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This study focused on the perception of the students on entrepreneurship education. Entrepreneurship education is considered an effective tool for influencing students’ learning orientation and expression. This study examined the effects of entrepreneurship education and learning on the entrepreneurial implementation intentions of students at the Universities. This study employed an explanatory method. For the study, 600 questionnaires were collected from north Indian university students. Multiple regression was used for the analysis of the study. The results showed that teaching methods significantly impact entrepreneurship stimulate students’ interest and enhance students’ knowledge innovation for business start-ups. The findings of the analysis also revealed that practical activities are mainly based on vocational skill activities, the teaching methods should contain extensive attention to critical thinking and idea generation activities as graded mechanisms of the degree program. It was also recommended that engagement of students with entrepreneurial development initiatives provided by institutions should involve students across all degree levels. Therefore, to increase the prospect of assignation in entrepreneurial activities after graduation students should generate viable business ideas, identify market gaps, engage in business startups, and practical business plans, and engage in invention and innovations.

This article introduces a novel mathematical approach for modeling and analyzing Listeria infection dynamics by considering a system of fractional-order differential equations to understand the complexities. The homotopy perturbation general transform method (HPGTM) is applied to derive approximate solutions for the fractional-order Listeria infection model to obtain valuable insights. The obtained numerical and graphical solutions are rigorously analyzed to explore the effect of fractional orders on the dynamics of Listeria infections. Furthermore, we explore the existence, uniqueness, and stability properties of the solutions, unveiling the critical parameters influencing infection spread and persistence.

The present article showcases a novel approach for obtaining the approximate solution of the nonlinear Burgers' equation, a frequently occurring equation in the study of wave propagation and dispersion phenomena. The Double Power Series Method, a methodology not conventionally applied to this equation, introduces a unique analytical perspective. The method's versatility in handling two independent variables makes it particularly well-suited for addressing the complexities of the Burgers' equation, providing a comprehensive representation of fluid concentration for arbitrary distances and times. Through this novel approach, we study the intricate dynamics governing the relationship between convection and diffusion forces in longitudinal dispersion. This research not only enriches the theoretical foundation of nonlinear partial differential equations but also holds promise for practical applications across fluid dynamics, environmental engineering, and beyond. Both numerical and graphical solutions are meticulously computed through MATLAB coding, facilitating a robust physical interpretation of the results. This study contributes valuable insights into the behavior of fluids in dispersion scenarios, offering a practical approach to understanding and predicting such phenomena.

In this paper, we describe the new Adomian Decomposition General Transform Method (ADGTM). Further, the efficacy of the method is proved by applying it to well-known equations, such as the logistic equation, Emden–Lane–Fowler equation, Gardner equation, and Cahn–Hilliard equation, in fractional order to study the intrinsic behavior. We compare the results with other well-known methods like RPSM, and q-HATM to prove the reliability and accuracy of the proposed method. For the selected applications, we frame 2D and 3D graphs to explain how the fractional-order derivative affects the behavior of the obtained solutions.

This study investigates Diabetes Mellitus, focusing on global variations and complications for human health. We employ the ABC fractional derivative to develop a fractional-ordered diabetes model that incorporates complications for deeper understanding. This study is crucial for identifying patterns and trends by examining Diabetes Mellitus region-wise, aiding in targeted interventions and healthcare strategies, and using the ABC fractional derivative for a more accurate representation of the complexities associated with the disease, leading to more effective modeling and analysis. Our research yields important results that distinguish it from previous studies. Specifically, we investigate the stability and existence conditions of the proposed fractional-ordered diabetes model. Additionally, we employ the Adomian decomposition Laplace transform method to obtain solutions, enabling us to analyze the dynamics of the system comprehensively. Through graphical interpretations, we compare the recovery rates of diabetes in susceptible patients, both with and without complications. Regional analysis reveals varying prevalences and characteristics of Diabetes Mellitus, requiring tailored healthcare approaches. By incorporating complications into the fractional-ordered model, we enhance our understanding of the disease’s progression and its impact on recovery rates. These insights contribute to the broader field of diabetes research and offer valuable implications for clinical practice and public health policy.

Abstract Background Medication nonadherence can result in poor clinical outcomes and significant costs to health care providers. When treating venous thromboembolism (VTE), subtherapeutic anticoagulation may contribute to complications such as recurrent VTE or postthrombotic syndrome. Objectives To describe the extent, reasons for, and predictors of nonadherence to rivaroxaban for the treatment of VTE in clinical practice in the United Kingdom reported by participants of the FIRST registry. Patients/Methods The FIRST registry was an observational, multicenter registry reporting on the use of rivaroxaban in routine clinical practice. FIRST registry participants completed an adherence screening questionnaire during their treatment and follow‐up. Results In total, 1028 participants completed 1660 questionnaires over 2 years. One hundred thirteen of 1028 (11%) reported nonadherence at 28 days (interquartile range, 21‐45). Reasons given for nonadherence at 1 month were forgetfulness (8.6% vs 74.7%; P

Abstract Background Rivaroxaban was reported as effective as traditional therapies for the acute treatment of venous thromboembolism (VTE) with fewer major bleeding complications in the seminal Einstein program and is now a recommended option for the treatment of VTE around the world. Objective To report the safety and efficacy of rivaroxaban in daily care for the management of acute VTE in the United Kingdom. Patients/Method The FIRST registry is a UK‐only, multicenter, noninterventional, observational VTE study (NCT 02248610). Consecutive patients diagnosed with acute VTE, managed with rivaroxaban, were recruited and followed for up to 5 years. The primary outcomes were treatment‐emergent symptomatic objectively diagnosed recurrent VTE, major and clinically relevant nonmajor bleeding (CRNMB), and all‐cause mortality. Results A total of 1262 participants were recruited between 2014 and 2018. Participants were heterogeneous, with age range 18 to 95 years, weight 35 to 234 kg, and maximum body mass index 64.4 kg/m2. The median duration of treatment exposure was 135 days (interquartile range [IQR], 84‐307) and overall follow‐up 497 days (IQR, 175‐991). There were seven episodes of symptomatic VTE recurrence, 0.6%, (0.74/100 patient‐years; 95% confidence interval [CI], 0.19‐1.28). There were 79 of 1239 (6.4%), 8.66 of 100 patient‐years (95% CI, 6.90‐10.73) first episodes of major or CRNMB, which were most frequently reported by women aged

