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The psychological resilience of teachers has gained significant attention due to its positive effects on schools and students. This cross-sectional quantitative study investigates the moderating roles of gender and the length of time spent with the school principal in the relationship between principals' empowering leadership behaviors and teachers' psychological resilience. Data were collected from 362 teachers working in public primary, secondary, and high schools in Siirt, Türkiye. Descriptive statistics, correlation analysis, and moderation analysis using the bootstrapping method were applied to analyze the data. The findings reveal that the empowering leadership behaviors of school principals positively correlate with teachers' psychological resilience, with variations based on gender and time spent with the principal. Specifically, the relationship is stronger for female teachers compared to male teachers and for those who have spent more time with the school principal. These results offer theoretical insights and practical recommendations for enhancing teacher resilience through leadership practices, highlighting the importance of understanding contextual and demographic factors., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted by the ethical principles and guidance from the ethical committee. All study protocols were approved by the ethics committee of Siirt University. Further, informed consent was obtained from the individuals who participated in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated proteins) has undergone marked advancements since its discovery as an adaptive immune system in bacteria and archaea, emerged as a potent gene-editing tool after the successful engineering of its synthetic guide RNA (sgRNA) toward the targeting of specific DNA sequences with high accuracy. Besides its DNA editing ability, further-developed Cas variants can also edit the epigenome, rendering the CRISPR-Cas system a versatile tool for genome and epigenome manipulation and a pioneering force in precision medicine. This review explores the latest advancements in CRISPR-Cas technology and its therapeutic and biomedical applications, highlighting its transformative impact on precision medicine. Moreover, the current status of CRISPR therapeutics in clinical trials is discussed. Finally, we address the persisting challenges and prospects of CRISPR-Cas technology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Azeez, Hamad, Hamad, Shekha and Bergsten.)

Free sialic acid storage disorder (FSASD) is a rare, autosomal recessive, neurodegenerative disorder caused by biallelic mutations in SLC17A5, encoding the lysosomal transmembrane sialic acid exporter, SLC17A5. Defects in SLC17A5 lead to lysosomal accumulation of free sialic acid and other acid hexoses. The clinical spectrum of FSASD ranges from mild (Salla disease) to severe infantile forms. The pathobiology underlying FSASD remains elusive. In this study, two induced pluripotent stem cell (iPSC) lines were generated from a mild and an intermediate FSASD patient and characterized to provide much-needed additional models for basic and translational studies., 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., (Published by Elsevier B.V.)

This research aims to isolate, characterize, and analyze pure compounds from Leea macrophylla leaf extract to investigate its antibacterial, antidiabetic, cytotoxic, and phytotoxic effects. Fresh leaves were collected, dried, and subjected to methanol extraction to obtain a crude extract. From the petroleum ether fraction (PEF) of this extract, three fractions-designated LM1, LM2, and LM3-were prepared using column chromatography. The fractions were tried to be characterized in search for single compound by instrumental technique like ATR-FTIR, 1 H NMR and 13 C NMR but the 1 H NMR and 13 C NMR spectra were found complex which were difficult to interpret. To dispel the doubt and get clear idea about the structure, GC-MS analysis of the compounds was carried out whose result showed that all the three extracts were decomposed to several small organic compounds that made the structure elucidation difficult. For this complication, the characterization of the extracts was not possible. Numerous compounds were identified in the methanol extract of L. through GC-MS analysis. Among these compounds, Benzene, 1,2,3-trimethyl- and Undecane were found in higher percentages in LM1. LM2 contained Azulene and Bicyclo [4.4.1]undeca-1,3,5,7,9-pentaene, while LM3 was characterized by the presence of 9,9-Dimethoxybicyclo [3.3.1]nona-2,4-dione and 11-(2-Cyclopenten-1-yl)undecanoic acid, among others. The antibacterial activity of these fractions was evaluated against various bacterial strains, demonstrating broad-spectrum effectiveness. LM1 fraction showed the highest antibacterial activity against macrophylla through GC-MS analysis. Among these compounds, Benzene, 1,2,3-trimethyl- and Undecane were found in higher percentages in LM1. LM2 contained Azulene and Bicyclo [4.4.1]undeca-1,3,5,7,9-pentaene, while LM3 was characterized by the presence of 9,9-Dimethoxybicyclo [3.3.1]nona-2,4-dione and 11-(2-Cyclopenten-1-yl)undecanoic acid, among others. The antibacterial activity of these fractions was evaluated against various bacterial strains, demonstrating broad-spectrum effectiveness. LM1 fraction showed the highest antibacterial activity against Proteus sp. With zone of inhibition 25 mm and weak activity against S. sonnei with zone of inhibition 5 mm. LM2 showed the highest activity to both E. cocci and P. aeruginosa with the zone of inhibition of 18 mm and comparatively lower but significant against Proteus sp. LM3 was highly active to S. sonnei with zone of inhibition 20 mm and lower but quite significant against Proteus sp. Moreover, the anti-diabetic potential was assessed, with LM1 showing the strongest α-amylase inhibitory activity, outperforming quercetin (standard). The IC50 values of LM1, LM2, LM3, and quercetin were 57.36 μg/mL, 100.66 μg/mL, 164.92 μg/mL, and 97.45 μg/mL, respectively. In addition, cytotoxicity was assessed using a brine shrimp lethality bioassay, and phytotoxicity was evaluated through seed germination and growth assays. The results suggest that L. macrophylla leaf extracts have potential applications in antimicrobial, antidiabetic, and anti-cancer contexts. This comprehensive study bridges gaps in knowledge surrounding L. macrophylla's multifaceted properties, offering insights into its therapeutic and ecological potential for healthcare and environmental management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Authors.)

Chikungunya virus (CHIKV), a single-stranded RNA virus transmitted by Aedes mosquitoes, poses a significant global health threat, with severe complications observed in vulnerable populations. The only licensed vaccine, IXCHIQ, approved by the US FDA, is insufficient to address the growing disease burden, particularly in endemic regions lacking herd immunity. Monoclonal antibodies (mAbs), explicitly targeting structural proteins E1/E2, demonstrate promise in passive transfer studies, with mouse and human-derived mAbs showing protective efficacy. This article explores various vaccine candidates, including live attenuated, killed, nucleic acid-based (DNA/RNA), virus-like particle, chimeric, subunit, and adenovirus vectored vaccines. RNA vaccines have emerged as promising candidates due to their rapid response capabilities and enhanced safety profile. This review underscores the importance of the E1 and E2 proteins as immunogens, emphasizing their antigenic potential. Several vaccine candidates, such as CHIKV/IRES, measles vector (MV-CHIK), synthetic DNA-encoded antibodies, and mRNA-lipid nanoparticle vaccines, demonstrate encouraging preclinical and clinical results. In addition to identifying potential molecular targets for antiviral therapy, the study looks into the roles played by Toll-like receptors, RIG-I, and NOD-like receptors in the immune response to CHIKV. It also offers insights into novel tactics and promising vaccine candidates. This article discusses potential antiviral targets, the significance of E1 and E2 proteins, monoclonal antibodies, and RNA vaccines as prospective Chikungunya virus vaccine candidates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. AR-M declared to be speaker for Valneva in past years. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Shaikh, Faiyazuddin, Khan, Pathan, Syed, Gholap, Akhtar, Sah, Mehta, Sah, Bonilla-Aldana, Luna and Rodriguez-Morales.)

