Publications by authors named "Zafar Iqbal"

394 Publications

Concussion in European professional football: a view of team physicians.

BMJ Open Sport Exerc Med 2021 3;7(2):e001086. Epub 2021 Jun 3.

Amsterdam UMC, University of Amsterdam, Department of Orthopaedic Surgery, Amsterdam Movement Sciences, Meibergdreef 9, Amsterdam, Netherlands.

Objectives: The objective was to explore the view and thoughts of physicians working in professional football about several aspects (eg, education and use of video footages) likely to enhance concussions' recognition and on-field management.

Methods: An observational study based on a cross-sectional design by means of an electronic survey was conducted among physicians working for a professional football club in Belgium, England or France.

Results: A total of 96 physicians (95% male; mean age: 44 years) completed the survey. Nearly all participants (95%) were in favour of informational sessions about concussion for players or technical staff. Only 5%-10% of the participants mentioned that they had felt pressured by the technical staff or players not to substitute a player with a (potential) concussion. Most participants were in favour of an additional permanent concussion substitution and a temporary concussion substitution. Four out of five participants reported that the availability of instant video footages (side-line) would ease the recognition of concussion.

Conclusion: A better recognition and on-field management of concussions in professional football can only be achieved with a holistic approach, including adequate laws of the football game and protocols. Especially, regular education of players and technical staff should be made mandatory while the medical teams should be provided side-line with instant video footages.
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http://dx.doi.org/10.1136/bmjsem-2021-001086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183281PMC
June 2021

Effect of fresh pomegranate juice on the pharmacokinetic profile of artemether: An open-label, randomized, 2- period crossover study in healthy human volunteers.

J Pharm Biomed Anal 2021 Sep 27;203:114179. Epub 2021 May 27.

Research Department of Plant Biology and Biotechnology, Loyola College, Chennai-34, Tamil Nadu, India. Electronic address:

This study was designed to evaluate the effect of fresh pomegranate (Punica granatum L.) juice on the pharmacokinetic profile of artemether in healthy volunteers. A randomized, open-label, crossover study was conducted on healthy subjects (n = 26). Each volunteer received 250 mL of fresh pomegranate juice twice daily for 2 weeks. On day 14, they were administered a single oral dose of artemether (80 mg) with either water or 250 mL of pomegranate juice. Thirteen blood samples were collected up to 12 h and 6 electrocardiograms were recorded. Plasma concentrations of artemether and its metabolite dihydroartemisinin were analyzed by a noncompartmental method using LC-MS/MS. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for artemether were estimated as 0.3 and 0.8 ng/mL, respectively, while for dihydroartemisinin it was 0.2 and 0.6 ng/mL, respectively. The pharmacokinetic parameters of artemether and dihydroartemisinin were not significantly altered when co-administered with the fresh pomegranate juice. AUC was slightly increased from 742 to 859 ng/mL for artemether [geometric mean ratio: 1.14 (95 % CI, 1.08,1.18); P = 0.45] and from 699 to 818 ng/mL for dihydroartemisinin [geometric mean ratio: 1.15 (95 % CI, 1.09, 1.15); P = 0.4]. Difference in C for artemether was also statistically non-significant [173 vs 195 ng/mL; geometric mean ratio: 1.09 (95 % CI, 0.91, 1.15); P = 0.61]. Likewise, elimination half-life (t) for both artemether and dihydroartemisinin remained unchanged (P = 0.43 and 0.31, respectively). In addition, there was no significant difference in t for artemether (P = 0.66) and its metabolite (P = 0.65). In conclusion, findings of the present study demonstrated that the administration of pomegranate juice had no significant effect on the pharmacokinetic profile of artemether.
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http://dx.doi.org/10.1016/j.jpba.2021.114179DOI Listing
September 2021

Comparative anthelmintic efficacy of Arundo donax, Areca catechu, and Ferula assa-foetida against Haemonchus contortus.

Rev Bras Parasitol Vet 2021 28;30(2):e001221. Epub 2021 May 28.

Department of Parasitology, University of Agriculture, Faisalabad, Pakistan.

In the present study, anthelmintic activities of Arundo (A.) donax L., Areca (Ar.) catechu L., and Ferula (F.) assa-foetida L. were determined. Leaves of A. donax L., latex of F. assa-foetida L. and seeds of Ar. catechu L. in different solvent fractions were subjected to in vitro (egg hatch assay; EHA, and adult motility assay; AMA) and in vivo (faecal egg count reduction test; FECRT) tests of anthelmintic activity using Haemonchus contortus model. In the AMA, crude aqueous methanol extracts (CAME) and ethyl acetate fractions of F. assa-foetida at 10 hr post-treatment showed maximum mortality of H. contortus at 12.5-50 mg mL-1. In the EHA, CAME of F. assa-foetida was identified as a potent ovicide based on its low LC50 (16.9 µg mL-1), followed in order by Ar. catechu and A. donax. Results from the FECRT also showed the extract of F. assa-foetida L. to be more effective than those of Ar. catechu L. and A. donax L., against the gastrointestinal parasitic nematodes. Chloroform and ethyl acetate fractions showed better anthelmintic activities against the adult worms in vitro, while CAME of these plants were better than their crude powders in vivo. It is recommended to document and investigate indigenous knowledge of possible medicinal plants to plan scientific trials that may justify their endorsement.
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http://dx.doi.org/10.1590/S1984-29612021028DOI Listing
June 2021

Green synthesis of multifunctional carbon coated copper oxide nanosheets and their photocatalytic and antibacterial activities.

Sci Rep 2021 May 24;11(1):10781. Epub 2021 May 24.

