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Background: Breast cancer (BC) has now surpassed lung cancer as the leading cause of global cancer incidence in 2020, with an estimated 2.3 million new cases, representing 11.7% of all cancer cases. It is a highly heterogeneous disease with a variety of morphologic and clinical manifestations which results in a range of responses to treatment. Recently, targeted therapies based on the genetic, hormonal, or immunohistochemical (IHC) subtypes of breast cancer have been used. Objective: The study was a prospective hospital-based observational study with a sample size of 150 cases. The study aimed to determine the distribution of various molecular subtypes of breast carcinoma and also correlate the expression status of ER, PR, Her2neu, and Ki 67 with the patient's age, tumor size, tumor type, histological grade, lymph node status, and TNM staging. Results: 96.7% of cases were invasive ductal carcinoma (NOS). Most of the grade 1 tumors (68.8%) were both ER and PR positive. Grade 2 tumors had almost equal distribution with 39.4% of patients being ER & PR positive and 43.7% being both ER & PR negative. Almost all grade 3 tumors (88.9%) were both ER and PR -negative. Conclusion: IHC markers are cost-effective and easily available worldwide even in resource-poor countries like India. A greater understanding of the molecular classification of breast carcinoma based on triple markers will help in the development of targeted therapies that will lead to increased efficacy, decreased toxicity, increased disease-free survival, and better selection of patients who will benefit from treatment.

To assess the hospitalized sick children admitted to the pediatric emergency department (ED) and to find new patterns of clinical and laboratory attributes using association rule mining (ARM).In this observational study, 158 children with median (IQR) age 11 months and a PRISM III score of 5 (2-9) were enrolled. Hotspot data mining method was applied to assess clinical attributes, lab investigations and pre-defined outcome parameters of children and their association in sick hospitalized children aged 1 month to 12 years.We obtained 30 rules with value for outcome as discharge is given attributes as follows: duration of hospitalization4 days, lactate1.2 mmol/L, platelet = 3.67/μL, dur_ventil = 0 h, serumARM is an effective data analysis technique to find meaningful patterns using clinical features with actual numbers in pediatric critical illness. It can prove to be important while analysing the association of clinical attributes with disease pattern, its features, and therapeutic or intervention success patterns.

Abstract: Computer-based modelling and simulation are developing as effective tools for supplementing biological data processing and interpretation. It helps to accelerate the creation of dosage forms at a lower cost and with the less human effort required to conduct the work. This paper aims to provide a comprehensive description of the different computer simulation models for various drugs along with their outcomes. The data used are taken from different sources, including review papers from Science Direct, Elsevier, NCBI, and Web of Science from 1995- 2020. Keywords like – pharmacokinetic, pharmacodynamics, computer simulation, whole-cell model, and cell simulation, were used for the search process. The use of computer simulation helps speed up the creation of new dosage forms at a lower cost and less human effort required to complete the work. It is also widely used as a technique for researching the structure and dynamics of lipids and proteins found in membranes. It also facilitates both the diagnosis and prevention of illness. Conventional data analysis methods cannot assess and comprehend the huge amount, size, and complexity of data collected by in vitro, in vivo, and ex vivo experiments. As a result, numerous in silico computational e-resources, databases, and simulation software are employed to determine pharmacokinetic (PK) and pharmacodynamic (PD) parameters for illness management. These techniques aid in the provision of multiscale representations of biological processes, beginning with proteins and genes and progressing through cells, isolated tissues and organs, and the whole organism.

Delirious mania has been described as a state of acute excitement, fluctuating sensorium, affective and catatonic symptoms. Electroconvulsive therapy (ECT) despite being an effective treatment modality in such cases, has been under-utilised during pregnancy, mainly due to safety concerns. Here, we report the effectiveness of ECT in acute management of delirious mania in a 24 weeks pregnant woman who also tested COVID-19 positive during hospitalisation. Patient presented with three weeks history of acute manic excitement with period of altered sensorium and catatonic symptoms with no response to trials of two antipsychotic agents. After organic causes ruled out, patient was planned for ECT while ongoing antipsychotic was continued. After the first ECT session, patient tested positive for COVID-19, though asymptomatic and had to be shifted to COVID-19 isolation facility. Complete resolution of psychiatric symptoms occurred after fifth ECT. All five ECT sessions, including those in COVID-19 isolation facility were carried out under supervision of a multidisciplinary team. None of the ECT sessions had any major adverse event. Symptom remission sustained even following ECT discontinuation. No neonatal or maternal adverse effects observed after an uneventful delivery at 35 weeks. Both mother and child continued to maintain well in follow-up period of one year on oral olanzapine. In this unusual concurrent presentation of mania, delirium and catatonic symptoms during second trimester pregnancy, we highlighted the effectiveness and safety of ECT as a viable treatment modality. Additionally, management challenges posed by patient testing COVID-19 positive and then, administering ECT in COVID-19 isolation facility using personal protective equipment by multidisciplinary team has been highlighted.

Environmental factors like ionizing radiation induced generation of reactive oxygen species (ROS) cause macromolecular damage under physiological conditions. Proteins are the potential targets of ROS induced oxidative damage because of their abundance and their critical functions in the biological systems. The present study investigates the protective potential of ethyl pyruvate (EP) against ionizing radiation induced oxidative damage of bovine serum albumin (BSA) using spectroscopic, biochemical and SDS-PAGE techniques. Spectroscopic data shows that EP prevents the build up of protein damage markers like bityrosine formation and oxidation of tryptophan. Protein melting studies shows that the melting temperature (Tm) of the irradiated protein does not change significantly in the presence of EP. Biochemical assays indicate that ionizing radiation causes the generation of carbonyls and malondialdehyde and the loss of thiol content in proteins that is prevented by EP. The SDS-PAGE profile of gamma irradiated BSA shows the radioprotective effect of EP. These results indicate the radiation induced oxidative and molecular changes in the protein and that the EP protected the BSA from these modifications. Therefore, these results imply that EP has a good antiradical property and hence it can be proposed as a good radioprotective agent.

