Top 50 Highly Cited Publications in Facelift Surgery: A 50-Year Bibliometric Analysis Review.

INTRODUCTION: Facelift surgery, also known as rhytidectomy, is a commonly performed procedure to address aging-related changes in the face and neck. Over the years, its techniques and methodologies have evolved. This study aimed to provide a bibliometric analysis of the top 50 most cited publications related to facelift surgery over a fifty-year period (1973-2023). METHODS: The authors obtained data from the Web of Science Core Collection on July 15, 2023. Using a predefined search strategy, the most cited articles from 1973 to 2023 on facelift surgery were identified. The publications were analyzed for their type of study, journal of publication, geographic origin, and primary outcomes. Furthermore, the authorship gender distribution was assessed. RESULTS: The majority of the publications (34 out of 50) were published in the "Plastic and Reconstructive Surgery" journal. The USA contributed to 72% of the research, followed by the UK, Mexico, Australia, and Germany. The primary outcomes varied from surgical techniques, anatomical studies, risk factors, patient-specific outcomes, and facial rejuvenation techniques, to comparative and historical progression of techniques. Notably, male authors dominated the field with 47 out of 50 papers having both a first and senior male author. CONCLUSION: Facelift surgery has seen substantial research development over the past fifty years. The USA has been at the forefront of this research, with a predominant focus on surgical techniques and anatomical studies. Male dominance in authorship indicates potential scope for increased gender diversity in this specialty. Annual updates are recommended for continued insights. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy of Exclusive Fat Grafting for Breast Reconstruction: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Exclusive fat grafting is an alternative method to implant- or flap- based reconstruction techniques following mastectomies or breast conservation therapies. Its efficacy has been explored before but new data has come to light, resulting in previous results becoming outdated. Concerns have also been raised about the oncological safety of this procedure which must be evaluated alongside the efficacy to gain a comprehensive understanding of the merits of this alternative technique. METHODS: We queried the PubMed electronic database from its inception until August 2023 for studies evaluating the efficacy and oncological safety of exclusive fat grafting breast reconstruction following cancer-related mastectomy or breast conservation therapy. Results of the analysis were pooled and presented as means or valid proportions. Results of the analysis were pooled using a random-effects model and presented with 95% confidence intervals (95% CIs) where appropriate. RESULTS: 41 studies were included in our analysis. Pooled results show that on average, 1.7 sessions of exclusive fat grafting were required to complete reconstruction in Breast Conservation Therapy (BCT) patients, with an average volume of 114.2 ml being injected. For mastectomy patients with irradiated breasts, 4.7 sessions were needed on average with 556.8 ml being required to complete reconstruction, compared to their non-irradiated Counterparts requiring only 2.6 sessions and 207.2 ml to complete reconstruction. Oncological recurrence events were found in 29/583 non-irradiated mastectomy patients (p = 0.014) and in 41/517 BCT patients (p = 0.301) CONCLUSION: Exclusive fat grafting is an oncologically safe and reasonably efficacious alternative to more common methods of breast reconstruction. More data is needed to fully characterize the oncological safety of this procedure in irradiated and non-irradiated mastectomy patients. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comprehensive Systematic Review of Breast Implant Illness: Symptoms, Management, and Long-Term Outcomes.

BACKGROUND: Breast augmentation using silicone implants is common, with over 300,000 annual US surgeries. It was initially approved in 1962, there were safety concerns with the use of silicone implants, leading to a 1992-2006 FDA moratorium. Recently, Breast Implant Illness (BII) was described as a cluster of symptoms associated with silicone implants, with a lack of diagnostic criteria, which increased the likelihood of implant removal and a variety of treatment options. This comprehensive review aims to shed light on the extent, symptoms, management, and outcomes of BII. METHODS: Multiple electronic databases were systematically searched in May 2023 for studies on Breast Implant Illness utilizing terms related to BII and its symptoms, diagnosis, and treatment. Out of 1204 studies, 20 met the inclusion criteria and were included in the systematic review. The Newcastle-Ottawa Scale for the included cohort prospective and retrospective studies, and the tool for evaluating the methodological quality of case reports and case series were utilized during quality assessment. RESULTS: There were 20 papers on Breast Implant Illness published between 1995 and 2022, including a peak of papers published in 2020 and 2022. The majority of the studies came from the USA, with a variety of research methods, including case reports. Reports of arthralgia and fatigue were common findings. These symptoms were frequently alleviated by surgical procedures such as en bloc explantation and capsulectomy, highlighting the intricacy of the problem and the need for individualized treatment plans. CONCLUSION: The review underscores the critical need for further research into BII, advocating for a multidisciplinary strategy that prioritizes patient safety, informed decision-making, and comprehensive care. As the medical community progresses in understanding and managing BII, emphasizing evidence-based practices and patient-provider communication will be essential in addressing this complex condition effectively. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluating the Efficacy of Platelet-Rich Fibrin Matrix versus Subepithelial Connective Tissue Grafts in Dental Root Coverage: A Comparative Study Using Modified Ruben's Technique.

