Decoy peptides that inhibit TNF signaling by disrupting the TNF homotrimeric oligomer.

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine and its functional homotrimeric form interacts with the TNF receptor (TNFR) to activate downstream apoptotic, necroptotic, and inflammatory signaling pathways. Excessive activation of these pathways leads to various inflammatory diseases, which makes TNF a promising therapeutic target. Here, 12-mer peptides were selected from the interface of TNF-TNFR based upon their relative binding energies and were named 'TNF-inhibiting decoys' (TIDs). These decoy peptides inhibited TNF-mediated secretion of cytokines and cell death, as well as activation of downstream signaling effectors. Effective TIDs inhibited TNF signaling by disrupting the formation of TNF's functional homotrimeric form. Among derivatives of TIDs, TID3c showed slightly better efficacy in cell-based assays by disrupting TNF trimer formation. Moreover, TID3c oligomerized TNF to a high molecular weight configuration. In silico modeling and simulations revealed that TID3c and its parent peptide, TID3, form a stable complex with TNF through hydrogen bonds and electrostatic interactions, which makes them the promising lead to develop peptide-based anti-TNF therapeutics.

A transition from enemies to allies: how viruses improve drought resilience in plants.

Global crop production is severely affected by environmental factors such as drought, salinity, cold, flood etc. Among these stresses, drought is one of the major abiotic stresses reducing crop productivity. It is expected that drought conditions will further increase because of the increasing global temperature. In general, viruses are seen as a pathogen affecting the crop productivity. However, several researches are showing that viruses can induce drought tolerance in plants. This review explores the mechanisms underlying the interplay between viral infections and the drought response mechanisms in plants. We tried to address the molecular pathways and physiological changes induced by viruses that confer drought tolerance, including alterations in hormone signaling, antioxidant defenses, scavenging the reactive oxygen species, role of RNA silencing and miRNA pathway, change in the expression of several genes including heat shock proteins, cellulose synthase etc. Furthermore, we discuss various viruses implicated in providing drought tolerance and examine the range of plant species exhibiting this phenomenon. By applying current knowledge and identifying gaps in understanding, this review aims to provide valuable insights into the complex dynamics of virus-induced drought tolerance in plants, paving the way for future research directions and practical applications in sustainable agriculture.

Arabidopsis PROTODERMAL FACTOR2 binds lysophosphatidylcholines and transcriptionally regulates phospholipid metabolism.

Plant homeodomain leucine zipper IV (HD-Zip IV) transcription factors (TFs) contain an evolutionarily conserved steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain. While the START domain is required for TF activity, its presumed role as a lipid sensor is not clear. Here we used tandem affinity purification from Arabidopsis cell cultures to demonstrate that PROTODERMAL FACTOR2 (PDF2), a representative member that controls epidermal differentiation, recruits lysophosphatidylcholines (LysoPCs) in a START-dependent manner. Microscale thermophoresis assays confirmed that a missense mutation in a predicted ligand contact site reduces lysophospholipid binding. We additionally found that PDF2 acts as a transcriptional regulator of phospholipid- and phosphate (Pi) starvation-related genes and binds to a palindromic octamer with consensus to a Pi response element. Phospholipid homeostasis and elongation growth were altered in pdf2 mutants according to Pi availability. Cycloheximide chase experiments revealed a role for START in maintaining protein levels, and Pi starvation resulted in enhanced protein destabilization, suggesting a mechanism by which lipid binding controls TF activity. We propose that the START domain serves as a molecular sensor for membrane phospholipid status in the epidermis. Our data provide insights toward understanding how the lipid metabolome integrates Pi availability with gene expression.

Early Postoperative Small Bowel Obstruction after Colorectal Surgery: Incidence and Exploratory Analysis of Potential Risk Factors.

