Publications by authors named "Nitin Sharma"

119 Publications

Clinical and molecular implications of NAB2-STAT6 fusion variants in solitary fibrous tumour.

Pathology 2021 Mar 18. Epub 2021 Mar 18.

Department of Tumour Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address:

Solitary fibrous tumour (SFT) is a mesenchymal neoplasm characterised by pathognomonic NAB2-STAT6 gene fusions. The clinical implications and prognostic value of different fusion variants has not been clarified. In the current study, we explore the clinicopathological, prognostic and molecular differences between tumours with different fusions. Thirty-nine patients with localised, extrameningeal SFT were included, of whom 20 developed distant recurrence and 19 were without recurrence after long term follow-up. Capture-based RNA sequencing identified 12 breakpoint variants, which were categorised into two groups based on the STAT6 domain composition in the predicted chimeric proteins. Twenty-one of 34 (62%) sequenced tumours had fusions with most of the STAT6 domains intact and were classified as STAT6-Full. Thirteen tumours (38%) contained only the transactivation domain of STAT6 and were classified as STAT6-TAD. Tumours with STAT6-TAD fusions had a higher mitotic count (p=0.016) and were associated with inferior recurrence-free interval (p=0.004) and overall survival (p=0.012). Estimated 10-year recurrence-free survival was 25% for patients with STAT6-TAD tumours compared to 78% for the STAT6-Full group. Distinct transcriptional signatures between the fusion groups were identified, including higher expression of FGF2 in the STAT6-TAD group and IGF2, EGR2, PDGFRB, STAT6 and several extracellular matrix genes in STAT6-Full tumours. In summary, we demonstrate that NAB2-STAT6 fusion variants are associated with distinct clinicopathological and molecular characteristics and have prognostic significance in extrameningeal SFT.
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http://dx.doi.org/10.1016/j.pathol.2020.11.010DOI Listing
March 2021

Intranasal delivery of Naloxone-loaded solid lipid nanoparticles as a promising simple and non-invasive approach for the management of opioid overdose.

Int J Pharm 2021 Apr 1;599:120428. Epub 2021 Mar 1.

Department of Pharmaceutics, School of Pharmaceutical sciences, Delhi Pharmaceutical Science and Research University, Delhi 110017, India. Electronic address:

Naloxone is an opioid receptor antagonist that can eradicate all pre-indications of the toxicity and inverse the opioid overdose. However, oral administration of naloxone offers limitations such as its extensive first-pass metabolism that results in poor therapeutic effects. In order to resolve this issue, we developed intranasal solid-lipid nanoparticles in which naloxone was incorporated for the higher brain disposition of naloxone with superior therapeutic effects for the reversal of toxicity of opioid overdose. The preparation of naloxone loaded solid-lipid nanoparticles was done by employing the solvent evaporation method. Later, the designed formulation was optimized by Quality by Design approach, specifically, Box-Behnken method. The composition of optimized formulation was Glyceryl monostearate as a solid lipid (40 mg), Pluronic127 (0.5%) and Tween 80 (0.1%) as a surfactant and co-surfactant, respectively. Furthermore, the characterization of optimized formulation was achieved in terms of particle size, PDI, zeta potential, entrapment efficiency, and drug loading which were 190.2 nm, 0.082, -16 mV, 95 ± 0.532% and 19.08 ± 0.106%, respectively. Afterwards, in vitro, ex vivo and in vivo experiments were performed in which higher drug release and superior drug uptake by nasal membrane were observed for naloxone-loaded solid-lipid nanoparticles, later it was confirmed by confocal microscopy of ex vivo nasal membrane tissue. The findings of gamma scintigraphy investigation exhibited better deposition of naloxone-loaded solid-lipid nanoparticles as compared to naloxone solution. Also, the better deposition of naloxone by gamma scintigraphy was further validated by the investigation through the biodistribution study. Additionally, the key findings of the pharmacokinetic study revealed C, T, AUC, AUC, T and K was found to be 163.95 ± 2.64 ng/ml, 240 ± 2.1 min, 17.75 ± 1.08 ng.hr/ml, 18.82 ± 2.51 ng.hr/ml, 70.71 ± 0.115 min, 0.098 ± 0.01 h respectively. Lastly, investigations such as weight variation and histopathological proved the plausible potential of naloxone-loaded solid-lipid nanoparticles in terms of safety as no toxicity was noticed even after the administration of the three-folds dose of the normal dose. Therefore, considering all these findings, it could be easy to say that these developed naloxone-loaded solid-lipid nanoparticles could be administrated via intranasal route and can act as successful novel nanoformulation for the effective treatment of opioid overdose.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120428DOI Listing
April 2021

Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways.

Front Pharmacol 2021 10;12:618773. Epub 2021 Feb 10.

Department of Chemistry, Center for Molecular Science Informatics, University of Cambridge, Cambridge, United Kingdom.

Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituents is currently not fully understood. The combination of ginsenosides Rb2 and Rg3 were studied in human umbilical vein endothelial cells (HUVECs) for their proangiogenic effects. To understand the mode of action of the combination in more mechanistic detail, RNA-Seq analysis was conducted, and differentially expressed genes (DEGs), pathway analysis and Weighted Gene Correlation Network Analysis (WGCNA) were applied to further identify important genes that a play pivotal role in the combination treatment. The effects of pathway-specific inhibitors were observed to provide further support for the hypothesized mode of action of the combination. Ginsenosides Rb2 and Rg3 synergistically promoted HUVEC proliferation and tube formation under defined culture conditions. Also, the combination of Rb2/Rg3 rescued cells from homocysteine-induced damage. mRNA expression of was significantly elevated by the Rb2/Rg3 treatment, and representative signaling pathways induced by these genes were found. The increase of protein levels of phosphorylated-Akt and ERK42/44 by the Rb2/Rg3 combination supports the notion that it promotes endothelial cell proliferation the PI3K/Akt and MAPK/ERK signaling pathways. The present study provides the hypothesis that SBP, ginsenosides Rb2 and Rg3, involves the CXCR1/2 CXCL8 (IL8)-mediated PI3K/Akt and MAPK/ERK signaling pathways in achieving its proangiogenic effects.
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http://dx.doi.org/10.3389/fphar.2021.618773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902932PMC
February 2021

Intranasal solid lipid nanoparticles for management of pain: A full factorial design approach, characterization & Gamma Scintigraphy.