The paper investigates the potential of circular economy of authorized e-waste collectors, dismantlers, and recyclers of Maharashtra. The study determines the drivers and barriers associated with e-waste collection in the region. Furthermore, it explores the handling techniques including dismantling, recycling, and scrap disposal. This is done through a case study of a recycling company based in Mumbai, Maharashtra. A questionnaire-based survey is used to study e-waste processing units. The qualitative analysis of the questionnaire shows that lack of awareness of environmental impact is the greatest constraint in the collection of e-waste and data security is the most crucial driver for enhancing the collection of e-waste. The case study reveals that the quantity and type of e-waste are more important than the distance between the processing unit and the collection point. It discloses that the primary factor for building trust between e-waste collectors and waste holders is data security.

Background: Pits and Fissures are recognized as being highly susceptible to caries. Pit and fissure sealants are one of the best methods of preventing caries as it occludes the fissures and pits from the accumulation of plaque and cariogenic microflora. There are different methods of cleaning and preparing occlusal pits and fissures for preventing caries which helps in alleviating oral health status of paediatric population. Aim: The aim of the present study was to evaluate and compare the microleakage of pit and fissure sealants after using five different preparation techniques, namely: A) Conventional technique using pumice prophylaxis, B) enameloplasty with round carbide bur, C) enameloplasty with fissurotomy bur, D) air polisher, and E) air abrasion. Materials and Methods: The study was conducted on 50 caries-free premolars extracted for orthodontic purpose. These teeth were randomly assigned to five groups, 10 teeth in each for receiving fissure sealant after different surface preparation; thermocycling and sectioning of samples were performed and microleakage was assessed under a stereomicroscope after methylene blue dye immersion. Results: The results of air abrasion groups were significantly superior with “0” microleakage when compared to all other groups followed by round bur, fissurotomy bur, air polisher and pumice prophylaxis. Conclusion: To improve the marginal adaptation of the sealants, minimally invasive methods are the most favoured methods of occlusal preparation. This study promises to show positive results for fissure sealants which are likely to play an important role in caries prevention and techniques that are intended to protect caries susceptible surfaces.

Vildagliptin (VDG)is a frontier drug for diabetes mellitus. It is prescribed both in the monotherapy as well as in an amalgamation with other antidiabetic drugs. Drug-serum protein binding is an essential parameter which influences ADME properties of the drug. In current study, binding of VDG with serum protein (bovine serum albumin: BSA) was investigated using multi-spectroscopic techniques. A computational approach was also employed to identify the binding affinity of VDG with BSA at both Sudlow I and II sites. An enzyme activity assay specific for esterase was also investigated to know the post-binding consequences of VDG with BSA. Fluorescence spectra of BSA samples treated with VDG shows static quenching with binding parameters for VDG-BSA complex show single class of equivalent binding stoichiometry(n = 1.331) and binding constant 1.1 x 104M−1 at 298.15 K. The binding constant indicates important role of non-polar interactions in the binding process. Fluorescence resonance energy transfer (FRET) analysis of VDG absorption spectra and emission spectrum of BSA confirmed no significant resonance in energy transfer. Synchronous fluorescence of BSA after binding with VDG show maximum changes in emission intensity at tryptophan (Trp) residues. Post binding with VDG, BSA conformation changes as suggested by circular dichorism (CD) spectra of BSA and this lead to enhanced protein stability as indicated by a thermal melting curve of BSA. Communicated by Ramaswamy H. Sarma

G-quadruplex (GQ) architecture is adopted by guanine rich sequences, present throughout the eukaryotic genome including promoter locations and telomeric ends. The in vivo presence indicates their i...

The human β-globin gene Locus Control Region (LCR), a dominant regulator of globin gene expression contains five tissue-specific DNase I-hypersensitive sites (HSs). A single nucleotide polymorphism (SNP) (A → G) present in HS4 region of locus control region (LCR), have shown a notable association between the G allele and the occurrence of β-thalassemia. This SNP site exhibiting a hairpin - duplex equilibrium manifested in A → B like DNA transition has previously been reported from this laboratory. Since, DNA is a dynamic and adaptable molecule, so any change of a single base within a primary DNA sequence can produce major biological consequences commonly manifested in genetic disorders such as sickle cell anemia and β-thalassemia. Herein, the differential behavior of sequential single base substitutions G → A on the quasi-palindromic sequence (d-TGGGGGCCCCA; HPG11) has been explored. A combination of native gel electrophoresis, circular dichroism (CD), and UV-thermal denaturation (Tm) techniques have been used to investigate the structural polymorphism associated with various variants of HPG11 i.e. HPG11A2 to HPG11A5. The CD spectra confirmed that all the HPG11 variants exhibit a hairpin - duplex equilibrium. Oligomer concentration dependence on CD spectra has been correlated with A → B DNA conformational transition. However, as revealed in gel electrophoresis, HPG11A2 → A5 exhibit the formation of a tetramolecular structure (four-way junction) at higher oligomer concentration. UV-melting studies also supported the melting of hairpin, duplex and four-way junction structure. This polymorphism pattern may possibly be significant for DNA-protein recognition, in the process of regulation of LCR in the β-globin gene.

