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Background Objectives: Theileriosis is an important tick-bome hemoprotozoan disease of cattle which causes severe economic loss due to morbidity and mortality. A diagnostic test having high sensitivity, specificity and easy application at the field level is the need of the hour. In this regard Loop-mediated isothermal amplification (LAMP) is proven to be a sensitive, easy and time efficient method. One of the major obstacles for the application of LAMP is the difficulty in maintaining the cold chain to preserve reagents. Thus, the challenge is to develop a LAMP kit in a ready-to-use format with dried reagents useful for quick and simple application in field conditions., Methods: The optimized reaction of wet LAMP was followed for the standardization of dry LAMP with certain modifications which are needful. The major modification is vitrification technology of enzyme using trehalose., Results: LAMP assay (dry and wet LAMP) was found to be more sensitive (100%) when compared to microscopy (69.5%) and PCR (86.9%). It was observed that the dry LAMP reaction tubes at room temperature as well as refrigeration temperature provided successful amplification till 7 weeks., Interpretation Conclusion: The drying conditions of LAMP reagents were optimized, and finally managed to dry them in a single reaction tube without reducing the sensitivity. This technology enables us to transport LAMP kits to areas where the cold chain is not easily available., (Copyright © 2024 Copyright: © 2024 Journal of Vector Borne Diseases.)

Introduction: We evaluated a potential move from one rapid-acting insulin analog to another, or their biosimilars, to aid better and faster decisions for diabetes management., Methods: A systematic literature review was performed according to PRISMA reporting guidelines. The MEDLINE/EMBASE/COCHRANE databases were searched for randomized control trials (RCTs) comparing aspart/lispro in type-1 (T1D) and type-2 (T2D) diabetes. The methodological quality of the included studies was assessed using the Cochrane Collaboration's risk of bias assessment criteria., Results: Of the 753 records retrieved, the six selected efficacy/safety RCTs and the additional three hand-searched pharmacokinetics/pharmacodynamics RCTs showed some heterogeneity in the presentation of the continuous variables; however, collectively, the outcomes demonstrated that lispro and aspart had comparable efficacy and safety in adult patients with T1D and T2D. Both treatments yielded a similar decrease in glycated hemoglobin (HbA1c) and had similar dosing and weight changes, with similar treatment-emergent adverse events (TEAE) and serious adverse event (SAE) reporting, similar hypoglycemic episodes in both T1D and T2D populations, and no clinically significant differences for hyperglycemia, occlusions or other infusion site/set complications., Conclusions: Aspart and lispro demonstrate comparative safety and efficacy in patients with T1D/T2D. Since both are deemed equally suitable for controlling prandial glycemic excursions and both have similar safety attributes, they may be used interchangeably in clinical practice., Prospero Registration Number: CRD42023376793.

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Xylooligosaccharides (XOS) obtained from lignocellulosic biomass after autohydrolysis primarily consist of lignin-derived impurities and autogenerated inhibitors like furfural, hydroxymethylfurfural, and acetic acid. In this study, graphene oxide-mediated purification (GOMP), a novel and environmentally friendly downstream processing method, was developed for the purification of XOS from hydrolysate obtained after ozone-assisted autohydrolysis of wheat bran. GOMP resulted in appreciable recovery of total XOS from the hydrolysate (73.87 ± 4.25%, DP2-6) with near complete removal of autogenerated inhibitors (furfural 85.42%, HMF 87.38%, and acetic acid 84.0%). Recovery of XOS by GOMP was higher than the conventional membrane purification technique (44.07 ± 0.92%) and activated charcoal treatment (72.76 ± 0.84%) along with comparatively higher removal of inhibitor compounds. GOMP results in the selective adsorption of inhibitors on the graphene oxide matrix from the XOS-rich hydrolysate, resulting in its purification and concentration. The prebiotic function of the obtained XOS fractions (DP2-4.48%, DP3-39.69%, DP4-36.13%, DP5-8.38%, and DP6-13.10%) was evaluated, indicating the growth stimulation of tested probiotic cultures and differential utilization of XOS oligomers DP3 and DP4 and complete consumption of DP2, DP5, and DP6 along with short-chain fatty acids as a major fermentation product. These findings suggest that GOMP, which employs a common substance (i.e., graphene oxide) used in water treatment, exhibits potential as an efficient and economically viable single-step methodology for XOS purification., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Latinx populations have been more heavily impacted by the COVID-19 pandemic than the general population of the US, including higher rates of hospitalization due to COVID-19 in eastern Massachusetts. We conducted a qualitative study to better understand the experiences of Latinx and Spanish-speaking patients who had clinically significant COVID-19 in the early months of the pandemic., Methods: Thirteen qualitative, semistructured, phone interviews were conducted between December 2020 and April 2021 with Latinx and Spanish-speaking patients who had experienced clinically significant COVID-19 in the metro-north Boston area. Interviews were recorded and transcribed in their original languages. An a priori code tree was developed which was later iteratively revised based on emerging themes. Transcripts were thematically analyzed., Results: Participants discussed their overall experiences contracting the COVID-19 infection, as well as their experiences with the disease and with being hospitalized and the months after in recovery. Family and social networks were a common support, both emotional and financial. Although they survived the disease, hospitalization had serious impacts on the mental and physical health of participants, including the remnants of trauma from hospitalization itself., Implications: Latinx and Spanish-speaking patients in eastern Massachusetts had specific experiences in the early months of the COVID-19 pandemic that were shaped by their living conditions and culture. It is important for health care professionals to understand these experiences so that they can design appropriate medical interventions as well as target outreach efforts that are culturally appropriate. Finally, serious attention should be paid to the mental health-related consequences of hospitalization and policies that can alleviate them., Competing Interests: Conflict of interest: None., (© Copyright by the American Board of Family Medicine.)