Biology Department, Faculty of Science, Tabuk University, Tabuk, Saudi Arabia.

The studies of metal oxides in environmental remediation of chemical and biological pollutants are gaining colossal importance. Herein, we report the facile synthesis of multifunctional copper oxide nanosheets (CuO NS) using an aqueous extract of Rhazya stricta. The phytochemical investigation of R. stricta indicated the presence of saponins, tannins, and reducing sugars, responsible for the reduction and stabilization of CuO NS. A UV-Visible spectrophotometer initially confirmed the fabrication of CuO NS with specific Surface Plasmon Resonance at 294 nm. Field Emission Scanning Electron Microscopy (FE-SEM), Fourier-transform infrared spectroscopy FTIR, and XRD were further used to characterize the CuO NS. The obtained CuO NS were poly-dispersed with an average size of 20 nm. Interestingly these particles were aligned together in 3D cubical sheets layered above each other via self-assembly. The as-synthesized CuO NS showed enhanced antibacterial potential (17.63 mm, overall mean inhibition zone) in comparison to the known antibiotics (11.51 mm, overall mean inhibition zone) against both Solanaceous crop's wilt-causing bacteria (Ralstonia solanacearum and Clavibacter michiganensis). Furthermore, the appreciable photocatalytic potential of CuO NS has also been observed, causing 83% degradation of methylene blue (MB) upon solar irradiation. The synthesis methodology is devoid of any toxic waste or by-products. It could be used to produce eco-friendly CuO nanomaterial for industrial uses.
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http://dx.doi.org/10.1038/s41598-021-90207-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196103PMC
May 2021

SUST Bangla Emotional Speech Corpus (SUBESCO): An audio-only emotional speech corpus for Bangla.

PLoS One 2021 30;16(4):e0250173. Epub 2021 Apr 30.

Department of Computer Science and Engineering, Shahjalal University of Science and Technology, Sylhet, Bangladesh.

SUBESCO is an audio-only emotional speech corpus for Bangla language. The total duration of the corpus is in excess of 7 hours containing 7000 utterances, and it is the largest emotional speech corpus available for this language. Twenty native speakers participated in the gender-balanced set, each recording of 10 sentences simulating seven targeted emotions. Fifty university students participated in the evaluation of this corpus. Each audio clip of this corpus, except those of Disgust emotion, was validated four times by male and female raters. Raw hit rates and unbiased rates were calculated producing scores above chance level of responses. Overall recognition rate was reported to be above 70% for human perception tests. Kappa statistics and intra-class correlation coefficient scores indicated high-level of inter-rater reliability and consistency of this corpus evaluation. SUBESCO is an Open Access database, licensed under Creative Common Attribution 4.0 International, and can be downloaded free of charge from the web link: https://doi.org/10.5281/zenodo.4526477.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250173PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087046PMC
April 2021

Small organic molecules accelerate the expansion of regulatory T cells.

Bioorg Chem 2021 Jun 20;111:104908. Epub 2021 Apr 20.

Department of Pediatric Intensive Care Unit, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Joint Center for Infection and Immunity, Guangzhou Medical University, 510623 Guangzhou, China. Electronic address:

The regulatory T cells (T cells) expressing CD4 + CD25 + FOXP3 + markers are indispensable for the initiation of immune homeostasis and tolerance to self-antigens in both mice and humans. A decrease in regulatory T cells leads to various autoimmune pathologies. Herein, we report three low molecular weight, small organic molecules as a new series of T proliferators TRP-1-3. These small molecules were tested for their proliferative effect on regulatory T cells. It was found that TRP-1 (Oleracein E) strongly accelerates the T proliferation in vitro in a concentration-dependent manner. The effect was evident for all subsets of T cells tested, including naturally occurring, thymus-derived and peripherally-induced or adaptive T, indicating an effect independent of the maturation site. Importantly, increased T cells numbers by TRP-1 correlated with improved CD4 + CD25 + FOXP3 + expression in vitro, while propidium iodide-based staining showed low TRP-1-induced cytotoxicity. Molecular docking plus simulation studies of these TRP-1-3 with IL-2R, mTOR and TCR receptors suggest a TCR-based T cells activation mechanism. Because of its high T cells activities and low cellular cytotoxicity, TRP-1-3 may be useful in stimulating ex-vivo/in-vivo, T cell-specific responses for therapeutic applications.
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http://dx.doi.org/10.1016/j.bioorg.2021.104908DOI Listing
June 2021

Predicting the crystal structure of [Formula: see text] high energy density material using ab initio evolutionary algorithms.

Sci Rep 2021 Apr 12;11(1):7874. Epub 2021 Apr 12.

Department of Physics, Khalifa University, Abu Dhabi, UAE.

[Formula: see text] is the first successfully synthesized salt that has a polymeric nitrogen moeity ([Formula: see text]). Although 12 other [Formula: see text] salts followed, with [Formula: see text] and [Formula: see text] being the most stable, the crystal structure of [Formula: see text] remains unknown. Currently, it is impossible to experimentally determine the structures of [Formula: see text] due to its marginal stability and explosive nature. Here, following an ab initio evolutionary prediction and using only the stoichiometry of [Formula: see text] as a starting point, we were able to reveal the crystal structure of this high energy density material (HEDM). The [Formula: see text] symmetry of the [Formula: see text] cation, as suggested from earlier investigations, is confirmed to be the symmetry adopted by this polymeric nitrogen within the crystal. This result gave full confidence in the validity of this crystal prediction approach. While stability of the [Formula: see text] within the crystal is found to be driven by electronic considerations, the marginal stability of this HEDM is found to be related to a partial softening of its phonon modes.
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http://dx.doi.org/10.1038/s41598-021-86855-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041836PMC
April 2021

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes.

