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Background: A 49-year-old male presented with a delayed diagnosis of infective endocarditis leading to extensive intracardiac destruction. Such cases present technical challenges to operative debridement as crucial anchoring points for replacement conduits are compromised. Case Presentation: Our patient presented at age 49 with nausea, lethargy, and diarrhea 2 weeks after recent travel. His prior history included bioprosthetic valve replacement for a bicuspid aortic valve. The patient was first given a trial of antimicrobials for a suspected UTI. Subsequently, he was admitted briefly to an outside hospital for a “cardiac work-up,” which returned negative. The patient sought care for the third time, during which he developed unstable supraventricular tachycardia, prompting echocardiography 16 days following the onset of symptoms. Echocardiography demonstrated a 6 cm abscess cavity invading the interventricular septum with a fistula into the left ventricular outflow tract, multiple ventricular septal defects (VSD), and suspected fistulae into the right ventricular outflow tract. The patient was treated with valve explant and extensive debridement. A valved-conduit for the aorta could not be sewn to the aortic annulus in the usual fashion due to destruction and debridement of the annulus, so a neo-annulus was created using the anterior leaflet of the mitral valve and the left ventricular outflow tract of the heart below the level of the VSDs. A mechanical-valved conduit was implanted onto the neo-annulus. A pacemaker was subsequently implanted. Conclusion: In patients with extensive intracardiac destruction with the compromise of the aortic annulus due to infective endocarditis, a low-seated, mechanical-valved conduit implanted directly to the aorto-mitral curtain and left ventricular outflow tract should be considered a novel, durable reconstructive option that allows complete debridement of infected tissues.

For many of the 537 million adults living now with diabetes, the cost of insulin is becoming prohibitive as the insulin prices have tripled between 2002-2013. Globally, the direct annual cost of healthcare expenditure due to diabetes will soon be US$1 Trillion. Biosimilars provide access to high-quality, affordable biologic therapy that is otherwise inaccessible due to the high costs of original biologics.A primer to the development of biosimilars shows comparable structural and analytical characterization to the original biologics (e.g. insulins), with no clinically significant or meaningful differences in efficacy and safety. 'Interchangeability' status, a regulatory designation by the US FDA, bestowed to some biosimilars, enables confidence in high-quality, bio-equivalent biosimilar of insulin with key global approvals. This can allow rapid uptake of biosimilars by the prescribers, formulary decision-makers, and payors. Biocon-Viatris's biosimilar Insulin Glargine (Semglee®) is the first interchangeable biosimilar insulin approved by the US FDA.The 'interchangeable' status can prompt faster and wider uptake of insulin biosimilars and keep the insulin expenditure under control, especially for patients who otherwise practice non-adherence or rationing of life-saving insulin. Education, support, and awareness can ensure that interchangeable biosimilars gain wider acceptance.

The antibacterial properties of graphene oxide and the anti-cancer effects of TiO2particles play a vital role in the drug delivery system. Mixing these nanoparticles in the blood by considering the complex rheological natured Sutterby model can maximize drug delivery results. A theoretical analysis is made to evaluate the impact of resistive and radiative heat on the graphene oxide (GO), and titanium dioxide (TiO2) suspended Sutterby blood flow through the stenosed artery. A mathematical model is developed and resolved numerically using the Keller-box approach. The Darcy–Forchheimer, heat convection, and hydromagnetic conditions are considered for physical relevance. The outcomes are obtained for nano and hybrid nano cases and explored with tabular and pictorial representations. It is found that the addition of the GO nanoparticles to the blood-TiO2 combination boosts the heat transmission without affecting the wall friction. This minimizes the external pressure on the blood flow.