Chem Phys Lipids 2021 May 11;236:105060. Epub 2021 Feb 11.

Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organisation, Timarpur, Delhi, India. Electronic address:

Pain is a noxious stimulus caused due to tissue damage and varies from mild to severe. Nalbuphine (NLB) is an approved, inexpensive, non-controlled, opioid agonist/antagonist analgesic used worldwide in various clinical settings for pain management. The current study aims to formulate NLB loaded solid lipid nanoparticles (SLNs) using solvent injection technology. The morphological and chemical structure of the developed SLNs were characterized using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM) and Fourier Transformation Infrared Spectroscopy (FTIR). The results revealed from the point prediction confirmation in design expert software was the formulation of NLB-SLNs with an average particle size of (170.07 ± 25.1 nm), encapsulation efficiency (93.6 ± 1.5%) & loading capacity of 26.67%. The in-vitro permeation of developed NLB-SLNs was observed to be 94.18% at 8 h when compared with NLB solution whose maximum permeation was seen within 3 h of application. Efficacy of the formulation was also evaluated using eddy's hot plate method, where the onset of action started within 10 min of administration, and the maximum effect was observed at 1 h. The NLB-SLNs was screened for cytotoxicity in human embryonic kidney cells (HEK-293), and the dosage was considered safe when administered intranasally in animal since no detectable effect to the brain was observed. Biodistribution and gamma scintigraphy study of NLB-SLNs showed the prepared formulation reaching the target site, i.e. brain and was retained. Conclusively, the prepared NLB-SLNs formulation was safe and effective in producing an analgesic effect in vivo.
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http://dx.doi.org/10.1016/j.chemphyslip.2021.105060DOI Listing
May 2021

Predictability of 48-h delayed retention of contrast in barium enema in cases of chronic constipation.

Afr J Paediatr Surg 2020 Jan-Jun;17(1-2):15-17

Department of Anaesthesiology, CM Hospital and Associated Medical College, Bhilai, Chhattishgarh, India.

Introduction: Diagnosis of Hirschsprung's disease depends on rectal biopsy. This study was designed to find an alternate diagnostic modality to exclude Hirschsprung's disease.

Aim: The aim of this study was to find the predictive value of delayed retention of contrast in excluding Hirschsprung's disease.

Materials And Methods: All cases of chronic constipation presenting during the study duration from June 2014 to June 2016 were included. Those without any obvious history of conservative management were excluded. Parameters considered in barium enema were initial film, routine films, and delayed retention of contrast at 24, 48, and 72 h. They were then subjected to rectal biopsy. The results of rectal biopsy and barium enema were analyzed.

Results: One hundred and thirty-eight patients presented during the study duration. One hundred and twenty-eight formed the study group. The average age of presentation was 48 months (range, 1-144). The average duration of prior medical management was 8 months (range, 6-48 months). Forty-two cases were diagnosed as Hirschsprung's disease on rectal biopsy. The symptoms resolved in 31 cases after rectal biopsy and 42 cases after definitive surgery. In the remaining 55 cases, dietary modification along with laxatives was instituted, and they were kept under follow-up. The average follow-up was 12 months (range, 6-48 months). Of the various parameters in barium enema, delayed retention of contrast at 48 h had the highest negative predictive value of 99.67%.

Conclusion: Delayed retention of contrast at 48 h has the highest negative predictive value in excluding Hirschsprung's disease. This can safely be used to exclude Hirschsprung's disease in cases of chronic constipation.
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http://dx.doi.org/10.4103/ajps.AJPS_35_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818665PMC
March 2021

Efficacy of Single Transverse Neck Incision for Modified Radical Neck Dissection.

J Maxillofac Oral Surg 2020 Sep 26;19(3):342-346. Epub 2019 Jul 26.

Department of Head and Neck Oncology, HCG Cancer Centre, Ahmedabad, Gujarat 380060 India.

Background: To assess the viability of the single transverse neck incision (STNI) for modified radical neck dissection and to analyze the yield of lymph nodes using this approach.

Materials And Methods: We conducted a prospective observational study in the Department of Head and Neck Surgical Oncology at our Tertiary Cancer Care Centre from November 2013 to May 2017.

Results: A total of 257 patients underwent surgical treatment for malignant tumors of the head and neck which included 265 modified radical neck dissections (eight bilateral and 249 unilateral). Average of total dissected nodal yield was 37.07. Average yield of positive neck nodes was 2.78.

Conclusion: Single transverse neck incision is an acceptable technique for modified radical neck dissection as it provides adequate surgical exposure for achieving optimal nodal clearance with little technical difficulty.
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http://dx.doi.org/10.1007/s12663-019-01261-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410989PMC
September 2020

Small molecule inhibitors possibly targeting the rearrangement of Zika virus envelope protein.

Antiviral Res 2020 10 9;182:104876. Epub 2020 Aug 9.

School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India. Electronic address:

The recurrent public health threat imposed by Zika Virus (ZIKV) in various geographical areas necessitates the immediate development of antiviral compounds or vaccines. Flaviviral Envelope (E) proteins are essential for host-cell recognition and virion entry. Consequently, they represent an important target for antiviral therapy, with the aim of preventing viral spread during early stages of infection. Due to conformational rearrangement during entry, flavivirus E proteins present several alternative conformations as potential antiviral targets - for blocking entry or virus-host membrane fusion. We previously identified a conserved hydrophobic region, between DI/DIII of ZIKV E protein, with potential to act as an antiviral target. Here, we screened commercially available antiviral compound libraries against ZIKV E protein, using a structure-based drug discovery approach. The antiviral efficacy of the top ten screened compounds were experimentally validated for inhibition of ZIKV replication in Vero Cells. Compound F1065-0358 was observed to inhibit ZIKV replication with an IC50 of 14.0 μM. Ligand-protein complex molecular dynamic simulations confirmed the stability of ligand binding up to 100 ns. Together, results from this study indicate that F1065-0358 functions as a ZIKV virus inhibitor by interfering E protein conformational rearrangement. Furthermore, given that F1065-0358 interacts with highly conserved residues of E protein, this raises the potential for its efficacy against other pathogenic flaviviruses.
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http://dx.doi.org/10.1016/j.antiviral.2020.104876DOI Listing
October 2020

Evaluation of Non-Invasive Ankle Joint Effort Prediction Methods for Use in Neurorehabilitation Using Electromyography and Ultrasound Imaging.