Insulin therapy is indispensable for achieving glycemic control in all patients with type 1 diabetes mellitus and many patients with type 2 diabetes mellitus. Insulin injections are associated with negative connotations in patients owing to administration discomfort and adverse effects such as hypoglycemia and weight gain. Insulin administered orally can overcome these limitations by providing a convenient and effective mode of delivery with a potentially lower risk of hypoglycemia. Oral insulin mimics the physiologic process of insulin secretion, absorption into the portal circulation, and subsequent peripheral delivery, unlike the subcutaneous route that results in peripheral hyperinsulinemia. Insulin tregopil (IN-105), a new generation human recombinant insulin, methoxy (polyethylene glycol) hexanoyl human recombinant insulin, is developed by Biocon as an ultra-fast onset short-acting oral insulin analog. This recombinant oral insulin is a single short-chain amphiphilic oligomer modified with the covalent attachment of methoxy-triethylene-glycol-propionyl moiety at Lys-β 29 -amino group of the B-chain via an amide linkage. Sodium caprate, an excipient in the insulin tregopil formulation, is a permeation enhancer that increases its absorption through the gastrointestinal tract. Also, meal composition has been shown to non-significantly affect its absorption. Several global randomized, controlled clinical trials have been conducted in type 1 and type 2 diabetes patients towards the clinical development of insulin tregopil. The formulation shows post-prandial glucose control that is more effective than placebo throughout the meal period; however, compared with an active comparator insulin aspart, the post-prandial control is more effective mainly in the early post-meal period. It shows a good safety profile with a lower incidence of clinically significant hypoglycemia. This review covers the overall clinical development of insulin tregopil establishing it as an ultra-fast onset, short-acting oral insulin analog for optimizing post-prandial glucose., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Severe to profound Sensorineural Hearing Loss is a challenging medical problem, particularly if this condition is associated with an inner ear anomaly. This case series studies the prevalence of inner ear anomalies among 76 consecutive prospective cochlear implant candidates who presented to our tertiary care hospital over 2 years. Inner ear anomalies were identified in 11 cases with a prevalence rate of 14%. Narrow Internal Auditory Canal (IAC) is the most common inner ear anomaly (5) followed by Mondini (3) and Globular vestibule (3). Combined CT and MRI play an important role in the preoperative assessment of inner ear anomalies which may affect not only the decision to perform the Implant procedure and the prognosis but also the choice of implant and surgical technique., Competing Interests: Conflict of interestAll authors declared that have no conflict of interest., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: 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., Areas Covered: 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., Expert Opinion: 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.

Objective: Sternal dehiscence is frequently associated with wire-based closures cutting through fragile bone, allowing sternal motion, separation, and infection. We investigated whether bone cutting could be limited by using a newly available mesh suture with improved force distribution., Methods: Five sternal models were closed using 8 interrupted single sternal wires, double sternal wires, braided poly(ethylene terephthalate) sutures, single-wrapped mesh sutures, or double-wrapped mesh sutures. To simulate chest-wall forces, closed sternal models were pulled apart using 1020 N of axial force applied incrementally. Double sternal wire and double-wrapped mesh suture were further compared by closing 3 new models with each material and subjecting these models to cyclic loading cycles, simulating breathing and coughing. Image analysis of needle hole size measured "bone cutting" by each closure material and sternal distraction as a function of force., Results: All models exhibited maximal separation at the xiphoid. During axial loading, needle hole size increased 7.2% in the double-wrapped mesh suture model and 9.2% in the double-wire model. Single-wrapped mesh suture, single wires, and braided poly(ethylene terephthalate) extended needle hole size by 6.7%, 47.0%, and 168.3% of original size, respectively. The double-wire model resisted sternal distraction best, separating 0.285 cm at the xiphoid. During cyclic loading, mesh suture exhibited significantly less bone cutting ( P  = .02) than double wire, with comparable levels of sternal separation ( P  = .07)., Conclusions: Mesh suture may resist bone cutting seen in sternal wire closure in bone models with comparable distraction to currently used sternal closure methods., (© 2023 The Author(s).)

Aim: To compare the clinical efficacy and safety of glargine-U100 (Lantus/Gla-100) with glargine-U300 (Toujeo/Gla-300) in adult patients with type 2 diabetes (T2D) and type 1 diabetes (T1D)., Materials and Methods: A literature search on Gla-300/Gla-100 in diabetes management was conducted using the MEDLINE/Embase/Cochrane databases from inception to 10 January 2021. Eligible studies considered for inclusion were parallel-design, randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to evaluate the quality of the included studies. The random-effects model was applied for interpretation of the results., Results: Of 5348 records screened, 592 were assessed for eligibility and 15 RCTs were considered for data extraction and meta-analysis (T2D [N = 10; n = 7082]; T1D [N = 5; n = 2222]). In patients with T1D, all safety parameters were comparable between Gla-100 and Gla-300. In T2D, statistically significant differences were observed in favour of Gla-300 over Gla-100 for nocturnal and total hypoglycaemia. For efficacy parameters, a statistically and clinically significant difference favouring Gla-100 in basal insulin dose requirement was observed for both T2D and T1D. Change in HbA1c showed a statistically but not clinically significant reduction with Gla-100 compared with Gla-300 in T1D. Statistically significant but clinically less relevant differences favoured Gla-300 for control of body weight in T1D and T2D and Gla-100 for fasting blood glucose in T2D., Conclusions: Gla-100 and Gla-300 had comparable efficacy and safety profiles in both T1D and T2D populations. Gla-300 showed a lower risk of nocturnal and total hypoglycaemia, significant in insulin-experienced/exposed patients with T2D. Patients on Gla-300 required significantly more units of insulin daily than the Gla-100 group to achieve equivalent efficacy., (© 2023 Biocon Biologics Ltd. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To establish the pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of proposed biosimilar Insulin N (Biocon's Insulin-N; Biocon Biologics Ltd., Bangalore, India) and US-licensed Humulin® N (Humulin-N; Eli Lilly and Company, Indianapolis, IN, USA) in healthy subjects., Materials and Methods: This was a phase-1, single-centre, double-blind, randomized, three-period, six-sequence, partially replicated, crossover, 24-h euglycaemic clamp study. Overall, 90 healthy subjects were randomized, of whom 85 completed the study. The subjects received either two single doses of Biocon's Insulin-N and a single dose of Humulin-N or two single doses of Humulin-N and a single dose of Biocon's Insulin-N subcutaneously at a dose of 0.4 IU/kg. The primary PK endpoints were the area under the insulin concentration-time curve from 0 to 24 h (AUC ins.0-24h ) and the maximum insulin concentration (C ins.max ). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 h (AUC GIR.0-24h ) and the maximum GIR (GIR max )., Results: Biocon's Insulin-N was found to be equivalent to Humulin-N for the primary PK (geometric 90% confidence interval for the least squares mean ratio: AUC ins.0-24h , 100.98%-115.66% and C ins.max , 95.91%-110.16%) and PD endpoints (intra-subject variability ≥0.294; 95% upper confidence interval [(μT - μR) 2  - θσ 2 WR] <0; point estimates of geometric least squares mean ratio: AUC GIR.0-24h , 104.61% and GIR max , 100.81%). The safety profile of Biocon's Insulin-N was similar to that of Humulin-N, and no serious adverse events were reported., Conclusion: PK and PD equivalence was shown between Biocon's Insulin-N and Humulin-N in healthy subjects, and both treatments were well tolerated and considered safe., (© 2023 John Wiley & Sons Ltd.)