Neonatologist-performed echocardiography (NPE) is a useful tool for managing sick neonates and those with congenital heart disease and rhythm abnormalities.1 2 NPE is being adopted in UK clinical practice; however, not all units have neonatologists performing echocardiography or robust governance systems for peer review.3 Singh et al ’s survey informed that while almost all neonatal sub-specialty trainees would like to develop echocardiography skills, a significant proportion reported the lack of opportunities to do so.4 With the recognition of the need for training, peer review of echocardiograms and shared learning, a virtual learning platform was launched in the West Midlands Region. All neonatal units in the region were invited to lead the sessions on a rotational …

ObjectivesTo evaluate the continued impact of pulse oximetry screening (POS) in a regional neonatal unit (NNU) and identify trends in screening outcomes in comparison with our previous experience.DesignRetrospective review of admissions between April 2013 and March 2019 (the current study) and comparison with previously published data (the 2014 study).PatientsAll infants >34 weeks completed gestation admitted to NNU as a result of positive POS.Outcome measuresIndication for admission, diagnosis, investigations and management.ResultsThere were 49 375 livebirths and 253 NNU admissions as a result of positive POS (0.5% of livebirths; compared with 0.8% in 2014). 247/253 (97.6%) of those admitted had a significant diagnosis requiring medical intervention (compared with 79% in 2014) and the proportion of healthy babies (with transitional circulation) admitted decreased from 21% to 2.4%.22 (9%) babies admitted as a result of a positive POS were found to have a previously undiagnosed congenital heart defect (CHD) of which eight were critical CHDs (CCHDs). This accounted for 73% of all undiagnosed CCHD undergoing POS. The antenatal detection rate of CCHD was 75% compared with 46% in 2014. No baby died or collapsed on the postnatal ward during the study period. The proportion of babies with CCHD identified before discharge improved from 94% to 99%.ConclusionsRoutine POS, in addition to antenatal screening and postnatal examination, continues to contribute to the improvement of our overall CCHD detection rates. We have demonstrated an overall reduction in the admission of healthy babies and therefore workload following a positive test.

Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) that are associated with epithelial cell dysfunction, cilia shortening, and mucociliary clearance disruption. Exposure to CS reduced cilia length and induced autophagy in vivo and in differentiated mouse tracheal epithelial cells (MTECs). Autophagy-impaired (Becn1+/– or Map1lc3B–/–) mice and MTECs resisted CS-induced cilia shortening. Furthermore, CS increased the autophagic turnover of ciliary proteins, indicating that autophagy may regulate cilia homeostasis. We identified cytosolic deacetylase HDAC6 as a critical regulator of autophagy-mediated cilia shortening during CS exposure. Mice bearing an X chromosome deletion of Hdac6 (Hdac6–/Y) and MTECs from these mice had reduced autophagy and were protected from CS-induced cilia shortening. Autophagy-impaired Becn1–/–, Map1lc3B–/–, and Hdac6–/Y mice or mice injected with an HDAC6 inhibitor were protected from CS-induced mucociliary clearance (MCC) disruption. MCC was preserved in mice given the chemical chaperone 4-phenylbutyric acid, but was disrupted in mice lacking the transcription factor NRF2, suggesting that oxidative stress and altered proteostasis contribute to the disruption of MCC. Analysis of human COPD specimens revealed epigenetic deregulation of HDAC6 by hypomethylation and increased protein expression in the airways. We conclude that an autophagy-dependent pathway regulates cilia length during CS exposure and has potential as a therapeutic target for COPD.

Objectives Maternal sepsis is a life-threatening condition. Biomarkers have been found to be useful in early detection of sepsis in the critical care setting. We aimed to determine the diagnostic performance of different biomarkers such as procalcitonin, C-reactive protein (CRP), absolute eosinophil count, and activated partial thromboplastin time (aPTT) in maternal sepsis. Methods A total of 35 patients were enrolled in this prospective observational study. Patients with suspected sepsis were evaluated for multi-organ dysfunction. The blood samples for testing of these biomarker levels were obtained at the time of enrollment in the study (day 1), and on day 3 and day 7. Trends of each marker were followed and correlated with the clinical picture. Results Of 35 enrolled patients, 30 completed the study. Among these, 18 had sepsis and 12 were designated as without sepsis. Sensitivities of procalcitonin, CRP, aPTT, and absolute eosinophil count were 83.33%, 77.78%, 55.56%, and 58.82% whereas their specificities were 66.67%, 75.0%, 100%, and 75%, respectively. Area under the curve was highest for procalcitonin (0.813) followed in decreasing order by CRP (0.778), aPTT (0.731), and eosinophil count (0.642), respectively. Conclusion Procalcitonin and CRP may be used as a valuable adjunct in the clinical stepwise approach for the prompt diagnosis of maternal sepsis.

DNA is the store house of all necessary hereditary information for growth of cells and tissues. Physiological functionality of DNA depends on its 3D helical structure and any distortion in a structure may lead to mutation and genomic instability that may translate into disease like cancer. In order to prevent DNA damage, an exogenous compound is required that can either scavenge the excess free radicals or enhance the structural integrity of DNA through binding. In the present study, the binding mechanism of ethyl pyruvate (EP) with DNA models using different spectroscopic techniques was investigated for their structural integrity. Besides, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays were performed to determine the antioxidant scavenging of EP. Plasmid DNA relaxation assay was performed to assess the radioprotection efficacy of EP in the plasmid DNA. Circular dichroism (CD) and UV–Vis absorbance spectroscopic data confirmed the conformation change in ctDNA upon binding with EP. The molecular docking visualized that EP stacks between the DNA bases with a glide score of −2.117 k c a l m o l while EP binds in the minor groove region of DNA with the glide score of −1.414 k c a l m o l . DPPH and FRAP data confirmed that EP scavenges significantly radicals at higher concentrations. In vitro radioprotection study in plasmid DNA pBR322 showed that EP retained the supercoiled form of plasmid DNA at 50 Gy radiation dose.