IEEE Trans Biomed Eng 2021 Mar 18;68(3):1044-1055. Epub 2021 Feb 18.

Objective: Reliable measurement of voluntary human effort is essential for effective and safe interaction between the wearer and an assistive robot. Existing voluntary effort prediction methods that use surface electromyography (sEMG) are susceptible to prediction inaccuracies due to non-selectivity in measuring muscle responses. This technical challenge motivates an investigation into alternative non-invasive effort prediction methods that directly visualize the muscle response and improve effort prediction accuracy. The paper is a comparative study of ultrasound imaging (US)-derived neuromuscular signals and sEMG signals for their use in predicting isometric ankle dorsiflexion moment. Furthermore, the study evaluates the prediction accuracy of model-based and model-free voluntary effort prediction approaches that use these signals.

Methods: The study evaluates sEMG signals and three US imaging-derived signals: pennation angle, muscle fascicle length, and echogenicity and three voluntary effort prediction methods: linear regression (LR), feedforward neural network (FFNN), and Hill-type neuromuscular model (HNM).

Results: In all the prediction methods, pennation angle and fascicle length significantly improve the prediction accuracy of dorsiflexion moment, when compared to echogenicity. Also, compared to LR, both FFNN and HNM improve dorsiflexion moment prediction accuracy.

Conclusion: The findings indicate FFNN or HNM approach and using pennation angle or fascicle length predict human ankle movement intent with higher accuracy.

Significance: The accurate ankle effort prediction will pave the path to safe and reliable robotic assistance in patients with drop foot.
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http://dx.doi.org/10.1109/TBME.2020.3014861DOI Listing
March 2021

Enhancement in brain uptake of vitamin D nanoemulsion for treatment of cerebral ischemia: formulation, gamma scintigraphy and efficacy study in transient middle cerebral artery occlusion rat models.

J Microencapsul 2020 Nov 6;37(7):492-501. Epub 2020 Aug 6.

Department of Pharmaceutical Technology, Meerut Institute of Engineering & Technology, Meerut, India.

Aim: For the treatment of cerebral ischaemia, vitamin-D loaded nanoemulsions were developed.

Method: Tween 20 and polyethylene glycol were chosen as surfactant/co-surfactant, while oleic acid as the oil phase. The formulation was characterised for various parameters. Targeting efficiency was investigated through radiometry, gamma scintigraphy and efficacy was studied in transient middle cerebral artery occlusion (MCAo) rat model.

Result: Vitamin D-nanoemulsion showed a mean size range of 49.29 ± 10.28 nm with polydispersity index 0.17 ± 0.04 and zeta potential 13.77 mV. The formulation was found stable during thermodynamic stability study and permeated within 180 min through sheep nasal mucosa (permeation coefficient 7.873 ± 0.884 cm/h). Gamma scintigraphy and radiometry assay confirmed better percentage deposition (2.53 ± 0.17%) of Tc-vitamin D-nanoemulsion through nasal route compared to IV administered Tc-vitamin D solution (0.79 ± 0.03%). Magnetic Resonance Imaging (MRI) of the ischaemic model confirmed better efficacy of vitamin D-nanoemulsion.

Conclusion: This work demonstrated better permeation, deposition, and efficacy of vitaminD-nanoemulsion through the intranasal route.
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http://dx.doi.org/10.1080/02652048.2020.1801870DOI Listing
November 2020

Polysaccharides like pentagalloylglucose, parishin a and stevioside inhibits the viral entry by binding the Zika virus envelope protein.

J Biomol Struct Dyn 2020 Jul 24:1-13. Epub 2020 Jul 24.

Indian Institute of Technology Mandi, VPO Kamand, Himachal Pradesh, India.

ZIKV belongs to a flavivirus family in which class II fusion proteins involve a low pH-dependent membrane fusion leading to infection of host cells. Envelope (E) protein is primarily responsible for the viral host membrane fusion and is the major target for inhibiting viral entry. Our findings reveal that compounds like PGG, Parishin A, and Stevioside have shown a high affinity for E protein and found to be active against various other viral infections. The binding of these molecules to E protein was found to decrease the RMSD and RMSF values of the ligand protein complex and restricted the Radius of Gyration in molecular dynamics simulation analysis. Further, the binding free energy calculations suggested the stability of complexes throughout simulations trajectory that could reduce the flexibility of the linker so as to block the folding back event of membrane fusion. A recent study has shown that PGG inhibits the early stages of viral entry in HCV and ZIKV. Therefore, we propose that PGG inhibits the entry of virion via binding the E protein and restricting the conformational rearrangement during membrane fusion. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1797538DOI Listing
July 2020

Using Person-Specific Muscle Fatigue Characteristics to Optimally Allocate Control in a Hybrid Exoskeleton - Preliminary Results.

IEEE Trans Med Robot Bionics 2020 May 2;2(2):226-235. Epub 2020 Mar 2.

Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA, USA.

Currently controllers that dynamically modulate functional electrical stimulation (FES) and a powered exoskeleton at the same time during standing-up movements are largely unavailable. In this paper, an optimal shared control of FES and a powered exoskeleton is designed to perform sitting to standing (STS) movements with a hybrid exoskeleton. A hierarchical control design is proposed to overcome the difficulties associated with developing an optimal real-time solution for the highly nonlinear and uncertain STS control model with multiple degrees of freedom. A higher-level robust nonlinear control design is derived to exponentially track a time-invariant desired STS movement profile. Then, a lower-level optimal control allocator is designed to distribute control between FES and the knee electric motors. The allocator uses a person's muscle fatigue and recovery dynamics to determine an optimal ratio between the FES-elicited knee torque and the exoskeleton assist. Experiments were performed on human participants, two persons without disability and one person with spinal cord injury (SCI), to validate the feedback controller and the optimal torque allocator. The muscles of the participant with SCI did not actively contract to FES, so he was only tested with the powered exoskeleton controller. The experimental results show that the proposed hierarchical control design is a promising method to effect shared control in a hybrid exoskeleton.
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http://dx.doi.org/10.1109/TMRB.2020.2977416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357894PMC
May 2020

Filgrastim loading in PLGA and SLN nanoparticulate system: a bioinformatics approach.

Drug Dev Ind Pharm 2020 Aug 9;46(8):1354-1361. Epub 2020 Jul 9.