Epoxy resin of 9,9′-bis-(3,5-dibromo-4-hydroxyphenyl) anthrone-10 (EANBr, EEW 490) was synthesized and was characterized by IR and 1HNMR . EANBr and EPK3251 cured resin (EANBrC) were characterized by DSC and TGA at 10°Cmin−1 under nitrogen atmosphere. Broad DSC endothermic transitions of EANBr (265.3 °C) and EANBrC (291.4 °C) are due to some physical change and further confirmed by no weight loss in their TG thermograms. EANBr and EANBrC are thermally stable up to 340 °C and 310 °C, respectively. EANBr has followed single step degradation kinetics, while EANBrC has followed two step degradation kinetics. EANBr followed apparently zero order kinetics, while EANBrC followed apparently second order (1.80) and first order (0.89) degradation kinetics, respectively. Ea and A values of EANBrC (299.7 kJmol−1 and 6.32 × 1020 s−1) were found higher than that of EANBr (201 kJmol−1 and 2.45 × 1013 s−1) due to more rigid nature of EANBrC. The ΔS* value of the first step degradation of EANBrC (146.3 JK−1 mol−1) was found much more than that of EANBr (4.6 JK−1 mol−1). Jute – EANBr composite (J-EANBr) was prepared by compression molding technique at 120 °C for 5 h and under 20 Bar pressure. The observed tensile strength, flexural strength, electric strength and volume resistivity of J-EANBr are 24.7 MPa, 19.0 MPa, 1.8 kVmm−1 and 3.5 × 1012 ohm cm, respectively. Water absorption in J-EANBr was carried out at 30 ± 2 °C against distilled water, 10% NaCl, 10% HCl, 10% HNO3, 10% H2SO4, 10% NaOH, and 10% KOH and also in boiling water. The equilibrium time and equilibrium water content for J-EANBr in different environments are 384–432 h; 12.7–15.2%, respectively. The observed equilibrium water content and diffusivity trends of J-EANBr are KOH>H2SO4>HCl>NaOH>H2O>NaCl and H2O>NaCl>NaOH>H2SO4>HCl>KOH, respectively. Good thermo-mechanical, electrical properties and excellent hydrolytic stability of J-EANBr may be useful for high temperature applications in diverse fields.

Introduction Venous thromboembolism (VTE) is a significant cause of maternal mortality with the greatest risk postpartum. Mode of delivery influences VTE risk, with emergency caesarean section (CS) associated with the highest risk (CS). Thromboprophylaxis is recommended for selected women to reduce the risk of VTE. We aimed to investigate the impact of mode of delivery and thromboprophylaxis on hypercoagulability as measured by thromboelastometry (TEM) and thrombin generation (TG) in women at high VTE risk. Materials and Methods Blood was collected from 99 pregnant women with VTE risk factors at up to five time points from pre- (T1) and post (T2)-delivery to 6 weeks postpartum (T5). Multiple linear regression was utilised to compare TG and TEM between those with vaginal delivery (VD) and CS at each time point. Paired sample t-test with post hoc Bonferroni correction was utilised to compare laboratory markers over time. Results Women in both groups had a median of three postpartum VTE risk factors, with higher body mass index and parity post-VD. In both the groups, TG and TEM parameters suggested hypercoagulability at T2 compared with T1, with resolution at T5. There were minimal differences between groups, apart from T2 with shorter clot formation time and higher maximum clot firmness in the VD group. Conclusion TG and TEM illustrate hypercoagulability associated with pregnancy and delivery. The pattern of postpartum hypercoagulability seen in women with VTE risk factors was similar irrespective of mode of delivery. Further research is required to establish the effect of labour on TG/TEM in the absence of low molecular weight heparin use.

Heterocyclic compounds containing pyrazolines were reported to possess significant biological activity. Synthesis of 2-(ω-chloroacetonyl)-3-p-fluorophenyl-6-bromoquinazoline-4(3H)-ones (2), 2-(ω-hydrazinoacetonyl)-3-p-fluorophenyl-6-bromoquinazoline-4(3H)-ones (3) and 1′-[3H-3-p-fluorophenyl-4-oxo-6-bromoquinazoline-2-acetonyl]-3′-[1-o-chlorophenyl-3-methyl-5-azomethine-2-pyrazolidene]-5′-(substituted phenyl)-Δ2-pyrazolines (4a–j) have been described. Some of the new compounds were tested against bacteria (Gram –ve and Gram +ve) and fungi.

In the present investigation, a series of 2(4-pyridyl)-5[(aryl/heteroarylamino)-1-oxoethyl]thio-1,3,4-oxadiazole were synthesized using isonicotinohydrazide and substituted aryl/heteroaryl amines using pyridine as solvent. Newly synthesized compounds were tested for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Among the synthesized compounds, compounds 2(4-pyridyl)-5((2-nitrophenylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5e), 2(4-pyridyl)-5((4-nitrophenylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5g) and 2(4-pyridyl)-5((2-pyrrolylamino)-1-oxoethyl)thio-1,3,4-oxadiazole (5k) produced highest efficacy and exhibited >90% inhibition at a concentration of 0.0077, 0.0052 and 0.0089 μM, respectively. All the new compounds were pharmacologically evaluated for their in vitro Antimicrobial activity.

The aim of this study was to develop and optimize a nanoparticulate carrier based on polymeric blends of cellulose acetate butyrate (CAB) and poly(vinyl pyrrolidone) (PVP) to enhance dissolution profile of an antiviral drug. These nanoparticles are studied by means of X-ray powder diffraction, FTIR and DSC while the morphology evaluated using SEM analysis. Drug-loaded nanoparticles were produced in spherical shape with sizes and encapsulation efficiency ranging from 322 to 434 nm and 50% to 70% respectively. The effects of different CAB/PVP ratios, concentration of drug and emulsifier on the nanoparticle size, drug encapsulation and in vitro release were studied in detail. In vitro release along with mechanism and kinetics were studied in different pHs indicating that the release of drug from nanoparticles was pH-responsive. All the nanoparticles displayed a slowed release pattern with the reduced burst release. The mechanism and kinetics of the drug delivery system was also systematically studied using various models such as zero order, first order, Higuchi model and Korsmeyer–Peppas. The results indicate that the new CAB/PVP nanoparticles have a promising potential to serve as an antiviral controlled delivery system.

Abstract Background Cervical cancer remains a significant public health concern, especially for low-and middle-income countries. This study explores the dual potential of medicinal plant extracts as both anticancer agents and immunomodulators, particularly in HPV-positive cervical cancer, while also addressing the limitations of conventional chemotherapy. Methods Extracts from Tinospora cordifolia, Boerhaavia diffusa, Berberis aristata, and Ocimum basilicum were tested on CaSki and HEK 293 cells alongside cisplatin. Cytotoxicity, genotoxicity, cell migration, HPV DNA inhibition, IFNG secretion, and cell cycle modulation were assessed using established biochemical and immunological assays, including qPCR, ELISA, and flow cytometry. Results Among the extracts, B. aristata demonstrated the strongest anticancer effects on cancer cells while exhibiting minimal impact on normal cells, highlighting its therapeutic potential. It also significantly reduced cell migration and has synergistic affect with cisplatin. B. diffusa emerged as the most effective in inhibiting HPV 16 DNA, suggesting its role in viral suppression. Immunomodulatory analysis revealed that T. cordifolia and O. basilicum significantly enhanced IFNG secretion, indicative of robust immune activation. Each tested extracts induced G0/G1 phase cell cycle arrest, with T. cordifolia showing the most pronounced effect. Conclusions This study highlights the novel therapeutic promise of integrating plant extracts into HPV-positive cervical cancer management. B. aristata stands out for its cytotoxicity and anti-migration properties, while T. cordifolia offers significant immunomodulatory benefits. These findings pave the way for further research into combining natural products with conventional therapies for safer, more effective cancer treatments.

Abstract Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials. We then used this virtual population to predict the results of clinical trials on the basis of disease severity, dosing regimen, time since diagnosis, and co-administered background therapies. The virtual population captured the effect of changes in trial design and patient subpopulation on clinical response. We also demonstrated the virtual trial workflow’s potential for enriching populations based on clinical biomarkers to increase likelihood of trial success.

