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1.
Cureus ; 15(11): e48465, 2023 Nov.
Article En | MEDLINE | ID: mdl-38074044

Helicobacter pylori is a gram-negative bacterium that chronically infects the gastric epithelium. Potassium-competitive acid blockers (P-CABs) are a promising alternative, being more potent than standard proton pump inhibitors (PPIs). The meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were randomized controlled trials (RCTs) comparing P-CAB and PPI-based therapy, confirmed H. pylori infection, and measured eradication rates after at least four weeks. Subgroup analyses were conducted based on therapy type and trial location. Quality assessment used the Cochrane risk-of-bias tool, RoB 2.0, and statistical analysis was performed using ReviewManager (RevMan) 5.4 (2020; The Cochrane Collaboration, London, United Kingdom). A p-value of <0.05 is considered statistically significant. In the intention-to-treat (ITT) analysis, P-CABs demonstrated superior overall efficacy, consistently observed in the first-line treatment subgroup. However, no significant difference was found in the subgroup receiving salvage therapy. Another ITT subgroup analyzed the impact of geographical location, favoring P-CABs in the overall study population and the Japanese subgroup. However, no statistically significant differences were found in the subgroups of other countries. In the PPA, P-CABs showed superior efficacy overall, consistently seen in the first-line treatment subgroup. However, no significant difference was found in the subgroup receiving salvage eradication therapy. Another PPA subgroup analysis considered the geographical impact on eradication rates, revealing P-CABs as superior to PPIs in the overall study population and the Japanese subgroup, but not in other countries. No significant adverse event outcomes were observed. P-CAB-based triple therapy is more effective than PPI-based triple therapy as the primary treatment for H. pylori eradication, particularly in Japanese patients. Nevertheless, regarding salvage therapy, both treatments show comparable efficacy. Additionally, the tolerability of P-CAB-based and PPI-based triple therapy is similar, with a similar occurrence of adverse events.

2.
Vet Med (Praha) ; 68(7): 271-280, 2023 Jul.
Article En | MEDLINE | ID: mdl-37982055

The present study aims to evaluate the prevalence and antimicrobial sensitivity of Staphylococcus aureus associated with bovine mastitis to selected antibiotics and plant extracts. In the current study, 140 milk samples were collected from cows and buffaloes. Among the 140 samples, 93 samples were positive for sub-clinical mastitis based on the California Mastitis Test (CMT). Out of the total positive samples, 45 were confirmed for S. aureus on a Mannitol salt agar media. The antimicrobial susceptibility test revealed that 44.82% of the isolates were resistant to cefoxitin (oxacillin) confirming methicillin-resistant S. aureus (MRSA) with a higher percentage (51.61%) in the buffalo than in the cow samples. Furthermore, the PCR assay confirmed the presence of the mecA gene in all the MRSA isolates. Among the seven tested antibiotics, sulfamethoxazole + trimethoprim showed high efficacy (71.1%) against methicillin-susceptible S. aureus isolates (MSSA). Oxytetracycline and sulfamethoxazole + trimethoprim showed 20% efficacy against MRSA followed by enrofloxacin (10%). On the other hand, the tested samples from Pistacia chinensis revealed that the ethyl acetate extract of bark showed a maximum zone of inhibition of 21.3 mm against MSSA and MRSA isolates at 3 000 µg/disc. Moreover, the methanol extract of Cotoneaster microphyllus formed a 12.3 mm and 9.1 mm zone of inhibition against the MSSA and MRSA isolates, respectively.

