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Background and Objectives : The health-related mobile applications (app) might assist in promoting inclusive health and tele-treatment, especially for the less severe diseases. In this paper, a study had been done to determine the app's reliability in terms of raters and the app's agreement with the Snellen chart. Materials and Methods : A cross-sectional sectional study was conducted between November 2019 and September 2020. Participants were selected via purposive sampling from selected communities in Terengganu state. All participants underwent vision testing with the Vis-Screen app and Snellen chart for validity and reliability accordingly. Results : A total of 408 participants were involved, with a mean age of 29.3. The sensitivity of the presenting vision of the right eye (PVR) ranged from 55.6% to 88.4%, with specificity between 94.7% to 99.3%, while the positive and negative predictive values were between 57.9% and 81.7% and 96.8% and 99.0%, respectively. The positive likelihood ratios ranged between 16.73 and 73.89, whereas the negative likelihood ratios ranged from 0.12 to 0.45. The area under the receiver operating characteristic curve (AUC) for all cut-off points ranged between 0.93 and 0.97, and the optimum cut-off point was at 6/12. The kappa values for intra-rater and inter-rater were 0.85 and 0.75, respectively, while the app's reliability with the Snellen chart was 0.61. Conclusions : Vis-Screen was concluded to be valid and reliable for use as a screening tool for detecting individuals with visual impairment and blindness in the community. A valid and reliable portable vision screener like Vis-Screen will help expand the eye care feasibility while providing similar accuracy as the conventional charts in clinical practices.

Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski's rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future., 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 © 2023 Velayutham, Thamaraikani, Wahab, Khalid, Ramachawolran, Abullais, Wong, Sekar, Gan, Ebenezer, Ravikumar, Subramaniyan, Mat Rani, Wu and Jeyabalan.)

Background: Dodonaea viscosa Jacq. ( D. viscosa ) belongs to the family of Sapindaceae, commonly known as " Sinatha, " and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group ( p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds., 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 © 2023 Subramanian, Duraipandian, Alsayari, Ramachawolran, Wong, Sekar, Gan, Subramaniyan, Seethalakshmi, Jeyabalan, Dhanasekaran, Chinni, Mat Rani and Wahab.)

Objectives: Growing concern about children and adolescent physical inactivity has made the promotion of physical activity a public health priority. International recommendations suggest children should accumulate at least 30 min of moderate-to-vigorous physical activity (MVPA) during school hours. This study assessed levels of objectively-measured MVPA in a large nationally representative sample of Scottish children aged 10-11. Risk factors for not meeting the school-hours MVPA recommendation were examined., Design: Cross-sectional., Methods: Mean time spent in MVPA during school hours across five weekdays was measured using Actigraph accelerometry (May 2015-May 2016). Binary logistic regression, presented as odds ratio (O.R.) and confidence intervals (C.I.), explored associations between meeting/not meeting the recommendation by sex, socioeconomic status (SES), season, and urban/rural residence in 2022., Results: Valid data were obtained from 773 children (53.9% girls, 46.1% boys) from 471 schools. Mean daily school-hours MVPA was 29 (SD 11) minutes; 42.7% of children reached the recommendation. The odds of girls (O.R. 0.43; C.I. 0.32, 0.57) meeting the recommendation was significantly lower (p < 0.001) compared to boys. Children living in rural areas had higher odds (O.R. 1.49; C.I. 1.04, 2.15) of meeting the recommendation compared with those in urban areas (p = 0.032). No significant differences in meeting the recommendation by SES (p = 0.700). The overall trend for season was significant (p < 0.001), with lower odds of meeting the recommendation in winter compared to summer., Conclusions: Most Scottish children aged 10-11 did not meet the 30 minute MVPA recommendation. Interventions to increase MVPA during school hours are essential to promote public health., Competing Interests: Declaration of Interest Statement 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The industrial discharge of dye pollutant contaminated wastewater is the major cause of water and soil pollution. Photocatalysis is a promising and green remediation technology, which has received widespread attention in the remediation of hazardous dyes from aqueous environment and convert them into harmless compounds. Herein, we report the synthesis of chitosan (CS) functionalized bismuth oxychloride/zinc oxide (BiOCl/ZnO) nanocomposite by a modified hydrothermal route. The physiochemical characterization revealed that the synthesized nanocomposite have crystalline, agglomerated spherical along with rod shaped morphology and size range from 35 to 160 nm. FTIR peaks at 825, 727, 662 and 622 cm -1 specified the presence of BiO and ZnO bonds, whereas peak at 1635 cm -1 revealed the existence of amine groups which confirms the presence of CS in the synthesized CS-BiOCl/ZnO nanocomposite. Catalytic property of synthesized nanocomposite was evaluated by the degradation of Congo red (CR) under UV-light irradiation. CR dye degradation percentage was found to be 93 % within a short period of 40 min by utilizing UV-light. Furthermore, reusability of CS-BiOCl/ZnO photocatalyst was also investigated, and it remained significant photocatalytic activity after three consecutive cycles. Hence, the results obtained in this study revealed that CS-BiOCl/ZnO nanocomposite can be used as a potential photocatalyst to remediate organic pollutants in various industries., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Lately, smoking among adolescents is increasing despite various campaigns to address it being carried out. Previously, this habit was common among men, however, nowadays, smoking has become a habit for women as well. The purpose of this study was to determine the prevalence and its associated factors that influence smoking behavior among women inmates in Kelantan., Methods: A cross-sectional study was carried out among women inmates from Pengkalan Chepa Women's Prison, Kota Bharu, Kelantan. A total of 274 respondents were needed to answer a self-administered questionnaire. The data were analyzed using Multiple Logistic Regression., Results: A total of 183 participants were smokers. Women who were single and divorced had a lower chance of being influenced to smoke compared to married women. Parents with smoking habits were more associated with children who smoked compared to parents who did not smoke. A participant with secondary level education had higher odds of smoking compared to a participant with primary level education. Smoking peers significantly influenced their friends and, therefore, peer practice was a main factor influencing smoking among women inmates., Conclusion: The prevalence of smoking among women inmates in Kelantan was found to be quite high. Religion (majority (90.5%) of women in the study were Muslims; it would be inappropriate to draw conclusion that religion is an influencing factor), marital status, parents' practice, peer practice and education significantly influenced women inmates to smoke.