ICMR - National Institute of Pathology, New Delhi, India.

Objective: In this research work, we hypothesized to predict the nanoparticulate system, best suited for targeted delivery of filgrastim. Targeted delivery of filgrastim to bone marrow is required to decrease the incidence of neutropenia/febrile neutropenia. This is achieved by nanoparticulate systems, duly designed by bioinformatics approach.

Method: The targeted delivery of filgrastim in nanoparticulate system was achieved by molecular dynamics (MD) simulation studies. Two matrices comprising PLGA and SLN (tripalmitin, core component of SLN system) were modeled separately with proposed drug filgrastim. Energy minimization of all systems was done using the steepest descent method. PLGA and tripalmitin systems were equalized at 310 °C, at 1 bar pressure with Berendsen barostat for 200 ps using a v-rescale thermostat for 100 ps. Atomistic MD simulations of four model system and mass density of interacting systems were calculated.

Results: The mass density maps of each nanoparticle system, that is, PLGA and tripalmitin showed an increase in density toward the end of the simulation. The contact numbers attained equilibria with the average number of approx.. 1500 contacts in case of tripalmitin-filgrastim system. While PLGA-filgrastim system shows lesser contacts as compared to tripalmitin with average contacts of approx. 1000.The binding free energy was predicted to be -1104 kJ/mol in tripalmitin-filgrastim complex and -421 kJ/mol in PLGA-filgrastim system.

Conclusion: Findings of study revealed that both nanoparticle systems assumed to be good model for drug-carrier systems. Though SLN systems were thought to be more appropriate than PLGA, still the findings could ascertain this hypothesis in futuristic work.
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http://dx.doi.org/10.1080/03639045.2020.1788071DOI Listing
August 2020

Submental nalbuphine exhibits improved efficacy in ameliorating acute pain in prehospital emergent conditions; a comparative study with conventional intramuscular using gamma scintigraphy.

Injury 2020 Sep 20;51(9):1970-1978. Epub 2020 Jun 20.

Department of CEPIN, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization, Ministry of Defence, Govt. of India, Timarpur, Delhi, 110054, INDIA. Electronic address:

Background: Nalbuphine (NLB) is a kappa-agonist and mu-partial antagonist, widely used for opioid withdrawal de-addiction, opioid-induced pruritis and as emergent analgesia.

Objective: The present study aimed to assess the safety and efficacy of NLB in pain sensitization, through a submental route so as to provide faster management in emergent situations.

Materials & Methods: In-vivo efficacy and safety studies of NLB-submental injection were assessed in Sprague-Dawley(SD) rats. For eddy's hot plate study, animals were allocated into three groups, the first group served as normal control; group II received NLB (through submental route at 1.2 mg/kg); group III received NLB (through intramuscular route at 1.2 mg/kg). Response latency (in terms of response latency) was measured at 10, 30 & 60 min in all the experimental groups. Safety studies were carried out according to OECD 423. In-vitro release study was conducted using a cellulose dialysis membrane (12,000 KDa). The biodistribution and release kinetics studies were carried out using gamma scintigraphy studies in New Zealand rabbits and humans respectively.

Results: The response latency of NLB from the submental route was found to be 7.17 (SD 1.47) seconds and in the case of the intramuscular route it was calculated as 4.00 (SD 1.26) seconds at 10 min. The data depicts the better efficacy of submental injection in ameliorating pain than the intramuscular injection. Toxicity studies predict the safe profile through a submental route. The release kinetics in humans of submental NLB was 46% faster as compared to the intramuscular site of injection. The NLB injection through both routes was compared by non-invasive gamma scintigraphy technique and we found that submental injection has faster (within 10 min) onset of action & distributes rapidly.

Conclusion: The submental route of NLB is faster, more efficacious than the intramuscular route. Thus, we conclude that in the case of emergent scenarios (i.v or i.m. route is compromised), where immediate relief is necessary, the submental route is a preferred choice.
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http://dx.doi.org/10.1016/j.injury.2020.06.031DOI Listing
September 2020

A Phase 3, Randomised, Open-Label, Non-inferiority Trial Evaluating Anti-Rabies Monoclonal Antibody Cocktail (TwinrabTM) Against Human Rabies Immunoglobulin (HRIG).

Clin Infect Dis 2020 Jun 17. Epub 2020 Jun 17.

Saviour Hospital, Ahmedabad.

Background: Limited supply, cost and potential for severe adverse effects observed with the blood derived rabies immunoglobulin products has led to search for alternative therapies. This issue has been addressed by developing an antirabies monoclonal antibody cocktail.

Methods: This is a phase 3, randomized, open-label, noninferiority trial conducted in patients with WHO category III exposure with suspected rabid animal. Eligible patients were assigned to either the test arm, TwinrabTM (docaravimab and miromavimab) or the reference arm, Human rabies immunoglobulin (HRIG; Imogam® Rabies-HT), in a ratio of 1:1. The primary endpoint was the comparison of responder rates between the two arms assessed as percentage of those with rabies virus neutralizing antibodies titers ≥ 0.5 IU/mL on day 14.

Results: A total of 308 patients were equally randomized into the two arms. In the per-protocol (PP) population, there were 90.21% responders in the TwinrabTM arm and, 94.37% in the HRIG arm. The Geometric Mean of RFFIT titres in the PP on day 14 were 4.38 and 4.85 IU/mL, for the TwinrabTM and HRIG arms, respectively. There were no deaths or serious adverse events reported.

Conclusions: This study confirmed that TwinrabTM is non-inferior to HRIG in terms of providing an unbroken window of protection up to day 84. This trial in healthy adults with WHO category III exposure from suspected rabid animal also establishes the safety of TwinrabTM in patients with one WHO approved vaccine regimen (Essen).

Trials Registration: CTRI/2017/07/009038.
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http://dx.doi.org/10.1093/cid/ciaa779DOI Listing
June 2020

Ultra-High-Frame-Rate Ultrasound Monitoring of Muscle Contractility Changes Due to Neuromuscular Electrical Stimulation.

Ann Biomed Eng 2021 Jan 1;49(1):262-275. Epub 2020 Jun 1.

Department of Mechanical Engineering and Materials Science, University of Pittsburgh School of Engineering, Pittsburgh, PA, 15261, USA.