BACKGROUND Dental root coverage, crucial in managing gingival recessions, traditionally utilizes subepithelial connective tissue grafts. However, this approach has limitations such as donor site morbidity and graft availability. Recent studies have introduced platelet-rich fibrin (PRF) as an alternative, leveraging its regenerative potential and growth factors. Despite the promise, comparative assessments between PRF and conventional grafts remain limited. This research probes whether PRF, when used beneath a modified Ruben's mixed flap, could provide comparable or superior dental root coverage than a subepithelial connective tissue graft. MATERIAL AND METHODS We enrolled 30 patients exhibiting Miller's class I and II recession in this comparative case series. Patients were randomly assigned to receive either a connective tissue graft (15 patients) or a PRF matrix (15 patients), both covered by a modified Ruben's mixed flap. RESULTS Clinical parameters, including full mouth plaque scores, bleeding scores, probing sulcus depth, clinical attachment level, gingival position assessment, width, and thickness of attached gingiva, were assessed in both the control and test groups at baseline, 6 months, and 12 months post-surgery. Significant differences were observed at all intervals.At the 12-month mark, the control group (connective tissue graft) achieved 91% complete root coverage, while the test group (PRF matrix) achieved 86%. However, this difference was not statistically significant. CONCLUSIONS The study outcomes suggest comparable gains in root coverage and attached gingiva between the connective tissue graft and PRF matrix groups. Thus, the results support our hypothesis that a subepithelial PRF matrix can serve as a viable alternative to a subepithelial connective tissue graft for treating dental root coverage.

Treatment of Gingival Recession Defects with Pouch and Tunnel Technique Using Connective Tissue Graft and Lyophilized Chorion Membrane in Smokers.

BACKGROUND The chorion membrane has been used for several decades as an allograft in tissue repair and various periodontal regenerative procedures. The present study, conducted at a single center in India, aimed to evaluate and compare the clinical outcomes of 26 gingival recession sites in chronic smokers treated using a pouch and tunnel technique with connective tissue graft (CTG) and lyophilized chorion membrane (LCM). MATERIAL AND METHODS The study included 22 smokers with 26 sites of recession defect, with Miller's class I and class II gingival recession, which were allotted into control and test groups. The control group (13 sites) was treated with CTG, and the test group (13 sites) was treated with LCM. Clinical parameters like recession depth, recession width, relative clinical attachment level (RCAL), relative gingival position, width of attached gingiva, and width of keratinized gingiva were recorded at baseline and 6 months postoperatively. Visual analogue scores for pain and wound-healing index scores were assessed in the first week after surgery. RESULTS All clinical parameters showed significant improvements from baseline to 6 months postoperatively in the control and test groups. Recession width, RCAL, width of attached gingiva, and width of keratinized gingiva demonstrated significant differences, whereas mean root coverage percentage and recession depth did not show any significant differences between the study groups at 6 months postoperatively. CONCLUSIONS This study supports the role of LCM allograft as a scaffold to promote soft tissue regeneration and has demonstrated a favorable role for its use in root coverage procedures in patients who smoke.

Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Synthesis, Molecular Docking, and Preclinical Evaluation of a New Succinimide Derivative for Cardioprotective, Hepatoprotective and Lipid-Lowering Effects.

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = -7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = -7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.

Antibacterial Effects of Commiphora gileadensis Methanolic Extract on Wound Healing.