Objective: HAART 300 300 (BioStable Science and Engineering, Inc) aortic annuloplasty rings restore physiologic annular geometry during aortic valve repair. Transcatheter valve-in-ring implantation is appealing for recurrent valve dysfunction but may necessitate balloon fracture of downsized annuloplasty rings. We characterized the feasibility of ring fracture and changes in ring geometry preceding fracture., Methods: The 19-mm, 21-mm, and 23-mm HAART 300 annuloplasty rings were obtained, and 23-mm, 24-mm, 25-mm, and 26-mm valvuloplasty balloons were obtained. Under continuous fluoroscopy and video recording, a 23-mm balloon was inflated within a 19-mm ring at 1 atm/s until ring fracture or balloon failure occurred. If balloon failure occurred, experiments were sequentially repeated with 1-mm upsized balloons until ring fracture occurred or no larger-sized balloons were available., Results: Upon balloon inflation, all rings exhibited an irreversible conformational change from an elliptical, annular geometry to a circular shape with ring posts flaring outward. A 23-mm balloon burst at 21 atm without fracturing the 19-mm ring. The 24-mm balloon fractured the 19-mm ring at 15 atm. Likewise, a 24-mm balloon ruptured at 18 atm without fracturing the 21-mm annuloplasty ring. A 25-mm balloon fractured the 21-mm ring at 18 atm. Finally, a 26-mm balloon burst at 20 atm without fracturing a 23-mm annuloplasty ring, but it did elicit the confirmational changes described. All fractures occurred along the upslope of a ring post. The exposed metal frame was visible after the 21-mm ring fracture., Conclusions: Fracture of HAART 300 aortic annuloplasty rings is possible with an oversized, high-pressure balloon. However, the geometrical changes in the ring and subsequent rupture of its fabric covering may be obstacles to safe, in vivo ring fracture., (© 2023 The Author(s).)

Background: 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., Research Design and Methods: In this open-label, active-controlled trial, patients with T2D, HbA 1c ≥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 HbA 1c at week 24. Secondary outcomes included PPG excursion (PPGE) and PPG assessed from standardized test meal (STM) and 9-point self-monitored blood glucose., Results: The observed mean HbA 1c 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)., Conclusions: 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., Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03430856).

Aim: 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)., Materials and Methods: 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 - AUC ins.0-24h - and maximum insulin concentration - C ins.max . Primary PD endpoints were area under the GIR time curve from 0 to 24 hours - AUC GIR.0-24h - and maximum GIR - GIR max ., Results: Equivalence 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., Conclusion: 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., (© 2022 Biocon Biologics Ltd. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Technical skill is a proven predictor of surgical outcomes, yet no platform exists for continual technical skill development following training. We aim to characterize the perceived need for feedback on technical skill among practicing thoracic surgeons. Under the Thoracic Education Cooperative Group, a panel of cardiothoracic surgeons and trainees developed and distributed an online survey for cardiothoracic surgery faculty in the Thoracic Surgery Directors Association database. The survey solicited demographics, perceived need for constructive feedback, barriers to sharing critiques, and preferences of desired peer reviewers. One hundred forty surgeons responded to our survey (response rate: 19.6% [140/713]). Most respondents had practiced for greater than 15 years (49.3%, 69/140). About 76.4% (107/140) of responders agreed or strongly agreed receiving feedback on their technical skills would help them improve, and 71.5% (100/140) desired individualized skills feedback. While 61.4% (86/140) of surgeons received meaningful technical skill feedback as attending surgeons, this was infrequent, with 63.3% (88/139) last receiving feedback over 12 months prior. Commonly cited barriers to sharing feedback included lack of common practice, time constraints, and hierarchical barriers. About 66.2% (92/139) of participants would spend at least 10 minutes providing peer feedback to receive feedback on their own skills, while 45.3% (63/139) would spend greater than 20 minutes. Attending thoracic surgeons identify an unmet desire for ongoing, constructive feedback on their technical skills following training. Surgeons feel critique fosters improvement and would devote significant time to engaging in peer feedback. A platform for exchange of technical skill feedback is warranted., (Copyright © 2021. Published by Elsevier Inc.)