Abstract Background Equitable access to healthcare for rural, tribal, and underprivileged people has been an emerging area of interest for researchers, academicians, and policymakers worldwide. Improving equitable access to healthcare requires innovative interventions. This calls for clarifying which operational model of a service innovation needs to be strengthened to achieve transformative change and bring sustainability to public health interventions. The current study aimed to identify the components of an operational model of mobile medical units (MMUs) as an innovative intervention to provide equitable access to healthcare. Methods The study empirically examined the impact of scalability, affordability, replicability (SAR), and immunization performance on the sustainability of MMUs to develop a framework for primary healthcare in the future. Data were collected via a survey answered by 207 healthcare professionals from six states in India. Partial least squares structural equation modeling (PLS-SEM) was conducted to empirically determine the interrelationships among various constructs. Results The standardized path coefficients revealed that three factors (SAR) significantly influenced immunization performance as independent variables. Comparing the three hypothesized relationships demonstrates that replicability has the most substantial impact, followed by scalability and affordability. Immunization performance was found to have a significant direct effect on sustainability. For evaluating sustainability, MMUs constitute an essential component and an enabler of a sustainable healthcare system and universal health coverage. Conclusion This study equips policymakers and public health professionals with the critical components of the MMU operational model leading toward sustainability. The research framework provides reliable grounds for examining the impact of scalability, affordability, and replicability on immunization coverage as the primary public healthcare outcome.

Glioblastoma (GBM) is one of the most malignant forms of cancer with the lowest survival ratio. Our study aims to utilize an integrated bioinformatic analysis to identify hub genes against GBM and explore the active phytochemicals with drug-like properties in treating GBM. The study employed databases of DisGenet, GeneCards, and Gene Expression Omnibus to retrieve GBM-associated genes, revealing 142 overlapping genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the role of these genes, which were involved in cancer-associated cell signaling pathways with tyrosine kinase activities and mainly enriched in the Nucleus. Furthermore, the hub genes identification through Cytoscape identified the top 10 ranked genes in a network, which were used as targets to dock against phytochemicals retrieved from the NPACT database having the ability to pass the blood-brain barrier and drug-likeness properties. The molecular docking and dynamics simulation studies predicted the binding of Isochaihulactone and VismioneB to the active site residues of EGFR and SRC genes. In contrast, Resveratrol binds to key residues of PIK3CA. Further, the binding free energy of the docked complex was calculated by performing MM-GBSA analysis, providing a detailed understanding of the underlying molecular interactions. The results offer interactional and structural insights into candidate phytochemicals towards GBM-associated top-ranked proteins. However, validation studies must be done through both in vitro and in vivo disease models to strengthen our computational results.

BackgroundNeonatal Opioid Withdrawal Syndrome (NOWS) is a consequence of in-utero exposure to prenatal maternal opioids, resulting in the manifestation of symptoms like irritability, feeding problems, tremors, and withdrawal signs. Opioid use disorder (OUD) during pregnancy can profoundly impact both mother and fetus, disrupting fetal brain neurotransmission and potentially leading to long-term neurological, behavioral, and vision issues, and increased infant mortality. Drug resistance complicates OUD and NOWS treatment, with protein kinase regulation of drug transporters not fully understood.MethodsDNA methylation levels of ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, along with protein kinase C (PKC) genes, were assessed in 96 placental samples using the Illumina Infinium MethylationEPIC array (850K). Samples were collected from three distinct groups: 32 mothers with infants prenatally exposed to opioids who needed pharmacological intervention for NOWS, 32 mothers with prenatally opioid-exposed infants who did not necessitate NOWS treatment, and 32 mothers who were not exposed to opioids during pregnancy.ResultsWe identified 69 significantly differentially methylated SLCs, with 24 hypermethylated and 34 hypomethylated, and 11 exhibiting both types of methylation changes including SLC13A3, SLC15A2, SLC16A11, SLC16A3, SLC19A2, and SLC26A1. We identified methylation changes in 11 ABC drug transporters (ABCA1, ABCA12, ABCA2, ABCB10, ABCB5, ABCC12, ABCC2, ABCC9, ABCE1, ABCC7, ABCB3): 3 showed hypermethylation, 3 hypomethylation, and 5 exhibited both. Additionally, 7 PKC family genes (PRKCQ, PRKAA1, PRKCA, PRKCB, PRKCH, PRKCI, and PRKCZ) showed methylation changes. These genes are associated with 13 pathways involved in NOWS, including ABC transporters, bile secretion, pancreatic secretion, insulin resistance, glutamatergic synapse, and gastric acid secretion.ConclusionWe report epigenetic changes in PKC-related regulation of drug transporters, which could improve our understanding of clinical outcomes like drug resistance, pharmacokinetics, drug-drug interactions, and drug toxicity, leading to maternal relapse and severe NOWS. Novel drugs targeting PKC pathways and transporters may improve treatment outcomes for OUD in pregnancy and NOWS.

Abstract Glycogen synthase kinase-3β (GSK3β) is a pivotal protein kinase implicated in a spectrum of debilitating diseases, encompassing cancer, diabetes, and neurodegenerative disorders. While the therapeutic potential of GSK3β inhibition is widely recognized, there remains an unmet need for a rigorous, systematic analysis probing the theoretical inhibition dynamics of a comprehensive library of indirubin derivatives against GSK3β using advanced computational methodologies. Addressing this gap, this study embarked on an ambitious endeavor, leveraging indirubin—a renowned scaffold—as a template to curate a vast library of 1000 indirubin derivatives from PubChem. These were enriched with varied substitutions and modifications, identified via a structure similarity search with a Tanimoto similarity threshold of 85%. Harnessing a robust virtual screening workflow, we meticulously identified the top 10 contenders based on XP docking scores. Delving deeper, we gauged the binding free energy differentials (ΔGBind) of these hits, spotlighting the top three compounds that showcased unparalleled binding prowess. A comparative pharmacophore feature mapping with the reference inhibitor OH8, co-crystallized with GSK3β (PDB ID: 6Y9R), was undertaken. The binding dynamics of these elite compounds were further corroborated with 100 ns molecular dynamics simulations, underlining their stable and potent interactions with GSK3β. Remarkably, our findings unveil that these indirubin derivatives not only match but, in certain scenarios, surpass the binding affinity and specificity of OH8. By bridging this research chasm, our study amplifies the therapeutic promise of indirubin derivatives, positioning them as frontrunners in the quest for groundbreaking GSK3β inhibitors, potentially revolutionizing treatments for a myriad of ailments.