Commiphora gileadensis (CG) is a small tree distributed throughout the Middle East. It was traditionally used in perfumes in countries in this area. In Saudi Arabia, it was used to treat wounds burns and as an antidote to scorpion stings. This study aimed to evaluate the antimicrobial activity and cutaneous wound healing efficiency of the CG extracts using microbiological tests, rate of wound contraction and histopathological changes. CG plant were extracted using the methanol extraction technique; then, the methanolic extract was characterized using liquid chromatography coupled with mass spectrometry (LC−MS). Afterwards, a six-millimetre (mm) excision wound was induced in 60 male Balb/c mice. Mice were classified into two classes; each class consisted of three groups of 10 mice. In the non-infected wound class, the group I was assigned as control and received normal saline. Group II received gentamicin treatment, and group III treated with CG-methanolic extract. In the Staphylococcus aureus-infected class, group IV received normal saline, and groups V and VI were treated with gentamicin and CG-methanolic extract, respectively. The colonization of infected wounds was determined using colony-forming units (CFUs), and the percentage of wound contraction was measured in all groups. Finally, the histopathologic semi-quantitative determination of wound healing was evaluated by inflammatory cell infiltration, the presence of collagen fibres and granulation tissue, and the grade of re-epithelization. Composition analysis of the methanolic extract confirmed the presence of a high amount of ceramide (69%) and, to a lesser extent, hexosylceramide (18%) and phosphatidylethanolamine (7%) of the total amount. Additionally, there was a statistically significant difference between the percentage of wound contraction in the CG-treated and control groups in both Staphylococcus aureus-infected and non-infected wounds (p < 0.01). The colonization of the infected wounds was lower in the group treated with CG than in the control group (p < 0.01). In both non-infected and infected wounds, the CG-treated group showed significant statistical differences in inflammatory cell infiltration, collagen fibres, re-epithelization and granulation tissue formation compared with the control group (p < 0.01). The CG extract possesses antibacterial and anti-inflammatory properties that induce wound healing.

Interdental Papillary Reconstruction by Microtunnelling Technique Using Autologous Biomatrices-A Randomised Controlled Clinical Trial.

Background and objectives: The study aimed to evaluate and compare the amount of papillary gain and black triangle height reduction after intervention with a microtunnelling technique with either Connective tissue graft (CTG) or Platelet-rich fibrin (PRF) as a biomatrix at 6 months using a microsurgical approach. Materials and Methods: Twenty-six patients with interdental papillary loss were included in the study. The patients were selected randomly for the study groups with thirteen patients in each group: a control group where CTG was utilised as a matrix, and a test group where PRF was utilised as a matrix, for interdental papillary reconstruction. A microtunnelling technique was performed for both the study groups under a surgical microscope. The primary parameters assessed were interdental Papillary height (PH) and Black triangle height (BTH) at baseline, with secondary parameters Visual analogue score by dentist (VAS-D) and patient (VAS-P) assessed at 6 months. Results: Both the control and test groups showed a significant reduction in BTH within their respective group at six months (p < 0.05). The gain in papillary height significantly improved only in the CTG group at 6 months. However, significant differences could not be demonstrated for any of the variables such as BTH (p value = 0.582) and PH (p-value = 0.892) between the study groups at 6 months. Conclusions: IDP reconstruction utilising a microtunnelling approach with CTG or PRF was successful without any significant differences between the groups for the parameters assessed at 6 months.

The Effect of Laser Micro Grooved Platform Switched Implants and Abutments on Early Crestal Bone Levels and Peri-Implant Soft Tissues Post 1 Year Loading among Diabetic Patients-A Controlled Clinical Trial.

Background and Objectives: The study aimed to compare the mean crestal bone level (CBL) and peri-implant soft tissue parameters in laser micro-grooved (LMG) platform switched implants and abutments (I&A) post 1 year of functional loading among non-diabetic and type II diabetic individuals. Materials and methods: Patients with an edentulous site having minimum bone height and width of ≥13 mm and ≥6 mm, respectively, were divided into two groups: (i) Non-diabetic-8 (control) and (ii) diabetic-8 (test). LMG Implants were placed and loaded immediately with a provisional prosthesis. Mean crestal bone level (MCBL) was evaluated radiographically at baseline and at 1 year. Peri-implant attachment level (PIAL) and relative position of the gingival margin (R-PGM) were recorded. Implant stability quotient (ISQ) level and implant survival rate (ISR) were evaluated at 1 year. Results: Early MCBL within the groups 1 year postloading was similar both mesially and distally (control-0.00 to 0.16 mm and 0.00 to 0.17 mm, respectively; test-0.00 to 0.21 mm and 0.00 to 0.22 mm, respectively) with statistical significance (p ≤ 0.003, p ≤ 0.001 and p ≤ 0.001, p ≤ 0.001, respectively). However, intergroup comparison showed no significant difference statistically in the MCBL in 1 year post functional loading. The peri-implant soft tissue parameters showed no significant difference between the groups. ISQ level between both groups did not reveal any significant changes (p ≤ 0.92), and ISR was 100%. Conclusions: LMG Implants resulted in minimal and comparable early crestal bone loss and soft tissue changes post 1 year of functional loading in moderately controlled diabetic and non-diabetic individuals, suggesting that this could be a reliable system for use in systemically compromised individuals.