The process of producing the metallic nanoparticles (MNPs) in a sustainable and environment- friendly process is very desirable due to environmental hazards posed by climatic changes. Biomedical one of the fields classified under nanoscience, nanoparticles have a potential synthetic application, which makes it a vast area of research. These particles can be prepared using chemical, physical, and biological methods. One of the methods of synthesis of nanoparticles is by the use of plant extracts, known as green synthesis. Because of its low cost and nontoxicity, it has gained attention in recent times. This review was conducted to find the possible outcomes and uses of metallic nanoparticles synthesized using different parts like gum, root, stem, leaf, fruits, etc. of Azadirachta indica (AI). AI, a popular medicinal plant commonly known as neem, has been studied for the green synthesis of NPs by using the capping and reducing agents secreted by the plant. Various phytochemicals identified in neem are capable of metal ion reduction. Green synthesis of NPs from neem is an eco-friendly and low-cost method. These NPs are reported to exhibit good antimicrobial activity. The review covers the preparation, characterization, and mechanism associated with the antibacterial, anticancer, and neurological diseases of the MNPs. Furthermore, the limitations associated with the existing NPs and the prospects of these NPs are also examined., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It is possible for psoriasis to manifest at any point in a person's life, regardless of their age, gender, or geographic location. It is a chronic immune-linked inflammatory skin illness that affects individuals of various racial and ethnic origins. It is recognized to be a longlasting condition. Because of the significant contribution that natural products have made, there has been a significant advancement in the treatment of skin illnesses such as psoriasis. The biggest number of phytochemicals derived from a wide range of plants and herbs are now being used in a variety of applications throughout the whole world. Additionally, a number of phytochemicals, including aloe-emodin, psoralen, curcumin, and others, have been effectively extracted in pure or clear form, and they have shown a great deal of efficacy in the treatment of psoriasis illness. There is evidence that few herbal remedies are effective, and the occurrence of these phytochemicals provides more proof. When synthetic medications are used for chronic therapy, they may cause a variety of adverse consequences; hence, the exploration of natural pharmaceuticals can give a successful natural treatment with a minimal amount of adverse effects. Within the scope of this concise review, a number of plant sources that possess anti-psoriatic activity are investigated, and the antipsoriatic effects of these plant sources are shown on a number of animal models using particular pathways., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

As the global population ages, osteoporosis is becoming a more common silent disease. Osteoporosis is characterized by decreased bone quality and strength, which increases the risk of fragility fractures in the elderly. According to estimates, 50% of women eventually suffer from an osteoporotic fracture. Due to increasing disability, more frequent hospital hospitalizations, and most critically, fragility fractures have been linked to a reduced quality of life. Osteoporotic fractures have been linked to an increased mortality risk; and must be considered in awareness as a serious health concern. There are anti-osteoporotic medications available that improve bone quality. Considering the availability of various treatment options, still there are a lot of underserved needs in the treatment of fractures and osteoporosis. For example, the application of natural products and herbal resources for fracture healing, because of the androgen-like and antioxidant characteristics of the plants, they can play a crucial for accelerating the repair of bone fractures. In this article, we'll discuss the herbal remedies that are essential for treating osteoporosis (bone disease)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Myricetin (MC), 3,5,7,3',4',5'-hexahydroxyflavone, chemically belongs to a flavonoid category known to confer antioxidant, antimicrobial, antidiabetic, and neuroprotective effects. MC is known to suppress the generation of Reactive Oxygen Species (ROS), lipid peroxidation (MDA), and inflammatory markers. It has been reported to improve insulin function in the human brain and periphery. Besides this, it modulates several neurochemicals including glutamate, GABA, serotonin, etc. MC has been shown to reduce the expression of the enzyme Mono Amine Oxidase (MAO), which is responsible for the metabolism of monoamines. MC treatment reduces levels of plasma corticosterone and restores hippocampal BDNF (full form) protein in stressed animals. Further, MC has shown its protective effect against amyloid-beta, MPTP, rotenone, 6-OHDA, etc. suggesting its potential role against neurodegenerative disorders. The aim of the present review is to highlight the therapeutic potential of MC in the treatment of several neurological, neuropsychiatric, and neurodegenerative disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction  Traditionally, different fetal variable measurements are used in ultrasound to assess fetal growth. Ultrasound can detect abnormal fetal growth. Gestational diabetes mellitus (GDM) is linked to higher fetal obesity as early as 20 weeks of pregnancy. The amount of fetal adipose tissue may be measured by measuring the thickness of the anterior abdominal wall. Measuring the thickness of the fetus's anterior abdominal wall (AAWT) is a straightforward procedure that may be performed alongside standard abdominal circumference measurements. Objectives  To check the diagnostic accuracy of fetal AAWT as an early sonographic sign for diagnosing GDM, keeping oral glucose tolerance test as the gold standard. Study design  This research was conducted using a cross-sectional analysis. Study place and duration The study was conducted in the Radiology Department at Rawalpindi Medical University and Allied Hospitals from July 10, 2019 to January 9, 2020. Materials and methods  Women between the ages of 18 and 45 who had a family history of type 2 diabetes and were at risk for developing GDM were recruited. Exclusions were made for diabetic women, those carrying multiples, and those with autoimmune diseases. The AAWT measurement of the fetus, which included the skin and subcutaneous tissue, was acquired using the traditional anterior cranial view, 2-3 cm lateral to cord insertion. Pregnant patients at risk for GDM underwent screening using an oral glucose tolerance test. Those exhibiting any two abnormal values were diagnosed with GDM. Results  The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of fetal AAWT as an early sonographic sign for diagnosing GDM, with the oral glucose tolerance test as the gold standard, were 93.14%, 82.65%, 84.82%, 92.05%, and 88.0%, respectively. Conclusion  The study concludes that the diagnostic accuracy of fetal AAWT as an early sonographic indicator for identifying gestational diabetes is notably high., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sabir et al.)

A single negative metamaterial structure with hexagonal split-ring resonators (H-SRRs) is inserted within a two-port multiple-input multiple-output (MIMO) dielectric resonator antenna (DRA) in order to achieve a reduction of mutual coupling between closed multiple antenna elements. Between closed, tightly coupled, high-profile antenna elements, the single negative magnetic inclusions (H-SRRs) are embedded. By incorporating magnetic structures within antenna elements, the mutual coupling is significantly diminished. Mutual coupling reduction is attained by inserting an array of hexagonal split-ring resonators between the inter-spacing elements. An operative approach for the reduction of the mutual coupling between two × two MIMO DRAs initially operating at 5.2-GHz band is provided. To make the simulated design replica of the fabricated prototype, an air gap is introduced between the substrate, DRs, and H-SSRs. The addition of the air gap shifts the simulated results to 5.9 GHz, which closely resembles the measured values. The mutual coupling reduction is realized by integrating a meta-surface amid the two × two MIMO DRAs, which are settled in the H-plane. The meta-surface embraces an array of hexagonal split-ring resonator (H-SRR) cells that are unified along the E-plane. The H-SRR structure is designed to offer band-stop functionality within the antenna bandwidth. The proposed design has an overall dimension of 40 × 58.3 × 4.75 mm 3 (1.5λ × 1.02λ × 0.079λ). By stacking the DRA with a one × three array of H-SRR unit cells, a 30 dB reduction in the mutual coupling level is attained without compromising on the antenna performance. The corresponding mutual impedance of the MIMO DRA is better than 30 dB over 5.9-6.1 GHz operating bandwidth. The proposed design has a DG of 10 db, ECC < 0.02, CCL < 0.02 bits/s/Hz, and an MEG of 0 dB. The overall design has a promising performance, which shows its suitability for the target wireless application.