Introduction: Mandibular angle fracture is common in road traffic accidents. This study was conducted to compare 3D miniplate system with 2D plates for treatment of mandibular angle fractures. Materials and Methods: The study was conducted on 120 patients with mandibular angle fracture of both genders. After selecting patients, patients were divided into 2 groups of 60 each. In group I, patients were treated with 3D, 2.0-mm titanium plates, and in group II, patients were treated with 2D, 2.0-mm titanium miniplate in mandibular angle fracture. Patients were evaluated regularly after 1, 3, and 6 months for outcome of treatment. Results: In group I, males were 22 and females were 38. In group II, males were 40 and females were 20. Right angle fracture was seen in 32 patients in group I and 26 in group II. Left angle fracture was seen in 24 in group I and 28 in group II. Right angle and left parasymphysis fracture was seen in 3 in group I and 4 in group II. Left angle and right parasymphysis fracture was seen in 1 in group I and 2 in group II. [Table 3], [Graph 1] shows that in group I, after 1 month sensory deficit was present in 5 patients and in group II in 12 patients. After 3 months, there were no patients with sensory deficit in group I and 2 in group II. Preoperatively in group I, mouth opening was 24 mm and in group II patients was 25.80 mm, which increased to 31.20 mm in group I and 28.20 mm in group II at 1 month, 32 mm in group I and 30 mm in group II at 3 months, and 37.20 and 32.12 mm in groups I and II, respectively, at 6 months. The difference was significant (P < 0.05). Conclusion: 3D miniplate system is reliable and effective treatment modality for mandibular angle fractures as compared with traditional 2D miniplates.[INLINE:1]

Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this immune response is co-opted into contributing toward tumor growth instead of preventing its progression. We seek to reestablish an antitumor immune response by selectively targeting surface receptors and endogenous signaling processes of the macrophage subtypes driving cancer progression. RP-182 is a synthetic 10-mer amphipathic analog of host defense peptides that selectively induces a conformational switch of the mannose receptor CD206 expressed on TAMs displaying an M2-like phenotype. RP-182-mediated activation of this receptor in human and murine M2-like macrophages elicits a program of endocytosis, phagosome-lysosome formation, and autophagy and reprograms M2-like TAMs to an antitumor M1-like phenotype. In syngeneic and autochthonous murine cancer models, RP-182 suppressed tumor growth, extended survival, and was an effective combination partner with chemo- or immune checkpoint therapy. Antitumor activity of RP-182 was also observed in CD206(high) patient-derived xenotransplantation models. Mechanistically, via selective reduction of immunosuppressive M2-like TAMs, RP-182 improved adaptive and innate antitumor immune responses, including increased cancer cell phagocytosis by reprogrammed TAMs.

The paper provides a systematic literature review to investigate whether circular economy (CE) performance in the technical cycle will contribute to the sustainable development. Two academic databases, namely Scopus and Web of Science were used to retrieve research papers which span over the period 2000-2019. The research articles were classified according to the Sustainable Development Goals (SDG's) addressed, industries involved, key areas of CE, pillars of sustainability, CE principles (R-Imperatives and Systems perspective), type of cycle in CE, and transversality (generic, product-specific and sector-specific). The review highlights various research gaps concerning the proposed classification. The research gaps will provide new emerging areas to the CE and will help to align the CE performance with the SDGs.

Port site metastasis is a rare complication and carcinosarcoma is itself a rare malignant tumour of the ovary. Hereby, Authors report a case of an ovarian carcinosarcoma which was retrospectively diagnosed from the metastasis which developed at the specimen retrieval port site of primary laparoscopic surgery. A 48-year-old nulliparous lady underwent laparoscopic cystectomy previously for endometrioma. Six months postlaparoscopy, she developed pain and palpable mass at the trochar site. Fine Needle Aspiration Cytology (FNAC) showed metastatic adenocarcinoma of ovarian origin confirmed by immunohistochemistry. Six cycles of chemotherapy followed by total hysterectomy, resection of the mass and attached tubal segment, opposite salpingo-oophorectomy and omentectomy was done. Post-surgery, patient was followed-up with three chemotherapy sessions. Final histopathological report showed carcinosarcoma of ovary at port site with omental deposit.

Moving bed biofilm reactor (MBBR) is a highly effective biological treatment process applied to treat both urban and industrial wastewaters in developing countries. The present study investigated the technical performance of ten full-scale MBBR systems located across India. The biochemical oxygen demand, chemical oxygen demand, total suspended solid, pathogens, and nutrient removal efficiencies were low as compared to the values claimed in literature. Plant 1 was considered for evaluation of environmental impacts using life cycle assessment approach. CML 2 baseline 2000 methodology was adopted, in which 11 impact categories were considered. The life cycle impact assessment results revealed that the main environmental hot spot of this system was energy consumption. Additionally, two scenarios were compared: scenario 1 (direct discharge of treated effluent, i.e., no reuse) and scenario 2 (effluent reuse and tap water replacement). The results showed that scenario 2 significantly reduce the environmental impact in all the categories ultimately decreasing the environmental burden. Moreover, significant economic and environmental benefits can be obtained in scenario 2 by replacing the freshwater demand for non-potable uses. To enhance the performance of wastewater treatment plant (WWTP), there is a need to optimize energy consumption and increase wastewater collection efficiency to maximize the operating capacity of plant and minimize overall environmental footprint. It was concluded that MBBR can be a good alternative for upgrading and optimizing existing municipal wastewater treatment plants with appropriate tertiary treatment. Graphical abstract ᅟ.

Soil biotechnology (SBT) is a green engineering approach for wastewater treatment and recycling. Five SBT units located in the Mumbai region were under consideration of which holistic assessment of two SBT plants was carried out considering its technical, environmental and economic aspects and was compared with published research of other three. LCA has been done to evaluate the environmental impacts of construction and operation phase of SBT. Chemical oxygen demand (COD) and biochemical oxygen demand (BOD) removal of more than 90% can be achieved using this technology. Also, the nutrient removal proficiency (nitrate, nitrite, ammoniacal nitrogen, TKN, total nitrogen and phosphates) of this technique is good. On the other hand, SBT has low annual operation and maintenance cost, comparable to land-based systems and lower than conventional or advanced technologies. From the life cycle impact assessment, the main contributors for overall impact from the plant were identified as electricity consumption, discharges of COD, P-PO43- and N-NH4+ and disposal of sludge. The construction phase was found to have significantly more impact than the operation phase of the plant. This study suggests plant I is not relatively as efficient enough regarding sanitation. SBT provides several benefits over other conventional technologies for wastewater treatment. It is based on a bio-conversion process and is practically maintenance free. It does not produce any odorous bio-sludge and consumes the least energy.

