Publications by authors named "Muhammad Hanif"

297 Publications

Achieving Complete Radiological and Bio-Chemical Response as a Predictor of Long-Term Survival in Stage IV Epithelial Ovarian Cancer.

Cureus 2021 Nov 29;13(11):e20017. Epub 2021 Nov 29.

Medical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, PAK.

Objective Epithelial ovarian cancer (EOC) is common among ovarian cancers. The majority of existing literature shows combined data of stage III and stage IV. Therefore, we aimed to look for whether achieving complete radiological and biochemical response after initial treatment of stage IV epithelial ovarian cancer as a predictor of long-term survival in the Pakistani population. Methods A cross-sectional study was conducted of patients with stage IV epithelial ovarian cancer diagnosed and treated from 2006-2013 at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Overall survival was defined as the number of months between patients' diagnosis at the hospital and any cause of death or last follow-up date. Kaplan Meier curve was used to report the overall survival. The log-rank test was used to distinguish the survival difference in complete and no complete response. P-value <0.05 was considered statistically significant. Result A total of fifty patients of stage IV epithelial ovarian carcinoma, with a mean age of 53 ± 2 received neoadjuvant chemotherapy and suitable patients underwent interval-debulking surgery. Among these fifty patients, twenty-one (42%) patients who achieved complete radiological and biochemical response had a median survival of greater than five years. Patients without co-morbidities (46%) and having good performance status (52%) showed better results of the treatment. Patients' tolerance to chemotherapy with good response and fit enough to undergo interval-debulking surgery, achieving complete radiological and biochemical response after initial induction therapy were significantly associated with long-term survival (P<0.05). Conclusion Outcomes of patients who present with stage IV EOC remains dismal. Patients who achieved complete radiological and biochemical response after neoadjuvant chemotherapy and interval-debulking surgery was significantly associated with long-term survival.
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http://dx.doi.org/10.7759/cureus.20017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716327PMC
November 2021

Pediatric Chemotherapy Drugs Associated With Cardiotoxicity.

Cureus 2021 Nov 17;13(11):e19658. Epub 2021 Nov 17.

Cardiology, Larkin Community Hospital, South Miami, USA.

Pediatric cancers are a common cause of childhood morbidity. As a result, chemotherapeutic regimens have been designed to target childhood cancers. These medications are necessary to treat pediatric cancers, however, oncology management options are accompanied by multiple negative and potentially fatal adverse effects. Although anthracyclines are the most commonly used chemotherapeutic agents associated with cardiotoxicity, we also explore other chemotherapeutic drugs used in children that can potentially affect the heart. Genetic variations resulting in single nucleotide polymorphism (SNP) have the propensity to modify the cardiotoxic effects of the chemotherapy drugs. The clinical presentation of the cardiac effects can vary from arrhythmias and heart failure to completely asymptomatic. A range of imaging studies and laboratory investigations can protect the heart from severe outcomes. The physiology of the heart and the effect of drugs in children vary vividly from adults; therefore, it is crucial to study the cardiotoxic effect of chemotherapy drugs in the pediatric population. This review highlights the potential contributing factors for cardiotoxicity in the pediatric population and discusses the identification and management options.
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http://dx.doi.org/10.7759/cureus.19658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8679581PMC
November 2021

Hemimegalencephaly: A rare congenital malformation of cortical development.

Clin Case Rep 2021 Dec 18;9(12):e05238. Epub 2021 Dec 18.

Larkin Community Hospital South Miami Florida USA.

Hemimegalencephaly is a rare congenital malformation of cortical development usually associated with developmental delay and refractory epilepsy that sooner or later require hemispherectomy.
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http://dx.doi.org/10.1002/ccr3.5238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684578PMC
December 2021

Seasonal Variation, Fractional Isolation and Nanoencapsulation of Antioxidant Compounds of Indian Blackberry ().

Antioxidants (Basel) 2021 Nov 26;10(12). Epub 2021 Nov 26.

Chemistry Department, College of Science, King Saud University, Riyadh 1145, Saudi Arabia.

Indian blackberry ( L.) is an evergreen tree in the Myrtaceae family. It is used in traditional medicine due to its significant bioactivities and presence of polyphenols with antioxidant activities. The present study describes the effect of seasonal variations on Indian blackberry leaf essential oil yield and chemical composition, production of fractions from essential oil using high vacuum fractional distillation and slow cooling to low temperature (-50 °C) under vacuum, and bioactivities of the essential oil, fractions, and nanoparticles. The results show that Indian blackberry essential oil yield was higher in spring season as compared to winter season. Indian blackberry essential oil fractionation processes were effective in separating and concentrating compounds with desired bioactivities. The bioactivities shown by magnesium nanoparticles were comparatively higher than barium nanoparticles.
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http://dx.doi.org/10.3390/antiox10121900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750729PMC
November 2021

Synthetic Strategy Towards Heterodimetallic Half-Sandwich Complexes Based on a Symmetric Ditopic Ligand.

Front Chem 2021 3;9:786367. Epub 2021 Dec 3.

School of Chemical Sciences, University of Auckland, Auckland, New Zealand.