Environmental exposure to multiple metals and metalloids is widespread, leading to a global concern relating to the adverse health effects of mixed-metals exposure, especially in young children living around industrial areas. This study aimed to quantify the concentrations of essential and potentially toxic elements in blood and to examine the potential associations between multiple elements exposures, growth determinants, and liver and kidney function biomarkers in children living in several industrial areas in Dhaka, Bangladesh. The blood distribution of 20 trace elements As, Ag, Bi, Br, Cd, Co, Cr, Cu, I, Mn, Hg, Mo, Ni, Pb, Se, Sb, Tl, V, U, and Zn, growth determinants such as body mass index and body fats, blood pressure, liver and kidney injury biomarkers including serum alanine aminotransferase and alkaline phosphatase activities, serum calcium, and creatinine levels, blood urea nitrogen, and hemoglobin concentrations, and glomerular filtration rate were measured in 141 children, aged six to 16 years. Among these elements, blood concentrations of Ag, U, V, Cr, Cd, Sb, and Bi were measured below LOQs and excluded from subsequent statistical analysis. This comprehensive study revealed that blood concentrations of these elements in children, living in industrial areas, exceeded critical reference values to varying extents; elevated exposure to As, Pb, Br, Cu, and Se was found in children living in multiple industrial areas. A significant positive association between elevated blood Tl concentration and obesity (β = 0.300, p = 0.007) and an inverse relationship between lower As concentration and underweight (β = -0.351, p < 0.001) compared to healthy weight children indicate that chronic exposure to Tl and As may influence the metabolic burden and physical growth in children. Concentration-dependent positive associations were observed between the blood concentrations of Cu, Se, and Br and hepatic- and renal dysfunction biomarkers, an inverse association with blood Mo and I level, however, indicates an increased risk of Cu, Se, and Br-induced liver and kidney toxicity. Further in-depth studies are warranted to elucidate the underlying mechanisms of the observed associations. Regular biomonitoring of elemental exposures is also indispensable to regulate pollution in consideration of the long-term health effects of mixed-elements exposure in children., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background Biological variation (BV) as a prognostic marker implies that each individual has a "subject mean" or central tendency, control level, or "set point" concentration for maintaining homeostasis regulation, which is influenced by factors such as genes, diet, exercise, and age. Uses for information on BV include determining the value of population-based reference intervals, assessing the importance of variation in serial findings, and establishing criteria for judging correct analysis. Aims We focused on the assessment of BV parameters for these elements as within-subject BV (CV W ), between subject BV (CV G ), the index of individuality (II), and the reference change value (RCV) of important biochemical analytes in the Bangladeshi adult population. Methodology This is a cross-sectional analytical study of a representative sample in the population of Bangladesh to determine BV in clinical laboratory analytes. For the study, 758 people were requested to take part; among those 730 (ages 18-65) apparently, healthy adults were blood donors, hospital staff, laboratory personnel, or any individuals who presented themselves for health screening at a tertiary hospital in Dhaka, Bangladesh. Results The CV W for blood sugar, creatinine, urea, uric acid, sodium, potassium, chloride, calcium, magnesium, and phosphate were calculated as 5.10 %, 4.64%, 10.72%, 5.71%, 0.69%, 4.35%, 0.75%, 3.69%, 4.57%, and 4.72%, respectively. The CV G for blood sugar, creatinine, urea, uric acid, sodium, potassium, chloride, calcium, magnesium, and phosphate was 10.70%, 21.46%, 31.47%, 23.52%, 1.95%, 9.74%, 2.56%, 4.64%, 9.96 %, and 17.45%, respectively. The index of individuality (II) for blood sugar, creatinine, urea, uric acid, sodium, potassium, chloride, calcium, magnesium, and phosphate were 0.48, 0.22, 0.34, 0.24, 0.35, 0.45, 0.29, 0.79, 0.46, and 0.27, respectively. The RCV for blood sugar, creatinine, urea, uric acid, sodium, potassium, chloride, calcium, magnesium, and phosphate was 14.75%, 14.10%, 30.58%, 16.13%, 2.82%, 12.58%, 3.54%, 10.62%, 13.62 %, and 15.80%, respectively. Conclusions Nine serum biochemistry analytes (blood sugar, creatinine, urea, uric acid, sodium, potassium, chloride, magnesium, and phosphate) had low individuality, indicating that subject-based reference intervals are appropriate, only one analyte (calcium) had high individuality and, therefore, population-based reference intervals are more appropriate., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ali et al.)

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for "IBS mimickers" such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism., Competing Interests: The authors have declared that no competing interests exist.

In this study, the levels of indicator PCBs congeners and PAHs compounds were reported in cow milk from selected areas in Dhaka, Bangladesh, and the potential human health risks were assessed. A total of 100 milk samples were collected and analyzed using gas chromatography-tandem mass spectrometry (GC-MS/MS). Method validation was performed using recovery performance, linearity, limit of detection (LOD), and limit of quantification (LOQ) assays. PCBs congeners, including PCB No. 52 (2,2´,5,5´-tetrachlorobiphenyl), PCB No. 101 (2,2´,4,5,5´-pentachlorobiphenyl), PCB No. 153 (2,2,4,4,5,5-hexachlorobiphenyl), and PCB No 209 (Decachloro-1,1'-biphenyl perchlorobiphenyl) were detected, whereas PCB No 28 (2,2 ´,4-trichlorobiphenyl), PCB No. 138 (2,2´,3,4,4´,5´-hexachlorobiphenyl), and PCB No 180 (2,2´,3,4,4´,5,5´-heptachlorobiphenyl) were not detected in the analyzed milk samples. Among the 16 PAHs compounds, benzo (a) anthracene and chrysene were detected in milk samples. The Σ hazard risk index (HI) of all detected PCBs congeners was below the limit set by the European Food Safety Authority, which indicates limited health risks to animals and humans in the study area. However, the presence of PCBs and PAHs in milk samples from industrial areas may negatively affect human health, and further detailed studies are required to ensure public health safety., Competing Interests: 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., (© 2022 The Authors.)

Globally, neurodegenerative diseases cause a significant degree of disability and distress. Brain-derived neurotrophic factor (BDNF), primarily found in the brain, has a substantial role in the development and maintenance of various nerve roles and is associated with the family of neurotrophins, including neuronal growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). BDNF has affinity with tropomyosin receptor kinase B (TrKB), which is found in the brain in large amounts and is expressed in several cells. Several studies have shown that decrease in BDNF causes an imbalance in neuronal functioning and survival. Moreover, BDNF has several important roles, such as improving synaptic plasticity and contributing to long-lasting memory formation. BDNF has been linked to the pathology of the most common neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. This review aims to describe recent efforts to understand the connection between the level of BDNF and neurodegenerative diseases. Several studies have shown that a high level of BDNF is associated with a lower risk for developing a neurodegenerative disease.

