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Pesticides are chemical substances of natural or synthetic origin that are used to eradicate pests and insects. These are indispensable in the agricultural processes for better crop production. Pesticide use aims to promote crop yield and protect the crops from diseases and damage. Pesticides must be handled carefully and disposed of appropriately because they are dangerous to people and other species by default. Environmental pollution occurs when pesticide contamination spreads away from the intended plants. Older pesticides such as lindane and dichlorodiphenyltrichloroethane (DDT) may remain in water and soil for a longer time. These accumulate in various parts of the food chain and cause damage to the ecosystem. Biological techniques in the management of pest control such as importation, augmentation, and conservation, and the accompanying procedures are more efficient, less expensive, and ecologically sound than other ways. This review mainly focuses on the consequences on the targeted and non-targeted organisms including the health and well-being of humans by the use of pesticides and their toxicity. The side effects that occur when a pesticide's LD 50 exceeds the accepted limit through oral or skin penetration due to their binding to various receptors such as estrogen receptors, GABA, EGFR, and others. These pesticide classes include carbamates, pyrethroids, organochlorides, organophosphorus, and others. The current study seeks to highlight the urgent requirement for a novel agricultural concept that includes a major reduction in the use of chemical pesticides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Arylpiperazine clubbed various heterocyclic molecules present potential pharmacophoric structural features for the development of psychoactive drugs. There are various CNS active molecules possessing arylpiperazine moiety in their pharmacophore approved by USFDA. In the current study, we have explored the benzhydrylpiperazine moiety clubbed with various substituted oxadiazole moieties (AP1-12) for their monoamine oxidase (MAO) inhibition and antidepressant potential. Compounds AP3 and AP12 exhibited highly potent and selective MAO-A inhibition with IC 50 values of 1.34 ± 0.93 µM and 1.13 ± 0.54 µM, respectively, and a selectivity index of 10- and 13-folds, respectively. Both the compounds displayed reversible binding character at the active site of MAO-A. In further in vivo evaluation, both the compounds AP3 and AP12 displayed potential antidepressant-like character in FST and TST studies via significantly reduced immobility time in comparison to non-treated animals. These compounds displayed no cytotoxicity in SH-SY5Y cell lines, which indicates that these compounds are safe for further evaluation. In silico studies reveal that synthesized compounds possess drug-likeness with minimal to no toxicity. In silico studies were conducted to understand the binding interactions and stability of compounds at the binding pocket of enzyme and observed that both the best compounds fit well at the active site of MAO-A lined by amino acid residues Tyr69, Asn181, Phe208, Ile335, Leu337, Phe352, and Tyr444 similar to standard MAO-A inhibitor clorgiline. The molecular dynamic studies demonstrated that AP3 and AP12 formed quite a stable complex at the active site of MAO-A and did not break under small abruption forces. The favourable binding interactions and appropriate ADMET properties present the benzhydrylpiperazine clubbed oxadiazole pharmacophoric features as a potential structural skeleton for further clinical evaluation and development of a new antidepressant drug molecule., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Piperazine derivatives have been of great interest to medicinal chemists in the development of antidepressant drugs due to their distinct molecular and structural features along with their pharmacological profile. In this study, we have designed and synthesized a series of 10 compounds of piperazine clubbed oxadiazole derivatives (5a-j) and screened for their MAO inhibitory activity. Compound 5f and 5 g were found to be the most potent MAO-A inhibitors of the series with IC 50 values of 0.96 ± 0.04 µM µM and 0.81 ± 0.03 µM, respectively with a selectivity index of 18-folds and 9-folds over MAO-B isoform. The compounds were found to be reversible inhibitors of MAO-A with no cytotoxicity against SH-SY5Y neuronal cells. The compounds also displayed good antioxidant activity. Further, in vivo TST studies revealed that both the compounds 5f and 5 g possessed good anti-depressant-like activity and reduced the immobility time significantly although were found inactive in FST studies. The molecular docking studies revealed that both compounds fit well at the active site of MAO-A enzyme as similar to clorgyline and form a stable complex. The results were confirmed via molecular dynamic studies which demonstrate the stable complex formation between MAO-A and 5f & 5 g. The appropriate drug-like characteristics with favourable ADMET profile, these molecules presented this piperazine clubbed oxadiazole structural framework as a key pharmacophore for the development of new antidepressant molecules along with strong candidature for further clinical investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Egg consumption may play an important role in early-life growth given their high-quality