Beilstein J Org Chem 2021 12;17:711-718. Epub 2021 Mar 12.

Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan, Ningxia 750002, P.R. China.

The diazabicyclooctane (DBO) scaffold is the backbone of non-β-lactam-based second generation β-lactamase inhibitors. As part of our efforts, we have synthesized a series of DBO derivatives - containing amidine substituents at the C2 position of the bicyclic ring. These compounds, alone and in combination with meropenem, were tested against ten bacterial strains for their antibacterial activity in vitro. All compounds did not show antibacterial activity when tested alone (MIC >64 mg/L), however, they exhibited a moderate inhibition activity in the presence of meropenem by lowering its MIC values. The compound proved most potent among the other counterparts against all bacterial species with MIC from <0.125 mg/L to 2 mg/L, and is comparable to avibactam against both strains with a MIC value of <0.125 mg/L.
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http://dx.doi.org/10.3762/bjoc.17.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961884PMC
March 2021

Regulation of basal and norepinephrine-induced cAMP and I in hiPSC-cardiomyocytes: Effects of culture conditions and comparison to adult human atrial cardiomyocytes.

Cell Signal 2021 Jun 5;82:109970. Epub 2021 Mar 5.

Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany. Electronic address:

Background: There is ongoing interest in generating cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) to study human cardiac physiology and pathophysiology. Recently we found that norepinephrine-stimulated calcium currents (I) in hiPSC-cardiomyocytes were smaller in conventional monolayers (ML) than in engineered heart tissue (EHT). In order to elucidate culture specific regulation of β-adrenoceptor (β-AR) responses we investigated whether action of phosphodiesterases (PDEs) may limit norepinephrine effects on I and on cytosolic cAMP in hiPSC-cardiomyocytes. Results were compared to adult human atrial cardiomyocytes.

Methods: Adult human atrial cardiomyocytes were isolated from tissue samples obtained during open heart surgery. All patients were in sinus rhythm. HiPSC-cardiomyocytes were dissociated from ML and EHT. Förster-resonance energy transfer (FRET) was used to monitor cytosolic cAMP (Epac1-camps sensor, transfected by adenovirus). I was recorded by whole-cell patch clamp technique. Cilostamide (300 nM) and rolipram (10 μM) were used to inhibit PDE3 and PDE4, respectively. β-AR were stimulated with the physiological agonist norepinephrine (100 μM).

Results: In adult human atrial cardiomyocytes, norepinephrine increased cytosolic cAMP FRET ratio by +13.7 ± 1.5% (n = 10/9, mean ± SEM, number of cells/number patients) and I by +10.4 ± 1.5 pA/pF (n = 15/10). This effect was not further increased in the concomitant presence of rolipram, cilostamide and norepinephrine, indicating saturation by norepinephrine alone. In ML hiPSC-cardiomyocytes, norepinephrine exerted smaller increases in cytosolic cAMP and I (FRET +9.6 ± 0.5% n = 52/21, number of cells/number of ML or EHT, and I + 1.4 ± 0.2 pA/pF n = 34/7, p < 0.05 each) and both were augmented in the presence of the PDE4 inhibitor rolipram (FRET +16.7 ± 0.8% n = 94/26 and I + 5.6 ± 1.4 pA/pF n = 11/5, p < 0.05 each). Cilostamide increased the response to norepinephrine on FRET (+12.7 ± 0.5% n = 91/19, p < 0.05), but not on I. In EHT hiPSC-cardiomyocytes, norepinephrine responses on both, FRET and I, were larger than in ML (FRET +12.1 ± 0.3% n = 87/32 and I + 3.3 ± 0.2 pA/pF n = 13/5, p < 0.05 each). Rolipram augmented the norepinephrine effect on I (+6.2 ± 1.6 pA/pF; p < 0.05 vs. norepinephrine alone, n = 10/4), but not on FRET.

Conclusion: Our results show culture-dependent differences in hiPSC-cardiomyocytes. In conventional ML but not in EHT, maximum norepinephrine effects on cytosolic cAMP depend on PDE3 and PDE4, suggesting immaturity when compared to the situation in adult human atrial cardiomyocytes. The smaller I responses to norepinephrine in ML and EHT vs. adult human atrial cardiomyocytes depend at least partially on a non-physiological large impact of PDE4 in hiPSC-cardiomyocytes.
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http://dx.doi.org/10.1016/j.cellsig.2021.109970DOI Listing
June 2021

Silicon Alleviate Hypoxia Stress by Improving Enzymatic and Non-enzymatic Antioxidants and Regulating Nutrient Uptake in Muscadine Grape ( Michx.).

Front Plant Sci 2020 10;11:618873. Epub 2021 Feb 10.

Department of Agriculture, Nutrition and Food Systems, University of New Hampshire, Durham, NH, United States.