Aim: To establish equivalence in the pharmacokinetic (PK) and pharmacodynamic (PD) endpoints between proposed biosimilar Insulin-R (Biocon's Insulin-R) and Humulin® R using the euglycaemic clamp technique in healthy subjects., Materials and Methods: In this phase-1 automated euglycaemic glucose clamp study, 42 healthy subjects were randomized (1:1) to receive a single dose of 0.3 IU/kg of Biocon's Insulin-R and Humulin-R. Plasma insulin concentrations and glucose infusion rates (GIRs) were assessed over 12 hours. Primary PK endpoints were area under the insulin concentration-time curve from 0 to 12 hours (AUC ins.0-12h ) and maximum insulin concentration (C ins.max ). Primary PD endpoints were area under the GIR time curve from 0 to 12 hours (AUC GIR.0-12h ) and maximum GIR (GIR max )., Results: Equivalence was demonstrated between Biocon's Insulin-R and Humulin-R for the primary PK and PD endpoints. The 90% confidence intervals were within 80.00% to 125.00% limits. The PK and PD profiles were comparable. There were no significant differences in the safety profiles of the two treatments, and no serious adverse events were reported., Conclusion: PK and PD equivalence was demonstrated between Biocon's Insulin-R and Humulin-R in healthy subjects. Treatment with Biocon's Insulin-R and Humulin-R was well tolerated., (© 2022 Biocon Biologics Limited. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: To determine if treatment with a photobiomodulation (PBM) device results in greater improvement in central subfield thickness (CST) than 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 United States., 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 Measures: Change in CST on spectral-domain 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 years, 37% were women, and 82% were White. The 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, with the mean difference (95% confidence interval [CI]) being -2 (-20 to 16) μm (P = 0.84). CI-DME, based on DRCR Retina Network sex- and machine-based thresholds, was present in 61 (90%) PBM eyes and 57 (86%) placebo eyes at 4 months (adjusted odds ratio [95% CI] = 1.30 (0.44-3.83); P = 0.63). VA 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 = 0.64). There were 8 adverse events possibly related to the PBM device and 2 adverse events possibly related to the placebo device. None were serious., Conclusions: PBM as given in this study, although safe and well-tolerated, was not found to be effective for the treatment of CI-DME in eyes with good vision., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Indeterminate biliary strictures are defined as a narrowing of the bile duct that cannot be differentiated as malignant or benign after performing cross-sectional imaging and an ERCP. Identifying the etiology of a bile duct stricture is the single most important step in determining whether a complex and potentially morbid surgical resection is warranted. Due to this diagnostic and therapeutic dilemma, new technologies, laboratory tests, and procedures are emerging to solve this problem., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Chlorella-associated bacteria can have a significant influence on facilitating higher Chlorella biomass yield due to their symbiotic relationship. In this study, non-axenic Chlorella was cultivated in an airlift photobioreactor at high and low-yield conditions. The associated bacterial diversity was analyzed using 16S rRNA metagenome sequencing. At high-yield conditions, the bacterial load was observed in the range of 10 8 -10 10 CFU · mL -1 , whereas at low-yield conditions, bacteria were more dominant and observed in the range of 10 14 -10 15  CFU · mL -1 . The majority of the bacterial species associated with Chlorella at high-yield conditions belongs to Proteobacteria and Bacteroidetes. Further, Bacteroidetes levels were decreased at low-yield conditions and were highly diversified with Planctomycetes, Firmicutes, and 18 others. Predicted functional genes indicated that Chlorella-associated bacteria have the enzymes involved in the metabolism and biosynthesis of B-complex vitamins (i.e., vitamin B 12 , thiamin, biotin, pyridoxine, and riboflavin). A critical evaluation revealed that vitamin biosynthesis genes were more abundant at low-yield conditions; however, vitamin B 12 transport genes (B 12 transport ATP-binding protein, B 12 substrate-binding transportation, and B 12 permease protein) were less abundant, indicating even though vitamins production occurs, but their availability to Chlorella was limited due to the lack of vitamin transport genes. Further, at high yield, Chlorella-associated bacteria enabled higher growth by supplementing the vitamins. In contrast, at low-yield condition-an increased bacterial load, diversity, and limited vitamin transport functional genes affected the Chlorella yield. It can be inferred that Chlorella yield was significantly affected by three factors: associated bacterial load, diversity, and transport functional genes of vitamins., (© 2021 Phycological Society of America.)

In the present study, ozone assisted autohydrolysis (OAAH) was evaluated for enhanced generation of xylooligosaccharide (XOS) from wheat bran. The total XOS yield with optimum ozone dose of 3% (OAAH-3) was found to be 8.9% (w/w biomass) at 110 °C in comparison to 7.96% at 170 °C by autohydrolysis (AH) alone. Although, there was no significant difference in oligomeric composition (DP 2-6), significant decrease in degradation products namely furfural (2.78-fold), HMF (3.15-fold), acrylamide (nil) and acetic acid (1.06-fold), was observed with OAAH-3 as a pretreatment option. There was 1-fold higher xylan to XOS conversion and OAAH-hydrolysate had higher DPPH radical scavenging activity than AH. PCA plots indicated clear enhancement in XOS production and lower generation of inhibitors with decrease in treatment temperature. Results of the study therefore suggest OAAH can be an effective pretreatment option that can further be integrated with downstream processing for concentration and purification of XOS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Anthocyanins biosynthesis is a well-studied biosynthesis pathway in Daucus carota . However, the scale-up production at the bioreactor level and transporter involved in accumulation is poorly understood. To increase anthocyanin content and elucidate the molecular mechanism involved in accumulation, we examined D. carota cell culture in flask and bioreactor for 18 days under salt stress (20.0 mM NH 4 NO 3 /37.6 mM KNO 3 ) at 3 day intervals. The expression of anthocyanin biosynthesis and putative MATE (multidrug and toxic compound extrusion) transporter expression was analyzed by qRT-PCR. It was observed that there was a significant enhancement of anthocyanin in the bioreactor compared to the control culture. A correlation was observed between the expression of MATE and the anthocyanin biosynthesis genes ( CHS , C4H , LDOX , and UFGT ) on the 9th day in a bioreactor, where maximum anthocyanin accumulation and expression was detected. We hypothesize the involvement of MATE in transporting anthocyanin to tonoplast in D. carota culture under salt stress., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

BACKGROUNDAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.METHODSWe conducted a randomized, double-blind, controlled trial among adults hospitalized with severe and critical COVID-19 at 5 sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or normal control plasma. The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.RESULTSOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to receive normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval [CI] 0.83-2.68, P = 0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, P = 0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.CONCLUSIONIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.TRIAL REGISTRATIONClinicalTrials.gov, NCT04359810.FUNDINGAmazon Foundation, Skoll Foundation.

Background and Aims: Popliteal-Sciatic nerve block under Ultrasound Guidance (USG) using a local anesthetic agent like Ropivacaine is an established technique for providing analgesia and muscle relaxation for lower limb surgeries with minimal untoward events. Establishing the minimal volume of 0.2% ropivacaine required to provide intraoperative and postoperative analgesia will further reduce the drug requirements and adverse effects toward the patient., Material and Methods: This randomized prospective observational blinded study was done in a tertiary care referral hospital in South India over 9 months from August 2017 till April 2018. The block was performed on all recruited patients under ultrasound guidance with a starting volume of 16 ml 0.2% ropivacaine. Duration of time for loss of pin-prick sensation around the sole of the foot (tibial nerve) and the lateral malleolus (common peroneal nerve) was noted. If successful, the volume of the drug for subsequent patients was randomized by lottery method to either be kept the same or reduced. If the block failed, the subsequent patient recruited would have an increased volume of drug injected., Results: By Probit regression analysis using the biased coin up-and-down method we found that 9.3 ml (MEAV90) of 0.2% ropivacaine was sufficient for providing adequate analgesia. Factors such as patient age or weight had no role in efficacy of the block. There were no adverse effects such as allergy to the drug or systemic toxicity noted in the studied patients., Conclusion: 9.3 ml of 0.2% ropivacaine is sufficient to provide analgesia (assessed by pin-prick) in 90% of patients undergoing popliteal-sciatic block for lower limb surgeries., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Anaesthesiology Clinical Pharmacology.)