UTIs are majorly caused by species of bacteria in patients of almost all ages. The study was aimed to determine the prevalence rate of uropathogens, its antibiotic susceptibility pattern and associated risk factors. Urine samples were collected from n=470 participants using sterilized containers and were inoculated on culture media. The isolates were identified via gram-staining and biochemical characterization. A total of 43.20% samples were positive. Female contributed the highest prevalence rate, 78.82% as compared to male, 21.18%. The highest prevalence 40.90% was observed in the age-group 31-45, followed by 16-30 with 36.90%. Escherichia coli (47.80%) was the most prevalent, followed by Klebsiella pneumoniae (18.2%), Enterococcus faecalis (12.80%), Pseudomonas aeruginosa (10.30%) and Proteus mirabilis (7.40%). Staphylococcus aureus showed high sensitivity (100%) to amikacin, meropenem, imipenem, fosfomycin, vancomycin, clindamycin and linezolid while in case of E. faecalis, vancomycin and linezolid were highly potent. Amikacin and meropenem showed the highest (100%) potency followed by imipenem While Fosfomycin was highly potent to E. coli, K. pneumoniae, P. mirabilis and P. aeruginosa with potency rate 89.97%, 92.31%, 100% and 100% respectively. In the current study, the positivity rate was highly observed in female. E. coli and K. pneumoniae were found the most ubiquitous for UTI.

Arrhythmias in COVID-19 patients are associated with hypoxia, myocardial ischemia, cytokines, inflammation, electrolyte abnormalities, pro-arrhythmic or QT-prolonging medications, and underlying heart conditions such as severe congestive heart failure, inherited arrhythmia syndromes, or congenital heart conditions. In the pediatric population, multisystem inflammatory syndrome can lead to cardiac injury and arrhythmias. In addition, arrhythmias and cardiac arrests are most prevalent in the critically ill intensive care unit COVID-19 patient population. This review presents an overview of the association between COVID-19 and arrhythmias by detailing possible pathophysiological mechanisms, existing knowledge of pro-arrhythmic factors, and results from studies in adult and pediatric COVID-19 populations, and the clinical implications., 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 © 2021. Published by Elsevier Ltd.)

Escherichia coli is the most studied among those bacteria causing urinary tract infections. This study was aimed to find out antibacterial activity and minimum inhibitory concentration of selected antibacterial agents against E. coli isolates of hospitalized UTI patients. The specimens were inoculated on Eosin Methylene Blue medium. E. coli isolates were identified via colonial morphology, biochemical testing and API-20 kit. The susceptibility pattern of antibacterial agents was determined applying disc diffusion method (Kirby-Bauer) and dilution tube method. Among all, 38.82% (n=158/407) specimens were positive for E. coli, while the rest showed either no growth or exhibited colonies other than E. coli. while observing the susceptibility pattern, Imipenem was found the most effective (73.42%) antibacterial agent, followed by nitrofurantoin (52.53%), cefpirome (44.94%) and tazobactam/ piperacillin (44.94%), whereas the E. coli isolates were highly resistant to sulfamethoxazole/trimethoprim (71.52%), followed by Amoxicillin-clavulanic acid (67.72%), nalidixic acid (66.46%) and Tobramycin (62.03%), when tested by disc diffusion method. The isolates were susceptible to cefpirome (39.87%) and tobramycin (39.87%) and resistant to sulfamethoxazole/trimethoprim (75.32%), followed by levofloxacin (61.39%), when tested by tube dilution method. The study concluded high degree of resistance against Sulfamethoxazole/trimethoprim, in contrast, cephalosporin and Imipenem exhibited good potency which can be recommended for UTI.

Adolescents have been called the "digital natives of the technology age", but determining adolescents' awareness, attitudes and behavior with respect to technology addiction (TA) is important for developing balanced and effective approaches to support their physical and psychological well-being after the COVID-19 pandemic. For this reason, the present study investigates the impact of attitudes on TA behavior in 382 adolescents by gender and extent of technology use. Three scales were used to determine adolescents' TA awareness, attitude, and behavior. The results of the dual-moderated mediation model show that gender and duration of technology use (h) moderated the full mediation of attitude on awareness and behavior in TA ( F  = 39.29, df  = 9;372, p  < .01). The indirect effect in males with 16.04 h per day of technology use is stronger (.24) than the indirect effect in males with 4.90 h per day of technology use (.13). In addition, the simple slope plot shows that when attitude scores increase, addictive behavior rises in females (simple slope = .74, t  = 8.79, p  < .01). On the other hand, with 16.04 h per day of technology use, when attitude scores decrease, addictive behavior rises in females (simple slope = .69, t  = 7.59, p  < .01). Furthermore, when the attitude scores increase, addictive behavior rises in males (simple slope = .85, t  = 13.26, p  < .01). As a result, the psychoeducational intervention programs to be implemented for TA should not only focus on awareness, but should also encompass behavioral, cognitive and lifestyle changes., Competing Interests: Conflict of InterestNone of the authors had any conflicts of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature 2021.)