protein, essential fatty acids, and micronutrients., Objectives: Study objectives were to examine the longitudinal associations of infant age at egg introduction with obesity outcomes in early childhood, middle childhood (mid-childhood), and early adolescence., Methods: We used existing data from 1089 mother-child dyads from Project Viva to estimate age at egg introduction through a questionnaire completed by mothers at ∼1 y postpartum (mean ± SD, 13.3 ± 1.2 mo). Outcome measures included height and weight (early childhood, mid-childhood, and early adolescence), body composition including total fat mass, trunk fat mass, and lean mass (mid-childhood and early adolescence), and plasma adiponectin and leptin (early and mid-childhood and early adolescence). We defined childhood obesity as sex- and age-specific BMI ≥ 95th percentile. We estimated the associations of infant age at egg introduction with risk of obesity using multivariable logistic regression and multivariable linear regression models for BMI-z-score, body composition measures, and adiposity hormones; adjusted for maternal prepregnancy BMI and sociodemographics., Results: Among females, those introduced to egg by the 1-y survey had a lower total fat mass index (confounder-adjusted mean difference, -1.23 kg/m 2 ; 95% CI: -2.14, -0.31), and trunk fat mass index (confounder-adjusted mean difference, -0.57 kg/m 2 ; 95% CI: -1.01, -0.12) in early adolescence compared to those not introduced (reference group). However, no associations between infant age at egg introduction and risk of obesity were observed among males (confounder-adjusted odd ratio [aOR], 1.97; 95% CI: 0.90, 4.30) or females (aOR, 0.68; 95% CI: 0.38, 1.24) across all ages. Egg introduction in infancy was associated with lower plasma adiponectin among females (confounder-adjusted mean difference, -1.93 μg/mL; 95% CI: -3.70, -0.16) in early childhood only., Conclusions: Egg introduction during infancy among females is associated with lower total fat mass index in early adolescence and plasma adiponectin in early childhood. This trial was registered at clinicaltrials.gov as NCT02820402., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Pneumorrhachis is an uncommon radiographic finding and is typically found in adult patients secondary to trauma or pneumocephalus. It is extremely rare in the pediatric population. Our case report describes a young boy who was found to have pneumorrhachis, but initially presented with an isolated back laceration., Case Report: An 8-year-old boy arrived to the emergency department as a transfer from an outside hospital after initially presenting with a back laceration. After laceration repair, he developed severe headache and vomiting when sitting upright from a supine position. He was found to have T3 fractures and pneumocephalus secondary to pneumorrhachis and was managed conservatively per neurosurgery recommendations. Why Should an Emergency Physician Be Aware of This?Although extremely rare in the pediatric population, pneumorrhachis must still be considered in any pediatric patient with a penetrating injury to the abdomen, respiratory tract, or spinal column. Cases without clear etiology require further evaluation for occult spinal injuries and fractures. Conservative management is typically sufficient, although certain situations require further intervention., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This paper introduces methods to estimate aspects of physical activity and sedentary behavior from three-axis accelerometer data collected with a wrist-worn device at a sampling rate of 32 [Hz] on adults with type 1 diabetes (T1D) in free-living conditions. In particular, we present two methods able to detect and grade activity based on its intensity and individual fitness as sedentary, mild, moderate or vigorous, and a method that performs activity classification in a supervised learning framework to predict specific user behaviors. Population results for activity level grading show multi-class average accuracy of 99.99%, precision of 98.0 ± 2.2%, recall of 97.9 ± 3.5% and F1 score of 0.9 ± 0.0. As for the specific behavior prediction, our best performing classifier, gave population multi-class average accuracy of 92.43 ± 10.32%, precision of 92.94 ± 9.80%, recall of 92.20 ± 10.16% and F1 score of 92.56 ± 9.94%. Our investigation showed that physical activity and sedentary behavior can be detected, graded and classified with good accuracy and precision from three-axial accelerometer data collected in free-living conditions on people with T1D. This is particularly significant in the context of automated glucose control systems for diabetes, in that the methods we propose have the potential to inform changes in treatment parameters in response to the intensity of physical activity, allowing patients to meet their glycemic targets., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: Studies on the changes in the presentation and management of acute myocardial infarction (AMI) during the COVID-19 pandemic from low- and middle-income countries are limited. We sought to determine the changes in the number of admissions, management practices, and outcomes of AMI during the pandemic period in India., Methods & Results: In this two-timepoint cross-sectional study involving 187 hospitals across India, patients admitted with AMI between 15th March to 15th June in 2020 were compared with those admitted during