Objective : Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study. Methods : Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment. Results : Thirty-six patients were screened, five treated as first-dose-sentinels and rest randomized, while four patients were screen-failures. Two patients in Arm-A discontinued prior to receiving one complete infusion and were replaced. At end of 1-month, there were three deaths in Arm-B, and none in Arm-A (p = 0.0296; 95% CI = -0.3 [-0.61, -0.08]). At end of study, 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 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events. Conclusion : Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.

The coronavirus disease 2019 pandemic has upended life throughout the globe. Appropriate emphasis has been placed on developing effective therapies and vaccines to curb the pandemic. While awaiting such countermeasures, mitigation efforts coupled with robust testing remain essential to controlling spread of the disease. In particular, serological testing plays a critical role in providing important diagnostic, prognostic, and therapeutic information. However, this information is only useful if the results can be accurately interpreted. This pandemic placed clinical testing laboratories and requesting physicians in a precarious position because we are actively learning about the disease and how to interpret serological results. Having developed robust assays to detect antibodies generated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and serving the hardest-hit areas within the New York City epicenter, we found 3 types of discordances in SARS-CoV-2 test results that challenge interpretation. Using representative clinical vignettes, these interpretation dilemmas are highlighted, along with suggested approaches to resolve such cases., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Multilevel inverters play an important role in extracting the power from renewable energy resources and delivering the output voltage with high quality to the load. This paper proposes a new single-stage switched capacitor nine-level inverter, which comprises an improved T-type inverter, auxiliary switch, and switched cell unit. The proposed topology effectively reduces the DC-link capacitor voltage and exhibits superior performance over recently switched-capacitor inverter topologies in terms of the number of power components and blocking voltage of the switches. A level-shifted multilevel pulse width modulation scheme with a modified triangular carrier wave is implemented to produce a high-quality stepped output voltage waveform with low switching frequency. The proposed nine-level inverter's effectiveness, driven by the recommended modulation technique, is experimentally verified under varying load conditions. The power loss and efficiency for the proposed nine-level inverter are thoroughly discussed with different loads.

Background In complex congenital heart disease patients such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload, leading to RV hypertrophy and eventually RV failure. The mechanisms that promote the transition from stable RV hypertrophy to RV failure are unknown. We evaluated the role of mitochondrial bioenergetics in the development of RV failure. Methods and Results We created a murine model of RV pressure overload by pulmonary artery banding and compared with sham-operated controls. Gene expression by RNA-sequencing, oxidative stress, mitochondrial respiration, dynamics, and structure were assessed in pressure overload-induced RV failure. RV failure was characterized by decreased expression of electron transport chain genes and mitochondrial antioxidant genes (aldehyde dehydrogenase 2 and superoxide dismutase 2) and increased expression of oxidant stress markers (heme oxygenase, 4-hydroxynonenal). The activities of all electron transport chain complexes decreased with RV hypertrophy and further with RV failure (oxidative phosphorylation: sham 552.3±43.07 versus RV hypertrophy 334.3±30.65 versus RV failure 165.4±36.72 pmol/(s×mL), P <0.0001). Mitochondrial fission protein DRP1 (dynamin 1-like) trended toward an increase, while MFF (mitochondrial fission factor) decreased and fusion protein OPA1 (mitochondrial dynamin like GTPase) decreased. In contrast, transcription of electron transport chain genes increased in the left ventricle of RV failure. Conclusions Pressure overload-induced RV failure is characterized by decreased transcription and activity of electron transport chain complexes and increased oxidative stress which are associated with decreased energy generation. An improved understanding of the complex processes of energy generation could aid in developing novel therapies to mitigate mitochondrial dysfunction and delay the onset of RV failure.

Animal's well-being, growth, and production are modulated by environmental conditions, and managemental practices and can be deleteriously affected by global warming phenomenon. In the recent years, unprecedented climatic fluctuations like sustained higher temperatures and humidity, heat waves, and solar flares have led to economic losses in $ billions to both milk and meat industry. It is estimated that by 2050, the US dairy industry alone will borne more than $1.7 billion loss. As human dependency on animal products like milk, meat, and eggs for nutrition is exponentially rising, there is urgency for maximum production. The high yielding animals are already under tremendous metabolic pressure making them more susceptible to adverse climatic conditions. When exposed to heat stress, livestock display a variety of behavioral and physiological acclimatization as essential survival strategies, but at the cost of decreased milk, meat, or egg production. Most of the studies have explored the heat stress in animals and its effect on different milk productions in a specific region or country. A clear understanding of the impact of global warming on dairy enterprise is yet to be comprehended. So this exploratory study will analyze impact of global warming on current milk production trends, economics, and future perspectives.