Flooding induces low oxygen (hypoxia) stress to plants, and this scenario is mounting due to hurricanes followed by heavy rains, especially in subtropical regions. Hypoxia stress results in the reduction of green pigments, gas exchange (stomatal conductance and internal CO concentration), and photosynthetic activity in the plant leaves. In addition, hypoxia stress causes oxidative damage by accelerating lipid peroxidation due to the hyperproduction of reactive oxygen species (ROS) in leaf and root tissues. Furthermore, osmolyte accumulation and antioxidant activity increase, whereas micronutrient uptake decreases under hypoxia stress. Plant physiology and development get severely compromised by hypoxia stress. This investigation was, therefore, aimed at appraising the effects of regular silicon (Si) and Si nanoparticles (SiNPs) to mitigate hypoxia stress in muscadine ( Michx.) plants. Our results demonstrated that hypoxia stress reduced muscadine plants' growth by limiting the production of root and shoot dry biomass, whereas the root zone application of both Si and SiNP effectively mitigated oxidative and osmotic cell damage. Compared to Si, SiNP yielded better efficiency by improving the activity of enzymatic antioxidants [including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)], non-enzymatic antioxidants [ascorbic acid (AsA) and glutathione contents], and accumulation of organic osmolytes [proline and glycinebetaine (GB)]. SiNP also regulated the nutrient profile of the plants by increasing N, P, K, and Zn contents while limiting Mn and Fe concentration to a less toxic level. A negative correlation between antioxidant activities and lipid peroxidation rates was observed in SiNP-treated plants under hypoxia stress. Conclusively, SiNP-treated plants combat hypoxia more efficiently stress than conventional Si by boosting antioxidant activities, osmoprotectant accumulation, and micronutrient regulation.
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http://dx.doi.org/10.3389/fpls.2020.618873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902783PMC
February 2021

Synthesis and antibacterial evaluation of new monobactams.

Bioorg Med Chem Lett 2021 05 24;39:127878. Epub 2021 Feb 24.

Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan, Ningxia 750002, PR China. Electronic address:

Monobactams play an important role in antibiotic drug discovery. Based on the structural characteristics of aztreonam and its biological targets, six new monobactam derivatives (2a-c and 3a-c) were synthesized and their in vitro antibacterial activities were investigated. Compounds 2a-c showed higher activities against tested gram-negative bacteria than that of parent aztreonam. Monobactam 2c exhibited the most potent activities, with MIC ranging from 0.25 to 2 μg/mL against most bacteria.
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http://dx.doi.org/10.1016/j.bmcl.2021.127878DOI Listing
May 2021

Ensuring the Quality and Appropriate Use of Hand Sanitizers During the COVID-19 Pandemic: Suggestions and Recommendations With the Role of the Pharmacist.

Disaster Med Public Health Prep 2021 Feb 16:1-2. Epub 2021 Feb 16.

Department of Pharmaceutical Services, Armed Forces Hospital, King Abdulaziz Air Base, Dhahran, Kingdom of Saudi Arabia.

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http://dx.doi.org/10.1017/dmp.2021.55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129673PMC
February 2021

Next-Generation Sequencing and the CRISPR-Cas Nexus: A Molecular Plant Virology Perspective.

Front Microbiol 2020 12;11:609376. Epub 2021 Jan 12.

Department of Plant Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Muscat, Oman.

In recent years, next-generation sequencing (NGS) and contemporary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) technologies have revolutionized the life sciences and the field of plant virology. Both these technologies offer an unparalleled platform for sequencing and deciphering viral metagenomes promptly. Over the past two decades, NGS technologies have improved enormously and have impacted plant virology. NGS has enabled the detection of plant viruses that were previously undetectable by conventional approaches, such as quarantine and archeological plant samples, and has helped to track the evolutionary footprints of viral pathogens. The CRISPR-Cas-based genome editing (GE) and detection techniques have enabled the development of effective approaches to virus resistance. Different versions of CRISPR-Cas have been employed to successfully confer resistance against diverse plant viruses by directly targeting the virus genome or indirectly editing certain host susceptibility factors. Applications of CRISPR-Cas systems include targeted insertion and/or deletion, site-directed mutagenesis, induction/expression/repression of the gene(s), epigenome re-modeling, and SNPs detection. The CRISPR-Cas toolbox has been equipped with precision GE tools to engineer the target genome with and without double-stranded (ds) breaks or donor templates. This technique has also enabled the generation of transgene-free genetically engineered plants, DNA repair, base substitution, prime editing, detection of small molecules, and biosensing in plant virology. This review discusses the utilities, advantages, applications, bottlenecks of NGS, and CRISPR-Cas in plant virology.
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http://dx.doi.org/10.3389/fmicb.2020.609376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874184PMC
January 2021

Cellular and molecular mechanisms of Dementia: Decoding the causal link of Diabetes Mellitus in Alzheimer's disease.

CNS Neurol Disord Drug Targets 2021 Feb 11. Epub 2021 Feb 11.

Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah. Saudi Arabia.

Dementia and diabetes are the two major disorders that are linked at both biochemical and molecular levels which is due to the existing similarities between pancreatic beta-cells and neuronal cells at the transcription and translational levels. Both diseases have similar causative genes or factors and dementia is one of the advanced complications in about 50-52% of patients with type 2 diabetes mellitus (T2DM). Further, patients with T2DM are at a higher risk of neuronal degeneration and Alzheimer's disease (AD). Dementia, which is most common in AD, is associated with diminished insulin receptors by nearly 80%. The impairment in insulin signaling thus leads to the development of dementia and AD. Biochemical changes in 'tau' protein and amyloid-beta proteins, make them critical players in the formation of plaques in patients with dementia and AD. Here, we decode various cellular and molecular mechanisms associated with the development of dementia in patients with diabetes and AD.
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http://dx.doi.org/10.2174/1871527320666210212114116DOI Listing
February 2021

Organochlorine pesticide residues in raw milk samples collected from dairy farms and urban areas of Lahore district, Pakistan.

J Food Sci Technol 2021 Jan 22;58(1):129-137. Epub 2020 May 22.

Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.