Multimetallic complexes have been shown in several examples to possess greater anticancer activity than their monometallic counterparts. The increased activity has been attributed to altered modes of action. We herein report the synthesis of a series of heterodimetallic compounds based on a ditopic ligand featuring 2-pyridylimine chelating motifs and organometallic half-sandwich moieties. The complexes were characterized by a combination of H NMR spectroscopy, electrospray ionization mass spectrometry, elemental analysis and single crystal X-ray diffraction. Investigations into the stability of representative complexes in DMSO- and 10% DMSO- /DO revealed the occurrence of solvent-chlorido ligand exchange. Proliferation assays in four human cancer cell lines showed that the Os-Rh complex possessed minimal activity, while all other complexes were inactive.
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http://dx.doi.org/10.3389/fchem.2021.786367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677676PMC
December 2021

The production of biodiesel from plum waste oil using nano-structured catalyst loaded into supports.

Sci Rep 2021 12 16;11(1):24120. Epub 2021 Dec 16.

Institute of Horticultural Sciences, University of Agriculture, Faisalabad, 38040, Pakistan.

The present study was undertaken with aims to produced catalyst loaded on low-cost clay supports and to utilize plum waste seed oil for the production of biodiesel. For this purpose, Bentonite-potassium ferricyanide, White pocha-potassium ferricyanide, Granite-potassium ferricyanide, Sindh clay-potassium ferricyanide, and Kolten-potassium ferricyanide composites were prepared. Transesterification of plum oil under the different conditions of reactions like catalysts concentrations (0.15, 0.3 and 0.6 g), temperature (50, 60, 70 and 80 °C), reaction time (2, 4 and 6 h) and oil to methanol ratio (1:10) was conducted. The maximum biodiesel yield was recorded for Bentonite-potassium ferricyanide composite. This composite was subjected to calcination process to produce Calcinized bentonite-potassium ferricyanide composite and a further improvement in biodiesel amount was recorded. The fuel quality parameters of all biodiesel samples were in standard range. Gas chromatographic mass spectrometric analysis confirmed the presence of oleic and linoleic acids in the plum seed oil. The characterization of composite was done using FTIR, SEM and EDX. Two infrared bands are observed in the spectrum from 1650 to 1630 cm indicates that the composite materials contained highly hydrogen bonded water. The presence of surface hydroxyls groups can also be confirmed from FTIR data. SEM image clearly show the presence of nano-rods on the surface of Granite-potassium ferricyanide and Kolten-potassium ferricyanide composites. Another interesting observation that can be recorded from SEM images is the changes in surface characteristic of Bentonite-potassium ferricyanide composite after calcination (at 750 °C, 1 atm for 4 h). Calcinized bentonite-potassium ferricyanide composite found to contain more nano rod like structures at its surface as compared to Bentonite-potassium ferricyanide composite which contained spherical particles. EDX data of Bentonite-potassium ferricyanide composite and Calcinized bentonite-potassium ferricyanide composite show that after calcination carbon and oxygen was reduced. The other lost volatile compounds after calcination were of Na, Mg, Al, Si, and S. The XRD spectrum of pure bentonite showed the average crystal size of 24.46 nm and calcinized bentonite of 25.59 nm. The average crystal size of bentonite and potassium ferricyanide composite and its calcinized form was around 33.76 nm and 41.05 nm, respectively.
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http://dx.doi.org/10.1038/s41598-021-03633-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677847PMC
December 2021

Microplastics and nanoplastics: Recent literature studies and patents on their removal from aqueous environment.

Sci Total Environ 2022 Mar 8;810:152115. Epub 2021 Dec 8.

Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, UTM Johor Bahru, 81310 Skudai, Johor, Malaysia.

The presence of microplastics (MP) and nanoplastics (NP) in the environment poses significant hazards towards microorganisms, humans, animals and plants. This paper is focused on recent literature studies and patents discussing the removal process of these plastic pollutants. Microplastics and nanoplastics can be quantified by counting, weighing, absorbance and turbidity and can be further analyzed using scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, surface-enhanced Raman spectroscopy and Raman tweezers. Mitigation methods reported are categorized depending on the removal characteristics: (i) Filtration and separation method: Filtration and separation, electrospun nanofiber membrane, constructed wetlands; (ii) Capture and surface attachment method: coagulation, flocculation and sedimentation (CFS), electrocoagulation, adsorption, magnetization, micromachines, superhydrophobic materials and microorganism aggregation; and (iii) Degradation method: photocatalytic degradation, microorganism degradation and thermal degradation; where removal efficiency between 58 and 100% were reported. As these methods are significantly distinctive, the parameters which affect the MP/NP removal performance e.g., pH, type of plastics, presence of interfering chemicals or ions, surface charges etc. are also discussed. 42 granted international patents related to microplastics and nanoplastics removal are also reviewed where the majority of these patents are focused on separation or filtration devices. These devices are efficient for microplastics up to 20 μm but may be ineffective for nanoplastics or fibrous plastics. Several patents were found to focus on methods similar to literature studies e.g., magnetization, CFS, biofilm and microorganism aggregation; with the addition of another method: thermal degradation.
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http://dx.doi.org/10.1016/j.scitotenv.2021.152115DOI Listing
March 2022

Cervical Cystic Teratoma: An Unusual Cause of Airway Obstruction in the Pediatric Population.

Cureus 2021 Oct 31;13(10):e19166. Epub 2021 Oct 31.

Internal Medicine, Nishtar Medical University Hospital, Multan, PAK.