Most Achilles tendon surgeries are performed with the patient in the prone position. Some advocate supine position but the access to the tendon is compromised. We describe an innovative technique wherein the patient is positioned lateral but the surgeon has full access to the Achilles tendon as if the patient were positioned prone. We consider that this technique could be easily reproduced and hence widely adopted., (Copyright © 2020 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: In patients with complex congenital heart disease, such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload stress, leading to RV hypertrophy and eventually RV failure. The role of lipid peroxidation, a potent form of oxidative stress, in mediating RV hypertrophy and failure in congenital heart disease is unknown., Methods: Lipid peroxidation and mitochondrial function and structure were assessed in right ventricle (RV) myocardium collected from patients with RV hypertrophy with normal RV systolic function (RV fractional area change, 47.3±3.8%) and in patients with RV failure showing decreased RV systolic function (RV fractional area change, 26.6±3.1%). The mechanism of the effect of lipid peroxidation, mediated by 4-hydroxynonenal ([4HNE] a byproduct of lipid peroxidation) on mitochondrial function and structure was assessed in HL1 murine cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes., Results: RV failure was characterized by an increase in 4HNE adduction of metabolic and mitochondrial proteins (16 of 27 identified proteins), in particular electron transport chain proteins. Sarcomeric (myosin) and cytoskeletal proteins (desmin, tubulin) also underwent 4HNE adduction. RV failure showed lower oxidative phosphorylation (moderate RV hypertrophy, 287.6±19.75 versus RV failure, 137.8±11.57 pmol/[sec×mL]; P =0.0004), and mitochondrial structural damage. Using a cell model, we show that 4HNE decreases cell number and oxidative phosphorylation (control, 388.1±23.54 versus 4HNE, 143.7±11.64 pmol/[sec×mL]; P <0.0001). Carvedilol, a known antioxidant did not decrease 4HNE adduction of metabolic and mitochondrial proteins and did not improve oxidative phosphorylation., Conclusions: Metabolic, mitochondrial, sarcomeric, and cytoskeletal proteins are susceptible to 4HNE-adduction in patients with RV failure. 4HNE decreases mitochondrial oxygen consumption by inhibiting electron transport chain complexes. Carvedilol did not improve the 4HNE-mediated decrease in oxygen consumption. Strategies to decrease lipid peroxidation could improve mitochondrial energy generation and cardiomyocyte survival and improve RV failure in patients with congenital heart disease.

Coupling of the El Niño-Southern Oscillation (ENSO) and Indian monsoon (IM) is central to seasonal summer monsoon rainfall predictions over the Indian subcontinent, although a nonstationary relationship between the two nonlinear phenomena can limit seasonal predictability. Radiative effects of volcanic aerosols injected into the stratosphere during large volcanic eruptions (LVEs) tend to alter ENSO evolution; however, their impact on ENSO-IM coupling remains unclear. Here, we investigate how LVEs influence the nonlinear behavior of the ENSO and IM dynamical systems using historical data, 25 paleoclimate reconstructions, last-millennium climate simulations, large-ensemble targeted climate sensitivity experiments, and advanced analysis techniques. Our findings show that LVEs promote a significantly enhanced phase-synchronization of the ENSO and IM oscillations, due to an increase in the angular frequency of ENSO. The results also shed innovative insights into the physical mechanism underlying the LVE-induced enhancement of ENSO-IM coupling and strengthen the prospects for improved seasonal monsoon predictions., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Introduction: The globally rampant SARS CoV-2 pandemic requires novel medical strategies to control the severity of disease and death due to complications. Of the 15-20% patients that develop pulmonary symptoms, a sub-set develops an acute respiratory distress syndrome (ARDS) rapidly progressing into a critical condition. Marked elevation of cytokines/chemokines is observed with elevation of additional markers of inflammation, coagulation, and organ damage such as CRP, D-dimer, LDH, Ferritin and Troponin-I. This hyperinflammation leads to worsening of oxygen saturation due to pulmonary infiltration and exudation, organ damage, and dysfunction of coagulation pathway and may lead to multi-organ failure., Areas Covered: The role of anti-inflammatory monoclonal antibodies such as Itolizumab, in cytokine storm., Expert Opinion: Itolizumab, an anti-CD6 humanized IgG1 mAb, binds to domain-1 of CD-6 that is responsible for priming, activation, and differentiation of T-cells. Itolizumab significantly reduces T-cell proliferation along with substantial downregulation of the production of cytokines/chemokines. Approved for moderate to severe chronic plaque psoriasis in 2013 it is currently being studied for addressing COVID-19 related cytokine storm and its complications. This article reviews its use in COVID-19 infections; its dose, administration protocol, contra-indications, and safety in treating moderate-to-severe ARDS by preventing and treating the cytokine storm and its complications.

The 3D MHD nonlinear radiative hybrid nanofluid flow across an irregular dimension sheet with slip effect is studied numerically. The hybrid nanofluid consists of copper oxide (CuO) and magnesium oxide (MgO) nanoparticles embedded in methanol or methyl alcohol (MA). The governing PDEs' are altered as ODEs' using similarities and numerical solutions are attained using shooting scheme. The role of corporal factors on the transport phenomenon is analyzed and reflected by plots and numerical interpretations. Simultaneous solutions presented for CuO-MA nanofluid and CuO-MgO/MA hybrid nanofluid. Results ascertain that the temperature and flow boundary layer thicknesses are not unique for the hybrid nanofluid and nanofluid. The heat transfer enactment of CuO-MA nanofluid is high when equated to CuO-MgO/MA hybrid nanofluid. This concludes that the CuO-MgO combination works as a good insulator.

The movement of the ferrous nanoparticles is random in the base fluid, and it will be homogeneous under the enforced magnetic field. This phenomenon shows a significant impact on the energy transmission process. In view of this, we inspected the stream and energy transport in magnetohydrodynamic dissipative ferro and hybrid ferrofluids by considering an uneven heat rise/fall and radiation effects. We studied the Fe 3 O 4 (magnetic oxide) and CoFe 2 O 4 (cobalt iron oxide) ferrous particles embedded in H 2 O-EG (ethylene glycol) (50-50%) mixture. The flow model is converted as ODEs with suitable similarities and resolved them using the 4th order Runge-Kutta scheme. The influence of related constraints on transport phenomena examined through graphical illustrations. Simultaneous solutions explored for both ferro and hybrid ferrofluid cases. It is found that the magnetic oxide and cobalt iron oxide suspended in H 2 O-EG (ethylene glycol) (50-50%) mixture effectively reduces the heat transfer rate under specific conditions.