The current study was employed to investigate the organochlorine pesticides (OCP) concentrations in milk, as the milk we consume, has residues of these notorious pesticides. The residual concentrations of OCP in milk have numerous harmful effects on health especially the children. Therefore, milk was analyzed using gas chromatography equipped with µECD for seven OCP residues, namely α-endosulfan, β-endosulfan, Endosulfan-sulphate, DDE, γ-HCH, Dieldrin, and DDT. Three hundred and sixty raw milk samples were collected from urban areas (10 areas of Lahore N = 300) and Dairy Farms (10 farms in Lahore N = 60) from September 2012 to September 2013. Samples were collected after an interval of 2 months, for 12 months. Mean values of OCPs in milk samples from urban areas were reported as α-endosulfan, β-endosulfan, Endosulfan-sulphate, DDE, γ-HCH, and Dieldrin with concentration of 17.44 ± 3.99, 35.74 ± 7.50, 20.28 ± 3.95, 2.51 ± 0.55, 0.93 ± 0.16 and 1.12 ± 0.18 µg kg, respectively, while the milk samples from dairy farms with concentration of 26.94 ± 4.63, 59.88 ± 6.76, 32.07 ± 4.51, 4.64 ± 0.48, 1.20 ± 0.17 and 1.93 ± 0.18 µg kg, respectively. None of the samples analyzed were found positive for the presence of DDT, just as none of the samples from area milk shops exceeded the Maximum Residual Limits (MRLs). γ-HCH and β-endosulfan were found higher in dairy farm milk samples than the MRLs. Conclusively, these pesticide residues are present in milk available in Lahore in enough quantity (some exceeding the MRLs) to threaten human health, particularly the infant and children.
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http://dx.doi.org/10.1007/s13197-020-04522-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813927PMC
January 2021

Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors.

Biomed Res Int 2020 24;2020:8867407. Epub 2020 Dec 24.

Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Pakistan.

A series of halo-substituted mixed ester/amide-based analogues have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines reacted with chloroacetyl chloride to afford intermediates , which were then reacted with different halo-substituted benzoic acids to prepare the title compounds . The chemical structures of final products were ascertained by FTIR, H NMR, C NMR, and mass spectra. The compound showed remarkable activity with IC1.6 ± 0.2 nM, better than the standard thiourea having IC472.1 ± 135.1 nM. The 2-chloro-substituted phenyl ring on one side of compound and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver-Burk plots (kinetics study) indicated about derivative as a mixed type of inhibitor. The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds and have binding energies of -7.8 and -7.9 Kcal/mol, respectively. Based upon our results, it was found that derivative is a highly potent urease inhibitor, better than the standard thiourea.
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http://dx.doi.org/10.1155/2020/8867407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775144PMC
May 2021

Assessment of heavy metal pollution in Brassica plants and their impact on animal health in Punjab, Pakistan.

Environ Sci Pollut Res Int 2021 May 10;28(18):22768-22778. Epub 2021 Jan 10.

Department of Environmental Sciences and Engineering, Government College University, Faisalabad, Allama Iqbal Road, Faisalabad, Punjab, 38000, Pakistan.

Growing Brassica rapa L. (Brassica rapa subsp. campestris (Linn.) Clapham) with wastewater and their use as a fodder for animals is a common practice in suburb of all cities in Punjab, Pakistan, despite the wastewater containing heavy metals is of public health concern. This study assessed the risk of heavy metals on animal health via consumption of B. rapa as fodder grown with wastewater, tube-well and canal water, and its source apportionment, in suburb of Multan City, Pakistan. Samples of B. rapa (n = 30) were collected from six agricultural farms and analyzed for cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), and lead (Pb) by inductively coupled plasma-optical emission spectrometry (ICP-OES). Total target health quotient (TTHQ) values ranged 47.22 to 136.64 in wastewater irrigation farm, 2.32 to 3.71 in canal water, and 4.86 to 7.50 in tube-well water irrigation farms, respectively exhibiting high carcinogenic health risk to animals across the farms. B. rapa grown with industrial effluents exhibited the highest carcinogenic health risk, while the canal water posed the lowest risk. Multivariate statistical analyses indicated that the wastewater samples containing heavy metals and contaminated soils were common sources of B. rapa contamination. Proper treatment of wastewater for removal of toxic elements before application in agricultural fields may safeguard the health of animals, public, and the ecosystem.
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http://dx.doi.org/10.1007/s11356-021-12370-6DOI Listing
May 2021

Discovery and Protein Modeling Studies of Novel Compound Mutations Causing Resistance to Multiple Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.

Asian Pac J Cancer Prev 2020 12 1;21(12):3517-3526. Epub 2020 Dec 1.

College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS)/ KAIMRC/SSBMT, National Guards Health Affairs, Al-Ahsa, Kingdom of Saudi Arabia.

Objective: BCR-ABL fusion oncogene is the hallmark of chronic myeloid leukemia (CML), causing genomic instability which leads to accumulation of mutations in BCR-ABL as well as other genes. BCR-ABL mutations are the cause of tyrosine kinase inhibitors (TKIs) resistance in CML. Recently, compound BCR-ABL mutations have been reported to resist all FDA approved TKIs. Therefore, finding novel compound BCR-ABL mutations can help and clinically manage CML. Therefore, our objective was to find out novel drug-resistant compound BCR-ABL mutations in CML and carry out their protein modelling studies.

Methodology: Peripheral blood samples were collected from ten imatinib resistant CML patients receiving nilotinib treatment. BCR-ABL transcript mutations were investigated by employing capillary sequencing. Patient follow-up was carried out using European LeukemiaNet guidelines. Protein modeling  studies were carried out for new compound mutations using PyMol to see the effects of mutations at structural level.