The mismatch repair (MMR) system plays a major role in removing DNA polymerization errors, and loss of this pathway results in hereditary cancers characterized by microsatellite instability. We investigated microsatellite stability during DNA replication within human postmeiotic segregation 2 (hPMS2)–deficient and proficient human lymphoblastoid cell lines. Using a shuttle vector assay, we measured mutation rates at reporter cassettes containing defined mononucleotide, dinucleotide, and tetranucleotide microsatellite sequences. A mutator phenotype was observed in the hPMS2-deficient cell line. The mutation rate of vectors containing [G/C]10 or [GT/CA]10 alleles was elevated 20-fold to 40-fold in hPMS2-deficient cells, relative to an hPMS2-expressing cell line. We observed a 6-fold and 12-fold relative increase in mutation rate of [TTTC/AAAG]9 and [TTCC/AAGG]9 sequences, respectively, in hPMS2-deficient cells. Mutational specificity analyses suggested that repair by hPMS2 is biased. In the absence of hPMS2, a greater number of microsatellite expansion versus deletion mutations was observed, and expansion rates of the tetranucleotide alleles were similar. In the presence of hPMS2, we observed a 29-fold decrease in the [TTCC/AAGG]9 expansion rate but only a 6-fold decrease for the [TTTC/AAAG]9 allele. Our data indicate that hPMS2 is more protective of tetranucleotide expansions than deletions and that hPMS2 displays a sequence bias, wherein [TTCC/AAGG] sequences are stabilized to a greater extent than [TTTC/AAAG]. Our results allow for greater accuracy during identification of MMR defects by providing a mutational signature characteristic of hPMS2 defect. This study also provides clues to possible mechanisms of repair by hPMS2 in the context of the MMR system. [Cancer Res 2009;69(3):1143–9]

Supplementary Figures 1-3 from Human Postmeiotic Segregation 2 Exhibits Biased Repair at Tetranucleotide Microsatellite Sequences

Purpose To determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness as compared with placebo in eyes with center-involved diabetic macular edema (CI-DME) and good vision Design Phase 2 randomized clinical trial Participants Participants had CI-DME and visual acuity (VA) 20/25 or better in the study eye and were recruited from 23 clinical sites in the US. Methods One eye of each participant was randomly assigned 1:1 to a 670-nm light-emitting PBM eye patch or an identical device emitting broad-spectrum white light at low power. Treatment was applied for 90 seconds twice daily for 4 months. Main Outcome Measure Change in central subfield thickness (CST) on spectral-domain optical coherence tomography (OCT) at 4 months. Results From April 2019 to February 2020, 135 adults were randomly assigned to either PBM (N = 69) or placebo (N = 66); median age was 62, 37% were female and 82% were white. Median device compliance was 92% with PBM and 95% with placebo. OCT CST increased from baseline to 4 months by a mean (SD) of 13 (53) μm in PBM eyes and 15 (57) μm in placebo eyes (mean difference (95% CI) = -2 (-20 to 16) μm; p = .84). CI-DME, based on DRCR Retina Network sex and machine-based thresholds, was present in 61 (90%) of PBM eyes and 57 (86%) of placebo eyes at 4 months (adjusted odds ratio (95% CI) = 1.30 (0.44 to 3.83); p = .63). Visual acuity decreased by a mean (SD) of -0.2 (5.5) letters and -0.6 (4.6) letters in the PBM and placebo groups, respectively (difference (95% CI) = 0.4 (-1.3 to 2.0) letters; p = .64). There were eight adverse events possibly related to the PBM device, and two adverse events possibly related to the placebo device. None were serious. Conclusions PBM as given in this study, while safe and well tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision.

Supplemental material, sj-docx-1-pie-10.1177_09544089231171036 for Relative analysis on fluid flow models for graphene oxide suspended blood flow: A Keller-box approach by Niraj Rathore and N. Sandeep in Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering

Supplemental material, sj-docx-1-pie-10.1177_09544089231160496 for Numerical simulation of melting heat transfer in cylindrical slip flow of complex nanofluid by Jeevankumar and N Sandeep in Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering

Supplemental material, sj-docx-1-pie-10.1177_09544089231160496 for Numerical simulation of melting heat transfer in cylindrical slip flow of complex nanofluid by Jeevankumar and N Sandeep in Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering

In this paper, a numerical computational work is carried out to investigate the significance of nanoparticle shape on magnetohydrodynamic stagnation-point flow of Carreau nanoliquid caused by a horizontally moving thin needle. The drive and thermal transport nature of Ti6Al4V+Ethylene glycol nanoliquid under the stimulus of space-dependent heat source and magnetized force is discussed numerically. The novelty of this work is to obtain the simultaneous solutions for three different shapes of nanoparticles namely spherical, cylindrical and laminar. The flow governing partial differential equations are transformed into ordinary differential equations with appropriate similarity variables and solved numerically by using Runge–Kutta and Newton's approach. Numerical outcomes of velocity and thermal distributions under the influence of different physical parameters are illustrated via graphical trends, wall friction and rate of heat transfer are interpreted using tabular values. It reveals from results that the thermal transfer performance of the Carreau nanoliquid is advanced when spherical shaped nanoparticles are used as compared with cylindrical and laminar-shaped nanoparticles. Also, it is witnessed that needle thickness parameter plays vital role in augmenting thermal transport rate of the nanoliquid.