Malaria is a critical human disease with extensive exploration yet unestablished due to occurrence of frequent drug resistance. This aspect of malaria pharmacology calls for the introduction of new antimalarial. The drugs reported till date targeted different stages of the parasites in order to stop their growth and proliferation. Beside this, various drugs that could inhibit the imperative enzymes of the parasite have also been reported. Amid them, dihydroorotate dehydrogenase (DHODH) has a key worth. DHODH is involved in the de novo pyrimidine biosynthesis of the malarial parasite which acts as a primary source of energy for its survival. Since life of the parasite utterly depends on pyrimidine biosynthesis, so it can be used as an apt drug target for malaria eradication. In addition to this, DHODH is also present in human and their active sites have significant structural dissimilarities, so the development of selective inhibitors may prove to be a milestone in search of new antimalarials. Inhibitors of human DHODH have been used to treat autoimmune diseases such as, rheumatoid arthritis or multiple sclerosis and have been investigated in the treatment of cancer, viral diseases, as well as in plant pathology. Here, we have reviewed the important role of DHODH as a viable drug target against malaria, its importance for the survival of the parasite, and DHODH inhibitors reported so far. The rate of success of the reported DHODH inhibitors and further required improvements have also been accounted.

Ecolabeling helps consumers to select environment friendly products, while meeting high demands on occupational health, safety, and usability. Ecolabeling undertakes cradle-to-grave approach which helps in minimizing the toxicological impacts at every stage of the product life cycle. The ecolabeling procedure calls for substitution or reduction of hazardous substances thereby reducing the toxicity caused due to these chemicals. China, Japan, Australia, European Union, and Nordic countries are leading in the race of awareness and implementation of ecolabeling schemes. In India, the ecolabeling scheme (Ecomark) was initiated in 1991. The Ecomark scheme lacked adoption of the green marketing principles and thus failed to create an impact. This study presents an overview of ecolabels in European Union, Nordic countries, Germany, China and India. Furthermore, it assesses the awareness of ecolabels among the retailers and traders of environment friendly products in India through a survey. The study highlights that the ecolabels are a success in most of the countries studied and are applied across a range of industrial sectors. The survey is administered to 80 retailers and traders of stores selling environment friendly products across different Indian cities. A correlation is established with the variables identified. The survey results indicate that although the retailers and traders of environment friendly products have low awareness of the ecolabels on environment friendly products, they are taking considerable efforts to promote and deliver environment friendly products to consumers. Large-scale awareness drives initiated by the Ministry of Environment, Forests & Climate Change permeating at grass root levels with the involvement of stakeholders could prove beneficial for promotion of the ecolabeling schemes.

The physicochemical and functional characteristics of grain, meal and flour of timely sown wheat (TSW) and delayed sown wheat (DSW) were compared to see the effects of heat stress (HS). TSW and DSW of different lines were sown as per the approved timings. DSW experienced higher temperature during flowering and had shorter vegetative and maturation period than TSW. Pasting and dough rheological properties were measured using Rapid Visco-Analyser and Farinograph, respectively, while gliadins and glutenins profiling was done by SDS-PAGE. Delayed sowing decreased grain yield and diameter while increased protein and all categories of gliadins and high molecular weight glutenins. DSW showed higher peak viscosity, breakdown-viscosity and dough stability and lower setback viscosity, damaged starch, arabinoxylans and water absorption than TSW. HS in DSW appeared to lower starch synthesis causing proportionate increase in grain hardness and proteins content leading to changes in milling and rheological characteristics.

Wheatgrass juice powder (WJP) from four wheat varieties grown using soil, coco-peat with nutrient solution (CNS) and water (soaked (8 h), germinated (36 h) and harvested on 10th day) were examined for proximate composition, mineral, amino acid, phenolic (free and bound) composition and antioxidant properties. The yield, ash and protein contents of WJP ranged between 4.88–7.87%, 5.18–15.93% and 38.75–50.17%, respectively. The total phenolic, flavonoid, chlorophyll content (TCC) and antioxidant activity varied from 12.02 to 17.44 mg GAE/g, 4.38–10.10 mg QE/g, 3.01–5.63 mg/g, and 13.54–17.33 μmol TE/g, respectively. HD-3086 grown using soil exhibited highest antioxidant properties, TCC and Mg content. WJP of C-306 grown using CNS had abundant essential amino acids (AAs). Phenolic acids (ferulic, syringic and sinapic acids) and flavonoids (catechin, rutin, vitexin and isovitexin) and minerals (K, P, Ca, Mg, Na and Fe) were predominant in WJP. The AAs and free phenolics were more in CNS and soil grown WJP, respectively.

Solar retinopathy (SR) results from unprotected solar eclipse viewing and also from gazing at the sun for a long duration. It has been known for a long that direct viewing of the sun causes visual disruption. Usually, there is a disruption of the inner segment–outer segment junction, but an association of central serous chorioretinopathy (CSCR) with SR is quite rare. We report a case of CSCR associated with solar eclipse viewing.

