Language bias in orthodontic systematic reviews: A meta-epidemiological study.

BACKGROUND: Orthodontic systematic reviews (SRs) include studies published mostly in English than non-English languages. Including only English studies in SRs may result in a language bias. This meta-epidemiological study aimed to evaluate the language bias impact on orthodontic SRs. DATA SOURCE: SRs published in high-impact orthodontic journals between 2017 and 2021 were retrieved through an electronic search of PubMed in June 2022. Additionally, Cochrane oral health group was searched for orthodontic systematic reviews published in the same period. DATA COLLECTION AND ANALYSIS: Study selection and data extraction were performed by two authors. Multivariable logistic regression was implemented to explore the association of including non-English studies with the SRs characteristics. For the meta-epidemiological analysis, one meta-analysis from each SRs with at least three trials, including one non-English trial was extracted. The average difference in SMD was obtained using a random-effects meta-analysis. RESULTS: 174 SRs were included in this study. Almost one-quarter (n = 45/174, 26%) of these SRs included at least one non-English study. The association between SRs characteristics and including non-English studies was not statistically significant except for the restriction on language: the odds of including non-English studies reduced by 89% in SRs with a language restriction (OR: 0.11, 95%CI: 0.01 0.55, P< 0.01). Out of the sample, only fourteen meta-analyses were included in the meta-epidemiological analysis. The meta-epidemiological analysis revealed that non-English studies tended to overestimate the summary SMD by approximately 0.30, but this was not statistically significant when random-effects model was employed due to substantial statistical heterogeneity (ΔSMD = -0.29, 95%CI: -0.63 to 0.05, P = 0.37). As such, the overestimation of meta-analysis results by including non-English studies was statistically non-significant. CONCLUSION: Language bias has non-negligible impact on the results of orthodontic SRs. Orthodontic systematic reviews should abstain from language restrictions and use sensitivity analysis to assess the impact of language on the conclusions, as non-English studies may have a lower quality.

Beyond the silence: A comprehensive exploration of long non-coding RNAs as genetic whispers and their essential regulatory functions in cardiovascular disorders.

Long non-coding RNAs (lncRNAs) are RNA molecules that regulate gene expression at several levels, including transcriptional, post-transcriptional, and translational. They have a length of more than 200 nucleotides and cannot code. Many human diseases have been linked to aberrant lncRNA expression, highlighting the need for a better knowledge of disease etiology to drive improvements in diagnostic, prognostic, and therapeutic methods. Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide. LncRNAs play an essential role in the complex process of heart formation, and their abnormalities have been associated with several CVDs. This Review article looks at the roles and relationships of long non-coding RNAs (lncRNAs) in a wide range of CVDs, such as heart failure, myocardial infarction, atherosclerosis, and cardiac hypertrophy. In addition, the review delves into the possible uses of lncRNAs in diagnostics, prognosis, and clinical treatments of cardiovascular diseases. Additionally, it considers the field's future prospects while examining how lncRNAs might be altered and its clinical applications.

Single-cell RNA Sequencing (scRNA-seq): Advances and Challenges for Cardiovascular Diseases (CVDs).

Implementing Single-cell RNA sequencing (scRNA-seq) has significantly enhanced our comprehension of cardiovascular diseases (CVDs), providing new opportunities to strengthen the prevention of CVDs progression. Cardiovascular diseases continue to be the primary cause of death worldwide. Improving treatment strategies and patient risk assessment requires a deeper understanding of the fundamental mechanisms underlying these disorders. The advanced and widespread use of Single-cell RNA sequencing enables a comprehensive investigation of the complex cellular makeup of the heart, surpassing essential descriptive aspects. This enhances our understanding of disease causes and directs functional research. The significant advancement in understanding cellular phenotypes has enhanced the study of fundamental cardiovascular science. scRNA-seq enables the identification of discrete cellular subgroups, unveiling previously unknown cell types in the heart and vascular systems that may have relevance to different disease pathologies. Moreover, scRNA-seq has revealed significant heterogeneity in phenotypes among distinct cell subtypes. Finally, we will examine current and upcoming scRNA-seq studies about various aspects of the cardiovascular system, assessing their potential impact on our understanding of the cardiovascular system and offering insight into how these technologies may revolutionise the diagnosis and treatment of cardiac conditions.