Neurodegenerative diseases are a heterogeneous group of disorders among aging populations worldwide characterized by the progressive degeneration of the structure and function of brain cells and the nervous system. Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases (NDs). Classic pathological features of AD are the accumulation of the amyloid betaprotein and aggregates of hyperphosphorylated tau protein around the brain cells. Dopaminergic neuronal death in the midbrain and accumulation of α- synuclein in the neurons are the hallmark of Parkinson's disease. The pathogenesis is multifactorial, and both neurodegenerative disorders have complex etiology. Oxidative stress closely linked with mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation, is anticipated to trigger neuronal death. Ample evidence has implicated that oxidative stress and inflammation contribute to the pathology of neurodegeneration in AD and PD. Currently, acetylcholinesterase inhibitors are the main treatment option for AD, while L-DOPA is the gold standard therapy for PD. Along with the main therapy, many endogenous antioxidants, like vitamin E, selenium, etc., are also given to the patients to combat oxidative stress. Current treatment for these NDs is limited due to the blood-brain barrier (BBB) that hinders drug targeting towards neurons. In this review, we emphasize adjunct treatment with anti-inflammatory agents that act at the site of the disease and can halt the disease progression by attenuating the effect of ROS triggering neuro-inflammatory response. Polyphenols, either as purified compounds or extracts from various natural plant sources, have been well studied and documented for anti-inflammatory effects, but their use for ND is limited due to their physicochemical attributes. Nanoparticle-mediated drug delivery system exhibits immense potential to overcome these hurdles in drug delivery to the CNS, enabling nanoparticle-based therapies to directly target the inflammation and release bioactive compounds with anti-inflammatory properties to the site of action., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Among conventional treatment methodologies, surgery, hyperthermia, radiation, and chemotherapy have become integral components of treatment for most cancers. Radiation therapy in the treatment of many malignancies is always the better choice over surgery and chemotherapy. Ionizing radiation produced as a consequence of using these radiations has always been a concern in these treatment methods. Synthetic radio-protectors with their inherent limitations are being used to date to reduce the mortality of these radiations; still, it compromises the clinical efficacy of these administrations. Hence, investigations for alternative methods, including natural resources such as plant and fruit extracts, are being explored to treat radiation-mediated ailments. The present review article endeavors to provide a comprehensive, updated, and chronological account of these promising plants and fruit extracts and their bioactive principles as radio-protectors. We present the merits and demerits of radiation therapy and cell stress generation of reactive oxygen species (ROS) associated with radiation need and availability of radio-protectors. Finally, we discuss green-based bioactive compounds that have radioprotective properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Significant efforts have been made in research to discover newer neurotherapeutics, however, the rate of reported neurological disorders has been increasing at an alarming speed. Neurotherapeutics delivery in the brain is still posing a significant challenge, owing to the blood-brain barrier and blood-cerebrospinal fluid barrier. These physiological barriers restrict the passage of systemically available fractions of neurotherapeutics into the brain, owing to low permeability and drug localization factors. Neurotherapeutics encapsulating lipid carriers favor a significant increase in bioavailability of poorly water-soluble drugs by enhancing solubility in the gastrointestinal tract and favoring stability. Due to their small size and lipid-based composition, these carriers offer enhanced permeability across the semi-permeable blood-brain barrier to effectively transport encapsulated loads, such as synthetic drugs, nutraceuticals, phytoconstituents, herbal extracts, and peptides, thereby reducing incidences of off-target mediated adverse impacts and toxicity. The most significant advantage of such lipid-based delivery systems is non-invasive nature and targeting of neurotherapeutics to the central nervous system. Critical attributes of lipid-based carriers modulate release rates in rate-controlled manners, enable higher penetration through the blood-brain barrier, and bypass the hepatic first-pass metabolism leading to higher CNS bioavailability neurotherapeutics. The current review discusses a brief and introductory account of the limitations of neurotherapeutics, pharmacological barriers, challenges in brain-targeted delivery, and the potential of nanotechnology- processed lipid-based carriers in the clinical management of neuronal disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chemo- and radiation therapy-based clinical management of different types of cancers is associated with toxicity and several side effects. Therefore, there is always an unmet need to explore agents that reduce such risk factors. Among these, natural products have attracted much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer., Methods: Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics., Results: Apart from excellent anti-cancer abilities, probiotics alleviate toxicity & side effects of chemotherapeutics, with a high degree of safety and efficiency., Conclusion: Preclinical and clinical evidence suggests that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Fermi level alignment between electrodes and two-dimensional (2D) materials is significant in characterizing sensors based on their reversibility, response time, sensitivity, and long-term stability. Here, we have demonstrated that the modulation of the Schottky barrier height between the interface of metal (Pd/Au) and multilayered ReSe 2 nanoflakes caused the change in the transfer curve (I ds -V bg ) of FETs based devices and rectifying characteristics (I ds -V ds ) of the Schottky diodes at various hydrogen concentrations at T = 22 °C, fluctuating from 50 to 350 ppm with a response (R%) from 669 to 1198%, respectively. Sensors based on a mono- or bilayer system did not exhibit sensitivity to hydrogen gas owing to metal electrodes diffused into materials. The value of the ideality factor of the Schottky diode-based sensor changed from 4 to 1.6 as the hydrogen concentration was changed from 50 to 900 ppm, while the relative response increased from 0 to 3.5 as the hydrogen concentration was increased from 0 to 900 ppm. This research can offer a real solution for developing cost-effective, faster, and room temperature sensors based on 2D materials., 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 © 2021 Elsevier Inc. All rights reserved.)

Background: Cytoplasmic inclusions of α-synuclein (α-syn) in brainstem neurons are characteristic of idiopathic Parkinson's disease (PD). PD also entails α-syn buildup in sympathetic nerves. Among genetic forms of PD, the relative extents of sympathetic intraneuronal accumulation of α-syn have not been reported., Objective: This cross-sectional observational study compared magnitudes of intraneuronal deposition of α-syn in common and rare genetic forms of PD., Methods: α-Syn deposition was quantified by the α-syn-tyrosine hydroxylase colocalization index in C2 cervical skin biopsies from 65 subjects. These included 30 subjects with pathogenic mutations in SNCA (n = 3), PRKN [biallelic (n = 7) and monoallelic (n = 3)], LRRK2 (n = 7), GBA (n = 7), or PARK7/DJ1 [biallelic (n = 1) and monoallelic (n = 2)]. Twenty-five of the mutation carriers had PD and five did not. Data were also analyzed from 19 patients with idiopathic PD and 16 control participants., Results: α-Syn deposition varied as a function of genotype (F = 16.7, P < 0.0001). It was above the control range in 100% of subjects with SNCA mutations, 100% with LRRK2 mutations, 95% with idiopathic PD, 83% with GBA mutations, and 0% with biallelic PRKN mutations. α-Syn deposition in the biallelic PRKN group was significantly higher than in the control group. In addition, patients with biallelic PRKN mutations had higher α-syn deposition than their unaffected siblings., Conclusions: Individuals with SNCA, DJ-1, LRRK2, or GBA mutations have substantial intraneuronal α-syn deposition in sympathetic noradrenergic nerves in skin biopsies, whereas those with biallelic PRKN mutations do not. Biallelic PRKN patients may have mildly increased α-syn deposition compared with control subjects. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Continuously increasing human population demands increased food production, which needs greater fertilizer's input in agricultural lands to enhance crop yield. In this respect, different fertilization practices gained acceptance among farmers. We reviewed effect of three main fertilization practices (Conventional-, Organic-, and Bio-fertilization) on soil microbial diversity, activity, and community composition. Studies reported that over application of inorganic fertilizers decline soil pH, change soil osmolarity, cause soil degradation, disturb taxonomic diversity and metabolism of soil microbes and cause accumulation of extra nutrients into the soil such as phosphorous (P) accumulation. On the contrary, organic fertilizers increase organic carbon (OC) input in the soil, which strongly encourage growth of heterotrophic microbes. Organic fertilizer vermicompost application provides readily available nutrients to both plants as well as microbes and encourage overall microbial number in the soil. Most recently, role of beneficial bacteria in long-term sustainable agriculture attracted attention of scientists towards their use as biofertilizer in the soil. Studies documented favorable effect of biofertilization on microbial Shannon, Chao and ACE diversity indices in the soil. It is concluded from intensive review of literature that all the three fertilization practices have their own way to benefit the soil with nutrients, but biofertilization provides long-term sustainability to crop lands. When it is used in integration with organic fertilizers, it makes the soil best for microbial growth and activity and increase microbial diversity, providing nutrients to soil for a longer time, thus improving crop productivity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is considerable interest in identifying effective and safe drugs for neurodegenerative disorders. Cell culture and animal model work have demonstrated that modulating gene expression through RXR-mediated pathways may mitigate or reverse cognitive decline. However, because RXR is a dimeric partner for several transcription factors, activating off-target transcription is a concern with RXR ligands (rexinoids). This off-target gene modulation leads to unwanted side effects that can include low thyroid function and significant hyperlipidemia. There is a need to develop rexinoids that have binding specificity for subsets of RXR heterodimers, to drive desired gene modulation, but that do not induce spurious effects. Herein, we describe experiments in which we analyze a series of novel and previously reported rexinoids for their ability to modulate specific gene pathways implicated in neurodegenerative disorders employing a U87 cell culture model. We demonstrate that, compared to the FDA-approved rexinoid bexarotene ( 1 ), several of these compounds are equally or more effective at stimulating gene expression via LXREs or Nurr1/NBREs and are superior at inducing ApoE and/or tyrosine hydroxylase (TH) gene and protein expression, including analogs 8 , 9 , 13 , 14 , 20 , 23 , and 24 , suggesting a possible therapeutic role for these compounds in Alzheimer's or Parkinson's disease (PD). A subset of these potent RXR agonists can synergize with a presumed Nurr1 ligand and antimalarial drug (amodiaquine) to further enhance Nurr1/NBREs-directed transcription. This novel discovery has potential clinical implications for treatment of PD since it suggests that the combination of an RXR agonist and a Nurr1 ligand can significantly enhance RXR-Nurr1 heterodimer activity and drive enhanced therapeutic expression of the TH gene to increase endogenous synthesis of dopamine. These data indicate that is it possible and prudent to develop novel rexinoids for testing of gene expression and side effect profiles for use in potential treatment of neurodegenerative disorders, as individual rexinoids can have markedly different gene expression profiles but similar structures.

Self-medication is the use of medicines by people on the basis of their own experience without consulting a doctor. People use medicines for pain management or to cure a disease and sometime this may be unnecessary. There are a lot of public and professional health concerns about misuse of medicines and globally physicians agree upon this rising issue that leads to antibiotic resistance. In developing countries, medicines without prescription are easily available which results in many adverse outcomes, especially bacterial resistance. Insufficient healthcare services and socioeconomic factors result in increased proportion of self-medication compared to drugs prescribed by physicians. The current narrative review was planned to focus on indicating prevalence rate of self-medication in different developed and under-developed countries, major risk factors and control of self-medication due to which antibiotic resistance rate can be minimised. The issue needs urgent attention of representative authorities for taking serious actions. Furthermore, arranging awareness seminars and implementing new policies/regulations to prevent the sale of any drug/antibiotic without prescription could play a vital role in bringing this alarming issue under control.

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered., Competing Interests: Declaration of Interests S.P.-B., A.B.S., J.A.H., H.R.M., and B.J.T. hold US, EU, and Canadian patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9 or f72. S.W.S. serves on the scientific advisory council of the Lewy Body Dementia Association and is an editorial board member for the Journal of Parkinson’s Disease. B.J.T. is an editorial board member for JAMA Neurology, JNNP, and Neurobiology of Aging. V.S. is on the journal editorial boards of Amyotrophic Lateral Sclerosis, European Neurology, American Journal of Neurodegenerative Diseases, and Frontiers in Neurology. He has also received compensation for consulting services and speaking activities from AveXis, Cytokinetics, Italfarmaco, and Zambon. J.B.R. is an editor for Brain and has received compensation for consulting services from Asceneuron, Biogen, UCB, Astex, and SV Health. J.E.L. is a member of the scientific advisory board for Cerevel Therapeutics and a consultant and provides expert testimony for Perkins Coie., (Published by Elsevier Inc.)

Background: Professionally, private security guards are expected to manage their anger and stress successfully., Objective: The primary purpose of this study is to determine stress and anger levels of private security guards working in the Ankara Electricity, Gas and Bus Operations Organization. The secondary aim of this research is to determine the effectiveness of the training program given to private security guards within the scope of anger and stress control. The effects of training on 690 private security guards who participated in the training program were investigated., Methods: In the first part of the study, the validity and reliability of the Trait Anger, Anger Expression Scale and Coping with Stress Scale were investigated, and in the second part, the effectiveness of training given to 690 private security guards was examined. Also, as a comparison group, 201 private security guards who did not participate in the training were reached and the scales were applied., Results: The results showed that private security guards had an inability to cope with stress and anger was triggered easily. The average treatment effect was E[Y(1) - Y(0)| X] = -0.111 and statistically significant. It shows that training had a significant effect on anger. Anger decreased when stress-coping behaviours increased and the training was effective., Conclusions: It is important that training about anger and stress control should be given to security forces at regular intervals.

Exploring and analyzing data using visualizations is at the heart of many decision-making tasks. Typically, people perform visual data analysis using mouse and touch interactions. While such interactions are often easy to use, they can be inadequate for users to express complex information and may require many steps to complete a task. Recently natural language interaction has emerged as a promising technique for supporting exploration with visualization, as the user can express a complex analytical question more easily. In this paper, we investigate how to synergistically combine language and mouse-based direct manipulations so that the weakness of one modality can be complemented by the other. To this end, we have developed a novel system, named Multimodal Interactions System for Visual Analysis ( MIVA ), that allows user to provide input using both natural language (e.g., through speech) and direct manipulation (e.g., through mouse or touch) and presents the answer accordingly. To answer the current question in the context of past interactions, the system incorporates previous utterances and direct manipulations made by the user within a finite-state model. The uniqueness of our approach is that unlike most previous approaches which typically support multimodal interactions with a single visualization, MIVA enables multimodal interactions with multiple coordinated visualizations of a dashboard that visually summarizes a dataset. We tested MIVA's applicability on several dashboards including a COVID-19 dashboard that visualizes coronavirus cases around the globe. We further empirically evaluated our system through a user study with twenty participants. The results of our study revealed that MIVA system enhances the flow of visual analysis by enabling fluid, iterative exploration and refinement of data in a dashboard with multiple-coordinated views., (This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.)

Mediated by the nuclear vitamin D receptor (VDR), the hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin D 3 (1,25D), is known to regulate expression of genes impacting calcium and phosphorus metabolism, the immune system, and behavior. Urolithin A, a nutrient metabolite derived from pomegranate, possibly acting through AMP kinase (AMPK) signaling, supports respiratory muscle health in rodents and longevity in C. elegans by inducing oxidative damage-reversing genes and mitophagy. We show herein that urolithin A enhances transcriptional actions of 1,25D driven by co-transfected vitamin D responsive elements (VDREs), and dissection of this genomic effect in cell culture reveals: 1) urolithin A concentration-dependency, 2) occurrence with isolated natural VDREs, 3) nuclear receptor selectivity for VDR over ER, LXR and RXR, and 4) significant 3- to 13-fold urolithin A-augmentation of 1,25D-dependent mRNA encoding the widely expressed 1,25D-detoxification enzyme, CYP24A1, a benchmark vitamin D target gene. Relevant to potential behavioral effects of vitamin D, urolithin A elicits enhancement of 1,25D-dependent mRNA encoding tryptophan hydroxylase-2 (TPH2), the serotonergic neuron-expressed initial enzyme in tryptophan metabolism to serotonin. Employing quantitative real time-PCR, we demonstrate that TPH2 mRNA is induced 1.9-fold by 10 nM 1,25D treatment in culture of differentiated rat serotonergic raphe (RN46A-B14) cells, an effect magnified 2.5-fold via supplementation with 10 μM urolithin A. This potentiation of 1,25D-induced TPH2 mRNA by urolithin A is followed by a 3.1- to 3.7-fold increase in serotonin concentration in culture medium from the pertinent neuronal cell line, RN46A-B14. These results are consistent with the concept that two natural nutrient metabolites, urolithin A from pomegranate and 1,25D from sunlight/vitamin D, likely acting via AMPK and VDR, respectively, cooperate mechanistically to effect VDRE-mediated regulation of gene expression in neuroendocrine cells. Finally, gedunin, a neuroprotective natural product from Indian neem tree that impacts the brain derived neurotropic factor pathway, similarly potentiates 1,25D/VDR-action., (© 2020 The Author(s).)