Aim: With the characteristics such as low toxicity, high total surface, ability to inhibit the growth of pathogenic microorganisms, zinc oxide nanoparticles (ZnO NPs), as one of the metallic nanoparticles, have been chosen as an antibacterial agent to treat various skin infections. The present study was aimed to determine the antibacterial potential of ZnO NPs on Bacillus subtilis, the Gram-positive bacterium that can cause skin and wound infections., Methods: B. subtilis was exposed to 5 to 150 μg/mL of ZnO NPs for 24 h. The parameters employed to evaluate the antimicrobial potential of ZnO NPs were the growth inhibitory effect on B. subtilis, the surface interaction of ZnO NPs on the bacterial cell wall, and also the morphological alterations in B. subtilis induced by ZnO NPs., Results: The results demonstrated a significant (p <0.05) inhibition of ZnO NPs on B. subtilis growth and it was in a dose-dependent manner for all the tested concentrations of ZnO NPs from 5 to 150 μg/mL at 24 h. Fourier transformed infrared (FTIR) spectrum confirmed the involvement of polysaccharides and polypeptides of bacterial cell wall in surface binding of ZnO NPs on bacteria. The scanning electron microscopy (SEM) was used to visualize the morphological changes, B. subtilis illustrated several surface alterations such as distortion of cell membrane, roughening of cell surface, aggregation and bending of cells, as well as, the cell rupture upon interacting with ZnO NPs for 24 h., Conclusion: The results indicated the potential of ZnO NPs to be used as an antibacterial agent against B. subtilis. The findings of the present study might bring insights to incorporate ZnO NPs as an antibacterial agent in the topical applications against the infections caused by B. subtilis.

The primary and considerable weakening event affecting elderly individuals is age-dependent cognitive decline and dementia. Alzheimer's disease (AD) is the chief cause of progressive dementia, and it is characterized by irreparable loss of cognitive abilities, forming senile plaques having Amyloid Beta (Aβ) aggregates and neurofibrillary tangles with considerable amounts of tau in affected hippocampus and cortex regions of human brains. AD affects millions of people worldwide, and the count is showing an increasing trend. Therefore, it is crucial to understand the underlying mechanisms at molecular levels to generate novel insights into the pathogenesis of AD and other cognitive deficits. A growing body of evidence elicits the regulatory relationship between the mammalian target of rapamycin (mTOR) signaling pathway and AD. In addition, the role of autophagy, a systematic degradation, and recycling of cellular components like accumulated proteins and damaged organelles in AD, is also pivotal. The present review describes different mechanisms and signaling regulations highlighting the trilateral association of autophagy, the mTOR pathway, and AD with a description of inhibiting drugs/molecules of mTOR, a strategic target in AD. Downregulation of mTOR signaling triggers autophagy activation, degrading the misfolded proteins and preventing the further accumulation of misfolded proteins that inhibit the progression of AD. Other target mechanisms such as autophagosome maturation, and autophagy-lysosomal pathway, may initiate a faulty autophagy process resulting in senile plaques due to defective lysosomal acidification and alteration in lysosomal pH. Hence, the strong link between mTOR and autophagy can be explored further as a potential mechanism for AD therapy., 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 © 2022 Subramanian, Tamilanban, Alsayari, Ramachawolran, Wong, Sekar, Gan, Subramaniyan, Chinni, Izzati Mat Rani, Suryadevara and Wahab.)

Cell function can be directly influenced by the mechanical and structural properties of the extracellular environment. In particular, cell morphology and phenotype can be regulated via the modulation of both the stiffness and surface topography of cell culture substrates. Previous studies have highlighted the ability to design cell culture substrates to optimise cell function. Many such examples, however, employ photo-crosslinkable polymers with a terminal stiffness or surface profile. This study presents a system of polyacrylamide hydrogels, where the surface topography can be tailored and the matrix stiffness can be altered in situ with photoirradiation. The process allows for the temporal regulation of the extracellular environment. Specifically, the surface topography can be tailored via reticulation parameters to include creased features with control over the periodicity, length and branching. The matrix stiffness can also be dynamically tuned via exposure to an appropriate dosage and wavelength of light, thus, allowing for the temporal regulation of the extracellular environment. When cultured on the surface of the hydrogels, the morphology and alignment of immortalised human mesenchymal stem cells can be directly influenced through the tailoring of surface creases, while cell size can be altered via changes in matrix stiffness. This system offers a new platform to study cellular mechanosensing and the influence of extracellular cues on cell phenotype and function.

The Movement Control Order (MCO) enacted during the COVID-19 pandemic has profoundly altered the social life and behaviour of the Malaysian population. Because the society is facing huge social and economic challenges that need individuals to work together to solve, prosocial behaviour is regarded as one of the most important social determinants. Because it is related with individual and societal benefits, participating in prosocial activities may be a major protective factor during times of global crisis. Rather than focusing only on medical and psychiatric paradigms, perhaps all that is necessary to overcome the COVID-19 risks is for individuals to make personal sacrifices for the sake of others. In reality, a large number of initiatives proven to be beneficial in decreasing viral transmission include a trade-off between individual and collective interests. Given its crucial importance, the purpose of this concept paper is to provide some insight into prosocial behaviour during the COVID-19 period. Understanding prosocial behaviour during the COVID-19 pandemic is crucial because it may assist in the establishment of a post-COVID society and provide useful strategies for coping with future crises.

Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein's anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC 50 ) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC 50 values (1,000 μg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress., 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 © 2022 Selvaraj, Jeyabalan, Wong, Sekar, Logeshwari, Umamaheswari, Premkumar, Sekar, Begum, Gan, Izzati Mat Rani, Chidambaram, Subramaniyan, Al Fatease, Alamri, Sathasivam, Selvaraj, Vijeepallam, Fuloria and Fuloria.)

Introduction: Community pharmacies are high-performance workplaces; if the environment is not conducive to safe practice, mistakes can occur. There has been increasing demand for pharmacists during the COVID-19 pandemic as they have become integral to the response. Suboptimal practices in the work environment and with pharmacists and their teams can impact the safe delivery of services. New Zealand pharmacists' perceptions of the current work environment and beliefs around whether suboptimal practice have increased within the last five years and the effect of the COVID-19 pandemic on their practices are unknown. Aim/Objectives : To assess what New Zealand pharmacists associate with suboptimal practice in their workplace and investigate the effect of the COVID-19 pandemic on pharmacists and their workplaces. Methods : We employed an anonymous online questionnaire derived from a human factors framework utilised in the aviation industry to explore the potential environment, team and organisational factors as the determinants of suboptimal work practices. The software, hardware, environment and liveware (S.H.E.L.L) model was adapted to create questions classifying the risk factors to potentially identify aspects of work systems that are vulnerable and may provide risks to optimal practice. Additional perceptions around the effect of COVID-19 on their workplace and roles as pharmacists were explored. Participants were community pharmacists working in New Zealand contacted via a mailing list of the responsible authority for the profession. Findings : We received responses from 260 participants. Most participants indicated that suboptimal practice had increased in the last 5 years (79.8%). The majority of participants indicated that COVID-19 had impacted their workplaces (96%) and their roles as pharmacists (92.1%). Participants perceived that suboptimal practice was associated with a lack of leadership and appropriate management; poor access to resourcing, such as adequate staff and narrow time constraints for work tasks; a lack of procedures; competition; and stress. A lack of experience, professionalism and poor communication between staff, patients and external agencies were also issues. COVID-19 has affected pharmacists personally and their work environments. Further study in this area is required. Conclusion s: We have identified that pharmacists across all sectors of New Zealand agreed that suboptimal practices had increased in the last 5 years. A human factors S.H.E.L.L framework can be used to classify themes to understand the increases in suboptimal practice and the role of COVID-19 on pharmacist practice. Many of these themes build on the growing body of the international literature around the effect of the pandemic on pharmacist practice. Areas for which there are less historical data to compare longitudinally include pharmacist wellbeing and the impact of COVID-19.

Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and chronic renal diseases. The mechanisms of CNPG are complicated and involved the interaction of the cutaneous, immune, and nervous systems. Diverse immune cells, including eosinophils, neutrophils, T cells, macrophages, and mast cells infiltrated the lesional skin of CNPG, which initiated the inflammatory cytokines and pruritogens release. In addition, the interaction between the immune cells and activated peripheral sensory nerve fibers by neurotransmitters caused neuroinflammation in the skin and intractable itch. This itch-scratch vicious cycle of CNPG results in disease exacerbation. CNPG is difficult to treat with traditional therapies. Recently, great advances have been made in the pathophysiology of both inflammation and pruritus transmission in CNPG. In this review, we summarize the updated mechanisms and novel therapies for CNPG.

Background: Arthrospira platensis is farmed worldwide due to its nutrient-rich properties and provides multiple benefits to human health. However, the wide usage of silver nanoparticles (Ag NPs) causes pollution which may affect the nutritional quality of A. platensis . Hence, this study aimed to investigate the interaction and accumulation of Ag NPs on A. platensis , and determine the changes in biomass and nutritional value of A. platensis due to the exposure to Ag NPs., Methods: The interaction and accumulation of Ag NPs on A. platensis were examined through Fourier transformed infrared (FTIR) spectroscopy and scanning electron microscope (SEM). The loss in biomass together with the macromolecules, pigments, and phenolic compounds of A. platensis was investigated upon treating with various concentrations of Ag NPs (5, 10, 25, 50 and 100 µg/mL) for 24, 48, 72 and 96 h., Results: The results showed that the treatment of A. platensis with Ag NPs caused a dose and time-dependent reduction in biomass, macronutrients, pigments and phenolic compounds. The highest detrimental effects were found at 96 h with the reported values of 65.71 ± 2.79%, 67.21 ± 3.98%, 48.99 ± 4.39% and 59.62 ± 3.96% reduction in biomass, proteins, carbohydrates and lipids, respectively, along with 82.99 ± 7.81%, 67.55 ± 2.63%, 75.03 ± 1.55%, and 63.43 ± 2.89% loss in chlorophyll- a , carotenoids, C-phycocyanin, and total phenolic compounds of A. platensis for 100 µg/mL of Ag NPs. The EDX analysis confirmed the surface accumulation of Ag NPs on Arthrospira cells, while SEM images evidenced the surface alterations and damage of the treated cells. The functional groups such as hydroxyl, amine, methyl, amide I, amide II, carboxyl, carbonyl and phosphate groups from the cell wall of the A. platensis were identified to be possibly involved in the interaction of Ag NPs with A. platensis ., Conclusion: The study confirmed that the exposure of Ag NPs is detrimental to A. platensis where the interaction and accumulation of Ag NPs on A. platensis caused reduction in biomass, macromolecules, pigments, and total phenolic compounds., Competing Interests: The authors declare that they have no competing interests., (© 2022 Liang et al.)

The growth of cancerous cells and their responses towards substantial therapeutics are primarily controlled by inflammations (acute and chronic) and inflammation-associated products, which either endorse or repress tumor progression. Additionally, major signaling pathways, including NF-κB, STAT3, inflammation-causing factors (cytokines, TNF-α, chemokines), and growth-regulating factors (VEGF, TGF-β), are vital regulators responsible for the instigation and resolution of inflammations. Moreover, the conventional chemotherapeutics have exhibited diverse limitations, including poor pharmacokinetics, unfavorable chemical properties, poor targetability to the disease-specific disease leading to toxicity; thus, their applications are restricted in inflammation-mediated cancer therapy. Furthermore, nanotechnology has demonstrated potential benefits over conventional chemotherapeutics, such as it protected the incorporated drug/bioactive moiety from enzymatic degradation within the systemic circulation, improving the physicochemical properties of poorly aqueous soluble chemotherapeutic agents, and enhancing their targetability in specified carcinogenic cells rather than accumulating in the healthy cells, leading reduced cytotoxicity. Among diverse nanomaterials, polyester-based nanoparticulate delivery systems have been extensively used to target various inflammation-mediated cancers. This review summarizes the therapeutic potentials of various polyester nanomaterials (PLGA, PCL, PLA, PHA, and others)-based delivery systems targeting multiple signaling pathways related to inflammation-mediated cancer., Competing Interests: Conflict of interest statement The authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Obsessive-compulsive disorder (OCD) is a chronic and complex psychiatric disorder that usually includes both obsessions and compulsions. Morinda citrifolia L. (Noni) is a functional food and it is a well-known plant due to its potential therapeutic effects on human health in many disorders including neurological and neurodegenerative diseases. The purpose of this study was to evaluate the potential effect of M. citrifolia fruits extract (MCFE) against obsessive-compulsive disorder using the marble burying and nestlet shredding behavior mice models. In addition, brain neurotransmitters such as dopamine (DA), serotonin and noradrenaline (NA) were also assessed. Five mice were placed in each of the different groups, and the treatment was given to the animals for a period of 15 days. The marble burying test was evaluated for 30 min on days 1, 7, and 14 while the nestlet shredding test was evaluated for 60 min on days 2, 8, and 15. Treatments with MCFE (100 and 200 mg/kg, p.o.) significantly improved in both behavior tasks when compared to the control group. In addition, diazepam (2 mg/kg, i.p.) and fluoxetine (15 mg/kg, p.o.) were also significantly improved in both tasks when compared with the control mice. Further locomotor activity study revealed that MCFE and fluoxetine did not affect the locomotor functions when compared to vehicle treated mice. In contrast, diazepam significantly decreased locomotion when compared to the control group. The significant amelioration of biogenic amines were observed in the MCFE-treated animals with increased serotonin levels. The histopathology of the brain, liver, and kidney tissues after MCFE administration revealed normal morphological structure with no signs of toxicity or abnormalities. All these results together suggest that MCFE can be a potential drug candidate for the treatment of OCD. Future research should focus on theidentification and the anti-compulsive activity of the constituents from M . citrifolia ., 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 © 2022 Jeyabalan, Bala, Subramanian, Jabaris, Sekar, Wong, Subramaniyan, Chidambaram, Gan, Mat Rani, Begum, Safi, Selvaraj, Al Fatease, Alamri, Vijeepallam, Fuloria, Fuloria and Djearamane.)