The quick onset of muscle fatigue is a critical issue when applying neuromuscular electrical stimulation (NMES) to generate muscle contractions for functional limb movements, which were lost/impaired due to a neurological disorder or an injury. For in situ assessment of the effect of NMES-induced muscle fatigue, a novel noninvasive sensor modality that can quantify the degraded contractility of a targeted muscle is required. In this study, instantaneous strain maps of a contracting muscle were derived from ultra-high-frame-rate (2 kHz) ultrasound images to quantify the contractility. A correlation between strain maps and isometric contraction force values was investigated. When the muscle reached its maximum contraction, the maximum and the mean values of the strain map were correlated with the force values and were further used to stage the contractility change. During the muscle activation period, a novel methodology based on the principal component regression (PCR) was proposed to explore the strain-force correlation. The quadriceps muscle of 3 able-bodied human participants was investigated during NMES-elicited isometric knee extension experiments. Strong to very strong correlation results were obtained and indicate that the proposed measurements from ultrasound images are promising to quantify the muscle contractility changes during NMES.
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http://dx.doi.org/10.1007/s10439-020-02536-7DOI Listing
January 2021

Japanese encephalitis virus - exploring the dark proteome and disorder-function paradigm.

FEBS J 2020 09 18;287(17):3751-3776. Epub 2020 Jun 18.

School of Basic Sciences, Indian Institute of Technology Mandi, India.

Japanese encephalitis virus (JEV) is one of the major causes of viral encephalitis all around the globe. Approximately 3 billion people in endemic areas are at risk of Japanese encephalitis. To develop a wholistic understanding of the viral proteome, it is important to investigate both its ordered and disordered proteins. However, the functional and structural significance of disordered regions in the JEV proteome has not been systematically investigated as of yet. To fill this gap, we used here a set of bioinformatics tools to analyze the JEV proteome for the predisposition of its proteins for intrinsic disorder and for the presence of the disorder-based binding regions (also known as molecular recognition features, MoRFs). We also analyzed all JEV proteins for the presence of the probable nucleic acid-binding (DNA and RNA) sites. The results of these computational studies are experimentally validated using JEV capsid protein as an illustrative example. In agreement with bioinformatic analysis, we found that the N-terminal region of the JEV capsid (residues 1-30) is intrinsically disordered. We showed that this region is characterized by the temperature response typical for highly disordered proteins. Furthermore, we have experimentally shown that this disordered N-terminal domain of a capsid protein has a noticeable 'gain-of-structure' potential. In addition, using DOPS liposomes, we demonstrated the presence of pronounced membrane-mediated conformational changes in the N-terminal region of JEV capsid. In our view, this disorder-centric analysis would be helpful for a better understanding of the JEV pathogenesis.
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http://dx.doi.org/10.1111/febs.15427DOI Listing
September 2020

The Impact of Ureteral Access Sheath Use on the Development of Abnormal Postoperative Upper Tract Imaging after Ureteroscopy.

J Urol 2020 11 27;204(5):976-981. Epub 2020 May 27.

Department of Urology, The Ohio State University Medical Center, Columbus, Ohio.

Purpose: Ureteral access sheaths are commonly used during ureteroscopy to facilitate stone removal, improve visibility and maintain low intrarenal pressures. However, the use of a ureteral access sheath can cause ureteral wall ischemia and ureteral tears, potentially increasing the risk of postoperative ureteral stricture and obstruction. We studied the impact of ureteral access sheath use on postoperative imaging studies. Secondary objectives included studying the impact of other intraoperative parameters on postoperative imaging studies.

Materials And Methods: A retrospective chart review was conducted of cases that underwent ureteroscopy for nephroureterolithiasis across 2 high volume institutions between January 2012 and September 2016. Patient demographics, cumulative stone size, operative time, use of ureteral access sheath, laser lithotripsy, basket extraction, preoperative ureteral stent and postoperative ureteral stent placement were extracted from the electronic medical record. Findings of followup renal ultrasound, kidney-ureter-bladder x-ray and/or computerized tomography at approximately 8 weeks after surgery were recorded.

Results: A total of 1,332 ureteroscopies were performed with 1,060 cases (79.6%) returning for routine upper tract imaging after ureteroscopy. Postoperative hydronephrosis was noted following 127 cases (12.0%). Factors predicting presence of hydronephrosis after ureteroscopy include lower body mass index (p=0.0016), greater cumulative stone size (p=0.0003), increased operative time (p <0.0001), preoperative ureteral stent (OR 1.49, p=0.0299) and postoperative ureteral stent placement (OR 6.43, p=0.0031). Postoperative hydronephrosis was not associated with use of ureteral access sheath, age, laser lithotripsy or basket extraction.

Conclusions: Use of ureteral access sheath did not have a significant impact on development of postoperative hydronephrosis, suggesting ureteral access sheath is safe for use during ureteroscopy. Ureteral strictures remain rare following ureteroscopy, seen in only 1.0% of our cohort. With an observed prevalence of hydronephrosis of 12.0% on followup imaging at 8 weeks, routine upper tract imaging after ureteroscopy remains a valuable prognostic tool.
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http://dx.doi.org/10.1097/JU.0000000000001147DOI Listing
November 2020

Mechanistic Insights into Zika Virus NS3 Helicase Inhibition by Epigallocatechin-3-Gallate.

ACS Omega 2020 May 4;5(19):11217-11226. Epub 2020 May 4.

School of Basic Sciences, Indian Institute of Technology Mandi, VPO Kamand, Mandi, Himachal Pradesh 175005, India.

Since 2007, repeated outbreaks of Zika virus (ZIKV) have affected millions of people worldwide and created a global health concern with major complications like microcephaly and Guillain Barre's syndrome. To date, there is not a single Zika-specific licensed drug present in the market. However, in recent months, several antiviral molecules have been screened against ZIKV. Among those, (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, has shown great virucidal potential against flaviviruses including ZIKV. The mechanistic understanding of EGCG-targeting viral proteins is not yet entirely deciphered except that little is known about its interaction with viral envelope protein and viral protease. We designed our current study to find inhibitory actions of EGCG against ZIKV NS3 helicase. NS3 helicase performs a significant role in viral replication by unwinding RNA after hydrolyzing NTP. We employed molecular docking and simulation approach and found significant interactions at the ATPase site and also at the RNA binding site. Further, the enzymatic assay has shown significant inhibition of NTPase activity with an IC value of 295.7 nM and Ki of 0.387 ± 0.034 μM. Our study suggests the possibility that EGCG could be considered as a prime backbone molecule for further broad-spectrum inhibitor development against ZIKV and other flaviviruses.
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http://dx.doi.org/10.1021/acsomega.0c01353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241040PMC
May 2020

polo-like kinase, Cdc5 exhibits ATP-dependent Mg-enhanced kinase activity .