Background: Improving equitable access to healthcare requires innovative interventions and strengthening a service innovation operational model to achieve transformative change and bring sustainability to public health interventions. The current study aims to identify the components of the Mobile Medical Units (MMUs) operational model as an innovative intervention to provide equitable and inclusive access to healthcare. Methods: The study used qualitative research to identify the components of the operational model of MMUs for primary healthcare in future. Data has been collected via semi-structured in-depth interviews with 103 healthcare professionals from six states representing India's Tier I, Tier II, and Tier III regions. A thematic analysis was performed to examine emergent salient themes. Results: The study identified and examined scalability, affordability, replicability, and sustainability as the four critical components of the operational model of MMUs. The findings of the study indicated that MMUs with these four components played a vital role in COVID-19 immunization, especially in resource-limited settings. The study found that MMUs are a cost-effective and scalable healthcare delivery model that can be easily replicated in primary healthcare service delivery. Conclusion: The findings underscore the significant role of MMUs in addressing healthcare disparities, particularly in resource-limited settings. The adaptability and cost-effectiveness of MMUs make them an ideal solution for primary healthcare delivery, especially in Tier I, II, and III regions of India. It lays a foundation for future research and policy-making, emphasizing the need for innovative, equitable, and sustainable healthcare delivery models like MMUs to transform and strengthen healthcare systems globally.

Abstract Ribavirin is an inosine monophosphate dehydrogenase inhibitor. Studies suggest ribavirin aerosol could be a safe and efficacious treatment option in the fight against coronaviruses. However, current treatment is long (12–18 h per day, 3–7 days), limiting clinical utility. A reduction in treatment time would reduce treatment burden. We aimed to evaluate safety and pharmacokinetics (PK) of four, single‐dose regimens of ribavirin aerosol in healthy volunteers. Thirty‐two subjects were randomized, to four cohorts of aerosolized ribavirin (active) or placebo. Cohort 1 received 50 mg/ml ribavirin/placebo (10 ml total volume); cohort 2, 50 mg/ml ribavirin/placebo (20 ml total volume); cohort 3, 100 mg/ml ribavirin/placebo (10 ml total volume); and cohort 4, 100 mg/ml ribavirin/placebo (20 ml total volume). Intense safety monitoring and PK sampling took place on days 1, 2, 3, and 40. Subjects were (mean ± SD, active vs. placebo) aged 57 ± 4.5 vs. 60 ± 2.5 years; 83% vs. 88% were female; and 75% vs. 50% were Caucasian. Some 12.5% (3/24) and 25% (2/8) experienced at least one treatment‐emergent adverse event (TEAE) (two moderate; five mild) in the active and placebo groups, respectively. No clinically significant safety concerns were reported. Mean maximum observed concentration (Cmax) and area under the curve (AUC) values were higher in cohort 4, whereas cohorts 2 and 3 showed similar PK values. Ribavirin absorption reached Cmax within 2 h across cohorts. Four single‐dose regimens of ribavirin aerosol demonstrated systemic exposure with minimal systemic effects. Results support continued clinical development of ribavirin aerosol as a treatment option in patients with coronaviruses.

Abstract Heart transplantation remains the definitive treatment for end stage heart failure. Because availability is limited, risk stratification of candidates is crucial for optimizing both organ allocations and transplant outcomes. Here we utilize proteomics prior to transplant to identify new biomarkers that predict post-transplant survival in a multi-institutional cohort. Microvesicles were isolated from serum samples and underwent proteomic analysis using mass spectrometry. Monte Carlo cross-validation (MCCV) was used to predict survival after transplant incorporating select recipient pre-transplant clinical characteristics and serum microvesicle proteomic data. We identified six protein markers with prediction performance above AUROC of 0.6, including Prothrombin (F2), anti-plasmin (SERPINF2), Factor IX, carboxypeptidase 2 (CPB2), HGF activator (HGFAC) and low molecular weight kininogen (LK). No clinical characteristics demonstrated an AUROC > 0.6. Putative biological functions and pathways were assessed using gene set enrichment analysis (GSEA). Differential expression analysis identified enriched pathways prior to transplant that were associated with post-transplant survival including activation of platelets and the coagulation pathway prior to transplant. Specifically, upregulation of coagulation cascade components of the kallikrein-kinin system (KKS) and downregulation of kininogen prior to transplant were associated with survival after transplant. Further prospective studies are warranted to determine if alterations in the KKS contributes to overall post-transplant survival.

Introduction: Cardiac resynchronization therapy (CRT) has revolutionized the treatment of cardiac dyssynchrony in chronic heart failure (HF), yet, complications and failures are reported in some patients. We aim to determine the predictors of response to CRT through clinical, electrocardiographic ECG, and echocardiographic assessment of patients following CRT and recommend the best practices to achieve optimum results for patients. Methodology: We analyzed the history, clinical examination, brain natriuretic peptide (BNP) levels, ECG, and echocardiography findings of 35 patients before CRT and on day 7 and day 180 following CRT. Observations: 71.4% of patients responded to CRT and 28.6% were nonresponders. The responders had fewer hospitalizations for HF. They showed a significant improvement in the New York Heart Association (NYHA) class, mean 6 min walk distance (6MWD), BNP level, QRS duration, and echocardiographic parameters on day 7 and day 180. The duration of HF ≤3 years, NYHA class III–IV symptoms, baseline 6MWD ≥240 m, QRS duration ≥150 ms, LVEF ≥25%, septal to posterior wall motion delay ≥130 ms, and mean pulmonary arterial pressure

Leaf - a significant part of the plant, produces food using the process called photosynthesis. Leaf disease can cause damage to the entire plant and eventually lowers crop production. Machine learning algorithm for classifying five types of diseases, such as Alternaria leaf diseases, Bacterial Blight, Gray Mildew, Leaf Curl and Myrothecium leaf diseases, is proposed in the proposed study. The classification of diseases needs front face of leafs. This paper proposes an automated image acquisition process using a USB camera interfaced with Raspberry PI SoC. The image is transmitted to host PC for classification of diseases using online web server. Pre-processing of the acquired image by host PC to obtain full leaf, and later classification model based on SVM is used to detect type diseases. Results were checked with a 97% accuracy for the collection of acquired images.

Abstract Background The direct factor Xa inhibitor rivaroxaban is approved for the treatment of venous thromboembolism (VTE), based on the results of large phase III trials. Objectives To confirm rivaroxaban's effectiveness and safety in routine clinical care of patients with VTE. Methods Data were obtained from prospective, noninterventional registries: the FIRST registry (United Kingdom), DRESDEN NOAC registry (Germany), and SWIVTER (Switzerland). Baseline characteristics of these registries and effectiveness and safety outcome rates for the FIRST and DRESDEN NOAC registries were compared. Results A total of 1841 rivaroxaban‐treated patients with acute VTE (57.9% male, 76.6% deep vein thrombosis [DVT]; 23.4% pulmonary embolism ± DVT; median age, 61 years) were included: 1217 from the FIRST registry, 418 from the DRESDEN NOAC registry, and 206 from SWIVTER. Median time between VTE diagnosis and initiation of rivaroxaban was 1.4 ± 1.81 days (25th–75th percentile 1–1; range, 0–15 days). On‐treatment outcome rates for the FIRST and DRESDEN NOAC registries were 0.74 per 100 patient‐years (95% confidence interval [CI], 0.35–1.54) versus 0.96 per 100 patient‐years (95% CI, 0.46–2.01) for VTE recurrence; 1.16 per 100 patient years (95% CI, 0.64–2.09) versus 2.51 per 100 patient‐years (95% CI, 1.58–3.98) for ISTH major bleeding and 1.69 per 100 patient‐years (95% CI, 1.21–2.35) versus 1.73 per 100 patient‐years (95% CI, 1.27–2.36) for all‐cause mortality (intention‐to‐treat analysis), respectively. Conclusion Overall treatment outcomes were consistent with the results of the phase III rivaroxaban trials in VTE treatment, indicating that the use of rivaroxaban offers acceptable treatment results also in routine care. However, we observed significant differences in patient characteristics and management patterns across Switzerland, the United Kingdom, and Germany, limiting direct comparisons of unadjusted outcome event rates between registries.