3.
PLoS One ; 18(9): e0286362, 2023.
Article En | MEDLINE | ID: mdl-37733720

Stock market forecasting is one of the most challenging problems in today's financial markets. According to the efficient market hypothesis, it is almost impossible to predict the stock market with 100% accuracy. However, Machine Learning (ML) methods can improve stock market predictions to some extent. In this paper, a novel strategy is proposed to improve the prediction efficiency of ML models for financial markets. Nine ML models are used to predict the direction of the stock market. First, these models are trained and validated using the traditional methodology on a historic data captured over a 1-day time frame. Then, the models are trained using the proposed methodology. Following the traditional methodology, Logistic Regression achieved the highest accuracy of 85.51% followed by XG Boost and Random Forest. With the proposed strategy, the Random Forest model achieved the highest accuracy of 91.27% followed by XG Boost, ADA Boost and ANN. In the later part of the paper, it is shown that only classification report is not sufficient to validate the performance of ML model for stock market prediction. A simulation model of the financial market is used in order to evaluate the risk, maximum draw down and returns associate with each ML model. The overall results demonstrated that the proposed strategy not only improves the stock market returns but also reduces the risks associated with each ML model.


Investments , Machine Learning , Humans , Computer Simulation , Random Forest , Research Personnel
4.
RSC Adv ; 13(29): 20198-20208, 2023 Jun 29.
Article En | MEDLINE | ID: mdl-37416915

Vertically aligned zinc oxide nanorod (ZnO-NR) growth was achieved through a wet chemical route over a comb-shaped working area of an interdigitated Ag-Pd alloy signal electrode. Field-emission scanning electron microscopy images confirmed the formation of homogeneous ZnO-NRs grown uniformly over the working area. X-ray diffraction revealed single-phase formation of ZnO-NRs, further confirmed by energy-dispersive X-ray spectroscopy analysis. Temperature-dependent impedance and modulus formalisms showed semiconductor-type behavior of ZnO-NRs. Two electro-active regions i.e., grain and grain boundary, were investigated which have activation energy ∼0.11 eV and ∼0.17 eV, respectively. The conduction mechanism was investigated in both regions using temperature-dependent AC conductivity analysis. In the low-frequency dispersion region, the dominant conduction is due to small polarons, which is attributed to the grain boundary response. At the same time, the correlated barrier hopping mechanism is a possible conduction mechanism in the high dispersion region attributed to the bulk/grain response. Moreover, substantial photoconductivity under UV light illumination was achieved which can be attributed to the high surface-to-volume ratio of zinc oxide nanorods as they provide high density of trap states which causes an increase in the carrier injection and movement leading to persistent photoconductivity. This photoconductivity was also facilitated by the frequency sweep applied to the sample which suggests the investigated ZnO nanorods based IDE devices can be useful for the application of efficient UV detectors. Experimental values of field lowering coefficient (ßexp) matched well with the theoretical value of ßS which suggests that the possible operating conduction mechanism in ZnO nanorods is Schottky type. I-V characteristics showed that the significantly high photoconductivity of ZnO-NRs as a result of UV light illumination is owing to the increase in number of free charge carriers as a result of generation of electron-hole pairs by absorption of UV light photons.

5.
Heliyon ; 9(6): e16597, 2023 Jun.
Article En | MEDLINE | ID: mdl-37292351

This article compares the operator splitting scheme to linearly stabilized splitting and semi-implicit Euler's schemes for the numerical solution of the Cahn-Hilliard equation. For the purpose of validation, the spinodal decomposition phenomena have been simulated. The efficacy of the three schemes has been demonstrated through numerical experiments. The computed results show that the schemes are conditionally stable. It has been observed that the operator splitting scheme is computationally more efficient.