Efficacy and safety of ultra-rapid acting oral prandial insulin Tregopil was compared with insulin aspart (IAsp) in patients with type 2 diabetes (T2D) on insulin glargine and metformin. In this open-label, active-controlled trial, patients with T2D, HbA1c ≥7%–≤9% and 2-h postprandial glucose (PPG) ≥180 mg/dL were randomized 1:1:1 to Tregopil (30 mg, n = 30; 45 mg, n = 31) and IAsp, n = 30. Primary outcome was change from baseline (CFB) in HbA1c at week 24. Secondary outcomes included PPG excursion (PPGE) and PPG assessed from standardized test meal (STM) and 9-point self-monitored blood glucose. The observed mean HbA1c did not improve at week 24 in Tregopil groups (30 mg [0.15%], 45 mg [0.22%] vs. a reduction in IAsp group [−0.77%]). Combined Tregopil group showed better 1-h PPGE control versus IAsp following STM (CFB, estimated treatment difference, 95% CI, −45.33 mg/dL [−71.91, −18.75], p = 0.001) and 1-h PPG trended toward better control. Tregopil showed lower PPGE at 15 min versus IAsp. Clinically significant hypoglycemia was lower with Tregopil versus. IAsp (rate ratio: 0.69). Tregopil demonstrated an ultrafast, short-duration prandial profile with good safety. While Tregopil’s early postprandial effects were comparable to IAsp, its late postprandial effects were inferior. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03430856).

A new approach is proposed to analyze the live crowd and to provide an alert at the time of congestion, over-crowding and sudden gathering of pedestrians in a particular region. This paper proposes a completely software-oriented approach using MATLAB where it uses object detection and object tracking using Faster R- CNN (Region Based Convolutional Neural Network) algorithm where inception model of Google is used as CNN model which is pre-trained. This proposed method gives significant result on proposed dataset and the crowd congestion using Faster R-CNN approach which gives an accuracy of 93.503% at the rate 28 frames per second and the crowd detected video frames are uploaded to cloud storage.

This study aimed to determine antimicrobial resistance pattern and predictors of adverse outcome in neonatal meningitis. A retrospective study by analyzing case files of 134 cases of neonatal meningitis. We noted an alarming degree of multidrug resistance (MDR) among both gram-negative (Klebsiella spp., 50%; Escherichia coli, 100%; and and Acinetobacter spp., 50%), as well as positive (Enterococcus, 100%) isolates in cerebrospinal fluid (CSF) culture. The incidence rate of adverse outcome (i.e., mortality and abnormal neurological examination at discharge) was 8.2 and 17.2%, respectively. On univariate analysis, delayed seeking of medical care, bulging anterior fontanelle, vomiting, positive sepsis screen, shock during hospital course, ventriculitis, diversion procedures for raised intracranial pressure, central line placement, low CSF sugar, and failed hearing screening test at discharge were associated with increased risk of adverse outcome. Further, delayed seeking of medical care, shock during hospital course, positive sepsis screen, thrombocytopenia, and MDR infections were independently found to be associated with adverse outcomes. An alarming degree of antimicrobial resistance among the CSF isolates necessitates the need to understand the pathogenesis of resistance and curtail the irrational prescription of antibiotics in neonatal meningitis. Further, delayed seeking of medical care, shock during hospital course, positive sepsis screen, thrombocytopenia, and MRD infection may have prognostic value in neonatal meningitis

The dilute acid (DA), steam explosion (SE), and a 2-step: steam explosion followed by alkali (SEA) were evaluated for pretreatment of rice husk. The maximum hemicellulose and lignin removal via degradation and dissolution was observed for SEA pretreatment, enabling higher cellulose enrichment (up to 44% w/w) and recovery (up to 78%). The hemicellulose solubilization was >90% for all the pretreatments, while maximum lignin removal (up to 62%) was observed for SEA pretreatment. The particle size in the range of 0.3-0.6 mm enabled higher pretreatment efficiencies in terms of cellulose enrichment. The liquid fraction obtained after DA pretreatment indicated higher COD values (20800-24440 mg/L) as compared to SEA (7800-11400 mg/L) due to lower cellulose recoveries in DAP (54-68%). SEM analysis of the biomass indicated disrupted regions with multiple pores. FTIR analysis revealed cleavage of lignin side chains, and XRD analysis confirmed the increase in cellulose crystallinity post-pretreatment.