Nickel oxide nanoparticles (NiO NPs) have received great interests in medical and biotechnological applications. However, their adverse impacts against biological systems have not been well-explored. Herein, the influence of NiO NPs on structural changes, heme degradation and aggregation of hemoglobin (Hb) was evaluated by UV-visible (Vis) spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM), and molecular modeling investigations. Also, the morphological changes and expression of Bax/Bcl-2 mRNA in human lymphocyte cell exposed to NiO NPs were assayed by DAPI staining and quantitative real-time PCR (qPCR), respectively. The UV-Vis study depicted that NiO NPs resulted in the displacement of aromatic residues and heme groups and production of the pro-aggregatory species. Intrinsic and Thioflavin T (ThT) fluorescence studies revealed that NiO NPs resulted in heme degradation and amorphous aggregation of Hb, respectively, which the latter result was also confirmed by TEM study. Moreover, far UV-CD study depicted that NiO NPs lead to substantial secondary structural changes of Hb. Furthermore, near UV-CD displayed that NiO NPs cause quaternary conformational changes of Hb as well as heme displacement. Molecular modelling study also approved that NiO NPs resulted in structural alterations of Hb and heme deformation. Moreover, morphological and genotoxicity assays revealed that the DNA fragmentation and expression ratio of Bax/Bcl-2 mRNA increased in lymphocyte cells treated with NiO NPs for 24   hr. In conclusion, this study indicates that NiO NPs may affect the biological media and their applications should be limited.Communicated by Ramaswamy H. Sarma.

The article has been withdrawn at the request of the editor of the journal Current Drug Metabolism due to incoherent content. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php., Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net)

Objective: To assess and compare the frequency of antibiotic-resistant staphylococcus aureus strains., Methods: A retrospective study was conducted at the privately-owned Welfare Medical Laboratory, Peshawar, Pakistan, and comprised record related to the period between 07th February 2017 and 23rd March 2018 of patients referred for pus-testing from Khyber Teaching Hospital, Lady Reading Hospital and the Hayatabad Medical Complex. Pus samples were obtained from various parts of body with cotton swabs. The samples were cultured and the isolated staphylococcus aureus strains were analysed against selected antibiotics. The frequency of the isolated strains was tested and compared using Prism 7 software., Results: Of the 6780 samples, staphylococcus aureus was found in 4315(63.64%). Wild-type staphylococcus aureus strains were 2133(31.46%), followed by 825(12.16%) methicillin resistant, 792(11.68%) vancomycin intermediate, and 565(8.33%) vancomycin-resistant staphylococcus aureus strains. The isolated strains were significant (p<0.0001) for operated wounds, and non-significant (p=0.8915) for diabetic foot cases., Conclusions: The frequency of antibiotic-resistant staphylococcu saureus strains was high.

Development of optical nanobiosensors has emerged as one of the most important bioresearch areas of interest over the past decades especially in the modern innovations in the design and utilization of sensing platforms. The application of nanobiosensors has been accelerated with the introduction of plasmonic NPs, which overcome the most of the limitations in the case of conventional optical nanobiosensors. Since the plasmonic AuNPs-based nanobiosensors provide high potential achievements to develop promising platforms in fully integrated multiplex assays, some well-developed investigations are clearly required to improve the current technologies and integration of multiple signal inputs. Therefore, in this literature, we summarized the performance and achievements of optical nanobiosensors according to plasmonic rules of AuNPs, including SPR, LSPR, SERS and chiroptical phenomena. Also, we investigated the effects of the physicochemical properties of AuNPs such as size, shape, composition, and assembly on the plasmonic signal propagation in AuNPs-based nanobiosensors. Moreover, we presented an overview on the current state of plasmonic AuNPs-based nanobiosensors in the biomedical activities. Besides, this paper looks at the current and future challenges and opportunities of ongoing efforts to achieve the potential applications of AuNPs-based optical plasmonic nanobiosensors in integration with other nanomaterials. Taken together, the main focus of this paper is to provide some applicable information to develop current methodologies in fabrication of potential AuNPs-based nanobiosensors for detection of a wide range of analytes., Competing Interests: Declaration of competing interest The authors have none to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The evidence to guide clinicians regarding rationale polytherapy with current antiepileptic drugs (AEDs) is lacking, and current practice recommendations are largely empirical.  The excessive drug loading with combinatorial therapies of existing AEDs are associated with escalated neurotoxicity, and that emergence of pharmacoresistant seizures couldn't be averted. In pursuit of judicious selection of novel AEDs in combinatorial therapies with mechanism based evidences, standardized dose of raloxifene, fluoxetine, bromocriptine and their low dose combinations, were experimentally tested for their impact on maximal electroshock (MES) induced tonic hind limb extension (THLE) in mice. Hippocampal neuropeptide Y (NPY) levels, oxidative stress and histopathological studies were undertaken. The results suggest the potentiating effect of 4 mg/kg raloxifene on 14 mg/kg fluoxetine against MES induced THLE, as otherwise monotherapy with 4 mg/kg raloxifene was unable to produce an effect. The results also depicted better efficacy than carbamazepine (20 mg/kg), standard AED. Most profoundly, MES-induced significant (P < 0.001) reduction in hippocampal NPY levels, that were escalated insignificantly with the duo-drug combination, suggesting some other mechanism in mitigation of electroshock induced seizures. These results were later corroborated with assays to assess oxidative stress and neuronal damage. In conclusion, the results demonstrated the propitious therapeutic benefit of duo-drug low dose combination of drugs; raloxifene and fluoxetine, with diverse mode of actions fetching greater effectiveness in the management of generalized tonic clonic seizures (GTCS)., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The efficacy of different modalities of treating breast cancer is inhibited by several limitations such as off-targeted drug distribution, rapid drug clearance, and drug resistance. To overcome these limitations, we developed Lf-Doxo-PMNSs for combined chemo-MF-PTT. The PMNSs were synthesized by hydrothermal method and their physicochemical properties were examined by FE-SEM, TEM, DLS, TGA, XRD investigations. The cytotoxicity of as-synthesized NPs against 4T1 cells was carried out by MTT and flow cytometry assays. Afterwards, the anti-cancer activities of as-synthesized Lf-Doxo-PMNSs on the tumor status, drug distribution and apoptosis mechanism were evaluated. The anti-cancer assays showed that Lf-Doxo-PMNSs significantly suppressed the cancer cell proliferation and tumor weight by prolonging drug availability and potential drug loading in tumor cells; whereas they showed a minimum cytotoxicity against non-cancerous cells. Likewise, combined chemo-MF-PTT using Lf-Doxo-PMNSs displayed the highest anti-cancer activity followed by combined chemo-PTT and combined chemo-MF therapy based on altering the apoptosis mechanism. Therefore, these results showed that combined chemo-MF-PTT based on Lf-Doxo-PMNSs can be used as a promising therapeutic platform with potential targeted drug delivery and high loading capacity features as well as reducing cancer drug resistance.