Beyond the beat: A pioneering investigation into exercise modalities for alleviating diabetic cardiomyopathy and enhancing cardiac health.

Patients with preexisting cardiovascular disease or those at high risk for developing the condition are often offered exercise as a form of therapy. Patients with cancer who are at an increased risk for cardiovascular issues are increasingly encouraged to participate in exercise-based, interdisciplinary programs due to the positive correlation between these interventions and clinical outcomes following myocardial infarction. Diabetic cardiomyopathy (DC) is a cardiac disorder that arises due to disruptions in the homeostasis of individuals with diabetes. One of the primary reasons for mortality in individuals with diabetes is the presence of cardiac structural damage and functional abnormalities, which are the primary pathological features of DC. The aetiology of dilated cardiomyopathy is multifaceted and encompasses a range of processes, including metabolic abnormalities, impaired mitochondrial function, dysregulation of calcium ion homeostasis, excessive cardiomyocyte death, and fibrosis. In recent years, many empirical investigations have demonstrated that exercise training substantially impacts the prevention and management of diabetes. Exercise has been found to positively impact the recovery of diabetes and improve several metabolic problem characteristics associated with DC. One potential benefit of exercise is its ability to increase systolic activity, which can enhance cardiometabolic and facilitate the repair of structural damage to the heart caused by DC, leading to a direct improvement in cardiac health. In contrast, exercise has the potential to indirectly mitigate the pathological progression of DC through its ability to decrease circulating levels of sugar and fat while concurrently enhancing insulin sensitivity. A more comprehensive understanding of the molecular mechanism via exercise facilitates the restoration of DC disease must be understood. Our goal in this review was to provide helpful information and clues for developing new therapeutic techniques for motion alleviation DC by examining the molecular mechanisms involved.

A machine learning-based Biding price optimization algorithm approach.

Trading companies of used product market are struggling to gain customers attentaion and to sell the products. The aim of this research is to develop a mechanism that can maximize the sale of products while considering profit implications. The literature review classifies the procurement mechanism. Given the limited-supply nature, that also includes unpredictable quality levels and a procurement mechanism that perceives the company offering prices to suppliers on a single-item basis. The academic literature has not covered such a mechanism. Techniques like those that improve the required bidding strategy are reviewed and considered fit to be included in the support tool as the procedures intention to maximize an objective function depending on the bidding price and contain the probability of winning the auction and the profit made from the proceeding, the motivation laid on the approach that predicts the probability. It is determined that this assembles a Response to Reverse Request for Quotation that meets the assumptions of a First-Price Sealed-Bid(FPSD) auction that potentially includes a hidden reservation price.

Discovery of 12 (BMS-986172) as a Highly Potent MGAT2 Inhibitor that Achieved Targeted Efficacious Exposures at a Low Human Dose for the Treatment of Metabolic Disorders.

A series of dihydropyridinone (DHP) compounds was prepared and evaluated for MGAT2 activity. The efforts led to the identification of novel tetrazolones with potent MGAT2 inhibitory activity and favorable in vitro profiles. Further tests of select analogues in mouse models revealed significant reduction in food intake and body weight. Subsequent studies in MGAT2 knockout mice with the lead candidate 12 (BMS-986172) showed on-target- and mechanism-based pharmacology. Moreover, its favorable pharmacokinetic (PK) profile and the lack of species variability in the glucuronidation potential resulted in a greater confidence level in the projection of a low dose for achieving targeted efficacious exposures in humans. Consistent with these projections, PK data from a phase 1 trial confirmed that targeted efficacious exposures could be achieved at a low dose in humans, which supported compound 12 as our second and potentially superior development candidate for the treatment of various metabolic disorders.

Corporate social responsibility stimulus on environmental problems: Spatial threshold model analysis.