Journalists and ethnographic researchers, such as anthropologists, sociologists or media scholars, have comparable ways of establishing initial contacts with people from their fields of interest. Due to the ongoing COVID-19 pandemic and consequential travel restrictions and social distancing, it has become increasingly difficult to access a field. Taking inspiration from social anthropologist Ulf Hannerz (2004, p. 226), who compared journalists and anthropologists as “neighboring groups engaged in a somehow parallel pursuit,” this article explores what researchers may learn from practitioners who conduct research without being on-site. Fed by various practical journalists’ experiences, the article aims to investigate how information and communication technologies (ICTs) and digitally mediated methods, such as online search tools and social media, can be used to establish contacts and gain trust remotely. Here, the relevance of these methods for accessing a field in general goes beyond the limitations imposed during the COVID-19 pandemic and can be of interest to all those who face difficulties of field access of any kind. Ultimately, this article reflects on corresponding ethical challenges that may arise while conducting research remotely.

BackgroundAllograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports.MethodsWe performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate.ResultsData were available from 19 centers in North America (n = 7), South America (n = 1), and Europe (n = 11), with a total of 110 patients. A median of 3 (IQR 2–8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (n = 62), coronary artery disease (CAD) (n = 16), constrictive pericarditis (n = 17), aortic pathology (n = 13), and myxoma (n = 2). The median age at CASH was 57.7 (47.8–63.1) years, with a median time from transplant to CASH of 4.4 (1–9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8–14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively.ConclusionCardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure.

Background We compared the in-hospital complications, outcomes, cost, and length of stay (LOS) between angiography-guided percutaneous coronary intervention (PCI) and intravascular ultrasound (IVUS)-guided PCI in patients with ST-elevation myocardial infarction (STEMI) in the USA. Methods A nationwide inpatient database was queried to identify patients >18 years with STEMI who underwent angiography-guided and IVUS-guided PCI from January 2016 to December 2016. We compared the in-hospital mortality, complications, cost, and LOS between the two groups. Results We identified 100,485 patients who underwent angiography-guided PCI and 5,460 patients who underwent IVUS-guided PCI. In-hospital mortality was not statistically different (odds ratio [OR] 0.76, 95% CI 0.46 − 1.22, P = 0.24). Patients who underwent PCI with IVUS were more likely to have coronary artery dissection (OR 4.26, 95% CI 2.34 − 7.7, p =

ABSTRACT Ehrlichia chaffeensis evades innate host defenses by reprogramming the mononuclear phagocyte through mechanisms that involve the exploitation of multiple evolutionarily conserved cellular signaling pathways, including Notch. This immune evasion strategy is directed in part by tandem repeat protein (TRP) effectors. Specifically, the TRP120 effector activates and regulates Notch signaling through interactions with the Notch receptor and the negative regulator, F-Box and WD repeat domain-containing 7 (FBW7). However, the specific molecular interactions and motifs required for E. chaffeensis TRP120-Notch receptor interaction and activation have not been defined. To investigate the molecular basis of TRP120 Notch activation, we compared TRP120 with endogenous canonical/noncanonical Notch ligands and identified a short region of sequence homology within the tandem repeat (TR) domain. TRP120 was predicted to share biological function with Notch ligands, and a function-associated sequence in the TR domain was identified. To investigate TRP120-Notch receptor interactions, colocalization between TRP120 and endogenous Notch-1 was observed. Moreover, direct interactions between full-length TRP120, the TRP120 TR domain containing the putative Notch ligand sequence, and the Notch receptor LBR were demonstrated. To molecularly define the TRP120 Notch activation motif, peptide mapping was used to identify an 11-amino acid short linear motif (SLiM) located within the TRP120 TR that activated Notch signaling and downstream gene expression. Peptide mutants of the Notch SLiM or anti-Notch SLiM antibody reduced or eliminated Notch activation and NICD nuclear translocation. This investigation reveals a novel molecularly defined pathogen encoded Notch SLiM mimetic that activates Notch signaling consistent with endogenous ligands. IMPORTANCE E. chaffeensis infects and replicates in mononuclear phagocytes, but how it evades innate immune defenses of this indispensable primary innate immune cell is not well understood. This investigation revealed the molecular details of a ligand mimicry cellular reprogramming strategy that involved a short linear motif (SLiM), which enabled E. chaffeensis to exploit host cell signaling to establish and maintain infection. E. chaffeensis TRP120 is a moonlighting effector that has been associated with cellular activation and other functions, including ubiquitin ligase activity. Herein, we identified and demonstrated that a SLiM present within each tandem repeat of TRP120 activated Notch signaling. Notch is an evolutionarily conserved signaling pathway responsible for many cell functions, including cell fate, development, and innate immunity. This study is significant because it revealed the first molecularly defined pathogen encoded SLiM that appears to have evolved de novo to mimic endogenous Notch ligands. Understanding Notch activation during E. chaffeensis infection provides a model to study pathogen exploitation of signaling pathways and will be useful in developing molecularly targeted countermeasures for inhibiting infection by a multitude of disease-causing pathogens that exploit cell signaling through molecular mimicry.

Pediatric Intensive Care Units (PICUs) provide multidisciplinary care to critically ill children and their families. Grief is present throughout the trajectory of illness and can peak around the time of death or non-death losses. The objective of this study was to assess how PICUs around the world implement grief and bereavement care (GBC) as part of an integrated model of care. This is a multicenter cross-sectional, prospective survey study. Questionnaires with multiple-choice and open-ended questions focusing on unit infrastructure, personnel, policies, limited patient data, and practices related to GBC for families and health care professionals (HCPs) were completed by on-site researchers, who were HCPs on the direct care of patients. PICU fulfillment of GBC goals was evaluated using a custom scoring based on indicators developed by the Initiative for Pediatric Palliative Care (IPPC). We compared average total and individual items fulfillment scores according to the respective country's World Bank income. Patient characteristics and details of unit infrastructure were also evaluated as potential predictors of total GBC fulfillment scores. Statistical analysis included multilevel generalized linear models (GLM) with a Gaussian distribution adjusted by child age/gender and clustering by center, using high income countries (HICs) as the comparative reference. Additionally, we applied principals of content analysis to analyze and summarize open-ended answers to contextualize qualitative data. The study included 34 PICUs from 18 countries: high-income countries (HICs): 32.4%, upper middle-income countries (UMICs): 44.1%, low middle-income and low-income countries (LMI/LICs): 23.5%. All groups reported some compliance with GBC goals; no group reported perfect fulfillment. We found statistically significant differences in GBC fulfillment scores between HICs and UMICs (specifically, HCP grief support), and between HICs and LMICs (specifically, family grief support and HCP grief support). PICUs world-wide provide some GBC, independent of income, but barriers include lack of financial support, time, and training, overall unit culture, presence of a palliative care consultation service, and varying cultural perceptions of child death. Disparities in GBC for families and HCPs exist and were related to the native countries' income level. Identifying barriers to support families and HCPs, can lead to opportunities of improving GBC in PICUs world-wide.