The utilization of AuNPs in therapeutic applications has been accelerated by discovering their catalytic activity consistent with the activity of natural enzymes. However, to reduce unwanted activities, it is imperative to fully understand their catalytic mechanisms to increase efficiency and safety. Therefore, along with other reports, we aimed to classify the enzymatic activity of Au nanozymes based on recent advance in their applications in biosensing and therapeutic activities. The results of the reported experiments indicate that the Au nanozymes can be used in biosensing of a wide range of agents such as molecule (H 2 O 2 and glucose), ions, nucleic acids, proteins, cells, and pathogens. Furthermore, they can be used as potential candidates in inhibition of neurodegenerative diseases, cancer therapy, and antibacterial activities. Biosensing and therapeutic activities are generally based on colorimetric assays and the controlling the ROS level in the targeted cells, respectively. Finally, a brief explanation of the current challenges of the Au nanozymes in biomedical approaches was discussed. Indeed, this review holds a great promise in understanding the Au nanozymes properties and their development in biotechnology, medicine, and related industries., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The neurological disorders affect millions of people worldwide, and are bracketed as the foremost basis of disability-adjusted life years (DALYs). The treatment options are symptomatic and often the movement of drugs is restricted by a specialized network of endothelial cell layers (adjoined by tight cell-to-cell junction proteins; occludin, claudins, and junctional adhesion molecules), pericytes and astroglial foot processes. In recent years, advances in nanomedicine have led to therapies that target central nervous system (CNS) pathobiology via altering signaling mechanisms such as activation of PI3K/Akt pathway in ischemic stroke arrests apoptosis, interruption of α-synuclein aggregation prevents neuronal degeneration in Parkinson's. Often such interactions are limited by insufficient concentrations of drugs reaching neuronal tissues and/or insufficient residence time of drug/s with the receptor. Hence, lipid nanoformulations, SLNs (solid lipid nanoparticles) and NLCs (nanostructured lipid carriers) emerged to overcome these challenges by utilizing physiological transport mechanisms across blood-brain barrier, such as drug-loaded SLN/NLCs adsorb apolipoproteins from the systemic circulation and are taken up by endothelial cells via low-density lipoprotein (LDL)-receptor mediated endocytosis and subsequently unload drugs at target site (neuronal tissue), which imparts selectivity, target ability, and reduction in toxicity. This paper reviews the utilization of SLN/NLCs as carriers for targeted delivery of novel CNS drugs to improve the clinical course of neurological disorders, placing some additional discussion on the metabolism of lipid-based formulations.

In this study, we formulated silymarin-HSA nanoplex and assayed its ability to reduce LPS-induced toxicity in vitro and in vivo. Silymarin molecules were encapsulated into HSA nanoplex and the loading efficiency and characterization of fabricated nanoplex were performed by using HPLC, TEM, SEM, DLS, FTIR analysis, and theoretical studies. Afterwards, their protective effect against LPS (20 µg/ml) -induced toxicity in SH-SY5Y cells was investigated by MTT, ROS, and apoptosis assays. For in vivo experiments, rats were pre-treated with either silymarin or silymarin -HSA nanoplex (200 mg/kg) orally for 3 days and at third day received LPS by IP at a dose of 0.5 mg/kg, 150 min before scarification followed by SOD and CAT activity assay. The formulation of silymarin-HSA nanoplex showed a spherical shape with an average diameter between 50 nm and 150 nm, hydrodynamic radius of 188.3 nm, zeta potential of -26.6 mV, and a drug loading of 97.3%. In LPS-treated cells, pretreatments with silymarin-HSA noncomplex recovered the cell viability and decreased the ROS level and corresponding apoptosis more significantly than free silymarin. In rats, it was also depicted that, silymarin-HSA noncomplex can increase the SOD and CAT activity in brain tissue at LPS-triggered oxidative stress model more significantly than the free counterpart. Therefore, nanoformulation of silymarin improved its capability to reduce LPS-induced oxidative stress by restoring cell viability and elevation of SOD and CAT activity in vitro and in vivo, respectively. In conclusion, formulation of silymarin may hold a great promise in the development of antioxidant agents., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases., Objectives: To perform the largest PD genome-wide association study restricted to a single country., Methods: We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses., Results: We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls., Conclusions: Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Atypical parkinsonism syndromes are a heterogeneous group of neurodegenerative disorders that include corticobasal degeneration (CBD), Lewy body dementia (LBD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). The APOE ε4 allele is a well-established risk factor for Alzheimer's disease; however, the role of APOE in atypical parkinsonism syndromes remains controversial. To examine the associations of APOE ε4 and ε2 alleles with risk of developing these syndromes, a total of 991 pathologically-confirmed atypical parkinsonism cases were genotyped using the Illumina NeuroChip array. We also performed genotyping and logistic regression analyses to examine APOE frequency and associated risk in patients with Alzheimer's disease (n = 571) and Parkinson's disease (n = 348). APOE genotypes were compared to those from neurologically healthy controls (n = 591). We demonstrate that APOE ε4 and ε2 carriers have a significantly increased and decreased risk, respectively, of developing Alzheimer's disease (ε4: OR: 4.13, 95% CI: 3.23-5.26, p = 3.67 × 10 -30 ; ε2: OR: 0.21, 95% CI: 0.13-0.34; p = 5.39 × 10 -10 ) and LBD (ε4: OR: 2.94, 95% CI: 2.34-3.71, p = 6.60 × 10 -20 ; ε2: OR = OR: 0.39, 95% CI: 0.26-0.59; p = 6.88 × 10 -6 ). No significant associations with risk for CBD, MSA, or PSP were observed. We also show that APOE ε4 decreases survival in a dose-dependent manner in Alzheimer's disease and LBD. Taken together, this study does not provide evidence to implicate a role of APOE in the neuropathogenesis of CBD, MSA, or PSP. However, we confirm association of the APOE ε4 allele with increased risk for LBD, and importantly demonstrate that APOE ε2 reduces risk of this disease., (Published by Elsevier Inc.)

Objective: Patients with corticobasal syndrome (CBS) present with heterogeneous clinical features, including asymmetric parkinsonism, dyspraxia, aphasia, and cognitive impairment; to better understand the genetic etiology of this rare disease, we undertook a genetic analysis of microtubule-associated protein tau ( MAPT )., Methods: We performed a genetic evaluation of MAPT mutations in 826 neurologically healthy controls and 173 cases with CBS using the Illumina NeuroChip genotyping array., Results: We identified 2 patients with CBS heterozygous for a rare mutation in MAPT (p.V363I) that is located in the highly conserved microtubule-binding domain. One patient was pathologically confirmed and demonstrated extensive 4-repeat-tau-positive thread pathology, achromatic neurons, and astrocytic plaques consistent with corticobasal degeneration (CBD)., Conclusions: We report 2 CBS cases carrying the rare p.V363I MAPT mutation, one of which was pathologically confirmed as CBD. Our findings support the notion that this rare coding change is pathogenic.

The present research work describes a novel method for green synthesis of silver nanoparticles using purple heart plant leaves extract, which is recognized as frequently found in households as an ornamental plant. The aqueous methanolic extract of purple heart plant leaves was prepared and employed in the synthesis of stable silver nanoparticles via biological reduction method. The purple heart plant leaves extract-mediated synthesized silver nanoparticles were systematically optimized using Box-Behnken design considering the effect of various independent variables (factors) like concentration of AgNO 3 , temperature and volume of purple heart plant leaves extract solution on the responses like particle size and polydispersity index of synthesized silver nanoparticles were optimized. Mathematical modelling was performed using quadratic polynomial model and response surface analysis was done to understand the factor-response relationship. The synthesized silver nanoparticles at optimum condition were found to be of spherical in shape under TEM with particle size of 98 nm and polydispersity index of 0.15. Optimized silver nanoparticles were further characterized through UV-VIS spectrophotometry, FTIR spectroscopy and TEM imaging studies. Also, the silver nanoparticles were evaluated for antibacterial activity on E. coli and S. aureus. In a nutshell, the studies construed successful synthesis of silver nanoparticles along with thorough understanding of the associated factors influencing their quality characteristics and significantly improved antibacterial activity as beneficial effect., (Copyright © 2019 Elsevier B.V. All rights reserved.)