A popular subject of general interest is the connection between corporate social responsibility, research and development, tax policy, and the purchase of green bonds. To encourage the coordinated growth of the economy and a pollution-free environment, it is crucial to understand how they interact. The paper develops a theoretical framework based on the general equilibrium theory's multi-sector model to examine how tax competition affects environmental degradation. The existence of such an effect, which is a threshold effect resulting from corporate social responsibility (CSR), and how it is impacted by CSR are theoretically established. The study used Moroccan province panel data from 2000 to 2022 and the spatial panel threshold model. The empirical finding demonstrates the importance of the threshold impact of CSR since reduced tax competition tends to worsen environmental degradation when CSR is above the threshold value and to reduce it when CSR is below the threshold value. The study also reveals that the impact of tax competitiveness varies regionally. Several policy suggestions are then put out to assist Morocco in reducing environmental pollution through taxation.

Optimization of investment strategies through machine learning.

The main objective of this research is to develop a sustainable stock quantitative investing model based on Machine Learning and Economic Value-Added techniques for optimizing investment strategies. Quantitative stock selection and algorithmic trading are the two features of the model. Principal component analysis and economic value-added criteria are used in quantitative stock model for efficiently stocks selection, which may repeatedly select valuable stocks. Machine learning techniques such as Moving Average Convergence, Stochastic Indicators and Long-Short Term Memory are used in algorithmic trading. One of the first attempts, the Economic Value-Added indicators are used to appraise stocks in this study. Furthermore, the application of EVA in stock selection is exposed. Illustration of the proposed model has been done on United States stock market and finding shows that Long-Short Term Memory (LSTM) networks can more accurately forecast future stock values. The proposed strategy is feasible in all market situations, with a return that is significantly larger than the market return. As a result, the proposed approach can not only assist the market in returning to rational investing, but also assist investors in obtaining significant returns that are both realistic and valuable.

Corporate social responsibilities, sustainable investment, and the future of green bond market: evidence from renewable energy projects in Morocco.

The study mainly focuses on identifying the links between corporate social responsibility disclosure activities and green bond investment performance utilizing GDP growth as a moderating variable in Morocco. The research is based on a unique technique combining a thorough literature review, market data analysis, and interviews with a vast spectrum of green bond market players. The data from 2015 to 2019 for the 450 Moroccan enterprises has been utilized to produce CSR and GDP growth rates based on a serial criterion. The data demonstrate that the more firms publicly disclose their CSR initiatives, and the better the financial outcomes. The relationship between CSR disclosure and green bond investment seems to be tempered by GDP considerably, while the effect of CSR on green bond investment Tobin's Q is dramatically lowered. As a consequence of the benefits that the business stands to get from CSR disclosure, legislators are moving in the direction of ensuring a long-term market. Overall, the issue of green bonds has a good influence on firms, may contribute to environmental development, encourages CSR and value creation, and helps to attract investors to some level. The research provided light on a strategy to measure CSR disclosure indices for emerging markets like Morocco. The results recommend that the business's management pay more attention to CSR disclosure activities owing to the positive advantage their firm may gain and suggest policymakers maintain a stable economic background for a sustainable market.

Therapeutic approaches for chronic hepatitis C: a concise review.

Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.

Polyvinyl alcohol and aminated cellulose nanocrystal membranes with improved interfacial compatibility for environmental applications.

Biogas up-gradation is a useful method to control CO2 emission and enhance the green process. The demand for renewable sources is increasing due to the depletion of fossil fuels. Thin-film nanocomposites functionalized with tunable molecular-sieving nanomaterials have been employed to tailor membranes with enhanced permeability and selectivity. In this work, the cellulose nanocrystals as a filler in the polyvinyl alcohol matrix are prepared to achieve high-performance facilitated transport membranes for CO2 capture. Considering the mechanical stability, interfacial compatibility and high moisture uptake of the filler, the main objective of this work was to develop a novel aminated CNC (Am-CNC)/polyvinyl alcohol nanocomposite membrane for biogas upgrading. The hydroxyl groups (O-H) on the reducing end of the cellulose nanocrystals were replaced by amino groups (N-H2). It was discovered through Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) that adding Am-CNCs in PVA membranes shows an increment in the CO2 removal and effectively upgrades the biogas. The effect of change in concentration of Am-CNC and feed pressure was investigated. The results showed that with increasing Am-CNC concentration up to 1.5 wt%, the thickness of the selective membrane layer increased from 0.95 to 1.9 µm with a decrease in the moisture uptake from 85.04 to 58.84%. However, the best CO2 permeance and selectivity were achieved at 0.306 m3/m2.bar.h (STP) and 33.55, respectively. Furthermore, there was a more than two-fold decrease in CO2 permeance and a 27% decrease in the CO2/CH4 selectivity when the feed pressure increased from 5 to 15 bar. It was revealed that PVA/Am-CNC membrane is high performing for the biogas upgradation.