Background: Gingival recession (GR) is a common clinical feature of periodontal disease and is an undesirable condition. More than 50% of the population has one or more sites with GR ≥ 1 mm., Material and Methods: In this study 15 subjects were subjected to initial periodontal therapy such as ultrasonic scaling and root planning with hand instruments and curettes. Patient is motivated for home care. The buccal fat pad is harvested and sutured in the gingival recession area and followed up for 6 months and root coverage was calculated., Results: At baseline mean recession of 5.60 ± 1.18 mm, probing depth of 0.73 ± 0.59 mm, clinical attachment loss of 6.40 ± 1.18 mm were recorded. At the end of 6 months, the mean recession was reduced from 5.60 ± 1.18 mm to 2.87 ± 0.74 mm, probing depth was increased from 0.73 ± 0.59 mm to 1.73 ± 0.70 mm and clinical attachment loss was decreased from 6.40 ± 1.18 mm to 4.53 ± 0.83 mm.The difference between baseline score and six months score for all three parameters are statistically significant., Conclusion: Buccal fat pad is a predictable procedure to cover Miller's class III and class IV gingival recession defects. There was a definitive improvement in clinical parameters (reduction in gingival recession, increased probing depth, gain in clinical attachment) after 6 months. There was 46.78% improvement in root coverage which was statistically significant., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

A 3-D magnetohydrodynamic flow of hybrid nanofluid across a stretched plane of non-uniform thickness with slip effects is studied. We pondered aluminum alloys of AA7072 and AA7072 + AA7075 in methanol liquid. The aluminum alloys amalgamated in this study are uniquely manufactured materials, possessing enhanced heat transfer features. AA7072 alloy is a composite mixture of Aluminum & Zinc in the ratio 98 & 1 respectively with added metals Silicon, ferrous and Copper. Equally, AA7075 is a mixture of Aluminum, Zinc, Magnesium, and Copper in the ratio of ~90, ~6, ~3 and ~1 respectively with added metals Silicon ferrous and Magnesium. Numerical solutions are attained using R-K based shooting scheme. Role of physical factors on the flow phenomenon are analyzed and reflected by plots and numerical interpretations. Results ascertain that heat transfer rate of the hybrid nanoliquid is considerably large as matched by the nanofluid. The impact of Lorentz force is less on hybrid nanofluid when equated with nanofluid. Also, the wall thickness parameter tends to improve the Nusselt number of both the solutions.

Chlorella vulgaris is used for food and feed applications due to its nutraceutical, antioxidant and anticancer properties. An airlift photobioreactor comprising transparent draft tube was used for C. vulgaris cultivation. The effect of reactor parameters like hydrodynamics (0.3-1.5 vvm), light intensity (85-400 μmol m -2  s -1 ), photoperiod (12-24 h) and gas-phase carbon dioxide (CO 2 ) concentration (5-15% v/v) were evaluated on microalgae and associated bacterial growth, biochemical profile; with special emphasis on ω-3, ω-6 fatty acids, and vitamin B 12 . The optimal growth of C. vulgaris without CO 2 supplementation was observed at 1.2 vvm, which was associated with higher algal productivity, chlorophyll, vitamin B 12 content, and bacterial load along with 72% of nitrate removal. The higher light intensity (400 μmol m -2  s -1 ) and photoperiod (24:0) increased biomass productivity and ω-3 fatty acid content (in lipid) up to 2-3 fold. The elevated levels of gas-phase CO 2 concentration (15% v/v) enhanced EPA content up to 7% and biomass productivity up to 171 mg L -1  day -1 . However, the increase in CO 2 concentration lowered vitamin B 12 content (up to 30%) and bacterial load (2-3 log). Also, all the cultivation conditions favoured desirable ω-6/ω-3 ratio(in the range of 1-2)., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Association of Food Scientists & Technologists (India) 2019.)

We evaluated the pharmacokinetics and pharmacodynamics of oral insulin tregopil in relation to premeal dosing time, between-meal interval, and meal composition type in type 2 diabetes mellitus patients in a randomized, placebo-controlled, crossover study consisting of 3 sequential cohorts. In Cohort 1, insulin tregopil administered 10 to 20 minutes before a meal resulted in optimal postmeal exposure and demonstrated better postprandial glucose-lowering effect (glucose area under concentration-time curve [AUC]) compared to the 30-minute group. In Cohort 2, insulin tregopil pharmacokinetic exposure (plasma AUC) showed a progressive increase through 4, 5, and 6 hours of between-meal interval. The 6-hour between-meal interval resulted in better absorption of insulin tregopil in comparison to 4- and 5-hour intervals. However, no significant differences were observed in pharmacodynamic parameters except for higher glucose AUC 0-180min in the insulin tregopil 4-hour group during the afternoon meal as compared to the morning meal. In Cohort 3, a high-fiber meal had the least impact on insulin tregopil absorption and resulted in the highest reduction in plasma glucose levels in the afternoon. A high-fat meal reduced insulin tregopil absorption in the afternoon meal; however, pharmacodynamic response was not diminished significantly. Insulin tregopil has a rapid onset of action of approximately 10 minutes and, when administered 10 to 20 minutes before a meal, demonstrated up to 13% to 18% reduction in blood glucose levels compared to baseline. A 5-hour between-meal interval minimizes the impact of a meal on absorption of subsequent (afternoon) insulin tregopil dose, and the pharmacodynamic response of insulin tregopil is not altered by meal composition. Insulin tregopil was well tolerated in patients with type 2 diabetes mellitus., (© 2019 Biocon Limited. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)

To combat food scarcity as well as to ensure nutritional food supply for sustainable living of increasing population, microalgae are considered as innovative sources for adequate nutrition. Currently, the dried biomass, various carotenoids, phycocyanin, phycoerythrin, omega fatty acids, and enzymes are being used as food additives, food coloring agents, and food supplements. Apart from nutritional importance, microalgae are finding the place in the market as "functional foods." When compared to the total market size of food and feed products derived from all the possible sources, the market portfolio of microalgae-based products is still smaller, but increasing steadily. On the other hand, the genetic modification of microalgae for enhanced production of commercially important metabolites holds a great potential. However, the success of commercial application of genetically modified (GM) algae will be defined by their safety to human health and environment. In view of this, the present study attempts to highlight the industrially important microalgal metabolites, their production, and application in food, feed, nutraceuticals, pharmaceuticals, and cosmeceuticals. The current and future market trends for microalgal products have been thoroughly discussed. Importantly, the safety pertaining to microalgae cultivation and consumption, and regulatory issues for GM microalgae have also been covered., (© 2019 Institute of Food Technologists®.)

This report presents the flow and heat transfer characteristics of MHD micropolar fluid due to the stretching of a surface with second order velocity slip. The influence of nonlinear radiation and irregular heat source/sink are anticipated. Simultaneous solutions are presented for first and second-order velocity slips. The PDEs which govern the flow have been transformed as ODEs by the choice of suitable similarity transformations. The transformed nonlinear ODEs are converted into linear by shooting method then solved numerically by fourth-order Runge-Kutta method. Graphs are drowned to discern the effect of varied nondimensional parameters on the flow fields (velocity, microrotation, and temperature). Along with them the coefficients of Skin friction, couple stress, and local Nussel number are also anticipated and portrayed with the support of the table. The results unveil that the non-uniform heat source/sink and non-linear radiation parameters plays a key role in the heat transfer performance. Also, second-order slip velocity causes strengthen in the distribution of velocity but a reduction in the distribution of temperature is perceived.