the corresponding period of 2019. We included 41,832 consecutive adults with AMI. Admissions during the pandemic period (n = 16414) decreased by 35·4% as compared to the corresponding period in 2019 (n = 25418). We observed significant heterogeneity in this decline across India. The weekly average decrease in AMI admissions in 2020 correlated negatively with the number of COVID cases (r = -0·48; r 2  = 0·2), but strongly correlated with the stringency of lockdown index (r = 0·95; r 2  = 0·90). On a multi-level logistic regression, admissions were lower in 2020 with older age categories, tier 1 cities, and centers with high patient volume. Adjusted utilization rate of coronary angiography, and percutaneous coronary intervention decreased by 11·3%, and 5·9% respectively., Conclusions: The magnitude of reduction in AMI admissions across India was not uniform. The nature, time course, and the patient demographics were different compared to reports from other countries, suggesting a significant impact due to the lockdown. These findings have important implications in managing AMI during the pandemic., Competing Interests: Declaration of competing interest Nothing to declare for all the authors., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

High fat diet (HFD) induced obesity has deleterious effect on bone micro-architecture and is associated with low-grade chronic inflammation. Exogenous glucocorticoids (GC) are used to treat inflammatory conditions but with concomitant adverse effect on musculoskeletal system. This study aims to highlight the effect of exogenous GCs on musculoskeletal system in mice fed on HFD. Adult BALB/c mice were fed either normal chow or high fat diet and were exogenously administered with GC for 10 weeks. At the end of the study, animals were autopsied and bone, muscle, serum samples were collected for micro-CT, gene expression and histological study. HFD induced obesity resulted in deterioration in bone micro-architecture predominant in trabecular region of long bones and was significantly amplified with GC administration. Approximately, 37% and 25% loss in femoral and tibial bone volume was observed in obese animals with exogenous GC. Further, deteriorating bone pathology was apparent from reduced bone mineral density (BMD) and bone strength parameter which was correlated to alteration in osteoblast and adipocytes pool of cells in bone marrow. Transcriptional analysis of osteoblast marker genes, bone morphogenetic protein 2 (BMP-2), osteocalcin (OCN) exhibited decreased formation. Moreover, similar degeneration was observed in skeletal muscle physiology with stimulation in muscle atrophy genes atrogin-1, muscle ring finger motif-1 (MuRF-1) and inflammatory markers accompanied with intra-myocellular lipid accumulation. Thus, our results showed that detrimental effect of GC on bone and skeletal muscle is aggravated with HFD, attributed to alteration in bone marrow cell population and skeletal muscle atrophy., (Copyright © 2019. Published by Elsevier Inc.)

Aim: Myokines are associated with regulation of bone and muscle mass. However, limited information is available regarding the impact of myokines on glucocorticoid (GC) mediated adverse effects on the musculoskeletal system. This study investigates the role of myokine fibroblast growth factor-2 (FGF-2) in regulating GC-induced deleterious effects on bone and skeletal muscle., Methods: Primary osteoblast cells and C2C12 myoblast cell line were treated with FGF-2 and then exposed to dexamethasone (GC). FGF-2 mediated attenuation of the inhibitory effect of GC on osteoblast and myoblast differentiation and muscle atrophy was assessed through quantitative PCR and western blot analysis. Further, FGF-2 was administered subcutaneously to dexamethasone treated mice to collect bone and skeletal muscle tissue for in vivo analysis of bone microarchitecture, mechanical strength, histomorphometry and for histological alterations in treated tissue samples., Key Findings: FGF-2 abrogated the dexamethasone induced inhibitory effect on osteoblast differentiation by modulating BMP-2 pathway and inhibiting Wnt antagonist sclerostin. Further, dexamethasone induced atrophy in C2C12 cells was mitigated by FGF-2 as evident from down regulation of atrogenes expression. FGF-2 prevented GC-induced impairment of mineral density, biomechanical strength, trabecular bone volume, cortical thickness and bone formation rate in mice. Additionally, skeletal muscle tissue from GC treated mice displayed weak myostatin immunostaining and reduced expression of atrogenes following FGF-2 treatment., Significance: FGF-2 mitigated GC induced effects through inhibition of sclerostin and myostatin expression in bone and muscle respectively. Taken together, this study exhibited the role of exogenous FGF-2 in sustaining osteoblastogenesis and inhibiting muscle atrophy in presence of glucocorticoid., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: SATB1, a global genome organizer, has been shown to play a role in the development and progression of some solid tumors, but its role in bladder cancer is undetermined. Moreover, there is conflicting data about the role of SATB1 in other tumors. This study was initiated to assess a potential role for SATB1 with the hypothesis that SATB1 acts as a tumor promoter in bladder cancer., Materials and Methods: We evaluated SATB1 expression in bladder cancer cell lines (HTB-5, HTB-9) and