Impact of inland waters on highly pathogenic avian influenza outbreaks in neighboring poultry farms in South Korea.

BACKGROUND: Since 2003, the H5 highly pathogenic avian influenza (HPAI) subtype has caused massive economic losses in the poultry industry in South Korea. The role of inland water bodies in avian influenza (AI) outbreaks has not been investigated. Identifying water bodies that facilitate risk pathways leading to the incursion of the HPAI virus (HPAIV) into poultry farms is essential for implementing specific precautionary measures to prevent viral transmission. OBJECTIVES: This matched case-control study (1:4) examined whether inland waters were associated with a higher risk of AI outbreaks in the neighboring poultry farms. METHODS: Rivers, irrigation canals, lakes, and ponds were considered inland water bodies. The cases and controls were chosen based on the matching criteria. The nearest possible farms located within a radius of 3 km of the case farms were chosen as the control farms. The poultry farms were selected randomly, and two HPAI epidemics (H5N8 [2014-2016] and H5N6 [2016-2017]) were studied. Conditional logistic regression analysis was applied. RESULTS: Statistical analysis revealed that inland waters near poultry farms were significant risk factors for AI outbreaks. The study speculated that freely wandering wild waterfowl and small animals contaminate areas surrounding poultry farms. CONCLUSIONS: Pet birds and animals raised alongside poultry birds on farm premises may wander easily to nearby waters, potentially increasing the risk of AI infection in poultry farms. Mechanical transmission of the AI virus occurs when poultry farm workers or visitors come into contact with infected water bodies or their surroundings. To prevent AI outbreaks in the future, poultry farms should adopt strict precautions to avoid contact with nearby water bodies and their surroundings.

Green Synthesis of BPL-NiONPs Using Leaf Extract of Berberis pachyacantha: Characterization and Multiple In Vitro Biological Applications.

An eco-friendly biogenic method for the synthesis of nickel oxide nanoparticles (NiONPs) using phytochemically rich Berberis pachyacantha leaf extract (BPL) was established. To achieve this purpose, 80 mL of BPL extract was used as a suitable reducing and capping agent for the synthesis of NiONPs. The synthesis of BPL-based nickel oxide nanoparticles (BPL@NiONPs) was confirmed using different microscopic and spectroscopic techniques: UV Visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS) and scanning electron microscopy (SEM) analysis. Spectroscopically, BPL-NiONPs was found with a pure elemental composition (oxygen and nickel), average size (22.53 nm) and rhombohedral structure with multiple functional groups (-OH group and Ni-O formation) on their surface. In the next step, the BPL extract and BPL@NiONPs were further investigated for various biological activities. As compared to BPL extract, BPL@NiONPs exhibited strong biological activities. BPL@NiONPs showed remarkable antioxidant activities in terms of 2,2-diphenyl-1-picrylhydrazyl (76.08%) and total antioxidant capacity (68.74%). Antibacterial action was found against Pseudomonas aeruginosa (27 mm), Staphylococcus aureus (20 mm) and Escherichia coli (19.67 mm) at 500 µg/mL. While antifungal potentials were shown against Alternaria alternata (81.25%), Fusarium oxysporum (42.86%) and Aspergillus niger (42%) at 1000 µg/mL. Similarly, dose-dependent cytotoxicity response was confirmed against brine shrimp with IC50 value (45.08 µg/mL). Additionally, BPL@NiONPs exhibited stimulatory efficacy by enhancing seed germination rate at low concentrations (31.25 and 62.5 µg/mL). In conclusion, this study depicted that BPL extract has important phytochemicals with remarkable antioxidant activities, which successfully reduced and stabilized the BPL@NiONPs. The overall result of this study suggested that BPL@NiONPs could be used as nanomedicines and nanofertilizers in biomedical and agrarian fields.