Objective: The objective of this systematic review was (a) to explore the current clinical applications of AI/ML (Artificial intelligence and Machine learning) techniques in diagnosis and treatment prediction in children with CLP (Cleft lip and palate), (b) to create a qualitative summary of results of the studies retrieved., Materials and Methods: An electronic search was carried out using databases such as PubMed, Scopus, and the Web of Science Core Collection. Two reviewers searched the databases separately and concurrently. The initial search was conducted on 6 July 2021. The publishing period was unrestricted; however, the search was limited to articles involving human participants and published in English. Combinations of Medical Subject Headings (MeSH) phrases and free text terms were used as search keywords in each database. The following data was taken from the methods and results sections of the selected papers: The amount of AI training datasets utilized to train the intelligent system, as well as their conditional properties; Unilateral CLP, Bilateral CLP, Unilateral Cleft lip and alveolus, Unilateral cleft lip, Hypernasality, Dental characteristics, and sagittal jaw relationship in children with CLP are among the problems studied., Results: Based on the predefined search strings with accompanying database keywords, a total of 44 articles were found in Scopus, PubMed, and Web of Science search results. After reading the full articles, 12 papers were included for systematic analysis., Conclusions: Artificial intelligence provides an advanced technology that can be employed in AI-enabled computerized programming software for accurate landmark detection, rapid digital cephalometric analysis, clinical decision-making, and treatment prediction. In children with corrected unilateral cleft lip and palate, ML can help detect cephalometric predictors of future need for orthognathic surgery.

Small-fiber neuropathy (SFN) is suggested to be involved in the pathogenesis of some types of autoimmune connective tissue diseases. SFN with a reduction in epidermal nerve fibers might affect sensory fibers and cause neuropathic symptoms, such as pruritus and pain, which are common in both dermatomyositis (DM) and cutaneous lupus erythematosus (CLE). Nerve growth factor (NGF) has been recognized as important in nociception by regulating epidermal nerve fiber density and sensitizing the peripheral nervous system. The present study aimed to investigate whether SFN was associated with the cutaneous manifestations of DM and CLE. We also investigated the relationship between SFN and axon guidance molecules, such as NGF, amphiregulin (AREG), and semaphorin (Sema3A) in DM and CLE. To explore the molecular signaling, interleukin (IL)-18 and IL-31, which have been implicated in the cutaneous manifestation and neuropathic symptoms in DM, were examined in keratinocytes. Our results revealed that intraepidermal nerve fiber density (IENFD) was unchanged in patients with DM, but significantly reduced in IENFD in patients with CLE compared with healthy control. Increased epidermal expression of NGF and decreased expression of Sema3A were demonstrated in patients with DM. Furthermore, IL-18 and IL-31 both induced the production of NGF from keratinocytes. Taken together, IL-18 and IL-31 mediated epidermal NGF expression might contribute to the cutaneous neuropathic symptoms in DM, while SFN might be important for CLE.

Pruritus is a well-known bothersome symptom among skin disorders, especially inflammatory skin disorders. Lately, a high prevalence of pruritus in patients with autoimmune connective tissue diseases (ACTDs) has been revealed. Patients with ACTDs may suffer from varying degrees of pruritus, which affect their quality of life. However, it is rarely recognized both by patients and physicians. Meanwhile, pruritus is not only a symptom but is also related to the disease severity of some ACTDs. The pathophysiology of ACTD related pruritus is ambiguous. This review summarizes the features and possible mechanisms of ACTD-related pruritus, which might lead to proper diagnosis and treatment.