Composting is a biological process in which the organic matter is degraded by the mixed population of microorganisms in a moist aerobic environment to more stable and humidified end products. The composting process involves an interaction between the organic waste, microorganisms, moisture and oxygen. The molasses-based biomethanated distillery wastewater is presently effectively utilized with sugarcane pressmud through the composting process. The aim of present work was to evaluate the effect of ozone pretreatment on the rate of composting process and the quality of compost obtained. The GC-MS & FTIR analysis of ozone pretreated wastewater indicated the degradation and/or transformation of the organic compounds to simpler compounds present in the wastewater. Composting was performed by mixing fixed weight ratios of pressmud and different ratios of ozone pretreated wastewater (1:3, 1:4 and 1:5). The composting process was found to occur faster in the ozone pretreated wastewater for all the ratios as compared to the untreated wastewater. The final compost characteristics were found to be optimum for the 1:3 and 1:4 ratios of pressmud and wastewater. The bio-oxidative phase duration of composting has been reduced for the ozone pretreated wastewater., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The effectiveness of O 3 , O 3 /Fe 2+ , and O 3 /nZVI processes on biomethanated distillery wastewater (BMDWW) was evaluated in terms of biodegradability index (BI) enhancement, biofuel production, COD, color & toxicity reduction. A significant increase in biodegradability, COD, color and toxicity reduction was observed in O 3 /nZVI compared with O 3 , O 3 /Fe 2+ due to more hydroxyl radical production. The O 3 /nZVI pretreated wastewater with enhanced BI (up to 0.71) showed 60% COD removal with additional biogas generation (64% methane content). From the Gas Chromatography Mass Spectrometry (GC-MS) analysis, 18 foremost organic compounds were predominantly detected in the raw distillery wastewater. The disappearance of the corresponding FTIR (Fourier Transform Infrared Spectroscopy) & GC-MS spectra during pretreatment processes signified the degradation or transformation of the recalcitrant present in the distillery wastewater. Subsequent (AnO + AO, AO) of pretreated BMDWW resulted in biodegradation rate enhancement by (1.83, 1.67), (3.5, 2.4) and (4.7, 2.9) times for O 3 , O 3 /Fe 2+ and O 3 /nZVI processes respectively., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The study reports the biodegradability enhancement of pharmaceutical wastewater along with COD (Chemical Oxygen Demand) color and toxicity removal via O 3 , O 3 /Fe 2+ , O 3 /nZVI (nano zero valent iron) processes. Nano catalytic ozonation process (O 3 /nZVI) showed the highest biodegradability (BI = BOD 5 /COD) enhancement of pharmaceutical wastewater up to 0.63 from 0.18 of control with a COD, color and toxicity removal of 62.3%, 93% and 82% respectively. The disappearance of the corresponding Fourier transform infrared (FTIR) and gas chromatography-mass spectrometry (GC-MS) peaks after pretreatment indicated the degradation or transformation of the refractory organic compounds to more biodegradable organic compounds. The subsequent aerobic degradation study of pretreated pharmaceutical wastewater resulted in biodegradation rate enhancement of 5.31, 2.97, and 1.22 times for O 3 /nZVI O 3 /Fe 2+ and O 3 processes respectively. Seed germination test using spinach (Spinacia oleracea) seeds established the toxicity removal of pretreated pharmaceutical wastewater., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Incorporation of Spirulina in milk as thermally dried powder has the disadvantages of non-uniform distribution with undesirable odor and flavor. Through homogenization (200 ± 10 bar), complete dispersion of fresh Spirulina biomass (7% w/w) in milk was achieved and thereafter a carotenoid enriched probiotic yogurt was developed. Confocal microscopy revealed porous Spirulina -milk protein matrix integrated with smaller fat globules in the yogurt. Spirulina led to a 29.56% increase in Lactobacillus acidophilus count, a 20% reduction in fermentation time and a total probiotic count of 1.2 × 10 7 CFU mL -1 . The protein, total chlorophyll, total carotenoid and β-carotene content (on dry w/w basis) were 3.58 ± 0.08 g 100 g -1 , 0.407 ± 0.018 mg g -1 , 0.235 ± 0.016 mg g -1 and 13.28 ± 0.08 µg g -1 , respectively. During storage (18 days at 6-8 °C), the L. acidophilus count reached 8.83 ± 0.11 log CFU mL -1 with 103.03% increase in the viability by day three and the yogurt retained 71.5% carotenoids. The probiotc Spirulina yogurt was found to be acceptable to consumers as evaluated by affective consumer test.

Background: Vascular rings with a Kommerell diverticulum (KD) most commonly occur in patients with a right aortic arch. We report on a less commonly seen subset of vascular ring patients-those with a double aortic arch and a KD., Methods: Between 2002 and 2017, 66 patients underwent an operation for a double aortic arch. Ten of those patients also had excision of a KD. We performed a retrospective medical record review of these patients to characterize their demographics and outcomes., Results: All 10 patients (7 male, 3 female) had a double aortic arch that was right dominant and also had a KD. The patients were a mean age of 4.9 ± 4.3 years (range, 6 months to 29 years), and median age was 4 years. All patients had preoperative computed tomographic angiography or magnetic resonance imaging and mean compression of the distal trachea of 63% ± 12% (range, 40% to 80%). The distal left arch was atretic in all patients. All patients underwent division of their left aortic arch, division of the ligamentum, and resection of the KD. The left subclavian artery was transferred to the left carotid artery in 2 patients. The mean size of the diverticulum was 9 × 10 mm. There were no major postoperative complications or readmissions. The postoperative length of stay was 3.1 ± 0.8 days. Five of the patients reported no related persisting symptoms. The remaining 5 patients reported substantial symptomatic relief with only minor respiratory symptoms., Conclusions: Vascular ring patients with a double aortic arch can also have a KD. In addition to dividing the smaller aortic arch and the ligamentum, we recommend excision of the KD., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)