6.
Front Microbiol ; 14: 1098323, 2023.
Article En | MEDLINE | ID: mdl-36910181

The Zika virus (ZIKV), which originated in Africa, has become a significant global health threat. It is an RNA virus that continues to mutate and accumulate multiple mutations in its genome. These genetic changes can impact the virus's ability to infect, cause disease, spread, evade the immune system, and drug resistance. In this study genome-wide analysis of 175 ZIKV isolates deposited at the National Center for Biotechnology Information (NCBI), was carried out. The comprehensive mutational analysis of these isolates was carried out by DNASTAR and Clustal W software, which revealed 257 different substitutions at the proteome level in different proteins when compared to the reference sequence (KX369547.1). The substitutions were capsid (17/257), preM (17/257), envelope (44/257), NS1 (34/257), NS2A (30/257), NS2B (11/257), NS3 (37/257), NS4A (6/257), 2K (1/257), NS4B (15/257), and NS5 (56/257). Based on the coexisting mutational analysis, the MN025403.1 isolate from Guinea was identified as having 111 substitutions in proteins and 6 deletions. The effect of coexisting/reoccurring mutations on the structural stability of each protein was also determined by I-mutant and MUpro online servers. Furthermore, molecular docking and simulation results showed that the coexisting mutations (I317V and E393D) in Domain III (DIII) of the envelope protein enhanced the bonding network with ZIKV-specific neutralizing antibodies. This study, therefore, highlighted the rapid accumulation of different substitutions in various ZIKV proteins circulating in different geographical regions of the world. Surveillance of such mutations in the respective proteins will be helpful in the development of effective ZIKV vaccines and neutralizing antibody engineering.

7.
Cureus ; 15(12): e51218, 2023 Dec.
Article En | MEDLINE | ID: mdl-38283474

Renal transplant aims to provide a healthy substitute for the chronically damaged kidney while also correcting the anemia of chronic disease by producing erythropoietin for effective erythropoiesis. However, in a small number of renal transplant patients, the hematocrit continues to rise even after correction of the anemia, ultimately leading to abnormally increased hemoglobin and hematocrit. This condition is termed "post-transplant erythrocytosis" (PTE). We present a case of a 50-year-old male who was diabetic, positive for hepatitis B surface antigen, and negative for polymerase chain reaction. He presented with symptoms of acute hepatitis. During the work-up, PTE was diagnosed. Our case sheds light on a common complication of renal transplant known as PTE, its possible complications in the patient, and the necessary interventions to prevent untoward outcomes. PTE, although a less common complication of renal transplant, can become serious and potentially fatal due to its sequelae of thromboembolism. The complications can range from simple thrombophlebitis and thrombosis of digital and brachial arteries to more severe events such as pulmonary embolism or stroke and cardiovascular events. Regular post-transplant follow-ups with frequent bloodwork will aid in the early diagnosis of PTE, allowing for timely intervention with appropriate treatment options such as venesection or angiotensin receptor blockers (ARBs)/angiotensin-converting enzyme (ACE) inhibitors.

8.
Front Immunol ; 13: 940756, 2022.
Article En | MEDLINE | ID: mdl-36003396

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the host immune system through a variety of regulatory mechanisms. The genome of SARS-CoV-2 encodes 16 non-structural proteins (NSPs), four structural proteins, and nine accessory proteins that play indispensable roles to suppress the production and signaling of type I and III interferons (IFNs). In this review, we discussed the functions and the underlying mechanisms of different proteins of SARS-CoV-2 that evade the host immune system by suppressing the IFN-ß production and TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)/signal transducer and activator of transcription (STAT)1 and STAT2 phosphorylation. We also described different viral proteins inhibiting the nuclear translocation of IRF3, nuclear factor-κB (NF-κB), and STATs. To date, the following proteins of SARS-CoV-2 including NSP1, NSP6, NSP8, NSP12, NSP13, NSP14, NSP15, open reading frame (ORF)3a, ORF6, ORF8, ORF9b, ORF10, and Membrane (M) protein have been well studied. However, the detailed mechanisms of immune evasion by NSP5, ORF3b, ORF9c, and Nucleocapsid (N) proteins are not well elucidated. Additionally, we also elaborated the perspectives of SARS-CoV-2 proteins.


COVID-19 , SARS-CoV-2 , Humans , Immune Evasion , Interferons/metabolism , Viral Proteins
9.
Comput Biol Med ; 141: 105170, 2022 02.
Article En | MEDLINE | ID: mdl-34968862