Background: Cerebral small vessel disease is a progressive disease of the brain's deep perforating blood vessels. It is usually diagnosed based on lesions seen on brain imaging. Cerebral small vessel disease is a common cause of stroke but can also cause a progressive cognitive decline. As antithrombotic therapy is an established treatment for stroke prevention, we sought to determine whether antithrombotic therapy might also be effective in preventing cognitive decline in people with small vessel disease., Objectives: To assess the effects of antithrombotic therapy for prevention of cognitive decline in people with small vessel disease on neuroimaging but without dementia., Search Methods: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Review Group's Specialised Register, and the Cochrane Stroke Group's Specialised Register; the most recent search was on 21 July 2021. We also searched MEDLINE, Embase, four other databases and two trials registries. We searched the reference lists of the articles retrieved from these searches. As trials with a stroke focus may include relevant subgroup data, we complemented these searches with a focussed search of all antithrombotic titles in the Cochrane Stroke Group database.  SELECTION CRITERIA: We included randomised controlled trials (RCT) of people with neuroimaging evidence of at least mild cerebral small vessel disease (defined here as white matter hyperintensities, lacunes of presumed vascular origin and subcortical infarcts) but with no evidence of dementia. The trials had to compare antithrombotic therapy of minimum 24 weeks' duration to no antithrombotic therapy (either placebo or treatment as usual), or compare different antithrombotic treatment regimens. Antithrombotic therapy could include antiplatelet agents (as monotherapy or combination therapy), anticoagulants or a combination., Data Collection and Analysis: Two review authors independently screened all the titles identified by the searches. We assessed full texts for eligibility for inclusion according to our prespecified selection criteria, extracted data to a proforma and assessed risk of bias using the Cochrane tool for RCTs. We evaluated the certainty of evidence using GRADE. Due to heterogeneity across included participants, interventions and outcomes of eligible trials, it was not possible to perform meta-analyses., Main Results: We included three RCTs (3384 participants). One study investigated the effect of antithrombotic therapy in participants not yet on antithrombotic therapy; two studies investigated the effect of additional antithrombotic therapy, one in a population already taking a single antithrombotic agent and one in a mixed population (participants on an antithrombotic drug and antithrombotic-naive participants). Intervention and follow-up durations varied from 24 weeks to four years. Jia 2016 was a placebo-controlled trial assessing 24 weeks of treatment with DL-3-n-butylphthalide (a compound with multimodal actions, including a putative antiplatelet effect) in 280 Chinese participants with vascular cognitive impairment caused by subcortical ischaemic small vessel disease, but without dementia. There was very low-certainty evidence for a small difference in cognitive test scores favouring treatment with DL-3-n-butylphthalide, as measured by the 12-item Alzheimer's Disease Assessment Scale-Cognitive subscale (adjusted mean difference -1.07, 95% confidence interval (CI) -2.02 to -0.12), but this difference may not be clinically relevant. There was also very low-certainty evidence for greater proportional improvement measured with the Clinician Interview-Based Impression of Change-Plus Caregiver Input (57% with DL-3-n-butylphthalide versus 42% with placebo; P = 0.01), but there was no difference in other measures of cognition (Mini-Mental State Examination and Clinical Dementia Rating) or function. There was no evidence of a difference in adverse events between treatment groups. The SILENCE RCT compared antithrombotic therapy (aspirin) and placebo during four years of treatment in 83 participants with 'silent brain infarcts' who were on no prior antithrombotic therapy. There was very low-certainty evidence for no difference between groups across various measures of cognition and function, rates of stroke or adverse events. The Secondary Prevention of Subcortical Stroke Study (SPS3) compared dual antiplatelet therapy (clopidogrel plus aspirin) to aspirin alone in 3020 participants with recent lacunar stroke. There was low-certainty evidence of no effect on cognitive outcomes as measured by the Cognitive Abilities Screening Instruments (CASI) assessed annually over five years. There was also low-certainty evidence of no difference in the annual incidence of mild cognitive decline between the two treatment groups (9.7% with dual antiplatelet therapy versus 9.9% with aspirin), or the annual stroke recurrence rate (2.5% with dual antiplatelet therapy versus 2.7% with aspirin). Bleeding risk may be higher with dual antiplatelet therapy (hazard ratio (HR) 2.15, 95% CI 1.49 to 3.11; low certainty evidence), but there may be no significant increase in intracerebral bleeding risk (HR 1.52, 95% CI 0.79 to 2.93; low-certainty evidence). None of the included trials assessed the incidence of new dementia., Authors' Conclusions: We found no convincing evidence to suggest any clinically relevant cognitive benefit of using antithrombotic therapy in addition to standard treatment in people with cerebral small vessel disease but without dementia, but there may be an increased bleeding risk with this approach. There was marked heterogeneity across the trials and the certainty of the evidence was generally poor., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Penttinen syndrome is a rare progeroid disorder caused by mutations in platelet-derived growth factor (PDGF) receptor beta (encoded by the PDGFRB proto-oncogene) and characterized by a prematurely aged appearance with lipoatrophy, skin lesions, thin hair and acro-osteolysis. Activating mutations in PDGFRB have been associated with other human diseases, including Kosaki overgrowth syndrome, infantile myofibromatosis, fusiform aneurysms, acute lymphoblastic leukaemia and myeloproliferative neoplasms associated with eosinophilia. The goal of the present study was to characterize the PDGFRB p.Val665Ala variant associated with Penttinen syndrome at the molecular level. This substitution is located in a conserved loop of the receptor tyrosine kinase domain. We observed that the mutant receptor was expressed at a lower level but showed constitutive activity. In the absence of ligand, the mutant activated STAT1 and elicited an interferon-like transcriptional response. Phosphorylation of STAT3, STAT5, AKT and phospholipase Cγ was weak or undetectable. It was devoid of oncogenic activity in two cell proliferation assays, contrasting with classical PDGF receptor oncogenic mutants. STAT1 activation was not sensitive to ruxolitinib and did not rely on interferon-JAK2 signalling. Another tyrosine kinase inhibitor, imatinib, blocked signalling by the p.Val665Ala variant at a higher concentration compared with the wild-type receptor. Importantly, this concentration remained in the therapeutic range. Dasatinib, nilotinib and ponatinib also inhibited the mutant receptor. In conclusion, the p.Val665Ala variant confers unique features to PDGF receptor β compared with other characterized gain-of-function mutants, which may in part explain the particular set of symptoms associated with Penttinen syndrome., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Zinc oxide nanoparticles (ZnO NPs) have been widely used in biomedical applications due to their high biocompatibility and low toxicity to humans. The present work aimed to investigate the antibacterial effects of different concentrations of ZnO NPs on two opportunistic pathogens, Serratia marcescens and Enterococcus faecalis . The surface interaction between nanoparticles and bacterial cell wall, and the subsequent morphological alterations on the bacterial surface, were examined through Fourier transform infrared spectroscopy and scanning electron microscope. The energy dispersive X-ray analysis was used to confirm the elemental composition of ZnO NPs and the cellular accumulation of ZnO NPs in bacteria. The growth-inhibitory test demonstrated a dose-dependent growth inhibitory effect of ZnO NPs against both the test bacteria, as the higher concentration of nanoparticles caused the higher bacterial growth inhibition. The results showed that ZnO NPs caused a higher growth inhibition (63.50 ± 2.50%) on the Gram-positive bacterium E . faecalis compared to the Gram-negative bacterium S. marcescens (51.27 ± 4.56%). Fourier transform infrared spectrum revealed the possible involvement of hydroxyl, carboxyl, amides, methylene, and phosphate groups from the biomolecules of bacterial cell wall such as proteins, carbohydrates, lipids, and phospholipids in the interaction of ZnO NPs on bacterial cell surface. Energy dispersive X-ray analysis showed the higher accumulation of ZnO NPs in E. faecalis than S. marcescens analogous to the bacterial growth inhibition. Scanning electron microscopy images confirmed the antibacterial properties of ZnO NPs, showing the loss of integrity of cell membrane and distortion of bacterial cells. Hence, the potential of ZnO NP as an antibacterial agent against S. marcescens and E. faecalis has been confirmed., 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 © 2022 Djearamane, Loh, Lee, Wong, Rajamani, Luque, Gupta and Liang.)

Uremic pruritus, or chronic kidney disease-associated pruritus, is common, bothersome, and sometimes debilitating in patients with chronic kidney disease or end-stage renal disease. Due to its variable clinical manifestations, the diagnosis of uremic pruritus requires exquisite evaluation. Excluding itch resulting from other dermatological causes as well as other systemic conditions is essential for a proper diagnosis. The pathophysiology of uremic pruritus remains uncertain. Hypotheses including toxin deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance are supposed. This review summarizes the way to accurately diagnose uremic pruritus and describes the latest treatment options.

Contrary to the assumption of arbitrariness in modern linguistics, sound symbolism, which is the non-arbitrary relationship between sounds and meanings, exists. Sound symbolism, including the "Bouba-Kiki" effect, implies the universality of such relationships; individuals from different cultural and linguistic backgrounds can similarly relate sound-symbolic words to referents, although the extent of these similarities remains to be fully understood. Here, we examined if subjects from different countries could similarly infer the surface texture properties from words that sound-symbolically represent hardness in Japanese. We prepared Japanese sound-symbolic words of which novelty was manipulated by a genetic algorithm (GA). Japanese speakers in Japan and English speakers in both Singapore and the United States rated these words based on surface texture properties (hardness, warmness, and roughness), as well as familiarity. The results show that hardness-related words were rated as harder and rougher than softness-related words, regardless of novelty and countries. Multivariate analyses of the ratings classified the hardness-related words along the hardness-softness dimension at over 80% accuracy, regardless of country. Multiple regression analyses revealed that the number of speech sounds /g/ and /k/ predicted the ratings of the surface texture properties in non-Japanese countries, suggesting a systematic relationship between phonetic features of a word and perceptual quality represented by the word across culturally and linguistically diverse samples., 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 © 2022 Wong, Kwon, Zheng, Styles, Sakamoto and Kitada.)