Heliyon 2019 Dec 24;5(12):e03050. Epub 2019 Dec 24.

Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, Bajhol, PO Sultanpur, District Solan, Himachal Pradesh, 173229, India.

Phosphorylation of proteins on serine/threonine residues represents an important biochemical mechanism to regulate several cellular processes. Polo-like kinases (PLKs) are a family of serine-threonine kinases that play an imminent role in cell cycle regulation in yeast to humans, and thus an important therapeutic target for cancers. The present study provides insights into the enzymatic features of PLK, Cdc5 using casein phosphorylation assays. The recombinant yeast PLK, GST-Cdc5 showed maximum casein phosphorylation activity at 30 °C, pH 9 and 45 min of incubation period. GST-Cdc5 exhibited a K of 1.35 μM for casein, and high affinity for ATP, since addition of non-radioactive ATP chased out casein phosphorylation by radiolabeled ATP. The recombinant enzyme showed maximum kinase activity at 2.7 μM of GST-Cdc5. Casein was found to be the best substrate of GST-Cdc5 followed by BSA (Bovine Serum Albumin) and MBP (Myelin Basic Protein). Of the metal ions tested, Mg (at 20 mM) was found to enhance GST-Cdc5 kinase activity, while Ca (at 5 mM) and Mn (at 10 mM) inhibited the same. The presence of EDTA, SDS and PMSF inhibited phosphorylation by GST-Cdc5, while DTT had no effect. The recombinant GST-Cdc5 can be used as a tool for deciphering PLKs' structure and functions, which are still at infancy.
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http://dx.doi.org/10.1016/j.heliyon.2019.e03050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201137PMC
December 2019

Model Predictive Control of a Feedback-Linearized Hybrid Neuroprosthetic System With a Barrier Penalty.

J Comput Nonlinear Dyn 2019 Oct 9;14(10):101009-1010097. Epub 2019 Sep 9.

Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261.

Functional electrical stimulation (FES) is prescribed as a treatment to restore motor function in individuals with neurological impairments. However, the rapid onset of FES-induced muscle fatigue significantly limits its duration of use and limb movement quality. In this paper, an electric motor-assist is proposed to alleviate the fatigue effects by sharing work load with FES. A model predictive control (MPC) method is used to allocate control inputs to FES and the electric motor. To reduce the computational load, the dynamics is feedback linearized so that the nominal model inside the MPC method becomes linear. The state variables: the angular position and the muscle fatigue are still preserved in the transformed state space to keep the optimization meaningful. Because after feedback linearization the original linear input constraints may become nonlinear and state-dependent, a barrier cost function is used to overcome this issue. The simulation results show a satisfactory control performance and a reduction in the computation due to the linearization.
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http://dx.doi.org/10.1115/1.4042903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104748PMC
October 2019

Micro-Mechanisms of Cortical Bone Failure Under Different Loading Conditions.

J Biomech Eng 2020 Mar 19. Epub 2020 Mar 19.

57 campus Drive Saskatoon, SK S7N 5A9 Canada.

Bone being a hierarchical composite material has a structure varying from macro to nano scale. The arrangement of the components of bone material and the bonding between fibers and matrix gives rise to its unique material properties. In the present study, the micro-mechanisms of cortical bone failure were examined under different loading conditions using scanning electron microscopy. The experimental tests were conducted in longitudinal and transverse directions of bone diaphysis under tensile as well as compressive loadings. The results show that bone material has maximum stiffness under longitudinal tensile loading, while the strength is higher under transverse compressive loading. A reverse trend of compressive mechanical properties of bone is observed for longitudinal and transverse loading as compared to trends reported in the previous studies. Therefore, micro-mechanisms of cortical bone failure were analyzed for different loading conditions to reveal such type of behavior of cortical bone and to correlate bone microstructure with mechanical response of bone.
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http://dx.doi.org/10.1115/1.4046688DOI Listing
March 2020

Thalictrum foliolosum: A lesser unexplored medicinal herb from the Himalayan region as a source of valuable benzyl isoquinoline alkaloids.

J Ethnopharmacol 2020 Jun 3;255:112736. Epub 2020 Mar 3.

Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566, Egypt; Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt.

Ethnopharmacological Relevance: Thalictrum foliolosum DC (Ranunculaceae) is a perennial flowering herb traditionally used as a tonic, antiperiodic, diuretic, febrifuge, purgative and stomachic and for the treatment of snakebite, jaundice, and rheumatism.

Aim Of The Study: To provide a critical assessment of the state-of-the-art related to the traditional uses, phytochemistry, and pharmacology of T. foliolosum with the ultimate objective of providing further research strategies to facilitate the exploitation of the therapeutic potential of T. foliolosum for the treatment of human disorders.

Materials And Methods: Exhaustive bibliographic research related to T. foliolosum plant was carried out using scientific research engines and databases such as Google Scholar, PubMed, Web of Science covering all retrieved relevant manuscripts written in English.

Results: Several alkaloids such as berberine, jatrorrhizine, palmatine, thalrugosidine, thalrugosaminine, thalisopine (thaligosine), thalirugidine, thalirugine, 8-oxyberberine (berlambine), noroxyhydrastinine, N,O,O-trimethylsparsiflorine, thalicarpine, thalidasine, thalfoliolosumines A and thalfoliolosumines B were reported from T. foliolosum. Ethnomedicinal studies revealed much wider scope of T. foliolosum in developing various drugs to solve multiple challenges in the health sector. Therapeutic effects were attributed to the bioactivities of the secondary metabolites present in T. foliolosum.

Conclusions: T. foliolosum is rich in berberine and other benzylisoquinoline alkaloids. T. foliolosum can be used as an excellent and effective herbal remedy for various human ailments since there are no reports on the toxicity of this herb.
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http://dx.doi.org/10.1016/j.jep.2020.112736DOI Listing
June 2020

Remodifying Omentopexy Technique Used with Laparoscopic Sleeve Gastrectomy: Does It Change any Outcomes?