compared them to a benign urothelial cell line (UROtsa). Short-hairpin RNA was used to silence SATB1 in multiple cell lines, and cell death and cell proliferation were assessed using multiple assays., Results: SATB1 expression was increased significantly in all cancer cell lines compared to benign urothelial cells. SATB1 expression was knocked down by short-hairpin RNA and functional outcomes, including cell number, cell-cycle arrest, cell viability, and apoptosis after cisplatin treatment, were measured. Surprisingly, knockdown of SATB1 in 2 high-grade cancer cell lines showed opposing functional roles. Compared to the non-silencing control, HTB-5 cells, showed decreased cellular proliferation and increased sensitivity to cisplatin, whereas HTB-9 cells, showed increased cell numbers and increased resistance to cisplatin., Conclusion: We conclude that our results in bladder cancer are consistent with the conflicting data reported in other cancers, and that SATB1 might have different roles in cancer dependent on genetic background and stage of the cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Kaempferol (KEM) has been observed to stimulate Krt-14 protein which subsequently contributes to matrix maturation and mineralization in rat primary osteoblast cells. Incorporation of Krt-14 siRNA results in reduced mRNA and protein expression after 48h post transfection and remained low for 9days. At day 9 Krt-14 siRNA significantly reduced mineralization without concomitant change in the cell number. ColI and OCN gene expression was reduced in Krt-14 siRNA-treated osteoblast cells. Soluble osteocalcin and collagen levels were markedly decreased in conditioned medium as well as in acid-salt soluble cell-ECM layer treated with Krt-14 siRNA compared to control siRNA treated cells corroborated at the ultrastructral level by AFM. Further, knockdown of Krt-14 and inhibitors against AMPK and mTOR, repressed the activation of mTOR and mineralization attenuated by KEM confirmed the role of Krt-14 in mineralization. These findings strongly suggest that Krt-14 regulates osteoblast mineralization by organizing osteoblast derived ECM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: L-Selectin (CD62L) is a vascular adhesion molecule constitutively expressed on leukocytes with a primary function of directing leukocyte migration and homing of lymphocytes to lymph nodes. In a gene expression microarray study comparing laser-captured microdissected high-grade muscle-invasive bladder cancer (MIBC) without prior treatment and low-grade bladder cancer (LGBC) human samples, we found CD62L to be the highest differentially expressed gene. We sought to examine the differential expression of CD62L in MIBCs and its clinical relevance., Methods: Unfixed fresh and formalin-fixed paraffin-embedded human bladder cancer specimens and serum samples were obtained from the University of Connecticut Health Center tumor bank. Tumor cells were isolated from frozen tumor tissue sections by laser-captured microdissected followed by RNA isolation. Quantitative polymerase chain reaction was used to validate the level of CD62L transcripts. Immunohistochemistry and enzyme-linked immunosorbent assay were performed to evaluate the CD62L protein localization and expression level. Flow cytometry was used to identify the relative number of cells expressing CD62L in fresh tumor tissue. In silico studies were performed using the Oncomine database., Results: Immunostaining showed a uniformly higher expression of CD62L in MIBC specimens vs. LGBCs specimens. Further, CD62L localization was seen in foci of metastatic tumor cells in lymph node specimens from patients with high-grade MIBC and known nodal involvement. Up-regulated expression of CD62L was also observed by flow cytometric analysis of freshly isolated tumor cells from biopsies of high-grade cancers vs. LGBC specimens. Circulating CD62L levels were also found to be higher in serum samples from patients with high-grade metastatic vs. high-grade nonmetastatic MIBC. In addition, in silico analysis of Oncomine Microarray Database showed a significant correlation between CD62L expression and tumor aggressiveness and clinical outcomes., Conclusion: These data confirm the expression of CD62L on urothelial carcinoma cells and suggest that CD62L may serve as biomarker to predict the presence of or risk for developing metastatic disease in patients with bladder cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A questionnaire-based cross-sectional survey was undertaken to assess the awareness and practice patterns of family planning among the antenatal women in North India. The study included 400 respondents. Three-fourths of the respondents (74.2%, n = 297) were aware of family planning methods. Condoms were the most commonly used family planning method (78.2%), while intrauterine devices and oral contraceptive pills were used by 25.5% and 16.7% respondents, respectively. The main reasons cited for not using contraception were inadequate knowledge and fear of side-effects. Post counseling, 90.5% (n = 362) of the respondents clearly conveyed their desire to use one of the family planning methods in the postpartum period. Awareness and acceptance of family planning methods in the Indian community needs strengthening. Family planning counseling during antenatal check-up is likely to increase the acceptance of family planning methods in the postpartum period.