Cystic teratoma is a germ cell tumor, which usually involves the gonads. However, it can be located occasionally in other organs. The most common extragonadal sites for germ cell tumors include midline structures such as the retroperitoneum, mediastinum, pineal body, and supra-sellar space. Here, we describe a case of a patient who presented with a cystic teratoma involving the anterior aspect of the neck. The chief complaints of the patient consisted of a large swelling in front of the neck, difficulty in breathing, and frequent regurgitation of milk during feeding. Initially, a diagnosis of cystic hygroma was instituted for which the patient underwent sclerotherapy utilizing bleomycin. However, no improvement was observed in the patient's condition. A detailed evaluation was planned, starting with a CT scan of the head and neck that suggested cystic teratoma as the likely etiology. Surgical excision of the mass was performed, and an excisional biopsy for histopathological examination was taken. A final diagnosis of cervical cystic teratoma was established based on the histopathological findings. The purpose of reporting this case is to raise awareness among fellow healthcare professionals that cystic teratoma can also present with a large swelling in the anterior neck with obstructive features.
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http://dx.doi.org/10.7759/cureus.19166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631485PMC
October 2021

Pharmacological evaluation of Vitis vinifera and Zingiber zerumbet on electrocardiographic, biochemical alterations and antioxidant status in isoproterenol-induced myocardial infarction in rats.

Pak J Pharm Sci 2021 Sep;34(5(Supplementary)):1929-1937

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

The Vitis vinifera (VV) and Zingiber zerumbet (ZZ) are popular functional foods which are used for the treatment of cardiovascular ailments. These possess antiproliferative, antiplatelet and antioxidant effects. The current study has been designed to ascertain their effectiveness against Isoproterenol (ISO)-induced myocardial infarction (MI). Chronic administration of VV and ZZ was accessed for its cardio-protective effect in ISO-induced MI rats. Male albino rats were treated with VV (250 mg/kg, p.o.), ZZ (200 mg/kg, p.o.) and its combination (Vitis vinifera + Zingiber zerumbet) VZ for 30 days prior to ISO administration (85 mg/kg, S/C). Electrocardiography (ECG) and Blood Pressure (BP) were measured using PowerLab data acquisition system. Biochemical serum markers, tissue histopathology and HPLC finger printing were performed. The VV, ZZ and its combination VZ showed significant protective effects on ST segment elevation, cardiac biomarkers; Troponin I (Trop I), creatine kinase-MB (CK-MB), alanine transaminase (ALT), aspartate amino transferase (AST), lactate dehydrogenase (LDH), enhanced the cardiac antioxidant defense system, restored the hematological (WBCs, RBCs, Platelets) & coagulation parameters and improved the lipid profile and histopathological alterations such as tissue necrosis, infiltration and edema which were observed only in ISO administered rats. These results indicate that V. vinifera and Z. zerumbet possess cardio protective effects possibly mediated through maintenance of endogenous antioxidant levels, cardiac biomarkers and lipid parameters.
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September 2021

Brain MR Image Enhancement for Tumor Segmentation Using 3D U-Net.

Sensors (Basel) 2021 Nov 12;21(22). Epub 2021 Nov 12.

Artificial Intelligence in Healthcare, Intelligent Information Processing Lab, National Center of Artificial Intelligence, University of Engineering and Technology, Peshawar 25120, Pakistan.

MRI images are visually inspected by domain experts for the analysis and quantification of the tumorous tissues. Due to the large volumetric data, manual reporting on the images is subjective, cumbersome, and error prone. To address these problems, automatic image analysis tools are employed for tumor segmentation and other subsequent statistical analysis. However, prior to the tumor analysis and quantification, an important challenge lies in the pre-processing. In the present study, permutations of different pre-processing methods are comprehensively investigated. In particular, the study focused on Gibbs ringing artifact removal, bias field correction, intensity normalization, and adaptive histogram equalization (AHE). The pre-processed MRI data is then passed onto 3D U-Net for automatic segmentation of brain tumors. The segmentation results demonstrated the best performance with the combination of two techniques, i.e., Gibbs ringing artifact removal and bias-field correction. The proposed technique achieved mean dice score metrics of 0.91, 0.86, and 0.70 for the whole tumor, tumor core, and enhancing tumor, respectively. The testing mean dice scores achieved by the system are 0.90, 0.83, and 0.71 for the whole tumor, core tumor, and enhancing tumor, respectively. The novelty of this work concerns a robust pre-processing sequence for improving the segmentation accuracy of MR images. The proposed method overcame the testing dice scores of the state-of-the-art methods. The results are benchmarked with the existing techniques used in the Brain Tumor Segmentation Challenge (BraTS) 2018 challenge.
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http://dx.doi.org/10.3390/s21227528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624231PMC
November 2021

Improved anti-inflammatory effect of curcumin by designing self-emulsifying drug delivery system.

Drug Dev Ind Pharm 2021 Nov 14:1-11. Epub 2021 Nov 14.

Department of Pharmaceutics Faculty of Pharmacy Bahauddin Zakariya University Multan.