The adequate assessment and management of pain remains a challenging task in the Pediatric Intensive Care Unit (PICU). Our goal is to describe how pain is assessed and managed in PICUs around the world and to examine how human and material resources impact achievement of this goal. An international multicenter cross-sectional observational study was designed with the participation of 34 PICUs located in urban, suburban, and rural areas of 18 countries. We evaluated how PICUs around the world assessed and managed pain according to the Initiative for Pediatric Palliative Care recommendations, and how human and material resources impacted achievement of this goal. Data was collected for this study from 2016 to 2018 using questionnaires completed by medical doctors and nurses. In this paper, we focus on the indicators related to how pain is managed and assessed. The average achievement of the goal of pain relief across all centers was 72.2% (SD: 21.1). We found a statistically significant trend of more effective pain management scores, routine assessment, proper documentation, and involvement of pain management experts by increasing country income. While there are efforts being made worldwide to improve the knowledge in pain assessment and management, there is a lack of resources to do so appropriately in low-middle-income countries. There is a mismatch between the existing guidelines and policies, which are mainly designed in high income countries, and the resources available in lower resourced environments.

Right ventricular infarction can precipitate severe right-to-left shunting and refractory hypoxia from a previously dormant patent foramen ovale. Right ventricle mechanical circulatory support and patent foramen ovale closure can play a crucial role in the treatment of hypoxia and right ventricular recovery. We report a case of successful percutaneous patent foramen ovale closure on right ventricle mechanical circulatory support in a patient with right ventricular shock. (Level of Difficulty: Intermediate.)

Aim: To describe the impact of extracorporeal membrane oxygenation (ECMO) assisted CPR (E-CPR) on cerebral oxygen delivery during in-hospital cardiac arrest (IHCA). Methods: Retrospective case series from a tertiary academic medical center. Regional cerebral oxygen saturation (rSO2) was measured continuously using cerebral oximetry in six patients who experienced IHCA. During CPR, the time of E-CPR initiation was recorded, and rSO2 values were subsequently analyzed for a period beginning 5 min before and ending 2.5 min after the initiation of E-CPR. Results: The average rSO2 value in the 2.5 min period following E-CPR initiation increased by 20.8% as compared to the 5-min period before E-CPR initiation. Conclusions: ECMO can be employed in parallel with cerebral rSO2 monitoring during CPR for adult IHCA patients. E-CPR is associated with rapid and significant increases in brain oxygen delivery.

Cancer is a multifactorial disease with a convoluted genesis and progression. The emergence of multidrug resistance to presently be offered drug and relapse is by far, the most critical concern to tackle this deteriorating disease. Henceforth, there is undeniably an inflated necessity for safe, promising, and less harmful new anticancer drugs. Natural compounds from various sources like plants, animals, and microorganisms have occupied a center stage in drug discovery due to their tremendous chemical diversity and potential as therapeutic agents. Endophytic microbes are symbiotically associated with plants and have been proven to produce novel or analogues of host bioactive metabolites exhibiting a variety of biological activities including anticancer activity. This review emphasizes on structurally diverse unprecedented anticancer natural compounds that have been reported exclusively from endophytic fungi from 2016 to 2020. It covers chemical nature of metabolites, its fungal source associated with terrestrial, as well as marine plants and anticancer activity based on their cytotoxicity profile against various cancer cell lines. Many of these fungal metabolites with promising anticancer activity can be used as lead molecules for in silico experiments and deserve special attention from scientists for further in vitro and clinical research.

Salinicoccus sp. BAB 3246 is a halophilic bacterium isolated from a marine water sample collected from the coastal region of Gujarat, India, from a surface water stream. Based on 16sRNA sequencing, the organism was identified as Salinicoccus sp. BAB 3246 (Genebank ID: KF889285). The present work was performed to determine the whole genome sequence of the organism using Ion Torrent PGM platform followed by assembly using the CLC genomics workbench and genome annotation using RAST, BASys and MaGe. The complete genome sequence was 713,204 bp identified by with second largest size for Salinicoccus sp. reported in the NCBI genome database. A total of 652 degradative pathways were identified by KEGG map analysis. Comparative genomic analysis revealed Salinicoccus sp. BAB 3246 as most highly related to Salinicoccus halodurans H3B36. Data mining identified stress response genes and operator pathway for degradation of various environmental pollutants. Annotation data and analysis indicate potential use in pollution control in industrial influent and saline environment.

Objective To examine temporal changes in the incidence and patterns of vitamin D supplementation prescribing by general practitioners (GPs) between 2008 and 2016.Design Population-based cohort study.Setting UK general practice health records from The Health Improvement Network.Participants Children aged 0 to 17 years who were registered with their general practices for at least 3 months.Outcome measures Annual incidence rates of vitamin D prescriptions were calculated, and rate ratios were estimated using multivariable Poisson regression to explore differences by sociodemographic factors. Data on the type of supplementation, dose, dosing schedule, linked 25-hydroxyvitamin D (25(OH)D) laboratory test results and clinical symptoms suggestive of vitamin D deficiency were analysed.Results Among 2 million children, the crude annual incidence of vitamin D prescribing increased by 26-fold between 2008 and 2016 rising from 10.8 (95% CI: 8.9 to 13.1) to 276.8 (95% CI: 264.3 to 289.9) per 100 000 person-years. Older children, non-white ethnicity and general practices in England (compared with Wales/Scotland/Northern Ireland) were independently associated with higher rates of prescribing. Analyses of incident prescriptions showed inconsistent supplementation regimens with an absence of pre-supplementation 25(OH)D concentrations in 28.7% to 56.4% of prescriptions annually. There was an increasing trend in prescribing at pharmacological doses irrespective of 25(OH)D concentrations, deviating in part from UK recommendations. Prescribing at pharmacological doses for children with deficient status increased from 3.8% to 79.4%, but the rise was also observed in children for whom guidelines recommended prevention doses (0% to 53%). Vitamin D supplementation at pharmacological doses was also prescribed in at least 40% of children with no pre-supplementation 25(OH)D concentrations annually.Conclusions There has been a marked and sustained increase in vitamin D supplementation prescribing in children in UK primary care. Our data suggests that national guidelines on vitamin D supplementation for children are not consistently followed by GPs.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an immune-mediated disorder of the central nervous system characterized by an inflammatory response to amyloid-beta (Aβ) deposition within cerebral blood vessel walls. Immunosuppressive therapy is the mainstay of treatment. We present a case of CAA-ri in a subject already on immunosuppressive therapy after orthotopic heart transplantation (OHT). A 57-year-old man 8 months post-OHT for sarcoid cardiomyopathy developed headaches and staring spells while hospitalized for disseminated mycobacterial infection. His brain MRI revealed bi-hemispheric T2-weighted fluid-attenuated inversion recovery white matter hyperintensities and widespread microhemorrhages. Two weeks later, he developed gait ataxia and alterations in mental status, and repeat brain MRI showed more extensive confluent white matter hyperintensities. Leptomeningeal and cortex biopsy revealed changes consistent with amyloid angiitis, with perivascular and intramural histiocyte and lymphocyte collections. Mass spectroscopy confirmed Aβ deposition. Notably, the patient was on immunosuppression with daily 5 mg oral prednisone and tacrolimus before biopsy. After high-dose intravenous followed by oral corticosteroids, he demonstrated significant clinical and radiographic improvement. No relapse was noted despite the relatively rapid tapering of the prednisone therapy over 3 months, as mandated by his systemic infection. Despite the lack of a standard treatment protocol for CAA-ri, case series have reinforced the benefit of prolonged courses of glucocorticoids as single agent or in combination with other immunomodulatory agents. Hence, management of CAA-ri in patients with disseminated mycobacterial infections or OHT is challenging. Our case is unique, as review of existing literature has not revealed any similar cases of patients on chronic immunosuppression at the time of CAA-ri diagnosis, which one would expect to protect against this disorder. In addition, CAA-ri in association with cardiopulmonary sarcoidosis was not previously reported; however, a common immunopathogenic mechanism may exist.