SARS-CoV-2, an RNA virus, has been prone to high mutations since its first emergence in Wuhan, China, and throughout its spread. Its genome has been sequenced continuously by many countries, including Pakistan, but the results vary. Understanding its genomic patterns and connecting them with phenotypic features will help in devising therapeutic strategies. Thus, in this study, we explored the mutation landscape of 250 Pakistani isolates of SARS-CoV-2 genomes to check the genome diversity and examine the impact of these mutations on protein stability and viral pathogenesis in comparison with a reference sequence (Wuhan NC 045512.2). Our results revealed that structural proteins mainly exhibit more mutations than others in the Pakistani isolates; in particular, the nucleocapsid protein is highly mutated. In comparison, the spike protein is the most mutated protein globally. Furthermore, nsp12 was found to be the most mutated NSP in the Pakistani isolates and worldwide. Regarding accessory proteins, ORF3A is the most mutated in the Pakistani isolates, whereas ORF8 is highly mutated in world isolates. These mutations decrease the structural stability of their proteins and alter different biological pathways. Molecular docking, the dissociation constant (KD), and MM/GBSA analysis showed that mutations in the S protein alter its binding with ACE2. The spike protein mutations D614G-S943T-V622F (-75.17 kcal/mol), D614G-Q677H (-75.78 kcal/mol), and N74K-D614G (-73.84 kcal/mol) exhibit stronger binding energy than the wild type (-66.34 kcal/mol), thus increasing infectivity. Furthermore, the simulation results strongly corroborated the predicted protein servers. Our analysis findings also showed that E, M, ORF6, ORF7A, ORF7B, and ORF10 are the most stable coding genes; they may be suitable targets for vaccine and drug development.


COVID-19 , SARS-CoV-2 , COVID-19/virology , Genome, Viral , Humans , Molecular Docking Simulation , Mutation , Pakistan , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
10.
J Biomol Struct Dyn ; 40(1): 523-537, 2022 Jan.
Article En | MEDLINE | ID: mdl-32897173

The outbreak of the recent coronavirus (SARS-CoV-2), which causes a severe pneumonia infection, first identified in Wuhan, China, imposes significant risks to public health. Around the world, researchers are continuously trying to identify small molecule inhibitors or vaccine candidates by targeting different drug targets. The SARs-CoV-2 macrodomain-I, which helps in viral replication and hijacking the host immune system, is also a potential drug target. Hence, this study targeted viral macrodomain-I by using drug similarity, virtual screening, docking and re-docking approaches. A total of 64,043 compounds were screened, and potential hits were identified based on the docking score and interactions with the key residues. The top six hits were subjected to molecular dynamics simulation and Free energy calculations and repeated three times each. The per-residue energy decomposition analysis reported that these compounds significantly interact with Asp22, Ala38, Asn40, Val44, Phe144, Gly46, Gly47, Leu127, Ser128, Gly130, Ile131, Phe132 and Ala155 which are the critical active site residues. Here, we also used ADPr as a positive control to compare our results. Our results suggest that our identified hits by using such a complicated computational pipeline could inhibit the SARs-CoV-2 by targeting the macrodomain-1. We strongly recommend the experimental testing of these compounds, which could rescue the host immune system and could help to contain the disease caused by SARs-CoV-2.Communicated by Ramaswamy H. Sarma.


COVID-19 , Pharmaceutical Preparations , Humans , Immune System , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors , SARS-CoV-2
11.
Front Microbiol ; 12: 789062, 2021.
Article En | MEDLINE | ID: mdl-34925297

Mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made this virus more infectious. Previous studies have confirmed that non-structural protein 13 (NSP13) plays an important role in immune evasion by physically interacting with TANK binding kinase 1 (TBK1) to inhibit IFNß production. Mutations have been reported in NSP13; hence, in the current study, biophysical and structural modeling methodologies were adapted to dissect the influence of major mutations in NSP13, i.e., P77L, Q88H, D260Y, E341D, and M429I, on its binding to the TBK1 and to escape the human immune system. The results revealed that these mutations significantly affected the binding of NSP13 and TBK1 by altering the hydrogen bonding network and dynamic structural features. The stability, flexibility, and compactness of these mutants displayed different dynamic features, which are the basis for immune evasion. Moreover, the binding was further validated using the MM/GBSA approach, revealing that these mutations have higher binding energies than the wild-type (WT) NSP13 protein. These findings thus justify the basis of stronger interactions and evasion for these NSP13 mutants. In conclusion, the current findings explored the key features of the NSP13 WT and its mutant complexes, which can be used to design structure-based inhibitors against the SARS-CoV-2 new variants to rescue the host immune system.