Urban open and green spaces provide various ecosystem services such as aesthetics, biodiversity, recreation and most importantly health. These spaces, especially in an urban area, are beneficial for the physical and mental health of people. These services become more important at the time of social and health crisis such as COVID-19. Access to urban open and green space with suitable precautionary measures such as social distancing and personal hygiene would have improved individuals resilience during the pandemic. Due to the COVID-19 imposed lockdown, people were forced to isolate with no access to any of the recreational spaces to combat the global challenge. Once the lockdown was eased in India, the public focus shifted towards the need for urban green and open spaces along with hygiene. The present study examined the change in need, usage patterns, hygiene and infrastructure facilities for such urban green and open spaces in cities. Multi-parameter analysis was conducted for the data collected from 27 cities, especially with respect to age and behavioral patterns. 170 valid responses for the designed survey were received from 27 Indian cities and towns. The results indicated that these areas were important for a wide range of activities, such as walking and jogging, relaxation, health, and yoga, meeting with friends, etc. The study results show that 62.35% of people feel that urban open and green spaces should be increased while 31.18% of people feel that more facilities should increase in current open and green spaces. 85% of people feel that yoga activities have increased in urban open and green spaces during post COVID-19 imposed lockdown compared to pre COVID-19 era. 99% of individuals agree that to make their immune system healthy and to mentally and physically prepare for such pandemic, they need to more often use green spaces for yoga and other health-related activities. Whereas, 90% of visitors admitted that urban green and open spaces help them cope with their physical and mental health concerns. People started using green and open spaces for productive purposes and avoided social gatherings as far as possible in such areas. The results were validated with statistical analysis using ANOVA in MINITAB14. The statistical analysis indicates a clear effect of age group and lockdowns on the people's activities, specially for Health and Yoga with p

Loss of function mutations in Kelch Like ECH Associated Protein 1 (KEAP1) or gain-of-function mutations in nuclear factor erythroid 2-related factor 2 (NRF2) are common in non-small cell lung cancer (NSCLC) and is associated with therapeutic resistance. To discover novel NRF2 inhibitors for targeted therapy, we conducted a quantitative high-throughput screen using a diverse set of ~400,000 small molecules (Molecular Libraries Small Molecule Repository Library, MLSMR) at the National Center for Advancing Translational Sciences. We identified ML385 as a probe molecule that binds to NRF2 and inhibits its downstream target gene expression. Specifically, ML385 binds to the Neh1, the Cap ‘N’ Collar Basic Leucine Zipper (CNC-bZIP) domain of NRF2, and interferes with the binding of the V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog G (MAFG)-NRF2 protein complex to regulatory DNA binding sequences. In clonogenic assays, when used in combination with platinum-based drugs such as doxorubicin or taxol, ML385 substantially enhances cytotoxicity in NSCLC cells compared to single agents alone. ML385 shows specificity and selectivity for NSCLC cells with KEAP1 mutation leading to gain of NRF2 function. In preclinical models of NSCLC with gain of NRF2 function, ML385 in combination with carboplatin showed significant anti-tumor activity. We demonstrate the discovery and validation of ML385 as a novel and specific NRF2 inhibitor and conclude that targeting NRF2 may represent a promising strategy for the treatment of advanced NSCLC.

In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aβ aggregation and antioxidant activity.

The relationship between protein molecular weight (MW) distribution, quality characteristics and muffin making properties amongst Indian wheat varieties were evaluated. Flours from varieties with higher grain weight showed lower proportion of fine particles. Lactic acid solvent retention capacity (LASRC), sedimentation value (SV) and dough stability (DS) correlated with the proportion of 0–55 μm size particles. Paste peak viscosity and breakdown viscosity showed positive correlation with polymeric protein and negatively with monomeric protein, α-amylase activity and sodium carbonate solvent retention capacity (NaSRC). Gluten strength indicators such as DS, dough development time (DDT), LASRC and gluten index (GI) were positively related to polymeric protein and negatively to monomeric protein. Both G’ and G ″ were correlated significantly with GI, LASRC, DS and DDT. The varieties that possesses high MW glutenin subunits combinations of 91 kDa + 84 kDa + 78 kDa + 74 kDa showed lower G ’ and G ″. Muffin volume was positively correlated with gluten content and LASRC.

The grain, flour, dough and noodle making properties of Indian durum wheat varieties were evaluated. Varieties having higher grain weight had lower hardness and higher yellow pigment content. Gluten performance index showed positive correlation with α-helix and negative with intermolecular+antiparallel-β-sheets in gluten. The proportion of extracted polymeric proteins was related to dough strength. Elastic (G') and loss (G″) modulus of dough were positively correlated to intermolecular+antiparallel-β-sheets and negatively with β-turn+ β-sheets proportion of dough and gluten. PDW291 with exceptionally higher G' and G″ and best noodle making properties showed the presence 90 kDa and 88 kDa polypeptides corresponding to 14+15 and type 2 banding pattern.

Shree Vishna Rasiah (known as Vish to friends, family, and colleagues) was a well respected and much loved consultant neonatologist at Birmingham Women’s Hospital. Born in Kuala Lumpur, Malaysia, Vish spoke Tamil, Mandarin, and Malay in addition to English. After completing his undergraduate medicine in Adelaide, he came to south Yorkshire, training in Bradford and Sheffield before joining Professor Andrew Ewer’s research group in Birmingham. He joined the Birmingham Women’s Hospital (BWH) as consultant neonatologist in 2007. He contributed to neonatal care at local, national, and international levels. He encouraged and mentored innumerable junior doctors and medical students, supporting original …

A Decentralized Wastewater Treatment System (DEWATS) provides an economically feasible and efficient wastewater treatment solution especially in developing countries. It has an enormous potential for developing a sustainable environmental sanitation system. In this study, the treatment efficiency of eight DEWATS plants was evaluated in the state of Maharashtra, India, for their performance in terms of selected physico-chemical parameters of the wastewater. Although the efficiency of some of the plants was lower than that reported in literature, the effluent quality of all the plants was within the permissible discharge limits of the Central Pollution Control Board for all the parameters. Comprehensive assessment of Plant I was carried in terms of its technical and socio-economic aspects. Moreover, LCA tool has been utilized to evaluate the environmental impacts of the operation stage of DEWATS. The midpoint, CML 2001 (April 2015) methodology was adopted, in which 11 impact categories were considered. From the life cycle impact assessment and interpretation, the main impacts are identified as releases of COD, P-PO43−, and N-NH4+ to water bodies and disposal of sludge. Due to negligible energy consumption, the operation stage was found to be less damaging to the environment. It was concluded that DEWATS can be a good alternative for treating wastewater with negligible energy and chemical consumption.