mecA and fdh: markers of pathogenicity and commensalism in Staphylococcus epidermidis of pediatric origin from Pakistan.

Staphylococcus epidermidis is an opportunistic bacterial pathogen. The study screened isolates of S. epidermidis of pediatric origin for genetic markers of discriminatory potential. 103 isolates (n = 75 clinical; n = 28 community) were screened for methicillin resistance (mecA), formate dehydrogenase (fdh) and an array of virulence factors through multiplex PCR and Congo red assay. The isolates were typed in four distinct categories, based on the presence of selected virulent factors. The type A clinical isolates carrying icaADBC operon (n = 22; 29.3%, P = 0.117) were not significantly differentiating the origin of isolates. The type B clinical isolates representing methicillin resistant S. epidermidis (MRSE) (n = 73; 97.3%, P < 0.00001) and the type C clinical isolates lacking formate dehydrogenase fdh (n = 62; 82.6%, P < 0.00001) were having significant discriminatory potential of clinical isolates, respectively. All type D community isolates were carrying fdh (n = 28; 100%, P < 0.00001). MecA and fdh are significant differential markers of pathogenicity and commensalism in S. epidermidis of pediatric origin.

Evolution of Superficial Muscular Aponeurotic System Facelift Techniques: A Comprehensive Systematic Review of Complications and Outcomes.

Background: Facelift procedures are a popular method of facial rejuvenation. The most common technique is superficial muscular aponeurotic system (SMAS) plication, with several variations. However, the optimal approach remains unclear. This review analyzed previous studies to compare SMAS facelift techniques, their outcomes, and complication rates. Methods: A systematic search was conducted using the MEDLINE, Cochrane, Embase, and Google Scholar electronic databases in September 2022. The search included studies published from January 2000 to September 2022 using keywords such as "facelift," "complications," and "outcomes." Results: This review examined 27 selected studies that evaluated 6 SMAS facelift techniques. The studies involved 6086 patients in total, over 85% of who were satisfied with the outcome of their surgery. The complication rates varied depending on the technique used, with the SMAS flap and composite SMAS technique having the highest (5.75%) and lowest (0.05%) complication rates, respectively. The most common complications were temporary facial nerve injury (0.85%) and skin necrosis (0.41%). To date, only one case of permanent facial nerve injury has been reported. Conclusions: On the basis of our findings, SMAS facelift techniques achieve high patient satisfaction rates, with complication rates that vary by technique. The composite SMAS technique showed the lowest complication rates, whereas the SMAS flap showed the highest rate. However, some studies have not reported all complications, making it difficult to determine the best approach. Therefore, future studies are required to identify the most aesthetically pleasing technique with the lowest complication risk.

Alkaloids as drug leads in Alzheimer's treatment: Mechanistic and therapeutic insights.

Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood-brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.

Different modalities to manage rheumatoid arthritis: an A to Z story.

Aim: To investigate different approaches to RA treatment that might lead to greater efficacy and better safety profiles. Methods: The Search strategy was based on medical subject headings, and screening and selection were based on inclusion/exclusion criteria. Results & discussion: Early therapy is critical for disease control and loss of bodily function. The most promising outcomes came from the development of disease-modifying anti-rheumatic drugs. Different foods have anti-inflammatory and antioxidant qualities that protect against the development of rheumatoid arthritis (RA). Some dietary patterns and supplements have been shown to have potential protective benefits against RA. Conclusion: Improvement in the quality of life of RA patients requires a tailored management approach based on the current patient medical data.