Background: Early postoperative small bowel obstruction (EPSBO) is a common complication following colorectal surgery, which can significantly impact patient outcomes. This study aimed to investigate the incidence of EPSBO and identify potential risk factors among patients who underwent colorectal surgery. Methods: A descriptive study was conducted on a cohort of 100 patients who underwent colorectal surgery at a tertiary center at SKIMS, Srinagar, Jammu & Kashmir, India. Descriptive, bivariate, and predictive screening analyses were performed to examine patient characteristics, assess association between different relevant variables and EPSBO, and identify significant predictors, respectively. Results: Our study included a total of 100 patients, with a mean age of 50.39 years. Postsurgery, 11% of the individuals in the cohort developed EPSBO. Early postoperative small bowel obstruction developed around 4.30 days after surgery, and radiographic data revealed dilated gut loops in 72.70% of EPSBO cases. Bivariate analysis revealed significant association between EPSBO and variables such as previously operated, medical comorbidities, smoking status, anemia, neoadjuvant chemoradiotherapy (NACRT), bowel preparation, operative procedure, surgery duration, and type of anastomosis (p < 0.05). History of previous bowel habits, previously operated, perioperative bowel preparation, and blood transfusion were identified as the most influential predictors of EPSBO in the predictive screening study. Conclusion: This study provides insights into the incidence of EPSBO and its potential risk factors for postcolorectal surgery among patients. The findings emphasize the need to take the patient's history of past bowel habits and other factors into account when determining the risk of EPSBO. Future studies should go deeper into these correlations and consider treatments to reduce the occurrence of EPSBO in this patient population. How to cite this article: Ahmad B, Ul Hag MF, Shah MA, et al. Early Postoperative Small Bowel Obstruction after Colorectal Surgery: Incidence and Exploratory Analysis of Potential Risk Factors. Euroasian J Hepato-Gastroenterol 2024;14(1):70-74.

Diagnostic Accuracy of Non-invasive Tests Versus Arthroscopy in Anterior Cruciate Ligament (ACL) Injuries.

BACKGROUND: The knee joint assessment to detect anterior cruciate ligament (ACL) injury after trauma involves clinical examination and radiography. The gold standard method is doing arthroscopy. We did this study seeking to evaluate the effectiveness of other non-invasive diagnostic methods, including the Anterior Drawer test, Lachman test and magnetic resonance imaging (MRI) in detecting ACL tears after trauma, compared to the reference standard method (the arthroscopy). METHODOLOGY: This descriptive cross-sectional study was conducted in the Orthopaedic Department of the Khyber Teaching Hospital, Peshawar, for six months. A total of 86 participants with knee injuries fulfilling the inclusion criteria were recruited for the study. Mechanism of injury, side of injury and body weight were recorded. The Anterior Drawer test and Lachman test for ACL injury were performed by orthopaedic surgeons with at least five years of post-fellowship experience in orthopaedic surgery. Sensitivities, specificities and accuracy of the clinical tests and MRI were calculated. RESULTS: The statistical analysis revealed that the mean age of participants was 35.73 (SD 12.7) years, with a range from 18 to 55 years. Among the participants, 67 (77.91%) were male and 19 (22.09%) were female. The side of injury was predominantly right in 50 (58.14%) and left in 36 (41.86%) participants. Road traffic accidents (RTAs) were the leading cause of knee injury, accounting for 63.95% (55) of cases, followed by sports injuries at 23.26% (20). Regarding diagnostic accuracy, MRI showed a sensitivity of 98.57%, specificity of 87.50% and diagnostic accuracy of 96.51% in detecting ACL tears. The Lachman test demonstrated a sensitivity of 90%, specificity of 87.5% and diagnostic accuracy of 89.53% compared to arthroscopy. Similarly, the anterior Drawer test exhibited a sensitivity of 88.57%, specificity of 87.50% and diagnostic accuracy of 88.37% against the gold standard of arthroscopy. These findings underscore the effectiveness of these diagnostic modalities in identifying ACL injuries. CONCLUSIONS: All three tests (MRI, Lachman test and anterior Drawer test) can be used for the diagnosis of anterior cruciate ligament injury with optimal results.