Spatial Variation in Risk for Highly Pathogenic Avian Influenza Subtype H5N6 Viral Infections in South Korea: Poultry Population-Based Case-Control Study.

Given the substantial economic damage caused by the continual circulation of highly pathogenic avian influenza (HPAI) outbreaks since 2003, identifying high-risk locations associated with HPAI infections is essential. In this study, using affected and unaffected poultry farms' locations during an HPAI H5N6 epidemic in South Korea, we identified places where clusters of HPAI cases were found. Hotspots were defined as regions having clusters of HPAI cases. With the help of the statistical computer program R, a kernel density estimate and a spatial scan statistic were employed for this purpose. A kernel density estimate and detection of significant clusters through a spatial scan statistic both showed that districts in the Chungcheongbuk-do, Jeollabuk-do, and Jeollanam-do provinces are more vulnerable to HPAI outbreaks. Prior to the migration season, high-risk districts should implement particular biosecurity measures. High biosecurity measures, as well as improving the cleanliness of the poultry environment, would undoubtedly aid in the prevention of HPAIV transmission to poultry farms in these high-risk regions of South Korea.

Interpolation of Point Prevalence Rate of the Highly Pathogenic Avian Influenza Subtype H5N8 Second Phase Epidemic in South Korea.

Humans and animals are both susceptible to highly pathogenic avian influenza (HPAI) viruses. In the future, HPAI has the potential to be a source of zoonoses and pandemic disease drivers. It is necessary to identify areas of high risk that are more vulnerable to HPAI infections. In this study, we applied unbiased predictions based on known information to find points of localities with a high probability of point prevalence rate. To carry out such predictions, we utilized the inverse distance weighting (IDW) and kriging method, with the help of the R statistical computing program. The provinces of Jeollanam-do, Gyeonggi-do, Chungcheongbuk-do and Ulsan have high anticipated risk. This research might aid in the management of avian influenza threats associated with various potential risks.

Role of globalziation defining the incidence of entrepreneurship.

Globalization boosts the process of market predictions in the pursuit of economic growth. When economic, political, and social forces gain traction by promoting policies and the climate favoring globalization, entrepreneurial results reach out. Policymakers are still searching for a context within which regional policies can be structured to foster long-term entrepreneurship opportunities. The literature on entrepreneurial phenomena is incomplete and uncertain as to how globalization forces establish a nonlinear mechanism to promote the entrepreneurial process. This study provides the basic context for identifying globalization forces to create a nonlinear effect on the entrepreneurial process in order to address this problem. The results propose that policymakers strengthen the social and political dimension of globalization to increase opportunities-based entrepreneurship.

Screening Hit to Clinical Candidate: Discovery of BMS-963272, a Potent, Selective MGAT2 Inhibitor for the Treatment of Metabolic Disorders.

MGAT2 inhibition is a potential therapeutic approach for the treatment of metabolic disorders. High-throughput screening of the BMS internal compound collection identified the aryl dihydropyridinone compound 1 (hMGAT2 IC50 = 175 nM) as a hit. Compound 1 had moderate potency against human MGAT2, was inactive vs mouse MGAT2 and had poor microsomal metabolic stability. A novel chemistry route was developed to synthesize aryl dihydropyridinone analogs to explore structure-activity relationship around this hit, leading to the discovery of potent and selective MGAT2 inhibitors 21f, 21s, and 28e that are stable to liver microsomal metabolism. After triaging out 21f due to its inferior in vivo potency, pharmacokinetics, and structure-based liabilities and tetrazole 28e due to its inferior channel liability profile, 21s (BMS-963272) was selected as the clinical candidate following demonstration of on-target weight loss efficacy in the diet-induced obese mouse model and an acceptable safety and tolerability profile in multiple preclinical species.

Cyclam-Modified Polyethyleneimine for Simultaneous TGFß siRNA Delivery and CXCR4 Inhibition for the Treatment of CCl4-Induced Liver Fibrosis.