An uncontrolled increase in cytokine production may lead to systemic hyperinflammation, vascular hypo-responsiveness, increased endothelial permeability, hypercoagulation, multi-organ dysfunction and eventually death in moderate to severely ill COVID-19 patients. Targeting T-cells, an important driver of the hyperinflammatory response, in the treatment of COVID-19, could potentially reduce mortality and improve survival rates. Itolizumab is an anti-CD6 humanized monoclonal antibody with an immunomodulating action on Teffector cells that downregulates T-cell activation, proliferation and subsequent production of various chemokines and cytokines. The efficacy and safety of Itolizumab for the treatment of cytokine release syndrome in patients with moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19 was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase 2 study. Eligible patients were randomized (2:1) to arm A (best supportive care + Itolizumab) and arm B (best supportive care). The primary outcome of interest was reduction in all-cause mortality 30 days after enrolment. Thirty-six patients were screened, 5 were treated as first dose sentinels and the rest were randomized, whilst 4 patients were considered screen failures. Two patients in the Itolizumab treatment arm discontinued prior to receiving the first dose and were replaced. At the end of 1 month, there were 3 deaths in arm B, and none in arm A (p= 0.0296). At the end of the follow-up period, more patients in Arm A had improved SpO2 without increasing FiO2 (p=0.0296), improved PaO2 (p=0.0296), and reduction in IL-6 (43 pg/ml vs 212 pg/ml; p=0.0296) and tumor necrotic factor-α (9 pg/ml vs 39 pg/ml; p=0.0253) levels. Itolizumab was generally safe and well tolerated, and transient lymphopenia (11 patients in Arm A) and infusion reactions (7 patients) were the commonly reported treatment related safety events. These encouraging results indicate that larger clinical trials are warranted to establish the role of Itolizumab in controlling immune hyperactivation in COVID-19.

Chlorella vulgaris is known for its protein, growth factor, and nutritional constituents. Chlorella vulgaris was cultivated in a 1000-L outdoor open raceway pond with a maximum volumetric productivity of 130 mg L-1 day-1. The harvested biomass was dried through different methods, viz., sun drying (30 °C), oven drying (60 °C), lyophilization (−110 °C), drum drying (120 °C), and spray drying (100–150 °C). The effect of the drying method on proximate composition, pigments (chlorophyll, carotenoids), bioactive compounds (total phenolic content, flavonoid content), vitamin B12, antioxidant properties (ferric reducing antioxidant power, DPPH, and total antioxidant activity), and the color quality of C. vulgaris biomass was evaluated. Surface characterization by scanning electron microscopy (SEM) and functional group characterization through Fourier transform infrared spectroscopy were also performed. The biomass dried through lyophilization and sun drying retained maximum bioactive compounds and antioxidant activities. In contrast, drum drying resulted in a loss of nutrients, viz., protein (up to 44%), lipid (up to 41%), vitamin B12 (up to 40%), total phenolic content (> 50%), total flavonoid content (> 50%), and antioxidant activity (> 50%). Oven drying led to a loss of 30% in total flavonoid content and 17% in ferric reducing antioxidant power. SEM showed the destruction of cell wall integrity in the drum-dried sample and porous structure in the spray-dried sample. This study suggests that drying methods affect the nutrients and bioactive compounds of C. vulgaris biomass, and therefore a drying method should be selected carefully depending on the end use of the biomass.

International audience; Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C)3-5. Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.

To establish the pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of proposed biosimilar insulin 70/30 (Biocon's Insulin-70/30) and HUMULIN® 70/30 (HUMULIN-70/30; Eli Lilly and Company, IN).In this phase 1, automated euglycaemic glucose clamp study, 78 healthy subjects were randomized (1:1) to receive a single dose of 0.4 IU/kg of Biocon's Insulin-70/30 and HUMULIN-70/30. Plasma insulin concentrations and glucose infusion rates (GIRs) were assessed over 24 hours. Primary PK endpoints were area under the insulin concentration-time curve from 0 to 24 hours - AUCEquivalence was shown between Biocon's Insulin-70/30 and HUMULIN-70/30 for the primary PK/PD endpoints. The 90% confidence intervals of the treatment ratios were entirely within the acceptance range of 80.00%-125.00%. The secondary PK/PD profiles were also comparable. There were no clinically relevant differences in the safety profiles of the two treatments and no serious adverse events were reported.PK/PD equivalence was demonstrated between Biocon's Insulin-70/30 and HUMULIN-70/30 in healthy subjects. Treatment with Biocon's Insulin-70/30 and HUMULIN-70/30 was well tolerated.