Transforming evidence-based clinical guidelines into implementable clinical decision support services: the CAREPATH study for multimorbidity management.

Introduction: The CAREPATH Project aims to develop a patient-centered integrated care platform tailored to older adults with multimorbidity, including mild cognitive impairment (MCI) or mild dementia. Our goal is to empower multidisciplinary care teams to craft personalized holistic care plans while adhering to evidence-based guidelines. This necessitates the creation of clear specifications for clinical decision support (CDS) services, consolidating guidance from multiple evidence-based clinical guidelines. Thus, a co-creation approach involving both clinical and technical experts is essential. Methods: This paper outlines a robust methodology for generating implementable specifications for CDS services to automate clinical guidelines. We have established a co-creation framework to facilitate collaborative exploration of clinical guidelines between clinical experts and software engineers. We have proposed an open, repeatable, and traceable method for translating evidence-based guideline narratives into implementable specifications of CDS services. Our approach, based on international standards such as CDS-Hooks and HL7 FHIR, enhances interoperability and potential adoption of CDS services across diverse healthcare systems. Results: This methodology has been followed to create implementable specifications for 65 CDS services, automating CAREPATH consensus guideline consolidating guidance from 25 selected evidence-based guidelines. A total of 296 CDS rules have been formally defined, with input parameters defined as clinical concepts bound to FHIR resources and international code systems. Outputs include 346 well-defined CDS Cards, offering clear guidance for care plan activities and goal suggestions. These specifications have led to the implementation of 65 CDS services integrated into the CAREPATH Adaptive Integrated Care Platform. Discussion: Our methodology offers a systematic, replicable process for generating CDS specifications, ensuring consistency and reliability across implementation. By fostering collaboration between clinical expertise and technical proficiency, we enhance the quality and relevance of generated specifications. Clear traceability enables stakeholders to track the development process and ensure adherence to guideline recommendations.

Cannabis use by individuals with spinal cord injury in the UK: a call for improved patient education and physician awareness for pain and spasticity management.

STUDY DESIGN: Prospective observational qualitative study. OBJECTIVE: Cannabis is used by patients for the treatment of chronic pain, spasticity, sleep issues or mood disorders such as anxiety and depression. Since 2018, it has been authorised in the United Kingdom for medical use as an unlicensed medicine. This study aims to determine if patients are using cannabis for the management of symptoms related to spinal cord injury, and if so, whether they are using medical or illicit cannabis. METHODS: Spinal cord injury patients from the Yorkshire Regional Spinal Injuries Centre and SPINE Community in the United Kingdom were surveyed. Participants were sent a 7-point electronic survey. All results were anonymous, and confidentiality was maintained throughout the process. RESULTS: In total, 223 patients completed the survey. Not all patients answered every question. Of those who responded 65.35% (n = 132) were paraplegic and 34.65% (n = 70) were tetraplegic. Patients were suffering from chronic pain (longer than 3 months), spasticity, loss of/difficulty in sleeping or anxiety/depression. Almost 15% (14.93%, n = 33 out of 221) used cannabis to manage their symptoms, out of those the majority used street cannabis (79.41%, n = 27 out of 34) were using street cannabis. CONCLUSION: This study demonstrates that there are spinal cord injury patients in the UK using cannabis to treat their symptoms. A majority appear to be using illicit cannabis. Given that cannabis can interact with other medications, and that the quality and content of illicit cannabis can be highly variable and at times dangerous, it is important for physicians to discuss cannabis use with their patients. This can inform prescribing and allow them to educate patients on the dangers of medical cannabis and potential alternatives.

Multi-Scale Digital Pathology Patch-Level Prostate Cancer Grading Using Deep Learning: Use Case Evaluation of DiagSet Dataset.