Results: A novel compound mutation (K245N mutation along with G250W mutation) and previously known T351I utation was detected in two of the nilotinib resistance CML patients respectively while in the rest of 8 nilotinib responders, no resistant mutations were detected. Protein modelling studies indicated changes in BCR-ABL mutant protein which may have negatively impacted its binding with nilotinib leading to drug resistance.

Conclusion: We report a novel nilotinib resistant BCR-ABL compound mutation (K245N along with G250W mutation) which impacts structural modification in BCR-ABL mutant protein leading to drug resistance. As compound mutations pose a new threat by causing resistance to all FDA approved tyrosine kinase inhibitors in BCR-ABL+ leukemias, our study opens a new direction for in vitro characterization of novel BCR-ABL compound mutations and their resistant to second  generation and third generation TKIs.
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http://dx.doi.org/10.31557/APJCP.2020.21.12.3517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046299PMC
December 2020

Factors Associated with Varicocele Recurrence After Microscopic Sub-Inguinal Varicocelectomy.

Res Rep Urol 2020 15;12:651-657. Epub 2020 Dec 15.

Division of Urology, Department of Surgery, Ministry of the National Guard - Health Affairs, Riyadh, Saudi Arabia.

Purpose: This study has been conducted to identify the rate of varicocele recurrence in patients who underwent microscopic subinguinal varicocelectomy at our center. We also aimed to determine the contributing factors to varicocele recurrence.

Patients And Methods: A total of 34 married male patients who underwent microscopic sub-inguinal varicocelectomy were retrospectively included in this study. The medical records of recruited patients were reviewed. The diagnosis of varicocele was based on physical examination, while recurrent varicocele was diagnosed based on both physical examination and colored doppler ultrasound. We investigated contributing factors to varicocele recurrence, including demographic characteristics (such as body mass index), clinical (varicocele grade and size of dilated veins), and laboratory data (semen analysis). Patients were followed up at 3 and 6 months after surgery.

Results: The mean age of patients was 32.53 years. The majority of patients had left-sided varicocele (70.6%) and underwent surgery due to scrotal pain (82.4%), with a mean operation duration of 92 minutes. Left-sided varicoceles were grade II in 51.7% of patients, while right-sided varicoceles were grade II in 16.1% of patients. Recurrence occurred in 2.9% after 3 and 6 months. Pain recurred in 8.8% and 10.5% of patients at 3 and 6 months, respectively. Pregnancy rates were 44.1% at 3 months and 11.8% at 6 months after surgery. The grade of varicocele (P = 0.24) and the size of the left dilated vein (P = 0.002) was significantly associated with recurrence.

Conclusion: There was a significant association of advanced grade on the left side and large vein diameter before and after surgery with an increased rate of recurrence; however, due to the small sample size of our study, more and larger studies are still warranted.
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http://dx.doi.org/10.2147/RRU.S281739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751726PMC
December 2020

New applications related to Covid-19.

Results Phys 2021 Jan 19;20:103663. Epub 2020 Dec 19.

University of Management and Technology, Lahore, Pakistan, The University of Lahore, Lahore, Pakistan.

Analysis of mathematical models projected for COVID-19 presents in many valuable outputs. We analyze a model of differential equation related to Covid-19 in this paper. We use fractal-fractional derivatives in the proposed model. We analyze the equilibria of the model. We discuss the stability analysis in details. We apply very effective method to obtain the numerical results. We demonstrate our results by the numerical simulations.
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http://dx.doi.org/10.1016/j.rinp.2020.103663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749318PMC
January 2021

Whole exome sequencing identifies a novel FANCD2 gene splice site mutation associated with disease progression in chronic myeloid leukemia: Implication in targeted therapy of advanced phase CML.

Pak J Pharm Sci 2020 May;33(3(Special)):1419-1426

Cancer and Medical Genetics, CAMS-A, King Saud Bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Centre (KAIMRC), King Abdulaziz Medical City, National Guard Health Affairs, Al Ahsa, Saudi Arabia.

Tyrosine Kinase Inhibitors (TKIs) have significantly improved the clinical outcome of BCR-ABL+ Chronic Phase-Chronic Myeloid Leukemia (CP-CML). Nonetheless, approximately one-third of the CP-CML patient's progress to advanced phases of CML (accelerated and blast phase). Impaired DNA repair including mutations in Fanconi anemia (FA) pathway genes are responsible for progression of many cancers. Nevertheless, FA-pathways genes have never been reported in myeloid cancers. Hence, this study was aimed to discover DNA repair genes associated with CML progression. AP-CML patients were subjected to whole exome sequencing along with appropriate controls. A novel splice site FANCD2 mutation was detected. FANCD2 is a well-known FA-pathway gene with established role in DNA repair. This is first report of FA-pathway DNA repair genes in myeloid cancers that can serve as a novel marker of CML progression to clinically intervene CML progression. Further studies are needed to establish the functional role of FANCD2 in CML progression that can provide novel insights into CML pathogenesis. This study also indicates that a combination TKIs and Poly (ADP-ribose) polymerase (PARP) inhibitors like Olaparib (FDA approved anti-cancer drug for FA-pathway gene mutations) could improve the clinical outcome CML patients in accelerated and blast-crisis phases of the disease.
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May 2020

Plant-growth-promoting Bacillus and Paenibacillus species improve the nutritional status of Triticum aestivum L.

PLoS One 2020 1;15(12):e0241130. Epub 2020 Dec 1.

Botany and Microbiology Department, College of Science, King Saud University, Riyadh, Saudi Arabia.