Rheumatoid arthritis is a complex disease with an unclear origin that affects the joints. In this systematic review, we aimed to investigate different effective ways of treating rheumatoid arthritis. Study results indicate that rheumatoid arthritis treatment requires coordination between different healthcare teams. As much as we can, when we start disease treatment early, this will lead to a better disease cure. Different drugs showed promising results in the treatment of rheumatoid arthritis, but the most promising treatment results came from a group of medicinal agents called 'disease-modifying anti-rheumatic drugs'. Different foods have anti-inflammatory and antioxidant effect and help in protection against rheumatoid arthritis, but others, such as red meat and salt, have the opposite effect. Some dietary patterns and supplements, such as the Mediterranean Diet, vitamin D and probiotics, have been shown to have potential protective benefits against rheumatoid arthritis. Improvement in the quality of patient life requires an individualized management roadmap based on current patient medical data.

Virtual screening, molecular dynamics and density functional theory on pain inhibitors against TRPV1 associating inflammatory conditions.

Transient receptor potential vanilloid 1 protein (TRPV1) is expressed widely in skin and sensory neurons that contribute to pain/heat sensation in the human system. TRPV1 gene polymorphisms are susceptible to multiple diseases and it is considered a therapeutic target for various inflammatory conditions. Among the TRPV1 variants, rs8065080 (1911 A > G) plays a vital role in painful osteoarthritis and migraine. The presence of rs8065080 polymorphism may render drug efficacy. This study aimed to identify better antagonists against wild-type and variant TRPV1 that may help in the relief of pain/inflammation. We constructed suitable TRPV1 protein structures for wild-type and rs8065080 variant through a homology modelling approach. A total of 3363 anti-inflammatory compounds with high chemical diversity and good drug-like properties were collected and screened against the generated structures. Molecular docking showed that nobilamide B had the highest binding affinity (-5.83 kcal/mol) towards the wild-type. Whereas, isoquinoline analogue displayed highest binding potency with the variant TRPV1 (-11.65 kcal/mol). Besides those, C18H15F3N4O showed affinity towards both wild-type (-5.53 kcal/mol) and variant TRPV1 (-9.75 kcal/mol). Then, molecular dynamic simulation revealed stable conformation in wild-type and variant TRPV1 upon binding of nobilmaide B, isoquinoline analogue and C18H15F3N4O. Additionally, density functional theory (DFT) using B3LYP hybrid function showed high chemical reactiveness of nobilamie B, isoquinoline analogue and C18H15F3N4O. Overall, our systematic investigations provide, C18H15F3N4O could be a potential analgesic inhibiting both wild-type and variant TRPV1 against inflammatory conditions.

Comparative assessment of anti-cancer drugs against NUDT15 variants to prevent leucopenia side effect in leukemia patients.

BACKGROUND: Human nucleotide triphosphate diphosphatase (NUDT15) is one of the essential proteins involved in the hydrolysis of anti-cancer drugs against leukemia. Polymorphisms in NUDT15 significantly affect the hydrolysis activity that leads to side effects, including leucopenia. Drugs having a better affinity with NUDT15 protein and contributing stable conformation may benefit patients from leucopenia. Most frequent NUDT15 polymorphisms causing structure variability and their association with leukemia were screened. The selected protein variants and anti-cancer drug structures were collected. Further, molecular docking was performed between drugs and NUDT15 variants along with the wild-type. Finally, molecular dynamics were executed for 100 ns to understand the stability of the protein with the anti-cancer drug based on molecular trajectories. RESULTS: Three-dimensional structures of NUDT15 wild, the most frequent variants (Val18Ile, Arg139Cys, and Arg139), and the anti-cancer drugs (azathioprine, mercaptopurine, and thioguanine) were selected and retrieved from structure databases. On molecular docking the binding energies of anti-cancer drugs against NUDT15 structures ranged from - 5.0 to - 5.9 kcal/mol. Among them, azathioprine showed the highest affinities (- 7.3 kcal/mol) for the wild and variant structures. Additionally, the molecular dynamics suggest all analyzed NUDT15 were stable with azathioprine based on the dynamic trajectories. CONCLUSION: Our results suggest azathioprine could be the preferable anti-cancer drug for the population with NUDT15 variants that could effectively be hydrolyzed as evidenced by molecular docking and dynamic simulation.

Rheumatoid arthritis treatment with zoledronic acid, a potentialinhibitorofGWAS-derived pharmacogenetics STAT3 and IL2 targets.