Acute urinary retention is a rare cause of hyponatremia. Symptomatic acute hyponatremia is of grave medical concern and needs to be managed aggressively. In our two cases with acute urinary retention, a simple bladder catheterization and drainage of urine followed by conservative management resulted in complete resolution of symptoms and normalization of sodium levels. Association of bladder distension and hyponatremia is considered to be due to release of vasopressin triggered by bladder distension itself or by pain due to bladder distension. These cases are presented to bring to light an unusual and easily treatable cause of hyponatremia.

Background Combined heart and kidney transplantation (HKTx) is performed in patients with severe heart failure and advanced renal insufficiency. We analyzed the long‐term survival after HKTx, the influence of age and dialysis status, the rates of cardiac rejection, and the influence of sensitization. Methods and Results From June 1992 to December 2016, we performed 100 HKTx procedures. We compared older (≥60 years, n=53) with younger (50%, and compared these survival rates with those from the United Network for Organ Sharing database. There was no difference in 15‐year survival between the 2 age groups (35±12.4% and 49±17.3%, ≥60 versus 0 or antibody‐mediated rejection>0) was 92±2.8% and 84±3.8%, acute cellular rejection (≥2R/3A) 98±1.5% and 94±2.5%, and antibody‐mediated rejection (≥1) 96±2.1% and 93±2.6% at 30 days and 1 year after HKTx. There was no difference in the 5‐year survival among recipients by sensitization status with panel‐reactive antibody levels 50% (82±5.9%, 83±10.8%, and 92±8.0%; P=0.55). There was no difference in 15‐year survival after HKTx between the United Network for Organ Sharing database and our center (38±3.2% and 40±10.1%, respectively; P=0.45). Conclusions HKTx is safe to perform in patients 60 years and older or younger than 60 years and with or without dialysis dependence, with excellent outcomes. The degree of panel‐reactive antibody sensitization did not appear to affect survival after HKTx.

Background/AimsTo investigate the various etiologies, yields, and effects of capsule endoscopy (CE) on management and complications, along with follow up of patients with obscure gastrointestinal (GI) bleeding.MethodsThe study group of patients included those having obscure, overt, or occult GI bleeding. The findings were categorized as (A) obvious/definitive, (B) equivocal, or (C) negative. Any significant alteration in patient management post CE in the form of drug or surgical intervention was noted.ResultsTotal patients included in the study were 68 (48 males and 20 females). The ratio of male:female was 2.4:1. The age ranged between 16 years to 77 years. Mean age for males was 62±14 years, for females 58±16 years. The total yield of CE with definitive lesions was in 44/68 (65.0%) of patients. In descending order (A) angiodysplasia 16/68 (23.53%), (B) Crohn's disease 10/68 (14.70%), (C) non-steroidal anti-inflammatory drug enteropathy 8/68 (11.76%), (D) small bowel ulcers 4/68 (5.88%), (E) jejunal and ileal polyps 2/68 (2.94%), (F) intestinal lymphangiectasis 2/68 (2.94%), and (G) ileal hemangiomas 2/68 (2.94%) were followed. Equivocal findings 12/68 (17.65%) and negative study 12/68 (17.65%) was found. Complications in the form of capsule retention in the distal ileum were noted in 2/68 (2.94%) subjects. Statistically, there was a higher probability of finding the etiology if the CE was done during an episode of bleeding.ConclusionsCE plays an important role in diagnosing etiologies of obscure GI bleeding. Its role in influencing the management outcome is vital.

Increased demand of farm products and depletion of natural resources compel the agriculture community to increase the use of Information and Communication Technology (ICT) in various farming processes. Agricultural Decision Support Systems (DSS) proved useful in this regard. The majority of available Agricultural DSSs are either crop or task specific. Less emphasis has been placed on the development of comprehensive DSS, which are non-specific regarding crops or farming processes. The crop or task specific DSSs are mainly developed with rule based or knowledge transfer based approaches. The DSSs based on these methodologies lack the ability for scaling up and generalization. The Knowledge engineering modeling approach is more suitable for the development of large and generalized DSS. Unfortunately the model based knowledge engineering approach is not much exploited for the development of Agricultural DSS. CommonKADS is one of the popular modeling frameworks used for the development of Knowledge Based System (KBS). The paper presents the organization, agent, task, communication, knowledge and design models based on the CommonKADS approach for the development of scalable Agricultural DSS. A specific web based DSS application is used for demonstrating the multi agent CommonKADS modeling approach. The system offers decision support for irrigation scheduling and weather based disease forecasting for the popular crops of India. The proposed framework along with the required expert knowledge, provides a platform on which the larger DSS can be built for any crop at a given location.

Introduction: Improving tissue oxygenation is one of most important tasks in management of low cardiac output. Central venous oxygen saturation (ScvO2 ) and lactate are established criteria for monitoring the adequacy of tissue oxygenation. The venous-to-arterial carbon dioxide difference [P(v-a)CO2 ] is inversely associated with cardiac output. Aim: To study the use of P(v-a)CO2 /C(a-v)O2 ratio as a marker of low cardiac output during Cardiopulmonary Bypass (CPB) in paediatric cardiac surgical patients. Materials and Methods: The present study was a prospective observational study conducted over a period of nine months from 1st August 2015 to 30th April 2016. A total of 110 children were enrolled, who underwent CPB during cardiac surgery. The CPB time, Mean Arterial Pressure (MAP), flow rate, cross clamp time, were recorded for all the patients as well as Arterial Blood Gas (ABG) and Venous Blood Gas (VBG) were checked at four different points of time: 1) Before CPB, 2) 10 minutes after initiation of CPB, 3) 30 minutes on CPB and 4) off CPB. Results: The results indicated that Receiver Operating Characteristic curve (ROC curve) at 30 minute of CPB time P(v-a)CO2 /C(a-v)O2 was more specific and sensitive than lactate to detect anaerobic metabolism. Decrease platelet count was significant on second postoperative day. Conclusion: The present study suggests the use of P(v-a) CO2 /C(a-v)O2 ratio as a marker to detect low flow on CPB. Our study was single centric and with a small size, studies involving large population and multiple centers are required to support the recent findings.