12.
Front Microbiol ; 12: 703145, 2021.
Article En | MEDLINE | ID: mdl-34335535

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been continuously mutating since its first emergence in early 2020. These alterations have led this virus to gain significant difference in infectivity, pathogenicity, and host immune evasion. We previously found that the open-reading frame 8 (ORF8) of SARS-CoV-2 can inhibit interferon production by decreasing the nuclear translocation of interferon regulatory factor 3 (IRF3). Since several mutations in ORF8 have been observed, therefore, in the present study, we adapted structural and biophysical analysis approaches to explore the impact of various mutations of ORF8, such as S24L, L84S, V62L, and W45L, the recently circulating mutant in Pakistan, on its ability to bind IRF3 and to evade the host immune system. We found that mutations in ORF8 could affect the binding efficiency with IRF3 based on molecular docking analysis, which was further supported by molecular dynamics simulations. Among all the reported mutations, W45L was found to bind most stringently to IRF3. Our analysis revealed that mutations in ORF8 may help the virus evade the immune system by changing its binding affinity with IRF3.

13.
Surg Neurol Int ; 12: 290, 2021.
Article En | MEDLINE | ID: mdl-34221621

BACKGROUND: Halo-traction device has been seen with favorable outcome in managing the patients with severe kyphotic deformities preoperatively, however, associated complications are inevitable. Slight modifications can improve the outcome and clinical efficacy. CASE DESCRIPTION: A 14-year-old boy was presented with severe kyphotic deformity of 141° from T1 to T10 thoracic vertebrae with diffuse paraspinal calcification in thoracic spine and complete loss of power of both lower limbs. A modified halo-pelvic distraction device was applied before the definitive surgery. The device comprised halo and pelvic assembly, the halo ring was connected to the head with 06 pins, while pelvic assembly had Ilizarov half pins connected to the arches. The assembly construct had four threaded rods, two of them were placed anterolateral and the other two were posterolateral. Distraction at the rate of 3 mm/day was started from 1st postoperative day for 35 days. The neurology improved in both lower limbs and kyphotic angle reduced to 56° from 141°. Surgery at this stage was done and a standalone solid titanium cage was placed from T1 to T10 vertebral body after debridement. No peri- or post-operative complications were observed. CONCLUSION: The application of halo-pelvic distraction before corrective surgeries can not only reduce the severity of the kyphotic deformity making the definitive surgery easy but neurology can also be improved. The high-risk complications associated with acute correction of deformities can be minimized using our modified halo-pelvic distraction device.

14.
Interdiscip Sci ; 13(3): 521-534, 2021 Sep.
Article En | MEDLINE | ID: mdl-34324157

The prolific spread of COVID-19 caused by a novel coronavirus (SARS-CoV-2) from its epicenter in Wuhan, China, to every nook and cranny of the world after December 2019, jeopardize the prevailing health system in the world and has raised serious concerns about human safety. Multi-directional efforts are made to design small molecule inhibitors, and vaccines and many other therapeutic options are practiced, but their final therapeutic potential is still to be tested. Using the old drug or vaccine or peptides could aid this process to avoid such long experimental procedures. Hence, here, we have repurposed a small peptide (ATLQAIAS) from the previous study, which reported the inhibitory effects of this peptide. We used in silico mutagenesis approach to design more peptides from the native wild peptide, which revealed that substitutions (T2W, T2Y, L3R, and A5W) could increase the binding affinity of the peptide towards the 3CLpro. Furthermore, using MD simulation and free energy calculation confirmed its dynamics stability and stronger binding affinities. Per-residue energy decomposition analysis revealed that the specified substitution significantly increased the binding affinity at the residue level. Our wide-ranging analyses of binding affinities disclosed that our designed peptide owns the potential to hinder the SARS-CoV-2 and will reduce the progression of SARS-CoV-2-borne pneumonia. Our research strongly suggests the experimental and clinical validation of these peptides to curtail the recent corona outbreak.