> Excellence is never an accident. It is always a result of high intention, sincere effort, and intelligent execution. > > — Aristotle1 We are reporting the results of implementing Learning from Excellence (LFE) initiative at Birmingham Women’s Neonatal Intensive Care Unit (NICU). This initiative was conceived and successfully implemented at Birmingham Children’s Paediatric Intensive Care Unit (PICU) with the aim to identify and learn from peer-reported excellent episodes and improve staff morale through positive feedback.2 There is evidence in literature demonstrating improved resilience and organisational climate following nurturing of positive approach in front line healthcare professionals and their teams.3 4 The PICU experience with LFE included sharing of good practice, identifying …

The key factors underlying the development of allergic diseases-the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules-remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13-producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment.

Formation of higher order structures, such as G-quadruplexes and G-quadruplex based large suprastructures into long G-wires and liquid crystals is promising elements for use in healthcare for drug delivery as they are mechanically and thermally stable. In this study, we studied the structures of short 11-mer oligonucleotide 5′-G2AG5AG2-3′(11Pu) which is observed in 3′-UTR region of c-jun protooncogene. We used circular dichroism, UV-thermal melting, native gel electrophoresis and atomic force microscopy to determine the structure of 11Pu. CD results showed that 11Pu formed a mixed G-quadruplex in the presence of Na+ with and without Mg2+, while it formed a parallel G-quadruplex in the presence of 100 mM K+ with or without Mg2+. Cation selectivity in inducing the formation of large superstructures was observed in the presence of 100 mM K+ with 10 mM Mg2+. On the contrary, 10 mM Ca2+ did not induce the suprastructures. It was further demonstrated that Mg2+ at low concentration induced a parallel G-quadruplex of 11Pu, whereas at 10 mM Mg2+ induced a large suprastructure. AFM Images showed that 11Pu formed a G-wire, a liquid crystals and a crystalline lattice depending on the concentration of 11Pu and Mg2+. These insights may be employed to design G quadruplex-based nanowires for targeted drug delivery as well as interesting candidates for molecular nanowires. Communicated by Ramaswamy H. Sarma

Regulatory regions in human genome, enriched in guanine-rich DNA sequences have the propensity to fold into G-quadruplex structures. On exploring the genome for search of G-tracts, it was interesting to find that promoter of Human Myosin Gene (MYH7) contains a conserved 23-mer G-rich sequence (HM-23). Mutations in this gene are associated with familial cardiomyopathy. Enrichment of MYH7 gene in G-rich sequences could possibly play a critical role in its regulation. We used polyacrylamide gel electrophoresis (PAGE), UV-Thermal denaturation (UV-Tm) and Circular Dichroism (CD), to demonstrate the formation of a G-quadruplex by 23-mer G-rich sequence HM23 in promoter location of MYH7 gene. We observed that the wild G-rich sequence HM23 containing consecutive G5 stretch in two stacks adopt G-quadruplexes of diverse molecularity by involvement of four-strand, three-strand and two-strands with same parallel topology. Interestingly, the mutated sequence in the absence of continuous G5 stretch obstructs the formation of three-stranded G-quadruplex. We demonstrated that continuous G5 stretch is mandatory for the formation of a unique three-stranded G-quadruplex. Presence of various transcription factors (TF) in vicinity of the sequence HM23 leave fair possibility of recognition by TF binding sites, and so modulate gene expression. These findings may add on our understanding about the effect of base change in the formation of varied structural species in similar solution condition. This study may give insight about structural polymorphism arising due to recognition of non-Watson-Crick G-quadruplex structures by cellular proteins and designing structure specific molecules.

Over the decades, oxidative stress has emerged as a major concern to biological researchers. It is involved in the pathogenesis of various lifestyle-related diseases such as hypertension, diabetes, atherosclerosis, and neurodegenerative diseases. The connection between oxidative stress and telomere shortening via oxidative guanine lesion is well documented. Telomeres are confined to guanine rich ends of chromosomes. Owing to its self-association properties, it adopts G-quadruplex structures and hampers the overexpression of telomerase in the cancer cells. Guanine, being the most oxidation prone nucleobase, when structured in G-quadruplex entity, is found to respond peculiarly towards oxidative stress. Interestingly, this non-Watson–Crick structural feature exists abundantly in promoters of various oncogenes, exons and other genomic locations. The involvement of G-quadruplex architecture in oncogene promoters is well recognized in gene regulation processes. Development of small molecules aimed to target G-quadruplex structures, have found to alter the overexpression of oncogenes. The interaction may lead to the obstruction of diseased cell having elevated level of reactive oxygen species (ROS). Thus, presence of short guanine tracts (Gn) forming G-quadruplexes suggests its critical role in oxidative genome damage. Present review is a modest attempt to gain insight on the association of oxidative stress and G-quadruplexes, in various biological processes.

Angioimmunoblastic T cell lymphoma (AITL) belongs to the subgroup of mature T cell lymphomas according to the World Health Organization and is one of the common T cell lymphomas in Western countries. Particularly in cases in which histological confirmation cannot be easily achieved, immunophenotyping of peripheral blood can give important information for the differential diagnosis of AITL. sCD3− CD4+ T cells are a typical feature of AILT in flow cytometry of peripheral blood. In this retrospective study, the diagnostic value of flow cytometry for the diagnosis ‘AITL’ was assessed by comparing the frequency of sCD3− CD4+ T cells in leukemic AITL patients and in patients with other leukemic CD4+ T cell lymphomas. Immunophenotyping of peripheral blood by flow cytometry was performed in a lymphocyte gate using fluorochrome-labelled antibodies against CD3, CD2, CD4, CD5, CD7, CD8, CD10, CD14, CD16, CD19, CD56, CD57 and T cell receptor. In 17/17 leukemic AITL patients, a small but distinct population of sCD3− CD4+ T cells was detected (mean percentage of sCD3− CD4+ T cells in the lymphocyte gate: 11.9 ± 15.4%, range 0.1–51.8%). In contrast, sCD3− CD4+ T cells were found in only 1/40 patients with other leukemic CD4+ T cell lymphomas (one patient with mycosis fungoides). sCD3− CD4+ T cells have a high positive predictive value (94%) for the diagnosis ‘AITL’. Flow cytometry is particularly useful in the differential diagnosis of AITL, even if the aberrant T cell population has a very low frequency. Further biological characterization of this subfraction of lymphoma cells is warranted. Copyright © 2013 John Wiley & Sons, Ltd.