Accurate estimation of evapotranspiration (ETo) is a key factor in weather-based irrigation scheduling methods. To estimate ETo using the Hargreaves equation, just the data on the minimum and maximum temperature and solar radiation are required. However, this procedure cannot offer consistent accuracy for different climate conditions. To attain the accuracy, calibration of the equation constants (CHand EH) for different climate conditions have successfully been attempted by many researchers. Because these calibration procedures are lengthy and location-specific, there is a need of a generalized calibration method to make the Hargreaves equation more pertinent and effective. In this paper, fuzzy logic based calibration method for the Hargreaves equation is proposed and validated. The fuzzy inference system is developed to compute appropriate values of the constants CHand EH on the basis of past data on humidity and wind velocity of a selected location. The underlying relationship between weather conditions and the best values of the constants CHand EH are used to establish a fuzzy rule base. The performance of the method is checked at eight geographically different locations of India with diverse climate conditions. The Mean Absolute Error (MAE) in ETovalues estimated by the calibrated modified Hargreaves equation and the Penman-Monteith (PM) equation is in the range of 0.3220-1.0325. It is far more lower than if the error is calculated using the original Hargreaves equation. It confirms the correctness of the calibration method for different climate conditions.

Introduction: Calcium pyrophosphate crystal deposition disease (CPPD) is the most common form of crystal arthropathy second only to gout. Common clinical presentation is an acute monoarticular arthritis commonly occurring in knee joints. We presented a case of bilateral olecranon bursitis in a calcium pyrophosphate crystal deposition disease. Case Report: A 42-year-old female patient is presented with golf ball sized painless swellings in the posterior aspect of her elbows. Elbow joints were clinically normal except for restriction of terminal flexion. X-ray showed mild erosion at the tip of olecranon. Excision biopsy of the swelling showed positive birefringent calcium pyrophosphate dehydrate crystals on the inner wall of the specimen on polarized light microscopy. Conclusion: Bilateral olecranon bursitis may be part of the extraarticular manifestations of calcium pyrophosphate dihydrate crystal deposition disease with good prognosis following in toto bursa excision

Eosinophilic gastroenteritis is characterized histologically by eosinophilic infiltration of the gut wall and clinically manifests by gastrointestinal (GI) symptoms. A high index of suspicion is required for the early diagnosis of this uncommon disease in patients who have concomitant GI symptoms and peripheral eosinophilia. This unusual case who initially had duodenal ulcer with duodenal stenosis, responded to Helicobacter pylori treatment and dilatation. He was symptom free for 2 years. Subsequently, developed evanescent eosinophilic gastritis and recurrent H. pylori infection with refractory prepyloric ulceration, but no duodenal stenosis. Eosinophilic gastritis and H. pylori infection initially responded to treatment, but subsequently the patient developed nonhealing prepyloric ulcer and refractory H. pylori infection and had persistent symptoms; all these necessitated surgical intervention consisting of antrectomy with gastrojejunostomy.

Abstract Cystatin 9 (CST9) is a member of the type 2 cysteine protease inhibitor family, which has been shown to have immunomodulatory effects that restrain inflammation, but its functions against bacterial infections are unknown. Here, we report that purified human recombinant (r)CST9 protects against the deadly bacterium Francisella tularensis (Ft) in vitro and in vivo. Macrophages infected with the Ft human pathogen Schu 4 (S4), then given 50 pg of rCST9 exhibited significantly decreased intracellular bacterial replication and increased killing via preventing the escape of S4 from the phagosome. Further, rCST9 induced autophagy in macrophages via the regulation of the mammalian target of rapamycin (mTOR) signaling pathways. rCST9 promoted the upregulation of macrophage proteins involved in antiinflammation and antiapoptosis, while restraining proinflammatory-associated proteins. Interestingly, the viability and virulence of S4 also was decreased directly by rCST9. In a mouse model of Ft inhalation, rCST9 significantly decreased organ bacterial burden and improved survival, which was not accompanied by excessive cytokine secretion or subsequent immune cell migration. The current report is the first to show the immunomodulatory and antimicrobial functions of rCST9 against Ft. We hypothesize that the attenuation of inflammation by rCST9 may be exploited for therapeutic purposes during infection.

Rickettsial infections continue to cause serious morbidity and mortality in severe human cases around the world. Host cell adhesion and invasion is an essential requisite for intracellular growth, replication, and subsequent dissemination of pathogenic rickettsiae. Heparan sulfate proteoglycans [HSPGs] facilitate the interactions between fibroblast growth factor(s) and their tyrosine kinase receptors resulting in receptor dimerization/activation and have been implicated in bacterial adhesion to target host cells. In the present study, we have investigated the contributions of fibroblast growth factor receptors [FGFRs] in rickettsial entry into the host cells. Inhibition of HSPGs by heparinase and FGFRs by AZD4547 (a selective small-molecule inhibitor) results in significant reduction in rickettsial internalization into cultured human microvascular endothelial cells (ECs), which represent the primary targets of pathogenic rickettsiae during human infections. Administration of AZD4547 during R. conorii infection in a murine model of endothelial-target spotted fever rickettsiosis also diminishes pulmonary rickettsial burden in comparison to mock-treated controls. Silencing of FGFR1 expression using a small interfering RNA also leads to similar inhibition of R. rickettsii invasion into ECs. Consistent with these findings, R. rickettsii infection of ECs also results in phosphorylation of tyrosine 653/654, suggesting activation of FGFR1. Using isobaric tag for relative and absolute quantitation [iTRAQ]-based proteomics approach, we further demonstrate association of β-peptide of rickettsial outer membrane protein OmpA with FGFR1. Mechanistically, FGFR1 binds to caveolin-1 and mediates bacterial entry via caveolin-1 dependent endocytosis. Together, these results identify host cell FGFR1 and rickettsial OmpA as another novel receptor-ligand pair contributing to the internalization of pathogenic rickettsiae into host endothelial cells and the potential application of FGFR-inhibitor drugs as adjunct therapeutics against spotted fever rickettsioses.

Endothelial cell interactions with lipopolysaccharide (LPS) involve both activating and repressing signals resulting in pronounced alterations in their transcriptome and proteome. Noncoding RNAs are now appreciated as posttranscriptional and translational regulators of cellular signaling and responses, but their expression status and roles during endothelial interactions with LPS are not well understood. We report on the expression profile of long noncoding (lnc) RNAs of human microvascular endothelial cells in response to LPS. We have identified a total of 10,781 and 8310 lncRNA transcripts displaying either positive or negative regulation of expression, respectively, at 3 and 24 h posttreatment. A majority of LPS-induced lncRNAs are multiexonic and distributed across the genome as evidenced by their presence on all chromosomes. Present among these are a total of 44 lncRNAs with known regulatory functions, of which 41 multiexonic lncRNAs have multiple splice variants. We have further validated splice variant-specific expression of EGO (NONHSAT087634) and HOTAIRM1 (NONHSAT119666) at 3 h and significant upregulation of lnc-IL7R at 24 h. This study illustrates the genome-wide regulation of endothelial lncRNA splice variants in response to LPS and provides a foundation for further investigations of differentially expressed lncRNA transcripts in endothelial responses to LPS and pathophysiology of sepsis/septic shock.