conclusions: BFL can exhibit a wide range of radiological patterns, and a high index of suspicion must be maintained, with particular attention to detailed exposure history in every case of interstitial lung disease

COUMARINS: A UNIQUE SCAFFOLD WITH VERSATILE BIOLOGICAL BEHAVIOR

Benzopyrones are the club of compounds that can be coumarins or flavonoids. The hydroxyl derivatives of coumarins such as 4-hydroxycoumarins and 7-hydroxycoumarins have extensive biological activities which have employed for the synthesis of miscellaneous coumarin derivatives. These derivatives have exhibited impressive pharmacological and physiological activities such as anticoagulant, antibacterial, antiviral, antitumor, bactericidal, fungicidal, anti-inflammatory agents, and anti-HIV activity. This review comprised pharmacokinetic studies, including absorption, distribution, and metabolism of coumarin analogs along with toxicological studies. The studies of coumarins and their derivatives exhibiting immense pharmacological activity are also summarized in the current study

Cardinal invariants and special maps of quasicontinuous functions with the topology of pointwise convergence

[EN] For topological spaces X and Y, let Qp(X,Y) be the space of all quasicontinuous functions from X to Y with the topology of pointwise convergence. In this paper, we study the cardinal invariants such as cellularity, character, weight, density, pseudocharacter and spread of the space Qp(X,Y). We also discuss the properties of the restriction and induced maps related to the space Qp(X,Y).The first author acknowledges the fellowship grant of University Grant Commission, India with Student-ID DEC18-414765.Kumar, M.; Tyagi, BK. (2022). Cardinal invariants and special maps of quasicontinuous functions with the topology of pointwise convergence. Applied General Topology. 23(2):303-314. https://doi.org/10.4995/agt.2022.1692530331423

Knowledge, attitude, and practice of healthcare professionals about adverse drug reaction in major tertiary care teaching hospital in Punjab

Background: Adverse drug reaction (ADR) has a severe morbidity and mortality associated with it. The safe use of medicines is a critical issue for all healthcare professionals, including physicians, pharmacists, and nurses as well as the public. The main objective of this study was to evaluate the knowledge, attitude, and practice (KAP) of healthcare professionals about ADRs in a tertiary care teaching hospital.Methods: A cross-sectional survey was carried out among the health care professionals in India using a pre-tested questionnaire with 30 questions (18 questions on knowledge, 6 on attitude, 5 on practice, and 1 on training about reporting of ADR). The study was conducted, over a period of 6 months.Results: The questionnaire was distributed to the respondents (n=200). The response rate of 85% was recorded. Among these, only 82 questionnaires were filled in pre-test and 88 questionnaires were filled in post-test after improving awareness through pamphlets. Of the total completed questionnaire (88), 34.88% were filled by physicians, 8.53% by pharmacists, 27.9% by nurses, and 31.3% by medical and paramedical interns.Conclusions: The health care professionals have little KAP toward ADR reporting. Healthcare professionals with higher experience such as (>10 years experience) have better KAP. With additional training on pharmacovigilance, the Indian healthcare professionals working in different sectors can become part of ADR reporting system

Effect of obesity and metabolic syndrome on severity, quality of life, sleep quality and inflammatory markers in patients of asthma in India

Introduction: The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients. Material and methods: 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study. Results: The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p < 0.05), high risk of OSA (p < 0.05), decreased lung volumes (FRC) (p < 0.05), higher levels of inflammatory markers (leptin and IL-6) (p < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients. Conclusions: The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control.  INTRODUCTION: The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients. MATERIAL AND METHODS: 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study. RESULTS: The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p  < 0.05), high risk of OSA (p < 0.05), decreased lung volumes (FRC) (p < 0.05), higher levels of inflammatory markers (leptin and IL-6) (p  < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients. CONCLUSIONS: The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control.