Wireless mesh networking (WMN) is an emerging technology that enables multihop wireless connectivity to areas where wiring or installing cables is difficult or expensive. Multicast is a form of communication that delivers information from a source to a group of destinations. In a single-channel WMN, all nodes share and communicate with each other via the same channel. In such a network, the throughput capacity of multicast degrades significantly as the network size increases. A critical factor that contributes to this rapid degradation is the co-channel interference in single-channel WMNs. The major advantage of WMN is that power is not the major issue as compare to other wireless network like MANET, Sensor etc. Hence Power can be optimally utilized in WMN to increase throughput and total network efficiency. In this paper, we propose a channel assignment algorithm for multicast based on high channel capacity with minimum interference. This scheme usesall overlapping and non overlapping channel for the channel assignment. By this scheme we provide better performance in terms of average packet delivery ratio, average throughput and average end to end delay with respect to multichannel multicast channel assignment schemes.

Aim: To review the findings and outcomes of predischarge echocardiography service for postnatal heart murmurs provided by neonatologists. Methods: We retrospectively reviewed all predischarge echocardiograms performed on babies from the postnatal wards (PNW) over the last 3 years. We evaluated the indications, median age, findings and outcome. Results: A total of 408 echocardiograms were performed on 350 babies on the PNW. The most common indication was presence of a murmur (58%). In babies with a heart murmur, 26% had a normal echocardiogram, 2% had major structural heart defects, 38% had minor structural heart defects and 34% had transient circulatory changes. 32% were discharged with no follow-up, 28% were followed up in the local cardiac clinic and 40% were referred to the cardiologist. Conclusion: Predischarge echocardiography service for postnatal heart murmurs provided by neonatologists has the benefit of providing an early diagnosis, counselling of the parents and arranging appropriate follow-up. It helps to triage the referrals to the cardiologist. We felt that we were able to alleviate parental anxieties by providing a definitive diagnosis and written information prior to discharge from hospital. We strongly believe that this service should only be provided by those appropriately trained and skilled in echocardiography.

Structural polymorphism is an extremely significant phenomenon of nucleic acids, in which DNA and RNA oligonucleotide sequences are able to adapt various canonical, alternative and multistranded structures. These alternative forms of DNA and RNA have an enormous potential of participating in various cellular processes by recognizing ligands such as proteins, drugs and metal ions in a sequence and structure-specific manner. Such DNA-ligand interactions prove to be highly beneficial when exploited for therapeutic purposes. Many of these DNA/ RNA structures recognizing drugs have already proved their potential as anticancer, antibacterial, anthelmintic and antiviral properties. Over the last 2-3 decades, many mechanisms of DNA-drug interactions have been documented, but still many other new mechanisms are being explored. Designing new drugs with improved efficacy and specificity is of prime concern for all researchers which not only deals with the experiments related to synthesizing drugs, but also takes care of searching novel routes or agents for administration or delivery of these therapeutic agents by increasing their nuclear and cellular uptake. This review aims at explaining the structural polymorphs/ multistranded DNA structures and their interactions with pharmaceutical drugs in a structure-specific manner, along with their modes of interactions and biological relevance. This detailed overview of multistranded DNA structures and interacting drugs might further facilitate our understanding about molecular targets and drug development in a more precise manner for the larger benefit of mankind.

Twelve Frankia strains isolated from HippOphae salicifolia D. Don or Alnus glutinosa or Comptonia peregrine, showed the significant variation in fatty acid composition viz. palmitic acid (16:0), oleic acid (18:1), linoleic acid (18:2), linolenic acid (18:3), arachidic acid (20:0) and erucic acid (22:1) suggesting the strain specific variability among the Frankia strains. Presence of Erucic acid (22:1), a major component of the oil obtained from the seeds of Brassica sp., albeit in lesser amount in the few studied frankial strains, is the first report. Cluster analysis on the basis of fatty acid composition suggests the presence of two distinct clusters with similitude coefficient ranging from 0.75 to 1.00. Cluster I with HsIi2 showed great divergence from other 11 frankial strains (Cluster II). The two sub groups were distinguished in cluster II: IIa contained five strains isolated from H. salicifolia and these strains are distantly related to the strains of cluster IIb isolated from different host. There is high degree of similarity among the frankial strains of Cluster IIb which suggests that the frankial strains might be evolved from the same ancestor. FAME profiling might be useful tool in the study of polyphasic approach based taxonomy and phylogenetic relationship. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Different Frankia strains (HsIi2, HsIi4, HsIi5, HsIi8, HsIi9, HsIi10, HsIi11, HsIi12, HsIi13, HsIi14) nodulating Hippophae salicifolia D. Don, were characterized on the basis of physiological, biochemical and molecular attributes. Results suggest that the physiological approaches i.e., nitrogenase activity, glutamine synthetase (GS) activity and ammonia excretion are strain specific. The highest rate of nitrogen fixation and maximum production of ammonia with low GS makes the strain HsIi11, a suitable biofertilizer as compared to other strains. Analysis of total protein pattern (SDS–PAGE) revealed that the most closely related strains HsIi10 and HsIi4 were found to be most distantly related to the most similar strains HsIi14, HsIi5, HsIi13, HsIi11 and HsIi12. RAPD PCR analyses with an arbitrary primer 1253 produced distinct, unique and specific DNA fingerprints for each of the Frankia strain and 100% polymorphism was observed which uncovers the genetic diversity. These approaches might be helpful in rapid identification, in designing the marker for the specific strains as well as in improving nitrogen fixation in agroforestry.