Obes Surg 2020 04;30(4):1527-1535

Bariatric and Metabolic Surgery, Penn Medicine Princeton Medical Centre, Suite 275, 5 Plainsboro Road, Plainsboro, NJ, 08536, USA.

Background: Gastric obstructions, leaks and staple line bleeding are reported after laparoscopic sleeve gastrectomy (LSG). There is no ideal method or technique to avoid these mishaps. We added modified omentopexy (OP) to LSG to determine if there is any effect on gastric leaks and some other complications.

Methods: This single institution case control study included two groups of morbidly obese patients undergoing LSG. They were grouped as omentopexy (OP) or no omentopexy (NP). Patient characteristics such as age, sex, ASA (American Society of Anesthesiologists) risk, body mass index (BMI), nutritional status and comorbidities were comparable. Postoperative follow-up was scheduled at 1 week, 1 month, 3 months, 6 months and 12 months. All received standard postoperative clinical, nutritional evaluation and PPI therapy for at least 3 months.

Results: Total 737 patients underwent LSG from January 2012 to December 2017. Out of these, 370 that had OP and 367 that had NP were analyzed. NP group was subdivided into Lemberted Staple line (LS) and bioabsorbable staple line reinforcement (BSLR) groups. Gastric leaks and perforations were clubbed together as gastric disruptions (GD). Patients with at least 15 months of postoperative follow-up were included. Those who failed to follow up were excluded. GD was reported in 7 out of 367 NP patients (1.9%), while no GD was seen in 370 OP patients (P = 0.01). Bleeding was seen in 1 OP versus 2 NP patients (P = 0.6). Venous thromboembolism was reported in 2 OP versus 1 NP patients (P = 1). Wound infection was seen in 1 OP versus 2 NP patients (P = 0.6). Readmissions were noted in 2 OP versus 6 NP patients (P = 0.1). Pneumonia was seen in 2 OP and 2 NP patients (P = 1). Postoperative dehydration was seen in zero OP versus 1 NP patients (P = 0.4). Gastric obstruction was not seen in any of the patients. Postoperative gastric reflux was present in 49/370(13.2%) OP versus 57/367(15.4%) NP patients (P = 0.4). Within NP group, LS (Lemberting of Staple line) patients (286/367) had 4 GD (1.39%) versus no GD in OP (P = 0.03). BSLR (Bioabsorbable Staple line re-enforcement) patients (81/367) had 3 GD (3.7%) versus no GD in OP (P = 0.005). None of the groups had any mortality.

Conclusions: GD (gastric disruptions) were statistically significant, but the following bleeding, venous thromboembolism and gastroesophageal reflux did not reach statistical significance, which indicates that OP, if performed correctly with LSG, has favorable effects on gastric leaks.
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http://dx.doi.org/10.1007/s11695-019-04357-7DOI Listing
April 2020

Folding perspectives of an intrinsically disordered transactivation domain and its single mutation breaking the folding propensity.

Int J Biol Macromol 2020 Jul 13;155:1359-1372. Epub 2019 Nov 13.

School of Basic Sciences, Indian Institute of Technology Mandi, Himachal Pradesh 175005, India; BioX Centre, Indian Institute of Technology Mandi, VPO Kamand, 175005, India. Electronic address:

Transcriptional regulation is a critical facet of cellular development controlled by numerous transcription factors, among which are E-proteins (E2A, HEB, and E2-2) that play important roles in lymphopoiesis. For example, primary hematopoietic cells immortalisation is promoted by interaction of the conserved PCET motif consisting of the Leu-X-X-Leu-Leu (LXXLL) and Leu-Asp-Phe-Ser (LDFS) sequences of the transactivation domains (AD1) of E-proteins with the KIX domain of CBP/p300 transcriptional co-activators. Earlier, it was shown that the LXXLL motif is essential for the PCET-KIX interaction driven by the PCET helical transition. In this study, we analyzed the dehydration-driven gain of helicity in the conserved region (residues 11-28) of the AD1 domain of E-protein. Particularly, we showed that AD1 structure was dramatically affected by alcohols, but was insensitive to changes in pH or the presence of osmolytes sarcosine and taurine, or high polyethylene glycol (PEG) concentrations and DOPC Liposomes. These structure-forming effects of solvents were almost completely absent in the case of L21P AD1 mutant characterized by weakened interaction with KIX. This indicates that KIX interaction-induced AD1 ordering is driven by PCET motif dehydration. The L21P mutation-caused loss of molecular recognition function of AD1 is due to the mutation-induced disruption of the AD1 helical propensity.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.11.111DOI Listing
July 2020

Prediction of Ankle Dorsiflexion Moment by Combined Ultrasound Sonography and Electromyography.

IEEE Trans Neural Syst Rehabil Eng 2020 01 14;28(1):318-327. Epub 2019 Nov 14.

To provide an effective and safe therapy to persons with neurological impairments, accurate determination of their residual volitional ability is required. However, accurate measurement of the volitional ability, through non-invasive means (e.g., electromyography), is challenging due to signal interference from neighboring muscles or stimulation artifacts caused by functional electrical stimulation (FES). In this work, a new model-based intention detection method that combines signals from both surface electromyography (sEMG) and ultrasound (US) sonography to predict isometric volitional ankle dorsiflexion moment is proposed. The work is motivated by the fact that the US-derived signals, unlike sEMG, provide direct visualization of the muscle activity, and hence may enhance the prediction accuracy of the volitional ability, when combined with sEMG. The weighted summation of sEMG and US imaging signals, measured on the tibialis anterior muscle, is utilized as an input to a modified Hill-type neuromusculoskeletal model that predicts the ankle dorsiflexion moment. The effectiveness of the proposed model-based moment prediction method is validated by comparing the predicted and the measured ankle joint moments. The new modeling method has a better prediction accuracy compared to a prediction model that uses sole sEMG or sole US sonography. This finding provides a more accurate approach to detect movement intent in the lower limbs. The approach can be potentially beneficial for the development of US sonography-based robotic or FES-assisted rehabilitation devices.
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http://dx.doi.org/10.1109/TNSRE.2019.2953588DOI Listing
January 2020

The history of mutational pressure changes during the evolution of adeno-associated viruses: A message to gene therapy and DNA-vaccine vectors designers.

Infect Genet Evol 2020 01 31;77:104100. Epub 2019 Oct 31.