Prostate cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. The accurate prediction of cancer grade is paramount for timely interventions. This paper introduces an approach to prostate cancer grading, framing it as a classification problem. Leveraging ResNet models on multi-scale patch-level digital pathology and the Diagset dataset, the proposed method demonstrates notable success, achieving an accuracy of 0.999 in identifying clinically significant prostate cancer. The study contributes to the evolving landscape of cancer diagnostics, offering a promising avenue for improved grading accuracy and, consequently, more effective treatment planning. By integrating innovative deep learning techniques with comprehensive datasets, our approach represents a step forward in the pursuit of personalized and targeted cancer care.

Ensemble Deep Learning-Based Image Classification for Breast Cancer Subtype and Invasiveness Diagnosis from Whole Slide Image Histopathology.

Cancer diagnosis and classification are pivotal for effective patient management and treatment planning. In this study, a comprehensive approach is presented utilizing ensemble deep learning techniques to analyze breast cancer histopathology images. Our datasets were based on two widely employed datasets from different centers for two different tasks: BACH and BreakHis. Within the BACH dataset, a proposed ensemble strategy was employed, incorporating VGG16 and ResNet50 architectures to achieve precise classification of breast cancer histopathology images. Introducing a novel image patching technique to preprocess a high-resolution image facilitated a focused analysis of localized regions of interest. The annotated BACH dataset encompassed 400 WSIs across four distinct classes: Normal, Benign, In Situ Carcinoma, and Invasive Carcinoma. In addition, the proposed ensemble was used on the BreakHis dataset, utilizing VGG16, ResNet34, and ResNet50 models to classify microscopic images into eight distinct categories (four benign and four malignant). For both datasets, a five-fold cross-validation approach was employed for rigorous training and testing. Preliminary experimental results indicated a patch classification accuracy of 95.31% (for the BACH dataset) and WSI image classification accuracy of 98.43% (BreakHis). This research significantly contributes to ongoing endeavors in harnessing artificial intelligence to advance breast cancer diagnosis, potentially fostering improved patient outcomes and alleviating healthcare burdens.

An update on existing therapeutic options and status of novel anti-metastatic agents in breast cancer: Elucidating the molecular mechanisms underlying the pleiotropic action of Withania somnifera (Indian ginseng) in breast cancer attenuation.

Major significant advancements in pharmacology and drug technology have been made to heighten the impact of cancer therapies, improving the life expectancy of subjects diagnosed with malignancy. Statistically, 99% of breast cancers occur in women while 0.5-1% occur in men, the female gender being the strongest breast cancer risk factor. Despite several breakthroughs, breast cancer continues to have a worldwide impact and is one of the leading causes of mortality. Additionally, resistance to therapy is a crucial factor enabling cancer cell persistence and resurgence. As a result, the search and discovery of novel modulatory agents and effective therapies capable of controlling tumor progression and cancer cell proliferation is critical. Withania somnifera (L.) Dunal (WS), commonly known as Indian ginseng, has long been used traditionally for the treatment of several ailments in the Indian context. Recently, WS and its phytoconstituents have shown promising anti-breast cancer properties and, as such, can be employed as prophylactic as well as therapeutic adjuncts to the main line of breast cancer treatment. The present review is an attempt to explore and provide experimental evidences in support of the prophylactic and therapeutic potential of WS in breast cancer, along with a deeper insight into the multiple molecular mechanisms and novel targets through which it acts against breast and other hormonally-induced cancers viz. ovarian, uterine and cervical. This exploration might prove crucial in providing better understanding of breast cancer progression and metastasis and its use as an adjunct in improving disease prognosis and therapeutic outcome.

Neurosurgery and Social Media: A Bibliometric Analysis of Scientific Production from 2004 to 2023.