Computer Simulation , Coronavirus 3C Proteases/antagonists & inhibitors , Molecular Dynamics Simulation , Mutagenesis , Peptides/chemistry , Peptides/pharmacology , SARS-CoV-2/drug effects , Severe acute respiratory syndrome-related coronavirus , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Humans , Molecular Docking Simulation , Peptides/genetics , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , Severe acute respiratory syndrome-related coronavirus/chemistry , Severe acute respiratory syndrome-related coronavirus/genetics , SARS-CoV-2/enzymology , Thermodynamics , COVID-19 Drug Treatment
15.
Environ Sci Pollut Res Int ; 28(32): 43417-43430, 2021 Aug.
Article En | MEDLINE | ID: mdl-33830421

Soil pollution due to potentially toxic elements is a worldwide challenge for health and food security. Chelate-assisted phytoextraction along with the application of plant growth regulators (PGRs) could increase the phytoremediation efficiency of metal-contaminated soils. The present study was conducted to investigate the effect of different PGRs [Gibberellic acid (GA3) and indole acetic acid (IAA)] and synthetic chelator (EDTA) on growth parameters and Cd phytoextraction potential of Dysphania ambrosioides (L.) Mosyakin & Clemants grown under Cd-spiked soil. GA3 (10-7 M) and IAA (10-5 M) were applied four times with an interval of 10 days through a foliar spray, while EDTA (40 mg kg-1 soil) was once added to the soil. The results showed that Cd stress significantly decreased fresh biomass, dry biomass, total water contents, and photosynthetic pigments as compared to control. Application of PGRs significantly enhanced plant growth and Cd phytoextraction. The combined application of GA3 and IAA with EDTA significantly increased Cd accumulation (6.72 mg pot-1 dry biomass) and bioconcentration factor (15.21) as compared to C1 (Cd only). The same treatment significantly increased chlorophyll, proline, phenolic contents, and antioxidant activities (CAT, SOD, and POD) while MDA contents were reduced. In roots, Cd accumulation showed a statistically significant and positive correlation with proline, phenolics, fresh biomass, and dry biomass. Similarly, Cd accumulation showed a positive correlation with antioxidant enzyme activities in leaves. D. ambrosioides showed hyperaccumulation potential for Cd, based on bioconcentration factor (BCF) > 1. In conclusion, exogenous application of GA3 and IAA reduces Cd stress while EDTA application enhances Cd phytoextraction and ultimately the phytoremediation potential of D. ambrosioides.


Soil Pollutants , Soil , Antioxidants , Biodegradation, Environmental , Biomass , Cadmium/analysis , Edetic Acid , Plant Growth Regulators , Plant Roots/chemistry , Soil Pollutants/analysis
16.
RSC Adv ; 11(48): 30132-30147, 2021 Sep 06.
Article En | MEDLINE | ID: mdl-35480256

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2-RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.

17.
Gene Rep ; 21: 100886, 2020 Dec.
Article En | MEDLINE | ID: mdl-32954047

Since December 2019, a severe pandemic of pneumonia, COVID-19 associated with a novel coronavirus (SARS-CoV-2), have emerged in Wuhan, China and spreading throughout the world. As RNA viruses have a high mutation rate therefore we wanted to identify whether this virus is also prone to mutations. For this reason we selected four major structural (Spike protein (S), Envelope protein (E), Membrane glycoprotein (M), Nucleocapsid phosphoprotein (N)) and ORF8 protein of 100 different SARS-CoV-2 isolates of fifteen countries from NCBI database and compared these to the reference sequence, Wuhan NC_045512.2, which was the first isolate of SARS-CoV-2 that was sequenced. By multiple sequence alignment of amino acids, we observed substitutions and deletion in S protein at 13 different sites in the isolates of five countries (China, USA, Finland, India and Australia) as compared to the reference sequence. Similarly, alignment of N protein revealed substitutions at three different sites in isolates of China, Spain and Japan. M protein exhibits substitution only in one isolates from USA, however, no mutation was observed in E protein of any isolate. Interestingly, in ORF8 substitution of Leucine, a nonpolar to Serine a polar amino acid at same position (aa84 L to S) in 23 isolates of five countries i.e. China, USA, Spain, Taiwan and India were observed, which may affect the conformation of peptides. Thus, we observed several mutations in the isolates thereafter the first sequencing of SARS-CoV-2 isolate, NC_045512.2, which suggested that this virus might be a threat to the whole world and therefore further studies are needed to characterize how these mutations in different proteins affect the functionality and pathogenesis of SARS-CoV-2.