Purpose of present study was to prepare and evaluate self-emulsifying drug delivery system (SEDDS) of curcumin (Cur) to enhance its solubility and percentage release for the evaluation of anti-inflammatory effect. Curcumin loaded SEDDS formulation was prepared, and zones of self-emulsification were recognized by dilution method for the construction of phase diagram. Lauroglycol FCC, Tween 80 (surfactant), and Transcutol HP (co-surfactant) were selected based on their solubility and highest emulsion region in phase diagram. Thermodynamic stability of Cur-SEDDS was calculated through globule size, zeta potential, polydispersity index (PDI), viscosity and pH. Cur-SEDDS were also characterized by encapsulation efficiency (EE %), FT-IR, release, and anti-inflammatory effect. Results revealed that droplet size of Cur-SEDDS was 19.77 ± 0.03 nm with their PDI 0.22 ± 0.19, zeta potential -19.33 ± 0.94 and viscosity 25.68 ± 0.86 cp. EE % of Cur-SEDDS was found to be 94.99 ± 0.38%, percentage release 65.83% compared with pure curcumin powder. The designed formulation possesses significant anti-inflammatory activity in paw edema when compared with positive control in carrageenan induced rat paw edema assay. Newly developed Cur-SEDDS with enhanced curcumin solubility, percentage release and better anti-inflammatory action may be an alternative source of oral delivery of curcumin.
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http://dx.doi.org/10.1080/03639045.2021.2001486DOI Listing
November 2021

SARS-CoV-2 UK, South African and Brazilian Variants in Karachi- Pakistan.

Front Mol Biosci 2021 25;8:724208. Epub 2021 Oct 25.

Department of Molecular Pathology, Hashmanis Group of Hospitals, Karachi, Pakistan.

The COVID-19 pandemic has been evolving in Pakistan with the emergence of the United Kingdom, South African, and Brazilian variants. These variants of concern (VOC) are known for increased transmissibility and can also be responsible for avoiding immune responses. The gold standard to detect VOC is sequencing, however routine genomic surveillance in resource-limited countries like Pakistan is not always readily available. The inadvertent detection of the B.1.1.7 (United Kingdom) VOC by a target failure due to the key deletion in spike Δ69-70 by commercially available PCR assay helps to understand target failures as an alternative approach to detect variants. In pursuit of VOC it was further discovered that a deletion in the ORF1a gene (ORF1a Δ3675-3677) is common in B.1.1.7, B.1.351 (South African), and P.1 (Brazilian) VOC. The Real-Time Quantitative PCR (RT-qPCR) assay can distinguish target failures and can discriminate SARS-CoV-2 VOC. The study uses positive samples archived in respective labs. Samples were divided into two groups. Group I constitutes 261 positive samples out of total of 16,964 (1.53%) performed from August till September 2020, while group II consists of 3501 positive samples out of a total of 46,041 (7.60%) performed, from November 2020 till January 2021. The RT-qPCR analysis showed that no VOC was present in positive samples of group I. However, a staggering difference in results was noted in group II where the positivity ratio increased exponentially and the VOC started appearing in significant numbers (53.64%). This concludes that the third wave in Pakistan is due to the importation of SARS-CoV-2 variants.
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http://dx.doi.org/10.3389/fmolb.2021.724208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572847PMC
October 2021

Prevalence and Associated Risk Factor of COVID-19 and Impacts of Meteorological and Social Variables on Its Propagation in Punjab, Pakistan.

Earth Syst Environ 2021 Jul 7:1-14. Epub 2021 Jul 7.

Shaheed Benazir Bhutto Hospital, Rawalpindi Medical University, Rawalpindi, Pakistan.

The current study identifies the spatial distribution of COVID-19 cases and its association with meteorological and social variables in Punjab (densely populated province of Pakistan). To identify the COVID-19 propagation, the weekly growth, recovery, and deaths rate have also been calculated. The geographic information system (GIS) has used to determine COVID-19 impacts on gender (male/female), age groups, and causalities over an affected population (km) for the period of 11th March to 12th August, 2020 in each district of province. Our results show that 43 peak days (where daily positive cases were above 900) have been observed in Punjab during 27th May to 8th July, 2020. The high population density districts, i.e., Lahore and Islamabad, have been affected (five persons per square kilometers) due to COVID-19, whereas the maximum death tolls (> 50 persons per millions) have also been observed in these urban districts. The meteorological variables (temperature, humidity, heat index, and ultraviolet index) show negative significant relationship to basic reproduction number (R0), whereas daily COVID-19 cases are positively correlated to aerosols concentration at 95% confidence level. The government intervention (stringency index) shows a positive impact to reduce the COVID-19 cases over the province. Keeping in view the COVID-19 behavior and climatology of the region, it has been identified that the COVID-19 cases may likely to increase during the dry period (high concentration of aerosols) i.e., October-December, 2020 and post-spring season (April to June), 2021 in urban areas of Pakistan. This study provides an overview on districts vulnerability that would help the policy makers, health agencies to plan their activities to reduce the COVID-19 impacts.
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http://dx.doi.org/10.1007/s41748-021-00218-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260326PMC
July 2021

Anti-Proliferative, Anti-Angiogenic and Safety Profiles of Novel HDAC Inhibitors for the Treatment of Metastatic Castration-Resistant Prostate Cancer.

Pharmaceuticals (Basel) 2021 Oct 4;14(10). Epub 2021 Oct 4.

Department of Pharmacology and Toxicology, University of Otago, Dunedin 9016, New Zealand.