BACKGROUND: Neurosurgery is a rapidly advancing surgical specialty. Social media has significantly impacted the landscape of advancements in the field of neurosurgery. Research on the subject of neurosurgery and social media plays a vital role in combating disability and mortality due to neurological diseases, especially in trauma-affected individuals by increasing cooperation and sharing of clinical experiences between neurosurgeons via social media. This study aimed to evaluate the global neurosurgery and social media research performance from 2004 to 2023. METHODS: All the data for neurosurgery and social media-related research publications from 2004 to 2023 were extracted from the Web of Science database and a comprehensive analysis was performed on the R-bibliometrix package. RESULTS: An increasing number of publications with an annual growth rate of 22.04% was observed, with >91% of total articles published in the last decade. The United States, the United Kingdom, Italy, France, Canada, and India made up of more than 67% of the global contribution. Out of 1449 authors, Chaurasia B was the most productive with 14 publications and the most globally cited document was JEAN WC, 2020 with 117 citations. The University of Cambridge was the leading institutional affiliation. World Neurosurgery was the most productive with >60 articles. CONCLUSIONS: Exploring neurosurgery on social media enhances global collaboration, utilizing dynamic platforms for real-time knowledge exchange and holds immense potential for the field's global advancement.

Silicon nanoparticles vs trace elements toxicity: Modus operandi and its omics bases.

Phytotoxicity of trace elements (commonly misunderstood as 'heavy metals') includes impairment of functional groups of enzymes, photo-assembly, redox homeostasis, and nutrient status in higher plants. Silicon nanoparticles (SiNPs) can ameliorate trace element toxicity. We discuss SiNPs response against several essential (such as Cu, Ni, Mn, Mo, and Zn) and non-essential (including Cd, Pb, Hg, Al, Cr, Sb, Se, and As) trace elements. SiNPs hinder root uptake and transport of trace elements as the first line of defence. SiNPs charge plant antioxidant defence against trace elements-induced oxidative stress. The enrolment of SiNPs in gene expressions was also noticed on many occasions. These genes are associated with several anatomical and physiological phenomena, such as cell wall composition, photosynthesis, and metal uptake and transport. On this note, we dedicate the later sections of this review to support an enhanced understanding of SiNPs influence on the metabolomic, proteomic, and genomic profile of plants under trace elements toxicity.

Genome-wide analysis of the mulberry (Morus abla L.) GH9 gene family and the functional characterization of MaGH9B6 during the development of the abscission zone.

Plant glycoside hydrolase family 9 genes (GH9s) are widely distributed in plants and involved in a variety of cellular and physiological processes. In the current study, nine GH9 genes were identified in the mulberry and were divided into two subfamilies based on the phylogenetic analysis. Conserved motifs and gene structure analysis suggested that the evolution of the two subfamilies is relatively conserved and the glycoside hydrolase domain almost occupy the entire coding region of the GH9s gene. Only segmental duplication has played a role in the expansion of gene family. Collinearity analysis showed that mulberry GH9s had the closest relationship with poplar GH9s. MaGH9B1, MaGH9B6, MaGH9B5, and MaGH9B3 were detected to have transcript accumulation in the stalk of easy-to drop mature fruit drop, suggesting that these could play a role in mulberry fruit drop. Multiple cis-acting elements related to plant hormones and abiotic stress responses were found in the mulberry GH9 promoter regions and showed different activities under exogenous abscisic acid (ABA) and 2,4- dichlorophenoxyacetic acid (2,4-D) stresses. We found that the lignin content in the fruit stalk decreased with the formation of the abscission zone (AZ), which could indirectly reflect the formation process of the AZ. These results provide a theoretical basis for further research on the role of GH9s in mulberry abscission.

Single-Image-Based 3D Reconstruction of Endoscopic Images.