'Masquerading' bundle branch block (right bundle branch block in the precordial leads with left bundle branch block in frontal leads and left axis deviation) is seen most commonly with coronary artery disease and hypertension. No definite explanation is available so far for these changes. We are presenting a case of rare congenital intranuclear inclusion myopathy with congestive heart failure and 'Masquerading' bundle branch block in ECG., (Copyright © 2013 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

AutoCapture algorithm helps the pacemakers to automatically adjust output close to the pacing threshold. This algorithm monitors the evoked response signal of myocardial depolarization, and delivers a high output back-up pulse if there is a loss of capture. This case, with two pacemaker spikes on the QRS complexes in a patient with VVI pacemaker, simulating a sensing failure, demands clear understanding of AutoCapture function before labeling the pacemaker malfunction., (Copyright © 2012 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

The present study compared the relative expression pattern of 10 orthologous CYP forms from families 1-4 in cDNA panels of human and mouse fetal and adult tissues. Except for CYP1A2, all of these CYPs exhibited specific patterns of expression during mouse ontogeny, suggesting possible involvement in development. Cyp1a1 and Cyp2r1 were the only two of the orthologs to be expressed only in the E7 mouse; Cyp2s1 was expressed in all stages, including E7, while Cyp2e1 appeared only at E17. Highest expression of the individual CYPs in the different late term human fetal tissues was: thymus, CYP1B1 and CYP2U1; liver, CYP2E1; brain, CYP2R1, CYP1A1 and CYP4X1; and lung, CYP4B1 and CYP2W1. In general, the level of individual human CYP transcripts was lower in the fetal than the corresponding adult tissues. The pattern of expression in adult mouse and human tissues was fairly similar for CYP1A1, CYP1A2, CYP1B1, CYP2S1, and CYP2U1 orthologs.

This study is the first systematic investigation of the gestational age-dependent and adult tissue-specific expression patterns of each known mouse CYP family (40 genes) using normalized cDNA panels and uniform reverse transcriptase polymerase chain reaction-based assays. Twenty-seven of the P450s were constitutively expressed during development. The number gradually increased through the phases of gastrulation E7 (n=14), neural patterning and somitogenesis E11 (n=17), organogenesis E15 (n=20), and fetal period E17 (n=21). Cyp2s1, Cyp8a1, Cyp20, Cyp21a1, Cyp26a1, Cyp46, and Cyp51 were detected in each of the four stages studied. Members of family CYP1 demonstrated complex, nonoverlapping embryonic patterns of expression, indicating that Cyp1a1 and Cyp1a2 may not compensate for Cyp1b1 deficiency associated with abnormal eye development. Multiple Cyp forms were found to be constitutively expressed in each of the adult tissues studied: liver (n=31), kidney (n=30), testis (n=26), lung (n=24), and heart (n=13). The tissue-specific P450-expression profiles reported in this study provide a reference for more focused analysis of the tissue-specific and developmental functions of the cytochrome P450 monooxygenases.

The effect of different doses of methylglyoxal (50-400 mg/kg body wt.) were examined using enzymes involved in the antioxidant function, glutathione (GSH) content and lipid peroxidation in the liver and spleen of Swiss albino mice (7-8 week old) after 6, 12 and 24 h. Significant changes were observed predominantly in the liver. The specific activities of superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase, glyoxalase I (gly I) and glyoxalase II (gly II) were found to decrease in the liver. The mode and magnitude of change in the specific activities was seen to depend on the dose of methylglyoxal and the time after its administration. Methylglyoxal also decreased the GSH content and enhanced the lipid peroxidation in the liver. These findings are suggestive of the adverse effect of methylglyoxal on the antioxidant defence system. It is likely that methylglyoxal undergoes a redox cycle and generates the free radicals which in turn lower the antioxidant status in animals. The increased levels of lipid peroxidation provide support for the involvement of free radical processes in the detrimental effects of methylglyoxal. The response of DT-diaphorase (DTD) seems to be adaptive.