Geopolymer concrete is produced from the geopolymerization process, in which molecules known as oligomers integrate to form geopolymer networks with covalent bonding. Its production expends less thermal energy and results in a smaller carbon footprint compared to Ordinary Portland Cement (OPC) concrete. It requires only an alkaline activator to catalyze its aluminosilicate sources such as metakaolin and fly ash, to yield geopolymer binder for the geopolymerization to take place. Because of its eco-friendly technology and practical application, current research interest is mainly concentrated on the endurance of geopolymer concrete to resist heat and chemical aggressions. As such, it is pertinent for this review article to provide critical insight into the recent progress in research on the durability of geopolymer concrete. One significant outcome of the review is that the admixture of geopolymer concrete could be blended with additives such as micro-silica and fibers such as polypropylene fibers, to enhance its durability. The review on the durability aspects of geopolymer concrete showed that it had high compressive strength at an optimal elevated temperature, low to medium chloride ion penetrability, and high resistance to acid attack and abrasion. This makes geopolymer concrete a viable candidate to replace OPC concrete in the construction industry.

Background & Aims: Long noncoding RNAs (lncRNAs) are found to have profound impacts on diverse cellular processes. Although high-throughput sequencing studies have shown the differential lncRNA expression profiles between hepatocellular carcinoma (HCC) and nontumor livers, the functional impacts of lncRNAs on HCC development await further investigation. Herein, we sought to address the functional roles of lncRNAs in HCC pathogenesis by in vivo functional screening., Methods: We performed genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/dead CRISPR-associated protein 9 (dCas9) lncRNA activation screening in HCC xenografts. We characterized the clinical relevance of positively selected lncRNAs using transcriptomic data sets. We used CRISPR-based gene activation and knockdown approaches to show the functional roles of positively selected lncRNAs including Cancer Susceptibility 11 (CASC11) in HCC. RNA sequencing and chromatin isolation by RNA purification sequencing were used to investigate the molecular mechanisms of CASC11 in HCC progression., Results: The in vivo functional screening identified 1603 positively selected lncRNAs, 538 of which were overexpressed in HCC patients. Systematic transcriptomic data analysis and clinical investigation showed that patients with high expression of these lncRNA candidates correlated with aggressive tumor behaviors. Overexpression of these lncRNAs aggravated HCC cell growth. Detailed characterization of a lncRNA candidate, CASC11, showed its pivotal role in cell proliferation and tumor growth. Mechanistically, chromatin isolation by RNA purification sequencing showed that CASC11 was bound to the CASC11/MYC proto-oncogene shared promoter region on chromosome 8q24. CASC11 modulated the transcriptional activity of MYC in a cis-regulatory manner, which affected the expression of MYC downstream target genes, consequently promoting G1/S progression., Conclusions: Our study showed the power of in vivo CRISPR screening, which comprehensively investigated the functionality of lncRNAs in HCC progression, providing a rationale for targeting these lncRNAs clinically., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent days, natural fibers are extremely influential in numerous applications such as automobile body building, boat construction, civil structure, and packing goods. Intensification of the properties of natural fibers is achieved by blending different natural fibers with resin in a proper mixing ratio. This investigation aims to synthesize a hybrid polymer matrix composite with the use of natural fibers of flax and loops of hemp in the epoxy matrix. The synthesized composites were characterized in terms of tribological and mechanical properties. The Taguchi L16 orthogonal array is employed in the preparation of composite samples as well as analysis and optimization of the synthesis parameters. The optimization of compression molding process parameters has enhanced the results of this investigation. The parameters chosen are percentage of reinforcement (20%, 30%, 40%, and 50%), molding temperature (150 °C, 160 °C, 170 °C, and 180 °C), molding pressure (1 MPa, 2 MPa, 3 MPa, and 4 MPa), and curing time (20 min, 25 min, 30 min, and 35 min). From the analysis, it was observed that the percentage of reinforcement is contributing more to altering the fatigue strength, and the curing time is influenced in the impact and wear analysis.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are members of the voltage-gated cation channel family known to be expressed in the heart and central nervous system. Ivabradine, a small molecule HCN channel-blocker, is FDA-approved for clinical use as a heart rate-reducing agent. We found that HCN2 and HCN3 are overexpressed in breast cancer cells compared with normal breast epithelia, and the high expression of HCN2 and HCN3 is associated with poorer survival in breast cancer patients. Inhibition of HCN by Ivabradine or by RNAi, aborted breast cancer cell proliferation in vitro and suppressed tumour growth in patient-derived tumour xenograft models established from triple-negative breast cancer (TNBC) tissues, with no evident side-effects on the mice. Transcriptome-wide analysis showed enrichment for cholesterol metabolism and biosynthesis as well as lipid metabolism pathways associated with ER-stress following Ivabradine treatment. Mechanistic studies confirmed that HCN inhibition leads to ER-stress, in part due to disturbed Ca 2+ homeostasis, which subsequently triggered the apoptosis cascade. More importantly, we investigated the synergistic effect of Ivabradine and paclitaxel on TNBC and confirmed that both drugs acted synergistically in vitro through ER-stress to amplify signals for caspase activation. Combination therapy could suppress tumour growth of xenografts at much lower doses for both drugs. In summary, our study identified a new molecular target with potential for being developed into targeted therapy, providing scientific grounds for initiating clinical trials for a new treatment regimen of combining HCN inhibition with chemotherapy., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: This systematic review aimed to synthesize recent evidence on interventions to increase moderate-to-vigorous physical activity (MVPA) content of physical education (PE) in children age 8 to 11., Methods: A search of 6 databases was conducted in December 2019. Controlled intervention studies were included so long as they used objective measures of MVPA. Methodological quality was assessed using the appropriate Joanna Briggs Institute (JBI) Checklist. Random effects meta-analysis was used where appropriate., Results: Of the 5459 records, only 5 studies met all inclusion criteria, reporting on 1452 participants; 3 quasi-experimental studies and 2 RCTs. All 5 eligible studies reported favorable intervention effects. Meta-analysis was possible from 4/5 studies: the mean difference between intervention and control groups at follow-up was +14.3% of lesson time in MVPA (confidence interval [CI] 2.7 to 25.8)., Conclusions: Efforts to increase the MVPA content of elementary school PE are achievable. Two studies employed PE specialist teachers and 1 study used an expert instructor as their intervention, 2 studies worked with the class teachers using self-determination theory. All studies focused on health (MVPA) outcomes and included either "fitness infusions" or physically active games to engage students' in physical activities and increase their activity level., (© 2021, American School Health Association.)