A wireless capsule endoscope (WCE) is a medical device designed for the examination of the human gastrointestinal (GI) tract. Three-dimensional models based on WCE images can assist in diagnostics by effectively detecting pathology. These 3D models provide gastroenterologists with improved visualization, particularly in areas of specific interest. However, the constraints of WCE, such as lack of controllability, and requiring expensive equipment for operation, which is often unavailable, pose significant challenges when it comes to conducting comprehensive experiments aimed at evaluating the quality of 3D reconstruction from WCE images. In this paper, we employ a single-image-based 3D reconstruction method on an artificial colon captured with an endoscope that behaves like WCE. The shape from shading (SFS) algorithm can reconstruct the 3D shape using a single image. Therefore, it has been employed to reconstruct the 3D shapes of the colon images. The camera of the endoscope has also been subjected to comprehensive geometric and radiometric calibration. Experiments are conducted on well-defined primitive objects to assess the method's robustness and accuracy. This evaluation involves comparing the reconstructed 3D shapes of primitives with ground truth data, quantified through measurements of root-mean-square error and maximum error. Afterward, the same methodology is applied to recover the geometry of the colon. The results demonstrate that our approach is capable of reconstructing the geometry of the colon captured with a camera with an unknown imaging pipeline and significant noise in the images. The same procedure is applied on WCE images for the purpose of 3D reconstruction. Preliminary results are subsequently generated to illustrate the applicability of our method for reconstructing 3D models from WCE images.

Comparing the Efficacy of Topical 4% Benzoyl Peroxide Versus Topical 0.1% Adapalene for Treatment of Acne Vulgaris in Skin of Color Population: A South Asian Perspective.

Introduction Acne vulgaris is one of the most common skin problems encountered in the dermatology department. It is a chronic, inflammatory disease of the pilosebaceous unit, clinically presenting with comedones, papules, pustules, nodules, and cysts. With its particularly high prevalence in the younger population, it has significant adverse sequelae on patient's quality of life. At present, due to an enhanced understanding of the pathogenesis of acne, various therapeutic modalities are available. The current management strategies generally follow a systematic treatment escalation based on disease severity and treatment response. However meticulous choice of appropriate anti-acne medicine for the acne type is the key to the management plan. Starting with mild to moderate types of acne as per the Leeds photometric grading scale, the most useful topical agents include topical retinoids, benzoyl peroxide, and topical antibiotics while systemic therapies such as oral antibiotics or isotretinoin are generally reserved for moderate to severe acne treatment. The skin of color (SOC) population is a relatively neglected group concerning the optimum and safe management strategies in different dermatological conditions and acne is no different, where there remains a need for comparing the available topical modalities for appropriate drug selection in the treatment of mild to moderate acne in SOC population. Objective The objective of this study was to compare the efficacy of topical 4% benzoyl peroxide versus topical 0.1% adapalene in the treatment of acne vulgaris in the SOC population. Methods The participants were divided into two groups, groups A and B. A total of 64 patients of both genders, with acne vulgaris (duration > three months) were included in the study. In group A, 32 patients were administered topical 0.1% adapalene whereas, in group B, 32 patients were given topical 4% benzoyl peroxide. Both medicines were applied at night daily. Patients were called for follow-up after 12 weeks. In both groups, the final efficacy evaluation was done using the Global Acne Grading System (GAGS) score after 12 weeks of treatment period. Results In group A, the age ranged from 15 to 40 years with a mean age of 25.781±3.93 years while the duration of complaint was 5.843±1.27 months. GAGS score was 25.281±2.65 and mean BMI was 23.092±3.51 kg/m2. In group B, the mean age was 25.187± 4.06 years, the duration of complaint was 7.375±2.25 months, the GAGS score was 23.906± 2.60 while the mean BMI was 21.485±3.88 kg/m2. Efficacy in group A was noted in 25 (78.1%) patients as compared to 24 (75%) patients in group B (p =0.768). Conclusion The present study showed that the safety and efficacy of 0.1% adapalene the traditional drug 4% benzoyl peroxide in the SOC population was comparable.

Adaptive responses of nitric oxide (NO) and its intricate dialogue with phytohormones during salinity stress.

Nitric oxide (NO) is a gaseous free radical that acts as a messenger for various plant phenomena corresponding to photomorphogenesis, fertilisation, flowering, germination, growth, and productivity. Recent developments have suggested the critical role of NO in inducing adaptive responses in plants during salinity. NO minimises salinity-induced photosynthetic damage and improves plant-water relation, nutrient uptake, stomatal conductance, electron transport, and ROS and antioxidant metabolism. NO contributes active participation in ABA-mediated stomatal regulation. Similar crosstalk of NO with other phytohormones such as auxins (IAAs), gibberellins (GAs), cytokinins (CKs), ethylene (ET), salicylic acid (SA), strigolactones (SLs), and brassinosteroids (BRs) were also observed. Additionally, we discuss NO interaction with other gaseous signalling molecules such as reactive oxygen species (ROS) and reactive sulphur species (RSS). Conclusively, the present review traces critical events in NO-induced morpho-physiological adjustments under salt stress and discusses how such modulations upgrade plant resilience.