Metastatic castration-resistant prostate cancer (CRPC) has a five-year survival rate of 28%. As histone deacetylases (HDACs) are overexpressed in CRPC, the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was trialled in CRPC patients but found to be toxic and inefficacious. Previously, we showed that novel HDAC inhibitors (Jazz90 1-hydroxy--(4-(pyridine-2-carbothioamido)phenyl)octanediamide) and Jazz167 ([chlorido(η-pentamethylcyclopentadieny[1-4](1-hydroxy--(4-(pyridine-2-carbothioamido-κ)phenyl)octanediamide)rhodium(III)] chloride) had a higher cancer-to-normal-cell selectivity and superior anti-angiogenic effects in CRPC (PC3) cells than SAHA. Thus, this study aimed to further investigate the efficacy and toxicity of these compounds. HUVEC tube formation assays revealed that Jazz90 and Jazz167 significantly reduced meshes and segment lengths in the range of 55-88 and 43-64%, respectively. However, Jazz90 and Jazz167 did not affect the expression of epithelial-to-mesenchymal transitioning markers E-cadherin and vimentin. Jazz90 and Jazz167 significantly inhibited the growth of PC3 and DU145 spheroids and reduced PC3 spheroid branching. Jazz90 and Jazz167 (25, 50 and 75 mg/kg/day orally for 21 days) were non-toxic in male BALB/c mice. The efficacy and safety of these compounds demonstrate their potential for further in vivo studies in CRPC models.
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http://dx.doi.org/10.3390/ph14101020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540814PMC
October 2021

The Role and Efficacy of Coenzyme Q10 in the Management of Erectile Dysfunction in a Hypertensive Male: An Interventional Study.

Cureus 2021 Sep 13;13(9):e17937. Epub 2021 Sep 13.

Internal Medicine, Khyber Medical College Peshawar, Hayatabad Medical Complex, Peshawar, PAK.

Introduction Erectile dysfunction (ED) is a prevalent medical condition that affects millions of men globally. A number of pharmacological and complementary options are used in the management of ED, including Coenzyme Q10 (CoQ10). Oxidative stress has been linked to the progression of ED, and Co Q10 protects against oxidative damages and improves erectile function as well as the activity of antioxidant enzymes. This study aimed to determine the efficacy of CoQ10 in the treatment of erectile dysfunction in hypertensive males. Method An open-labeled parallel arm interventional study was conducted in the cardiology unit of Hayatabad Medical Complex Hospital, Peshawar, Pakistan, from March 2020 to March 2021. Hypertensive male patients (n = 230) were randomly allocated to either receiving 200-gram CoQ10 daily along with their current antihypertensive therapy (n=104) or anti-hypertensive treatment only (n=105). The patient's erectile function was assessed at baseline and three months using the International Index of Erectile Function Test (IIEF-5) during the study period. Result Of the total 230, 209 (90.87%) patients were included in the final analysis. There were no significant differences in demographics, history of illness, co-morbid conditions, and current medication of both groups. After three months, 21 (20.1%) participants scored more than 17 in the IIEF-5 and no longer had ED. Overall, no significant difference was found in the mean IIEF-5 score between the study group and control group (14.41 ± 4.49 Vs. 15.61 ± 4.82; p=0.06). However, in subgroup analysis, significant improvement in the study group was seen in participants with mild ED (p=0.03). Conclusion With the demonstration of its efficacy in hypertensive patients with mild ED, co-enzyme Q10 supplementation can be proposed as a potential candidate in patients with long-term hypertension and can play a role in erectile dysfunction.
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http://dx.doi.org/10.7759/cureus.17937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513668PMC
September 2021

Formulation and evaluation of sustained release ocular inserts of betaxolol hydrochloride using arabinoxylan from Plantago ovata.

Pak J Pharm Sci 2021 May;34(3(Supplementary)):1069-1074

Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

The purpose of the current studies was to develop ocular insert of betaxolol hydrochloride (BXH), using arabinoxylan (AX) as a film former. The inserts were prepared by sandwiching I mg of BXH between two films of AX. Six different formulations of ocular inserts were prepared in such a way that first three formulations contained varying concentrations of AX along with glycerol as plasticizer, whereas, rest of the formulations were added with 0.5mg of sodium alginate, sandwiched between two films of AX along with 1mg of BXH. Chemical compatibilities of the ingredients were assessed by using FTIR. Prepared ocular inserts were subjected to various physicochemical characterizations. The dissolution studies showed that ocular inserts containing sodium alginate with the AX showed sustained release effect better than the formulations with AX alone. Addition of sodium alginate resulted in inhibition of sudden release in initial phase and further sustained the release of drug from ocular inserts. Ocular inserts were pH compatible to the eyes as well as there was no interaction among the drug and excipients, suggesting that the selected excipients were suitable for the development of sustained release ocular inserts of BXH.
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May 2021

Role of serum VEGF-A biomarker for early diagnosis of ovarian cancer instead of CA-125.

J Pak Med Assoc 2021 Sep;71(9):2192-2197

Gulab Devi Educational Complex, Lahore, Pakistan.

Objective: To assess the significance of serum vascular endothelial growth factor-A (VEGF-A) as a potential biomarker for the diagnosis of ovarian cancer instead of cancer antigen-125 (CA-125).

Methods: The case-control study was conducted at the obstetrics departments of Sir Ganga Ram Hospital and Jinnah Hospital, Lahore, Pakistan, from April to September 2018, and comprised cases of epithelial ovarian tumour and healthy female controls. Serum VEGF-A and CA-125 levels were evaluated using Luminex multi-analyte profiling technology and enzyme immunoassays technique. Age, stage, grading, metastasis and ascites of ovarian cancer patients were investigated and compared with serum VEGF-A and CA-125 levels. Data was analysed using SPSS 20.

Results: Of the 89 subjects, 44(49.4%) were cases and 45(49.6%) were controls. Among the cases, 13(29.5%) were benign and 31(70.5%) were malignant. The mean serum VEGF-A values were inversely proportional to the stages of ovarian cancer i.e. stage I, II, III and IV showed 762.2pg/ml, 267.3pg/ml, 233.1pg/ml and 125.5pg/ml VEGF-A levels respectively. A steady increase in the mean serum CA-125 values with the progression of the disease was observed i.e. in stage I, II, III and IV the levels of CA-125 were 146.2U/ml, 268.5U/ml and 477.2U/ml and 844.4U/ml respectively.

Conclusions: The detection of high concentrations of serum VEGF-A level supported its use as one of the diagnostic parameters in the timely investigation of ovarian cancer.
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http://dx.doi.org/10.47391/JPMA.05-688DOI Listing
September 2021

Anthracenyl Functionalization of Half-Sandwich Carbene Complexes: Anticancer Activity and Reactions with Biomolecules.

Inorg Chem 2021 Oct 16;60(19):14636-14644. Epub 2021 Sep 16.

OBT (Oral Health-Brain Health-Total Health) Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

N-Heterocyclic carbene (NHC) ligands are widely investigated in medicinal inorganic chemistry. Here, we report the preparation and characterization of a series of half-sandwich [M(L)(NHC)Cl] (M = Ru, Os, Rh, Ir; L = cym/Cp*) complexes with a N-flanking anthracenyl moiety attached to imidazole- and benzimidazole-derived NHC ligands. The anticancer activity of the complexes was investigated in cell culture studies where, in comparison to a Rh derivative with an all-carbon-donor-atom-based ligand (), they were found to be cytotoxic with IC values in the low micromolar range. The Ru derivative was chosen as a representative for stability studies as well as for biomolecule interaction experiments. It underwent partial chlorido/aqua ligand exchange in DMSO-/DO to rapidly form an equilibrium in aqueous media. The reactions of with biomolecules proceeded quickly and resulted in the formation of adducts with amino acids, DNA, and protein. Hen egg white lysozyme crystals were soaked with , and the crystallographic analysis revealed an interaction with an l-aspartic acid residue (Asp119), resulting in the cleavage of the -cymene ligand but the retention of the NHC moiety. Cell morphology studies for the Rh analog suggested that the cytotoxicity is exerted via mechanisms different from that of cisplatin.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01675DOI Listing
October 2021

Complete heart block in patients infected with SARS-CoV-2: A case series from a developing country.

Ann Med Surg (Lond) 2021 Sep 6;69:102828. Epub 2021 Sep 6.

Hayatabad Medical Complex Peshawar, KPK, Pakistan.

Coronavirus Disease 19 (COVID-19) has led to a global pandemic and has been the center of attention across the entire medical community. This novel virus was initially thought to affect primarily the respiratory system, but now it is evident that it has a multitude of effects on the human body. Our point of interest is to establish the effect of COVID-19 infection on the conducting system of the heart. We present a case series of four patients who developed complete heart block (CHB) shortly after being infected with COVID-19 without any previous known risk factors of complete heart block. There have only been a few previous case reports on the occurrence of CHB in COVID-19 patients highlighting the importance and the need of our case series to the literature of cardiovascular outcomes in COVID-19 patients. Our case series highlight that COVID-19 can indeed affect the conduction system of the heart and cause CHB in patients who then recovered spontaneously further elucidating the transient nature of cardiovascular effects caused by the novel virus.
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http://dx.doi.org/10.1016/j.amsu.2021.102828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420262PMC
September 2021

Large Emphysematous Bullae Mimicking As A Pneumothorax Leading To Unnecessary Chest Tube Insertion And Iatrogenic Pneumothorax.

J Ayub Med Coll Abbottabad 2021 Jul-Sep;33(3):526-528

Hayatabad Medical Complex Peshawar, Pakistan.

Pneumothorax (Pnx) is the presence of air or gas in the pleural space which hinders the lungs to function appropriately. Pneumothorax that presents in the absence of any underlying aetiology is called primary spontaneous pneumothorax (PSP) and on the other hand, it may present as a complication of underlying lung disease which is known as secondary spontaneous pneumothorax (SSP). Iatrogenic Pneumothorax (IP) is a type of SSP and is caused by medical interventional procedures which include transthoracic needle biopsy (24%), sub clavicular catheterization (22%), thoracocentesis (20%), transbronchial biopsy (10%), pleural biopsy (8%) and positive pressure ventilation (7%). We had a 51-year-old patient with a history of COPD/emphysema who presented with respiratory distress. Large bullae were mistaken as pneumothorax, unnecessary Chest Tube Insertion (thoracostomy) was performed resulting in IP. An extensive review of the literature shows there are only a few reported cases of unnecessary thoracotomy and IP in settings of giant bulla mimicking pneumothorax. Iatrogenic Pneumothorax resulting from giant bullae mimicking pneumothorax leading to unnecessary chest tube insertion. Physicians should be aware of such aetiology of pneumothorax as it has been rarely reported in the literature.
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November 2021

Detection of subclinical rheumatic heart disease in children using a deep learning algorithm on digital stethoscope: a study protocol.

BMJ Open 2021 08 5;11(8):e044070. Epub 2021 Aug 5.

Cardiology, Cardiology care for Children, Lancaster PA, AI DuPont Children's Hospital, Wilmington, Delaware, USA

Introduction: Rheumatic heart diseases (RHDs) contribute significant morbidity and mortality globally. To reduce the burden of RHD, timely initiation of secondary prophylaxis is important. The objectives of this study are to determine the frequency of subclinical RHD and to train a deep learning (DL) algorithm using waveform data from the digital auscultatory stethoscope (DAS) in predicting subclinical RHD.

Methods And Analysis: We aim to recruit 1700 children from a group of schools serving the underprivileged over a 12-month period in Karachi (Pakistan). All consenting students within the age of 5-15 years with no underlying congenital heart disease will be eligible for the study. We will gather information regarding sociodemographics, anthropometric data, history of symptoms or diagnosis of rheumatic fever, phonocardiogram (PCG) and electrocardiography (ECG) data obtained from DAS. Handheld echocardiogram will be performed on each study participant to assess the presence of a mitral regurgitation (MR) jet (1.5 cm), or the presence of aortic regurgitation (AR) in any view. If any of these findings are present, a confirmatory standard echocardiogram using the World Heart Federation (WHF) will be performed to confirm the diagnosis of subclinical RHD. The auscultatory data from digital stethoscope will be used to train the deep neural network for the automatic identification of patients with subclinical RHD. The proposed neural network will be trained in a supervised manner using labels from standard echocardiogram of the participants. Once trained, the neural network will be able to automatically classify the DAS data in one of the three major categories-patient with definite RHD, patient with borderline RHD and normal subject. The significance of the results will be confirmed by standard statistical methods for hypothesis testing.

Ethics And Dissemination: Ethics approval has been taken from the Aga Khan University, Pakistan. Findings will be disseminated through scientific publications and to collaborators.

Article Focus: This study focuses on determining the frequency of subclinical RHD in school-going children in Karachi, Pakistan and developing a DL algorithm to screen for this condition using a digital stethoscope.
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http://dx.doi.org/10.1136/bmjopen-2020-044070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344289PMC
August 2021

Acute Hepatitis as a Rare Presentation of COVID-19.

J Coll Physicians Surg Pak 2021 07;31(7):S125-S126

Department of Internal Medicine, Khyber Teaching Hospital, Peshawar, Pakistan.

Coronavirus disease 2019 (COVID-19) initially emerged in Wuhan, China, in December 2019, and now it has been declared a pandemic by the World Health Organization. COVID-19 commonly presents with respiratory manifestations like fever, cough, body aches, and shortness of breath. Neurological, myocardial, renal and gastrointestinal complications secondary to SARS-CoV-2 infection have been reported in the literature. Gastrointestinal symptoms reported with COVID-19 are mostly nausea, vomiting, and diarrhea. COVID-19 can rarely present with acute hepatitis. Here, we report a case of a 45-year male who presented with signs and symptoms of acute hepatitis secondary to SARS-CoV-2 infection. Key Words: SARS-CoV-2, COVID-19, Acute hepatitis.
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http://dx.doi.org/10.29271/jcpsp.2021.Supp2.S125DOI Listing
July 2021

COVID-19-induced Guillain-Barre Syndrome: A Rare Complication of SARS-CoV-2 Infection.

J Coll Physicians Surg Pak 2021 07;31(7):S123-S124

Department of Internal Medicine, Hayatabad Medical Complex, Peshawar, Pakistan.

SARS-CoV-2 causing COVID-19 initially began in Wuhan, China and now has been declared a pandemic by the World Health Organization (WHO). In addition to respiratory symptoms, it can cause various complications ranging from neurological to myocardial injuries. Guillain-Barre Syndrome (GBS) is an acute polyradiculoneuropathy affecting more often lower limbs than upper limbs and is often related to previous infectious diseases. We, herein, describe a case of a young female who presented with typical symptoms of GBS after having COVID-19 and was later on confirmed with nerve conduction study and lumbar puncture. Key Words: COVID-19, SARS-CoV-2, Guillain-barre syndrome.
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http://dx.doi.org/10.29271/jcpsp.2021.Supp2.S123DOI Listing
July 2021

Can COVID-19 Cause Pancreatitis? A Rare Complication of SARS-CoV-2 Infection.

J Coll Physicians Surg Pak 2021 07;31(7):S120-S122

Department of Internal Medicine, Hayatabad Medical Complex, Peshawar, Pakistan.

Coronavirus disease-2019 (COVID-19) emerged as a cluster of atypical pneumonia in Wuhan, China in December 2019. This disease has been declared a pandemic by the World Health Organization. COVID-19 patients mostly present with upper respiratory symptoms like dyspnea, cough and fever. Various neurological, myocardial, renal and gastrointestinal complications have been reported associated with SARS-CoV-2. Acute pancreatitis is one of the common causes of upper abdominal pain, caused by alcohol consumption, gall stones and various viruses and drugs. We present a case of a young female, who was recently diagnosed as COVID-19 and later on developed acute pancreatitis without any other risk factors.  Key Words: COVID-19, SARS-CoV-2, Acute pancreatitis.
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http://dx.doi.org/10.29271/jcpsp.2021.Supp2.S120DOI Listing
July 2021

Key considerations when using the sulforhodamine B assay for screening novel anticancer agents.

Anticancer Drugs 2022 01;33(1):6-10

Department of Pharmacology and Toxicology, University of Otago, Dunedin.