Background: Sensory nerves regulate cutaneous local inflammation indirectly through induction of pruritus and directly by acting on local immune cells. The underlying mechanisms for how sensory nerves influence cutaneous acquired immune responses remain to be clarified., Objective: This study aimed to explore the effect of peripheral nerves on cutaneous immune cells in cutaneous acquired immune responses., Methods: We analyzed contact hypersensitivity (CHS) responses as a murine model of delayed-type hypersensitivity in absence or presence of resiniferatoxin-induced sensory nerve denervation. We conducted ear thickness measurements, flow cytometric analyses, and mRNA expression analyses in CHS., Results: CHS responses were attenuated in mice that were denervated during the sensitization phase of CHS. By screening neuropeptides, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA expression was decreased in the dorsal root ganglia after denervation. Administration of PACAP restored attenuated CHS response in resiniferatoxin-treated mice, and pharmacological inhibition of PACAP suppressed CHS. Flow cytometric analysis of skin-draining lymph nodes showed that cutaneous dendritic cell migration and maturation were reduced in both denervated mice and PACAP antagonist-treated mice. The expression of chemokine receptors CCR7 and CXCR4 of dendritic cell s was enhanced by addition of PACAP in vitro., Conclusion: These findings indicate that a neuropeptide PACAP promotes the development of CHS responses by inducing cutaneous dendritic cell functions during the sensitization phase., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo., Methods and Analysis: 80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms-probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group., Ethics and Dissemination: This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences., Trial Registration Number: ACTRN12619000480189., Competing Interests: Competing interests: MLKT is a past member of Nestle Nutrition Institute Medical Advisory Board Oceania, past member of Nutricia global scientific advisory board; received speaker fees from Nestle Nutrition Institute and Abbott Nutrition; consultant to Bayer Pharmaceuticals; received research funding from Abbott Nutrition, Bayer Pharmaceuticals, Prota Therapeutics; employee of Prota Therapeutics and inventor on a patent owned by MCRI 'A method for inducing tolerance'. LP-CS has received reimbursement for speaking at conferences sponsored by Danone and Nestle and consulting for Mead Johnson and Nestle. LP-CS has received research funding from Danone. ALL has received funding from Aimmune Therapeutics., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

Since the early 2000s, extensive research has been performed to address numerous challenges in biochip and biosensor fabrication in order to use them for various biomedical applications. These biochips and biosensor devices either integrate biological elements (e.g., DNA, proteins or cells) in the fabrication processes or experience post fabrication of biofunctionalization for different downstream applications, including sensing, diagnostics, drug screening, and therapy. Scalable lithographic techniques that are well established in the semiconductor industry are now being harnessed for large-scale production of such devices, with additional development to meet the demand of precise deposition of various biological elements on device substrates with retained biological activities and precisely specified topography. In this review, the lithographic methods that are capable of large-scale and mass fabrication of biochips and biosensors will be discussed. In particular, those allowing patterning of large areas from 10 cm 2 to m 2 , maintaining cost effectiveness, high throughput (>100 cm 2 h -1 ), high resolution (from micrometer down to nanometer scale), accuracy, and reproducibility. This review will compare various fabrication technologies and comment on their resolution limit and throughput, and how they can be related to the device performance, including sensitivity, detection limit, reproducibility, and robustness.

The rapid development of the construction sector has led to massive use of raw construction materials, which are at risk of exhaustion. The problem is aggravated by the high demand for cement as binding powder and the mass production of clay bricks for construction purposes. This scenario has led to high energy consumption and carbon emissions in their production. In this regard, bio-cementation is considered a green solution to building construction, because this technology is environmentally friendly and capable of reducing carbon emissions, thus slowing the global warming rate. Most of the previously published articles have focused on microbiologically induced calcium carbonate precipitation (MICP), with the mechanism of bio-cementation related to the occurrence of urea hydrolysis as a result of the urease enzymatic activity by the microbes that yielded ammonium and carbonate ions. These ions would then react with calcium ions under favorable conditions to precipitate calcium carbonate. MICP was investigated for crack repair and the surface treatment of various types of construction materials. Research on MICP for the production of binders in construction materials has become a recent trend in construction engineering. With the development of cutting edge MICP research, it is beneficial for this article to review the recent trend of MICP in construction engineering, so that a comprehensive understanding on microbial utilization for bio-cementation can be achieved.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. HCC is associated with several etiological factors, including HBV/HCV infections, cirrhosis, and fatty liver diseases. However, the molecular mechanism underlying HCC development remains largely elusive. The advent of high-throughput sequencing has unveiled an unprecedented discovery of a plethora of long noncoding RNAs (lncRNAs). Despite the lack of coding capacity, lncRNAs have key roles in gene regulation through interacting with various biomolecules. It is increasingly evident that the dysregulation of lncRNAs is inextricably linked to HCC cancer phenotypes, suggesting that lncRNAs are potential prognostic markers and therapeutic targets. In light of the emerging research in the study of the regulatory roles of lncRNAs in HCC, we discuss the association of lncRNAs with HCC. We link the biological processes influenced by lncRNAs to cancer hallmarks in HCC and describe the associated functional mechanisms. This review sheds light on future research directions, including the potential therapeutic applications of lncRNAs.

Background/purpose: Atopic dermatitis (AD) is a chronic inflammatory disease commonly seen in children and increasingly recognized in adults. With recent advances in the therapeutic development for AD, the Taiwanese Dermatological Association (TDA) established a committee to update the consensus for AD management in Taiwan. This report describes the 2020 updated consensus for the management of AD., Methods: A panel of 11 core members was convened to review and discuss aspects of AD management and draft recommendation during the first two meetings. The 2015 TDA consensus and the 2017 European guideline, along with recent peer-reviewed articles, serve as the foundation for the update. In the third meeting, AD expert dermatologists selected on a national scale were invited to vote on the final statements. A total of 27 dermatologists attended the final meeting. The consensus was achieved when ratings of 7-9 (out of a total score of 9) accounted for ≥ 75% of the total votes., Results: Consensus was achieved on the therapeutic options for AD by lines of treatment. A treatment algorithm was presented to illustrate the place of each modality in terms of basic care, acute disease control, and maintenance therapy. Special considerations for the pediatric population, as well as for women during pregnancy and lactation, are discussed., Conclusion: Topical corticosteroids with long-term emollient-based therapies remain the cornerstone of AD treatment. Systemic treatments are indicated when topical therapies and phototherapy fail to control the disease. The recent approval of dupilumab and emerging targeted therapies are expected to bring significant clinical benefit for patients whose disease is inadequately managed by existing options., Competing Interests: Declaration of Competing Interest The authors declare that they have no financial or non-financial conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This paper investigated the static behaviour of glass fibre reinforced polymer (GFRP) built-up hollow and concrete filled built-up beams tested under four-point bending with a span-to-depth ratio of 1.67, therefore focusing their shear performance. Two parameters considered for hollow sections were longitudinal web stiffener and strengthening at the web-flange junction. The experimental results indicated that the GFRP hollow beams failed by web crushing at supports; therefore, the longitudinal web stiffener has an insignificant effect on improving the maximum load. Strengthening web-flange junctions using rectangular hollow sections increased the maximum load by 47%. Concrete infill could effectively prevent the web crushing, and it demonstrated the highest load increment of 162%. The concrete filled GFRP composite beam failed by diagonal tension in the lightweight concrete core. The finite element models adopting Hashin damage criteria yielded are in good agreement with the experimental results in terms of maximum load and failure mode. Based on the numerical study, the longitudinal web stiffener could prevent the web buckling of the slender GFRP beam and improved the maximum load by 136%. The maximum load may be further improved by increasing the thickness of the GFRP section and the size of rectangular hollow sections used for strengthening. It was found that the bond-slip at the concrete-GFRP interface affected the shear resistance of concrete-GFRP composite beam.