18.
Ann Med Surg (Lond) ; 52: 44-47, 2020 Apr.
Article En | MEDLINE | ID: mdl-32211188

INTRODUCTION: Optimal implant density for posterior spinal fusion in adolescent idiopathic scoliosis (AIS) remains controversial. We aimed to examine radiographic outcomes of AIS cases treated with limited density pedicle screw constructs. METHODS: This is a retrospective analysis of 96 patients (89 females and 7 males with mean age of 13.8 ± 4.4 years) with AIS who underwent posterior spinal instrumentation at Ghurki Trust Teaching Hospital between 2014 and 2016. Construct characteristics and radiographic measurements were compared preoperatively and at 2 year follow-up using paired t-test. Pearson's correlation coefficient between curve characteristics and metal density was calculated. RESULTS: Preoperative coronal Cobb angle was 68.5 ± 6.9°. Flexibility of the curve was 47.5 ± 10.3% based on push-prone films. The mean number of vertebrae in the fusion was 10.7 ± 1.6. The implant density was 62%. The mean postoperative Cobb angle was 18.6 ± 4.2°, giving a mean correction of 72.5 ± 6.8%. Metal density was not correlated with preoperative coronal or sagittal radiographic variables; MT Cobb angle (r = 0.02, p = 0.847), MT curve flexibility (r = 0.129, p = 0.210), preoperative thoracic kyphosis (r = -0.119, p = 0.247) or lumbosacral lordosis (r = -0.048, p = 0.645). There was a significant correlation between the flexibility of the curve as assessed by push-prone radiographs with the percentage correction achieved (r = 0.368, p < 0.0001) as well as absolute correction in degrees (r = 0.643, p < 0.0001). No significant correlations were present between metal density and MT curve coronal correction rate/percentage (r = 0.086, p = 0.407) or postoperative Cobb angle (r = 0.098, p = 0.344). CONCLUSION: Metal density does not influence the coronal and sagittal correction of AIS. Neither larger nor stiffer curves necessitate high metal density. LEVEL OF EVIDENCE: IV.

19.
Heliyon ; 5(12): e03060, 2019 Dec.
Article En | MEDLINE | ID: mdl-31890973

In this paper, an approximate analytical solution of the bistable Allen-Cahn equation is given. The Allen-Cahn equation is a mathematical model to study the phase separation process in binary alloys and emerged as a convection-diffusion equation in fluid dynamics or reaction-diffusion equation in material sciences. A phase transition occurs at the interface when one material changes its composition or structure. The homotopy perturbation method and homotopy analysis method are used for finding the approximate solution. These methods don't need the use of any transformation, discretization, unrealistic restriction and assumption. The error estimates are computed by comparing with a numerical method, and a good agreement is observed.

20.
Heliyon ; 4(12): e01024, 2018 Dec.
Article En | MEDLINE | ID: mdl-30582045

In this article, we apply the diffuse-interface model [developed by Shah and Yuan (2011) [21]] for collision and coalescence of two bubbles in a linear shear flow. The governing equations consist of a system of coupled nonlinear partial differential equations for conservation of mass, momentum and phase transport. In the two-phase flow, the diffuse-interface model relaxes certain numerical difficulties for tracking the moving interface. An artificial compressibility based numerical scheme is implemented to study the effects of surface tension on bubbles coalescence and separation. We found the critical value of the surface tension coefficient and observed that lowering the surface tension coefficient from the critical value prevent bubbles to coalesce.

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