Wheat is one of the best-domesticated cereal crops and one of the vital sources of nutrition for humans. An investigation was undertaken to reveal the potential of novel bio-inoculants enriching micronutrients in shoot and grains of wheat crop to eliminate the hazards of malnutrition. Sole as well as consortia inoculation of bio-inoculants significantly enhanced mineral nutrients including zinc (Zn) and iron (Fe) concentrations in shoot and grains of wheat. Various treatments of bio-inoculants increase Zn and Fe content up to 1-15% and 3-13%, respectively. Sole inoculation of Bacillus aryabhattai (S10) impressively improves the nutritious of wheat. However, the maximum increase in minerals contents of wheat was recorded by consortia inoculation of Paenibacillus polymyxa ZM27, Bacillus subtilis ZM63 and Bacillus aryabhattai S10. This treatment also showed a maximum bacterial population (18 × 104 cfu mL-1) in the rhizosphere. The consortium application of these strains showed up to a 17% increase in yield. It is evident from the results that the consortium application was more effective than sole and co-inoculation. A healthy positive correlation was found between growth, yield, and the accessibility of micronutrients to wheat crops at the harvesting stage. The present investigations revealed the significance of novel bacterial strains in improving the nutritional status of wheat crops. These strains could be used as bio-inoculants for the biofortification of wheat to combat hidden hunger in developing countries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241130PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707572PMC
January 2021

A Figure of Eight and a Circle Within a Circle: Is This Left Ventricular Geometry Responsible for Multiple Embolic Strokes Two Years After Inferior Wall Myocardial Infarction?

J Cardiothorac Vasc Anesth 2021 Jun 23;35(6):1892-1896. Epub 2020 Oct 23.

Anesthesiology Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI. Electronic address:

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http://dx.doi.org/10.1053/j.jvca.2020.10.038DOI Listing
June 2021

Post-Marketing Experience of Edaravone in Amyotrophic Lateral Sclerosis: A Clinical Perspective and Comparison With the Clinical Trials of the Drug.

Cureus 2020 Oct 6;12(10):e10818. Epub 2020 Oct 6.

Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease that affects the upper and lower motor neurons. Currently, the only treatment for ALS is riluzole, which only has a limited effect on increasing survival from 3 to 6 months. New therapies are needed in the clinical setting for ALS. We aim to compare and contrast the clinical trials of edaravone and the post-marketing experience of the drug during this study. For the method, a search strategy was made using PubMed with the search terms "Amyotrophic lateral sclerosis" (MeSH) and "Edaravone" (MeSH). For inclusion criteria, we used full papers, studies involving humans, and studies published in the English language. We exclude meta-analyses, literature reviews, systematic reviews, studies involving animals, and studies not published in English. After close examination, 20 papers were used for the discussion in this review. The clinical trials showed efficacy in patients in reducing the revised ALS functional rating scale (ALSFRS-R) in patients with early ALS with selective criteria. We documented edaravone's post-marketing experience in six countries: Kuwait, South Korea, Argentina, United States, Israel, and Italy. During the study we analyzed, the forced vital capacity (FVC) and ALSFRS-R scored, together with edaravone's safety in the clinical trials and post-marketing experience. Edaravone seems to be more effective in Asia, where the ALSFRS-R scores and the FVC decline were similar to the clinical trial results in Japan. Studies in Europe did not find the drug clinically useful. At the same time, studies in United States and Argentina were mainly descriptive, so more information is needed to evaluate the drug's efficacy in that part of the world. The drug was well-tolerated in all studies. In conclusion, more studies need to be done worldwide to carry out and clarify the effectiveness of edaravone in the clinical setting.
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http://dx.doi.org/10.7759/cureus.10818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645306PMC
October 2020

A new species of Sasajiscymnus Vandenberg (Coleoptera: Coccinellidae) from Pakistan.

Zootaxa 2020 Apr 3;4759(3):zootaxa.4759.3.4. Epub 2020 Apr 3.

Laboratory of Biosystematics, Department of Entomology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan..

A new species of a ladybird beetle, Sasajiscymnus nigritus sp. nov., is described and illustrated from Pakistan. An identification key to Pakistani species of Sasajiscymnus Vandenberg is provided. A preliminary checklist of species of Sasajiscymnus in Asia is also included.
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http://dx.doi.org/10.11646/zootaxa.4759.3.4DOI Listing
April 2020

Fecal Microbiota Transplantation in Recurrent Clostridium Difficile Infection: Is it Superior to Other Conventional Methods?

Cureus 2020 Aug 11;12(8):e9653. Epub 2020 Aug 11.

Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA.

() is a gram-positive species of spore-forming bacteria. infection (CDI) is one of the most common hospital-acquired infections in the United States, mainly caused by the use of recent antibiotics that leads to intestinal dysbiosis. Recurrent infection (rCDI) often occurs after the successful treatment of CDI. Approximately, 30% of patients experience a clinical recurrence of prior symptoms within eight weeks of antibiotic cessation. This present literature review covers the current pathophysiology of CDI, risk factors for infection, diagnostic methods, several treatment modalities, and the potential use of fecal microbial transplant (FMT) for patients with multiple recurrent CDIs. Recent studies have focused on FMT, with an efficacy rate of nearly 90% in multiple recurrent CDI settings. Despite its efficacy, it is not commonly used as first-line treatment. More studies are needed to establish this therapy as the first option in patients with rCDI.
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http://dx.doi.org/10.7759/cureus.9653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482981PMC
August 2020

How to Treat Asymptomatic and Symptomatic Urinary Tract Infections in the Kidney Transplant Recipients?

Cureus 2020 Aug 7;12(8):e9608. Epub 2020 Aug 7.

Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA.

Patients with end-stage renal functions are treated with renal transplantation. After the transplantation, kidney transplant recipients (KTR) are at the risk of urinary tract infection (UTI). UTI in KTR may be symptomatic and asymptomatic. Asymptomatic UTI is the presence of the organisms without any signs and symptoms. There are various ways suggested in the published research papers to deal with UTI in the KTR. The goal of this literature review is to explore how to treat symptomatic and asymptomatic UTI in KTR. A PubMed search was conducted to identify the studies explaining the methods used to deal with UTI in KTR. A total number of 2158 articles were found while searching for regular keywords; however, we found 996 articles with the medical subject heading (Mesh) keywords. After applying the inclusion/ exclusion criteria, 56 articles with the regular keywords search and 29 articles with the Mesh keywords search were selected. These articles included 24 randomized clinical trials, 16 clinical trials, 7 review articles, 5 case reports, 2 controlled clinical trials, 2 observational studies, and 1 cross-sectional study. Our analysis has shown that the early removal of the stent after the transplantation and the use of antibiotics are beneficial in reducing the incidence of symptomatic UTI in the KTR; whereas, treating asymptomatic UTI in KTR has not been proven helpful in reducing the incidence of developing symptomatic UTI later on.
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http://dx.doi.org/10.7759/cureus.9608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478741PMC
August 2020

Management of Fifth Metacarpal Neck Fracture (Boxer's Fracture): A Literature Review.

Cureus 2020 Jul 28;12(7):e9442. Epub 2020 Jul 28.

Emergency Medicine, Usman Memorial Hospital, Karachi, PAK.

Boxer's fracture is the fifth metacarpal neck fracture resulting from direct trauma to the clenched fist. Worldwide, this type of fracture is the most typical presentation to emergency departments. The management of fifth metacarpal fractures varies from one setting to another. Conservative management is the preferred option for closed, non-angulated, non-malrotated fractures while open fractures, significant angulation, rotational deformity, and intra-articular extension are recognised indications for surgical intervention. The scope of this article covers the results of a literature review examining the management strategies for such fractures.
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http://dx.doi.org/10.7759/cureus.9442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451089PMC
July 2020

Long term outcome of chronic myeloid leukemia patients treated with imatinib: Report from a developing country.

Pak J Pharm Sci 2020 Mar;33(2(Supplementary)):861-870

Cancer and Medical Genetics, CAMS-A, King Saud Bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Centre (KAIMRC), King Abdulaziz Medical City, National Guard Health Affairs, Al Ahsa, Saudi Arabia.

The outcome of chronic myeloid leukemia has been greatly improved by the use of Imatinib (IM), a selective BCR/ABL kinase inhibitor. The aim of present study was to report long term follow-up & outcome of IM-treated CML patients along with their clinicopathological features, risk group stratification, adverse events and to compare it with CML patients reported from western countries. The mean follow-up of 123 CML patients was 5.5 years in present study, who were treated with frontline IM 400mg daily in a tertiary care hospital in Pakistan. Risk stratification scores, response to treatment (ELN guidelines) and survival outcomes estimated by Kaplan-Meier analysis. Mean age: 35 years (9-67 years) and M: F: 1.5:1, mean follow up time: 5.5 years (1-15 years). Overall survival (OS): at 5.5, 8, 10 and 12 years were 93%, 88%, 81% and 73%, respectively. Progressions free survival (PFS) was 95%, 83%, 83% and 78% at 5.5, 8, 10 and 12 years, respectively. OS estimate by Sokal score was significant (P-value: 0.0019). Additional chromosomal aberrations: 1.6%. Eighteen (14.6%) patients progressed to AP/BC. Adverse events were moderate and tolerable. We present findings from a long term follow up of CML patients treated with IM in a developing country. CML mean age at onset was considerably lower than the western populations. Furthermore, 5.5 years OS are comparable to western CML population. IM in our patients as frontline choice proved to be very effective. IM was found to be well tolerated, safe with manageable moderate side effects.
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March 2020

Diurnal Differences in Human Muscle Isometric Force In Vivo Are Associated with Differential Phosphorylation of Sarcomeric M-Band Proteins.

Proteomes 2020 Aug 26;8(3). Epub 2020 Aug 26.

Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.

We investigated whether diurnal differences in muscle force output are associated with the post-translational state of muscle proteins. Ten physically active men (mean ± SD; age 26.7 ± 3.7 y) performed experimental sessions in the morning (08:00 h) and evening (17:00 h), which were counterbalanced in order of administration and separated by at least 72 h. Knee extensor maximal voluntary isometric contraction (MVIC) force and peak rate of force development (RFD) were measured, and samples of vastus lateralis were collected immediately after exercise. MVIC force was greater in the evening (mean difference of 67 N, 10.2%; < 0.05). Two-dimensional (2D) gel analysis encompassed 122 proteoforms and discovered 6 significant ( < 0.05; false discovery rate [FDR] = 10%) diurnal differences. Phosphopeptide analysis identified 1693 phosphopeptides and detected 140 phosphopeptides from 104 proteins that were more ( < 0.05, FDR = 22%) phosphorylated in the morning. Myomesin 2, muscle creatine kinase, and the C-terminus of titin exhibited the most robust (FDR < 10%) diurnal differences. Exercise in the morning, compared to the evening, coincided with a greater phosphorylation of M-band-associated proteins in human muscle. These protein modifications may alter the M-band structure and disrupt force transmission, thus potentially explaining the lower force output in the morning.
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http://dx.doi.org/10.3390/proteomes8030022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565642PMC
August 2020
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