Rheumatoid arthritis (RA) is an inflammatory condition that primarily affects the joints and progress to affect other vital organs. Variety of drugs are being recommended to control the disease progression that benefits patients to perform day-to-day activities. Few of these RA drugs have noticeable side effects; therefore, it's crucial to choose the appropriate drug for treating RA with an understanding of the disease's pathophysiology. Herein, we investigated the RA genes from GWAS data to construct protein-protein interaction (PPI) network and to define appropriate drug targets for RA. The predicted drug targets were screened with the known RA drugs based on molecular docking. Further, the molecular dynamics simulations were performed to comprehend the conformational changes and stability of the targets upon binding of the selected top ranked RA drug. As a result, our constructed protein network from GWAS data revealed, STAT3 and IL2 could be potential pharmacogenetics targets that interlink most of the RA genes encoding proteins. These interlinked proteins of both the targets showed involvement in cell signaling, immune response, and TNF signaling pathway. Among the 192 RA drugs investigated, zoledronic acid had the lowest binding energy that inhibit both STAT3 (-6.307 kcal/mol) and IL2 (-6.231 kcal/mol). Additionally, STAT3 and IL2 trajectories on zoledronic acid binding exhibit notable differences in MD simulations as compared to a drug-free environment. Also, the in vitro assessment with the zoledronic acid confirms the outcome of our computational study. Overall, our study identify zoledronic acid could be potential inhibitor against these targets, that will benefits patients with RA. Comparative efficiency assessments between the RA drugs through clinical trials are needed to validate our findings in the treatment of RA.

Noninvasive Neurally Adjusted Ventilation versus Nasal Continuous or Intermittent Positive Airway Pressure for Preterm Infants: A Systematic Review and Meta-Analysis.

The noninvasive neurally adjusted ventilatory assist (NIV-NAVA) is a newly developed noninvasive ventilation technique with promising clinical and ventilatory outcomes for preterm infants. This systematic review and meta-analysis aimed to investigate whether NIV-NAVA has better clinical and ventilatory outcomes than nasal continuous airway pressure (NCPAP) or noninvasive positive pressure ventilation (NIPP) on premature infants. MEDLINE, Embase, and CENTRAL were searched, and randomized controlled trials (RCTs) that compared NIV-NAVA with NCPAP or NIPP for preterm infants (gestational age: <37 weeks) were included. We evaluated the following outcomes in the neonatal intensive care unit: the desaturation rate, failure of noninvasive modality requiring intubation when received as the primary mode or the need for re-intubation after extubation from mechanical ventilation in the secondary mode (weaning), length of stay, and fraction of inspired oxygen. The mean difference and risk ratio were used to represent continuous and dichotomous outcomes, respectively. We included nine RCTs involving 339 preterm infants overall. NIV-NAVA showed similar clinical and ventilatory outcomes to NCPAP or NIPP, except for the maximum diaphragmatic electrical activity. The rate of failure of the noninvasive modality was not statistically different between NIV-NAVA and NCPAP. The pooled estimates for the maximum electrical activity were significantly reduced in NIV-NAVA compared with those in NIPP. The findings suggest that NIV-NAVA may be as safe and effective as NCPAP and NIPP for preterm neonates, particularly those who may not tolerate these alternative noninvasive methods. However, further trials are recommended for greater evidence.

Eleven Crucial Pesticides Appear to Regulate Key Genes That Link MPTP Mechanism to Cause Parkinson's Disease through the Selective Degeneration of Dopamine Neurons.

Pesticides kill neurons, but the mechanism leading to selective dopaminergic loss in Parkinson's disease (PD) is unknown. Understanding the pesticide's effect on dopaminergic neurons (DA) can help to screen and treat PD. The critical uptake of pesticides by the membrane receptors at DA is hypothesized to activate a signaling cascade and accelerate degeneration. Using MPTP as a reference, we demonstrate the mechanisms of eleven crucial pesticides through molecular docking, protein networks, regulatory pathways, and prioritization of key pesticide-regulating proteins. Participants were recruited and grouped into control and PD based on clinical characteristics as well as pesticide traces in their blood plasma. Then, qPCR was used to measure pesticide-associated gene expression in peripheral blood mononuclear cells between groups. As a result of molecular docking, all eleven pesticides and the MPTP showed high binding efficiency against 274 membrane receptor proteins of DA. Further, the protein interaction networks showed activation of multiple signaling cascades through these receptors. Subsequent analysis revealed 31 biological pathways shared by all 11pesticides and MPTP that were overrepresented by 46 crucial proteins. Among these, CTNNB1, NDUFS6, and CAV1 were prioritized to show a significant change in gene expression in pesticide-exposed PD which guides toward therapy.