School of Basic Sciences, Indian Institute of Technology Mandi, Himachal Pradesh 175005, India; BioX Centre, Indian Institute of Technology Mandi, VPO Kamand, 175005, India.

The use of virus-associated vectors for gene therapy and vaccination have emerged as safe and effective delivery system. Like all other genetic materials, these vehicles are also prone to spontaneous mutations. To understand what types of nucleotide mutations are expected in the vector, one needs to know distinct characteristics of mutational process in the corresponding virus. In this study we analyzed mutational pressure directions along the length of the genomes of all types of primate adeno-associated viruses (AAV) that are frequently used in gene therapy or DNA-vaccines. We observed clear evidences of transcription-associated mutational pressure in AAV: nucleotide usage biases are changing drastically after each of the three promoters: the higher the rate of transcription, the stronger the bias towards GC to AT mutations. Moreover, the usage of G decreased at the lower transcription rate (after P19 promoter) than the usage of C (after P40 promoter). Since nucleotide usage biases are retrospective indices, we created a scenario of changes in transcriptional map during the AAV evolution. Current mutational pressure directions are different for AAV types, while all of them demonstrate high rates of T to C transitions in the second long ORF. Since transcription rate and cell tropism are the main factors determining the preferable direction of nucleotide mutations in AAV, mutational pressure should be checked experimentally in DNA vectors before their final design with the aim to make the transferred gene more stable against those mutations.
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http://dx.doi.org/10.1016/j.meegid.2019.104100DOI Listing
January 2020

Surgical Correction of Pectus Excavatum Using a Rib Graft Strut Following Excision of Costal Cartilages.

J Indian Assoc Pediatr Surg 2019 Oct-Dec;24(4):252-256

Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India.

Background: A number of techniques are described for correction of pectus excavatum (PE). This article describes the experience with an innovative procedure which combines features from the Ravitch and Nuss procedures without using prosthetic material.

Methods: This cross-sectional study included 12 cases of PE from January 2000 to March 2017 managed by excision of deformed costal cartilages and support to the thoracic cage using an autologous free rib graft as a strut. Indication for surgery was Haller's Index above 3.2 with or without respiratory distress. Noncontrast computed tomography scans were done at 6 months after surgery to document the position of the strut and to see the final correction and new Haller's Index, respectively.

Results: The male-to-female ratio was 2:1. Preoperative Haller's Index in all cases was >3.2 (range 3.25-14). The average age at surgery was 5 years and 8 months (range: 7 months-15 years). Mean duration of hospital stay was 11 days (range 5-16 days).The 11 rib was used commonly although in two cases, the 10 rib was used as the 11 rib was considered relatively short. Pericardial effusion requiring strut removal was seen in one case; in another case, removal of the rib was needed because of nonhealing of a delayed dehisced surgical wound. Others had an uneventful postoperative period. The mean postoperative Haller's Index was 2.75 (range 2.0-7).

Conclusion: This modified procedure using an autologous rib strut is technically feasible and reproducible even with limited facilities and gives excellent results.
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http://dx.doi.org/10.4103/jiaps.JIAPS_68_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752060PMC
October 2019

A Study of Correlation between Apolipoprotein B and Dyslipidemia in Type 2 Diabetes Patients and its Relation with Proteinuria- A Tertiary Care Hospital Based Study.

J Assoc Physicians India 2019 Jul;67(7):30-33

Assistant Professor, Sardar Patel Medical College, Bikaner, Rajasthan.

Objectives: Individual with diabetes may have several from of Dyslipidemia. Dyslipidemia has been considered to be factor that plays a risk in progression of micro vascular disease, especially in diabetes.1 The present study is intended to Study of correlation between Apolipoprotein B and Dyslipidemia in type 2 diabetes patients and prevalence of dyslipidemia in type 2 diabetic patients.

Material And Methods: Prospective cross- sectional study conducted on 100 cases of type 2 diabetes mellitus. Groups are divided according to A/C ratio and association of dyslipidemia was seen. Serum Apolipoprotein B was measured using immunoturbidimetric method.

Results: Pearson's correlation analysis of Apo B with lipid parameters in diabetic patients showed that, LDL, TC and Tg were positively correlated with Apo- B. There was a positive and linear correlation between LDL and Tg. Apo- B was negatively correlated with HDL-C.

Conclusion: The majority of patients studied had low HDL-C, elevated non HDL- C, elevated total cholesterol, elevated triglycerides, elevated LDL -C and elevated apo B. Apolipoprotein B had a positive linear correlation with total cholesterol, triglycerides, LDL-C, non-HDL-C. The strongest positive correlation was with nonHDL-C. Patients with low HDL-C had high apo B levels.
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July 2019

A Comparative Study of Chitosan Gel and Soframycin in the Management of Wounds.

Int J Low Extrem Wounds 2020 Jun 9;19(2):148-157. Epub 2019 Sep 9.

Delhi Pharmaceutical Science and Research University, Delhi, India.

Wounds and related injuries remain a major cause of death and disability. Healing of wound is a complex, highly regulated process that includes cellular, molecular, biochemical, and physiological events that permit living organisms to repair accidental lesions. Therefore, dealing with wounds has always been a subject of concern to the world, and demand for products in wound management had increased to $9.3 trillion worldwide in the health care industry, affecting economic growth. The present work aimed to assess the wound healing effect of chitosan, and a comparative profile with soframycin is established in experimental animals. Enormous research reports, the wound healing properties of chitosan, but the protective mechanism implicated in wound healing activity of chitosan is unknown. In addition to this, we evaluated the anatomical, macroscopical, and histopathological alterations in wounds of experimental rats. Collagenase activity was performed to determine the granulation tissue formation and epithelialization of wounds treated with untainted chitosan. Wounds treated with glycerated chitosan gel, that is, GCG-3 (high degree of deacetylation), showed faster healing with highest percentage of contraction as compared with the soframycin-treated group. The healing of wounds was found to be 85% in GCG-3 on the sixth day of treatment, showing significant ( < .001) improvement in epithelial tissue. The collagenase activity in GCG-3 was 192 unit/mg of protein. Wound reepithelialization was found to be to 94 ± 4% in case of the GCG-3-treated group and 87 ± 5% in the soframycin-treated group. Higher degree of deacetylation in the chitosan, GCG-3, warrants its use in the treatment and management of dermal wounds.
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http://dx.doi.org/10.1177/1534734619870086DOI Listing
June 2020