The significance of chemical reaction, thermal buoyancy, and external heat source to optimization of heat transfer across the dynamics of Maxwell nanofluid via stretched surface.

Energy loss during the transportation of energy is the main concern of researchers and industrialists. The primary cause of heat exchange gadget inefficiency during transportation was applied to traditional fluids with weak heat transfer characteristics. Instead, thermal devices worked much better when the fluids were changed to nanofluids that had good thermal transfer properties. A diverse range of nanoparticles were implemented on account of their elevated thermal conductivity. This research addresses the significance of MHD Maxwell nanofluid for heat transfer flow. The flow model comprised continuity, momentum, energy transport, and concentration equations in the form of PDEs. The developed model was converted into ODEs by using workable similarities. Numerical simulations in the MATLAB environment were employed to find the outcomes of velocity, thermal transportation, and concentration profiles. The effects of many parameters, such as Hartman, Deborah, buoyancy, the intensity of an external heat source, chemical reactions, and many others, were also evaluated. The presence of nanoparticles enhances temperature conduction. Also, the findings are compared with previously published research. In addition, the Nusselt number and skin friction increase as the variables associated with the Hartman number and buoyancy parameter grow. The respective transfer rates of heat are 28.26 % and 38.19 % respectively. As a result, the rate of heat transmission increased by 14.23 % . The velocity profiles enhanced while temperature profiles declined for higher values of the Maxwell fluid parameter. As the external heat source increases, the temperature profile rises. Conversely, buoyancy parameters increase as it descends. This type of problem is applicable in many fields such as heat exchangers, cooling of electronic devices, and automotive cooling systems.

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy.

BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy. METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied. RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction. CONCLUSION: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.

Phytochemical profiling, antioxidant, cytotoxic, and anti-inflammatory activities of Plectranthus rugosus extract and fractions: in vitro, in vivo, and in silico approaches.

BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.

Comparative study of some non-Newtonian nanofluid models across stretching sheet: a case of linear radiation and activation energy effects.

The use of renewable energy sources is leading the charge to solve the world's energy problems, and non-Newtonian nanofluid dynamics play a significant role in applications such as expanding solar sheets, which are examined in this paper, along with the impacts of activation energy and solar radiation. We solve physical flow issues using partial differential equations and models like Casson, Williamson, and Prandtl. To get numerical solutions, we first apply a transformation to make these equations ordinary differential equations, and then we use the MATLAB-integrated bvp4c methodology. Through the examination of dimensionless velocity, concentration, and temperature functions under varied parameters, our work explores the physical properties of nanofluids. In addition to numerical and tabular studies of the skin friction coefficient, Sherwood number, and local Nusselt number, important components of the flow field are graphically shown and analyzed. Consistent with previous research, this work adds important new information to the continuing conversation in this area. Through the examination of dimensionless velocity, concentration, and temperature functions under varied parameters, our work explores the physical properties of nanofluids. Comparing the Casson nanofluid to the Williamson and Prandtl nanofluids, it is found that the former has a lower velocity. Compared to Casson and Williamson nanofluid, Prandtl nanofluid advanced in heat flux more quickly. The transfer of heat rates are 25.87 % , 33.61 % and 40.52 % at R d = 0.5 , R d = 1.0 , and R d = 1.5 , respectively. The heat transfer rate is increased by 6.91 % as the value of Rd rises from 1.0 to 1.5. This study is further strengthened by a comparative analysis with previous research, which is complemented by an extensive table of comparisons for a full evaluation.