In the non-conventional media like underwater and underground, the Radio Frequency (RF) communication technique does not perform well due to large antenna size requirement and high path loss. In such media, magnetic induction (MI) communication technique is very promising due to small coil size and constant channel behavior. Unlike the RF technique, the communication range in MI technique is relatively less. To enhance this range, a waveguide technique is already brought in practice. This technique employs single layer coils to enhance the performance of MI waveguide. To further enhance the system functioning, in this paper, we investigated the performance of multi-layer coil (MLC) antenna based MI waveguide communication system in terms of transmission range, path loss, bit error rate (BER) and bandwidth. Besides, the system performance is quantitatively evaluated in three different non-conventional media viz., dry soil, fresh water and wet soil. As compared with the single layer counterpart, the MLC system shows a significant improvement in transmission range, BER even in loosely coupled scenarios and shows a corresponding reduction in path loss. However, the bandwidth is observed to be low (< 1 KHz). In this analysis, the eddy current effects and parasitic capacitance are compared for single and multilayer coils. It is observed that the proposed system performs better in dry soil medium due to less medium conductivity.

OBJECTIVEEfficacy and safety of ultra-rapid acting oral prandial insulin Tregopil (Tregopil) was compared with insulin aspart (IAsp) in patients with type-2 diabetes on stable doses of insulin glargine and metformin.RESEARCH DESIGN AND METHODSIn this open-label, active-controlled trial, patients with type-2 diabetes, with HbA1c ≥7% and ≤9% and 2-h postprandial glucose (PPG) ≥180 mg/dL were randomized (1:1:1) to Tregopil (30 mg [n=30], 45 mg [n=31]) and IAsp (n=30; dose titrated based on self-monitored blood glucose [SMBG]). Postprandial plasma glucose excursion (PPGE) and PPG were assessed from the standardized test meal (STM) and 9- point SMBG. The primary outcome measure was change from baseline (CFB) in HbA1c at week 24.RESULTSThe Tregopil (30 mg) arm showed significantly lesser 1-h PPGE (CFB) excursion after the STM versus IAsp (Estimated Treatment Difference [ETD], 95% CI, -45.33 mg/dL [-71.91, -8.75], P=0.001) and 1-h PPG trended towards a better control. The combined Tregopil group (30+45 mg) showed lower PPGE at 15 mins as compared to IAsp. Meal-wise analysis showed lower 1-h PPGE and PPG in the Tregopil groups post-breakfast. Clinically significant hypoglycemia was lower with Tregopil groups versus IAsp (rate ratio: 0.69).CONCLUSIONSTregopil demonstrated an ultra-fast onset and short-duration prandial insulin profile with good safety. Tregopil improved the 1-h PPG and overall PPG control compared to IAsp. A further reduction in HbA1c compared to baseline was not observed, likely as a result of variability in the control of fasting glucose level over the duration of the study.

Introduction: Fissure in ANO is one of the most common ANO rectal problems. Anal fissure is a linear or oval shaped tear in the anal canal starting just below the dentate line extending to the anal verge. Aims: The present study aims at determining the clinical presentation, site, symptomatic relief, healing rate and best treatment modality of fissure in ANO. Materials and Methods: This study is observational study in patients with ANO rectal problems who were randomly selected in this study. The diagnosis was made on the basis of ANO rectal examination which included inspection, digital rectal examination, and proctoscopic examination. Results: Our study found out that out of the 50 patients with ANO rectal problems.50 patients (100%) were having anal fissures. Out of them, 30 were males and 20 were females, majority were 18-30 years age group. Pain during defecation, bleeding and constipation were reported as the common clinical symptoms. In this study we compare clinical presentation, site, symptomatic relief, healing rate of 0.2% GTN treatment, Manual anal dilatation and lateral internal sphincterotomy in the treatment of fissure in ANO. 20 patients were underwent lateral internal sphincterotomy and 20 underwent manual anal dilatation with 10 patients treated with 0.2% GTN ointment. We studies outcome of these each modality and compared them with different studies. Lateral internal sphincterotomy remains the gold standard for definitive management of anal fissure. Conclusion: Lateral internal sphincterotomy is one of the standard and best treatment modality for fissure in ANO.

Supplemental material, sj-docx-1-pie-10.1177_09544089221105938 for Effect of nanospray on hydrodynamic cylindrical film flow of Sutterby–Casson nanoliquids: A renewable energy application by Vasudeva Reddy Minnam Reddy, A Sreevallabha Reddy, R Suresh Babu and N Sandeep in Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering