Publications by authors named "Muhammad Idrees"

328 Publications

Central Pontine Myelinolysis in Pregnancy: A Case of Rare Occurrence.

Cureus 2021 Dec 8;13(12):e20281. Epub 2021 Dec 8.

Department of Internal Medicine, Medical Teaching Institution, Ayub Teaching Hospital, Abbottabad, PAK.

Central pontine myelinolysis is a non-inflammatory neurologic deficit and can have a wide array of clinical features, predisposing risk factors as well as different patterns of onset along with a big difference in prognosis ranging from asymptomatic cases to encephalopathy and also mortality. Apart from the common risk factors like hyponatremia and sudden correction of electrolyte imbalances, sometimes, the least prevalent risk factors such as pregnancy seem to link with the central pontine myelinolysis. Mostly its onset is sudden after the inciting factors. However, it is also likely to have cases of central pontine myelinolysis with gradual onset of clinical features. The purpose of the case report is to highlight the link between pregnancy and central pontine myelinolysis. The slow onset of clinical features in pregnancy-linked central pontine myelinolysis can also be considered. The patient in the case report presented with gradual onset clinical features of osmotic demyelination syndrome during the last months of pregnancy and immediately postpartum. All the possible predisposing risk factors for central pontine myelinolysis were ruled out through history, physical examination, and relevant investigations. The case study of the patient hypothesized that: (1) pregnancy should be considered as a risk factor for central pontine myelinolysis in pregnant and postpartum patients presenting with clinical features of the disease, (2) clinical features of central pontine myelinolysis in pregnancy can have a more gradual onset of symptoms compared to other causes of central pontine myelinolysis. Although, this case report signifies a relationship between pregnancy and osmotic demyelination syndrome. However, further studies should be done to develop a causal relationship and preventive measures for the condition.
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http://dx.doi.org/10.7759/cureus.20281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747984PMC
December 2021

Core-Proteomics-Based Annotation of Antigenic Targets and Reverse-Vaccinology-Assisted Design of Ensemble Immunogen against the Emerging Nosocomial Infection-Causing Bacterium .

Int J Environ Res Public Health 2021 Dec 24;19(1). Epub 2021 Dec 24.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

is a ubiquitous Gram-negative emerging pathogen that causes hospital-acquired infection in both immunocompromised and immunocompetent patients. It is a multi-drug-resistant bacterium; therefore, an effective subunit immunogenic candidate is of great interest to encounter the pathogenesis of this pathogen. A protein-wide annotation of immunogenic targets was performed to fast-track the vaccine development against this pathogen, and structural-vaccinology-assisted epitopes were predicted. Among the total proteins, only three, A0A1T3FLU2, A0A1T3INK9, and A0A1V3U124, were shortlisted, which are the essential vaccine targets and were subjected to immune epitope mapping. The linkers EAAK, AAY, and GPGPG were used to link CTL, HTL, and B-cell epitopes and an adjuvant was also added at the N-terminal to design a multi-epitope immunogenic construct (MEIC). The computationally predicted physiochemical properties of the ensemble immunogen reported a highly antigenic nature and produced multiple interactions with immune receptors. In addition, the molecular dynamics simulation confirmed stable binding and good dynamic properties. Furthermore, the computationally modeled immune response proposed that the immunogen triggered a strong immune response after several doses at different intervals. Neutralization of the antigen was observed on the 3rd day of injection. Conclusively, the immunogenic construct produces protection against ; however, further immunological testing is needed to unveil its real efficacy.
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http://dx.doi.org/10.3390/ijerph19010194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750920PMC
December 2021

Income inequality, financial development, and ecological footprint: fresh evidence from an asymmetric analysis.

Environ Sci Pollut Res Int 2022 Jan 4. Epub 2022 Jan 4.

School of Economics, Quaid-i-Azam University, Islamabad, Pakistan.

The emerging environmental concerns are entrenched in social issues, largely stem from income differences and power disparity. Income distribution and environmental disruption are increasingly pointed as obstacles in securing sustainable development goals and environmental preservation. The existing empirical studies have explored the environmental pollution impact of income inequality. However, the results are conflicting, and little attention has been paid to explore the short and long-run environmental impacts from a national viewpoint. Similarly, the role of aggregate income and financial sector for environmental quality has attracted considerable attention and many studies have provided conflicting empirical evidence. The literature generally ignores the importance of relative income in explaining environmental outcomes and also assumes symmetric association, ignoring asymmetric shocks. The present study explores the role of nonlinear associations in forming the links between income distribution and environmental quality using linear and nonlinear autoregressive distributed lag models from 1972 to 2018. The study follows the extended environmental Kuznets curve (EKC) approach. The results suggest that inequality promotes environmental pollution. Further financial development also escalates carbon emissions. The nonlinear analysis confirms the asymmetric effect of inequality on ecological footprint. The EKC, however, is not validated for Pakistan. The results suggest important policy implications.
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http://dx.doi.org/10.1007/s11356-021-18288-3DOI Listing
January 2022

Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy.