BACKGROUND: Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death. PURPOSE: This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor ß (TGFß) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFß silencing and CXCR4 Inhibition, respectively, to treat CCl4-induced liver fibrosis in a mouse model. METHODS: Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFß silencing of PEI-Cyclam polyplex was authenticated by Western blotting. RESULTS: The 1H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFß polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFß polyplex significantly downregulated α-smooth muscle actin, TGFß, and collagen type III. CONCLUSION: Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFß siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl4-induced liver fibrosis.

The effectiveness of surgical adjunctive procedures in the acceleration of orthodontic tooth movement: A systematic review of systematic reviews and meta-analysis.

OBJECTIVE: To identify and evaluate the body of the evidence regarding the effectiveness of surgical adjunctive procedures (SAPs) in accelerating orthodontic tooth movement (OTM). DATA SOURCES: Unrestricted search of three electronic databases and manual search up to 12 June 2020 were undertaken. DATA SELECTION: All systematic reviews of randomised and non-randomised controlled trials that investigate the effectiveness of the SAPs in accelerating OTM were included. DATA EXTRACTION: Study selection and data extraction were undertaken independently and in duplicate by two reviewers. A random-effects model with a 95% confidence interval (CI) was generated for comparable outcomes. Two reviewers assessed the quality of the included studies using AMSTAR2 and GRADE. RESULTS: Fourteen systematic reviews were included; however, four systematic reviews were assessed quantitatively. Meta-analysis showed that mean difference (MD) of canine retraction rate, for the first month after SAPs, was mild (MD = 0.65 mm/month). Compared to control, micro-osteoperforations (MOPs) statistically but temporally accelerate lower canine retraction and en masse retraction by 0.25 mm/month and 0.31 mm/month, respectively. There was no significant effect (P>0.05) in terms of molar anchorage loss (MAL) between control and MOP groups. Piezocision non-significantly shortens the duration of en masse retraction (4.30 months, P>0.05), but significantly shortens incisors retraction (101.64 days, P<0.001). MAL is mild but significantly less in the piezocision group compared to the control group (MD = 0.53 mm, P=0.03). Low-level evidence showed that SAPs have no significant effect on root resorption or periodontal health; however, piezocision is associated with transient acute inflammation and noticeable scars. CONCLUSION: Low-level evidence concludes that SAPs accelerate OTMs and reduce treatment duration, but the acceleration is minor and transient. The effect on anchorage loss is variable and technique related. Side effects of SAPs are transient, but some might be aesthetically noticeable. A cost-benefit analysis of SAPs should be considered while making the treatment decision.

Influence of single nucleotide polymorphism of LAT1 on therapeutic response to gabapentinoids in Pakistani patients with neuropathic pain.

Gabapentinoids are substrate of L-type amino acid transporter 1 (LAT1) for distribution across the blood-brain barrier. The present study aimed to evaluate the effect of LAT1 rs4240803 genetic polymorphism on the clinical efficacy and tolerability of gabapentinoids in Pakistani patients with neuropathic pain. Three-hundred and ninety-two patients were recruited, genotyped for SNP rs4240803, and followed up for eight weeks to evaluate the clinical response to gabapentinoids in terms of pain relief, inadequate response, and the emergence of adverse events. LAT1 rs4240803 GG, GA, and AA genotype frequency were 33.42%, 47.96% and 18.62%, respectively. Out of 392 patients, 323 responded to the treatment and 17.6% discontinued either due to insufficient response or intolerable adverse events (AEs). GA genotype was more frequent in non-responder group (P Ë‚ 0.001). Maximum pain responders (≥50%) in combination with the lowest incidence of AEs were observed in the GG group, whereas partial responders belonged to GA genotype and with the highest frequency of somnolence (83.6%) and dizziness (69.9%). Overall, 72.5% patients with GA genotype experienced AEs (P Ë‚ 0.001). In conclusion, clinical outcomes of gabapentinoids are influenced by LAT1 rs4240803 polymorphism and population pharmacogenetics should be considered to evaluate the maximum potential of gabapentinoids in the management of neuropathic pain.