Silicatein-α is a hydrolase found in siliceous sea sponges with a unique ability to condense and hydrolyse silicon-oxygen bonds. The enzyme is thus of interest from the perspective of its unusual enzymology, and for potential applications in the sustainable synthesis of siloxane-containing compounds. However, research into this enzyme has previously been hindered by the tendency of silicatein-α towards aggregation and insolubility. Herein, we report the development of an improved method for the production of a trigger factor-silicatein fusion protein by switching the previous hexahistidine tag for a Strep-II tag, resulting in 244-fold improvement in protein yield compared to previous methods. Light scattering and thermal denaturation analyses show that under the best storage conditions, although oligomerisation is never entirely abolished, these nanoscale aggregates of the Strep-tagged protein exhibit improved colloidal stability and solubility. Enzymatic assays show that the Strep-tagged protein retains catalytic competency, but exhibits lower activity compared to the His 6 -tagged protein. These results suggest that the hexahistidine tag is capable of non-specific catalysis through their imidazole side chains, highlighting the importance of careful consideration when selecting a purification tag. Overall, the Strep-tagged fusion protein reported here can be produced to a higher yield, exhibits greater stability, and allows the native catalytic properties of this protein to be assessed.

Background: Non-adherence to anti-seizure medication (ASM) therapy is an important contributing factor to the higher mortality rate and treatment failure of epilepsy. This study aimed to determine the rate and factors associated with non-adherence to ASM therapy through the WHO five dimensions of medication adherence framework., Methods: We conducted a cross-sectional study at an outpatient Neurology Clinic of a tertiary government hospital in Malaysia. Between March and July 2019, we identified 217 patients with a confirmed diagnosis of epilepsy, receiving oral ASM therapy and able to administer their medications. We performed a semi-structured interview to gather information on sociodemographic background, clinical and medication history, and perceptions on healthcare services. Adherence to ASM therapy was evaluated using the Medication Compliance Questionnaire (MCQ). Patient's illness perception was assessed by the Brief Illness Perception Questionnaire (B-IPQ)., Results: 208 patients participated in this study. The median age of the study participants was 35 years (IQR 26-44). 58.2% were females and majority, 55.8%, were from the Malay ethnic group. Based on the MCQ scoring, 89 patients (42.8%) were non-adherent. Multiple logistic regression demonstrated that being employed or students (adjusted odds ratio [aOR] 2.26, 95%CI: 1.19-4.29 p = 0.012) and having an average or below average perceived access to pharmacy services (aOR 2.94, 95%CI: 1.38-6.24, p = 0.005) were significant contributors to non-adherence., Conclusion: Being employed or students and having an average or below average perceived access to pharmacy services were associated with ASM non-adherence Efforts to improve ASM adherence should adopt a comprehensive approach considering the success of adherence is contingent on the interrelationship of multiple dimensions., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: It is well known that palatoplasty can often cause disturbances in maxillary growth. The use of a single-layer vomer flap for the early closure of the hard palate is controversy among surgeons. The aim of this study is to compare the 10-year facial growth of 2 surgical protocols in the treatment of patients with unilateral cleft lip and palate performed by a single surgeon., Methods: This retrospective analysis includes 43 nonsyndromic patients with complete unilateral cleft lip with or without a vomer flap for the closure of the hard palate during cleft-lip repair. Lateral cephalograms were obtained at the age of 5, 7, and 9 years old, and angular measurements were used to assess patient's facial growth. The Mann-Whitney U test was used to compare 2 treatment protocol groups., Result: A total of 23 patients in protocol 1 group (16 male, 7 female) and 20 patients in protocol 2 group (10 male, 10 female) were included. At the age of 5 and 7, there was no significant difference of maxillary and mandibular growth in both groups. At the age of 9 years, all the angular measurement revealed statistical significance with SNA (P = 0.02), SNB (P = 0.05), ANB (P < 0.01), and SNPg (P = 0.05)., Conclusions: The present study has shown that early anterior palate repair for 3-month-old cleft patients have better maxillary growth and less mandibular prognathism.

A photographic food atlas is a series of photographs showing different quantities of different foods. It serves as a portion size estimation aid (PSEA). In Malaysia, the existing food atlases, which display foods in exchanges and standard portion sizes, may not be representative of the actual sizes of the portions of food consumed by the local population. This paper aims to describe the development of a food atlas, namely the 'MY Food Album', and assess its usability as a PSEA. Thirty four participants (aged 31.6±20.9 y) served themselves, in a laboratory setting, what they considered to be typical, small, medium, and large portions of 23 amorphus food items. All food portions were weighed to obtain the mean and standard deviation of the range of food portion sizes to be displayed in the food atlas. Using standard camera and lighting settings, various local foods were photographed at an angle of 45º. A total of 393 food items were categorized into 14 food groups and presented as serial (n=101), guide (n=213) and range (n=79) photographs. The usability of MY Food Album was evaluated by six nutritionists and dietitians using an adapted questionnaire. The food atlas was perceived to be useful to aid in the quantification of food during dietary assessment. It was suggested that the function, dimension and application of fiducial markers be introduced in the food atlas to facilitate its use in size estimation. While MY Food Album was well-accepted as a PSEA, futher validation is required to evaluate the effectiveness of this newly developed food atlas in portion size estimation.

During primary cleft lip repair, a small triangular flap of about 2mm is sometimes required to achieve better symmetry of Cupid's bow. The aim of this study was to evaluate the symmetry of Cupid's bow, with and without the use of a small triangular skin flap (STSF). Forty-five children who underwent the repair of unilateral cleft lip between January 1999 and December 2000 were recruited. Twenty children had a STSF included in the repair (STSF group) an d 25 children underwent the same repair without the STSF (NSTSF group). Vermillion height was measured on the cleft and non-cleft sides using reference points. The t-test was used to compare the vermillion height ratio between the two groups. The mean age at surgery was 4±1.3months in the STSF group and 4.3±0.6years in the NSTSF group. There was no significant difference in vermillion height ratio at 5 years of age between the patients in the two groups. Thus, there is no difference in vermillion height ratio with or without a STSF in cleft lip repair. The use of a small triangular skin flap needs to be assessed carefully, as it will create an unsightly scar over the philtrum area., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)