Anticancer drug discovery programmes use a large number of in-vitro assays to screen the potency of compound libraries. The accuracy and reliability of these in-vitro assays are vital in selecting potent lead candidates for further (pre)clinical studies. Among the commonly used cell viability assays, the sulforhodamine B (SRB) assay has been a popular choice due to its simplicity, accuracy, reliability and reproducibility. SRB dye interacts with protein's basic amino acids and viable cell number is determined based on the cellular protein content. In this study, the cytotoxic potency of the novel hydroxythiopyridone derivatives towards A549 and H522 cells was determined using the SRB assay. The known drugs oxaliplatin and vorinostat were also examined. The resulting EC50 values were accurate, reliable and reproducible. However, all EC50 values calculated in 6-well plates were higher compared to those determined from 96-well plates. Furthermore, results from 6-well plates were also more variable compared to 96-well plates. Our results confirm that SRB assay is a reliable technique in screening the potency of anticancer drug candidates but plating conditions need to be carefully considered.
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http://dx.doi.org/10.1097/CAD.0000000000001131DOI Listing
January 2022

ResNet Based Deep Features and Random Forest Classifier for Diabetic Retinopathy Detection.

Sensors (Basel) 2021 Jun 4;21(11). Epub 2021 Jun 4.

Center of Excellence in Intelligent Engineering Systems, Department of Electrical and Computer Engineering, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Diabetic retinopathy, an eye disease commonly afflicting diabetic patients, can result in loss of vision if prompt detection and treatment are not done in the early stages. Once the symptoms are identified, the severity level of the disease needs to be classified for prescribing the right medicine. This study proposes a deep learning-based approach, for the classification and grading of diabetic retinopathy images. The proposed approach uses the feature map of ResNet-50 and passes it to Random Forest for classification. The proposed approach is compared with five state-of-the-art approaches using two category Messidor-2 and five category EyePACS datasets. These two categories on the Messidor-2 dataset include 'No Referable Diabetic Macular Edema Grade (DME)' and 'Referable DME' while five categories consist of 'Proliferative diabetic retinopathy', 'Severe', 'Moderate', 'Mild', and 'No diabetic retinopathy'. The results show that the proposed approach outperforms compared approaches and achieves an accuracy of 96% and 75.09% for these datasets, respectively. The proposed approach outperforms six existing state-of-the-art architectures, namely ResNet-50, VGG-19, Inception-v3, MobileNet, Xception, and VGG16.
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http://dx.doi.org/10.3390/s21113883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200077PMC
June 2021

Triazolyl-Functionalized N-Heterocyclic Carbene Half-Sandwich Compounds: Coordination Mode, Reactivity and in vitro Anticancer Activity.

ChemMedChem 2021 Oct 29;16(19):3017-3026. Epub 2021 Jul 29.

School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.

We report investigations on the anticancer activity of organometallic [M (η -p-cymene/η -pentamethylcyclopentadienyl)] (M=Ru, Os, Rh, and Ir) complexes of N-heterocyclic carbenes (NHCs) substituted with a triazolyl moiety. Depending on the precursors, the NHC ligands displayed either mono- or bidentate coordination via the NHC carbon atom or as N,C-donors. The metal complexes were investigated for their stability in aqueous solution, with the interpretation supported by density functional theory calculations, and reactivity to biomolecules. In vitro cytotoxicity studies suggested that the nature of both the metal center and the lipophilicity of the ligand determine the biological properties of this class of compounds. The Ir complex 5 d bearing a benzimidazole-derived ligand was the most cytotoxic with an IC value of 10 μM against NCI-H460 non-small cell lung carcinoma cells. Cell uptake and distribution studies using X-ray fluorescence microscopy revealed localization of 5 d in the cytoplasm of cancer cells.
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http://dx.doi.org/10.1002/cmdc.202100311DOI Listing
October 2021

Letter to the Editor on Type 1 diabetes onset triggered by COVID-19.

Acta Diabetol 2021 09 28;58(9):1283-1284. Epub 2021 Jun 28.

Department of Internal Medicine, Universitas Sebelas Maret Hospital, Surakarta, Indonesia.

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http://dx.doi.org/10.1007/s00592-021-01761-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236735PMC
September 2021

Carbon Monoxide is an Inhibitor of HIF Prolyl Hydroxylase Domain 2.

Chembiochem 2021 08 29;22(15):2521-2525. Epub 2021 Jun 29.

School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand.

Hypoxia-inducible factor prolyl hydroxylase domain 2 (PHD2) is an important oxygen sensor in animals. By using the CO-releasing molecule-2 (CORM-2) as an in situ CO donor, we demonstrate that CO is an inhibitor of PHD2. This report provides further evidence about the emerging role of CO in oxygen sensing and homeostasis.
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http://dx.doi.org/10.1002/cbic.202100181DOI Listing
August 2021

Microfilaria Positification Test Using Real-Time PCR Technique with HRM (High-Resolution Melting).

Acta Parasitol 2021 Jun 16. Epub 2021 Jun 16.

Dr Hasan Sadikin General Hospital, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.

Microscopic examination results in patients with filariasis are often not identified by the presence of microfilaria, so it needs to be checked by Polymerase Chain Reaction (PCR). One PCR method uses High-Resolution Melting (HRM). The purpose of this study was to compare qPCR-HRM with microscopic examination methods to determine the types of microfilaria found in patients with filariasis. 19 samples were examined using a microscopic method and qPCR-HRM. The results of microscopic examination found no type of microfilaria and in qPCR-HRM identified B.malayi and W.bancrofti with peak temperature melting 78.1-78.7 ℃ and 80.2-80.8 ℃. The results of the study based on the comparison of two methods show that the types of microfilaria W.bancrofti and B.malayi can be found using qPCR-HRM.
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http://dx.doi.org/10.1007/s11686-021-00412-5DOI Listing
June 2021
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