Front Mol Neurosci 2021 16;14:728128. Epub 2021 Dec 16.

Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.

Neuropathic pain refers to a lesion or disease of peripheral and/or central somatosensory neurons and is an important body response to actual or potential nerve damage. We investigated the therapeutic potential of two thiadiazine-thione [TDT] derivatives, 2-(5-propyl-6-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT1] and 2-(5-propyl-2-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT2] against CCI (chronic constriction injury)-induced neuroinflammation and neuropathic pain. Mice were used for assessment of acute toxicity of TDT derivatives and no major toxic/bizarre responses were observed. Anti-inflammatory activity was assessed using the carrageenan test, and both TDT1 and TDT2 significantly reduced carrageenan-induced inflammation. We also used rats for the induction of CCI and performed allodynia and hyperalgesia-related behavioral tests followed by biochemical and morphological analysis using RT-qPCR, immunoblotting, immunohistochemistry and immunofluorescence. Our findings revealed that CCI induced clear-cut allodynia and hyperalgesia which was reversed by TDT1 and TDT2. To determine the function of TDT1 and TDT2 in glia-mediated neuroinflammation, Iba1 mRNA and protein levels were measured in spinal cord tissue sections from various experimental groups. Interestingly, TDT1 and TDT2 substantially reduced the mRNA expression and protein level of Iba1, implying that TDT1 and TDT2 may mitigate CCI-induced astrogliosis. molecular docking studies predicted that both compounds had an effective binding affinity for TNF-α and COX-2. The compounds interactions with the proteins were dominated by both hydrogen bonding and van der Waals interactions. Overall, these results suggest that TDT1 and TDT2 exert their neuroprotective and analgesic potentials by ameliorating CCI-induced allodynia, hyperalgesia, neuroinflammation and neuronal degeneration in a dose-dependent manner.
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http://dx.doi.org/10.3389/fnmol.2021.728128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716630PMC
December 2021

Identification of a common polymorphism in acting as a modifier of thoracic aortic aneurysm severity.

HGG Adv 2022 Jan 17;3(1). Epub 2021 Sep 17.

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, United States of America.

Thoracic aortic aneurysm (TAA) predisposes to sudden, life-threatening aortic dissection. The factors that regulate interindividual variability in TAA severity are not well understood. Identifying a molecular basis for this variability has the potential to improve clinical risk stratification and advance mechanistic insight. We previously identified , a gene important for biosynthesis of coenzyme Q, as a candidate genetic modifier of TAA severity. Here, we investigated the physiological role of in human aortic smooth muscle cells (SMCs) and further tested its genetic association with TAA severity. We find COQ8B protein localizes to mitochondria in SMCs, and loss of mitochondrial COQ8B leads to increased oxidative stress, decreased mitochondrial respiration, and altered expression of SMC contractile genes. Oxidative stress and mitochondrial cristae defects were prevalent in the medial layer of human proximal aortic tissues in patients with TAA, and expression was decreased in TAA SMCs compared with controls. A common single nucleotide polymorphism (SNP) rs3865452 in (c.521A>G, p.H174R) was associated with decreased rate of aortic root dilation in young patients with TAA. In addition, the SNP was less frequent in a second cohort of early-onset thoracic aortic dissection cases compared with controls. COQ8B protein levels in aortic SMCs were increased in TAA patients homozygous for rs3865452 compared with those homozygous for the reference allele. Thus, is important for aortic SMC metabolism, which is dysregulated in TAA, and rs3865452 may decrease TAA severity by increasing COQ8B level. Genotyping rs3865452 may be useful for clinical risk stratification and tailored aortopathy management.
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http://dx.doi.org/10.1016/j.xhgg.2021.100057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670066PMC
January 2022

Large Cell Calcifying Sertoli Cell Tumor: A Clinicopathologic Study of 18 Cases With Comprehensive Review of the Literature and Reappraisal of Prognostic Features.

Am J Surg Pathol 2021 Dec 16. Epub 2021 Dec 16.

Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN Department of Pathology and Laboratory Medicine, University of Michigan, Ann Arbor, MI.

We present a series of 18 (8 clinically benign, 8 clinically ambiguous [ie, lacking sufficient follow-up to determine behavior], and 2 clinically malignant) large cell calcifying Sertoli cell tumors (LCCSCT) of the testis. The median patient age and size were 15.5 years and 1.9 cm for the benign tumors; 19 years and 1.6 cm for the ambiguous tumors; and 28.5 years and 2.3 cm for the malignant tumors. The most common presentation was a mass (n=12/18, 67%). Two patients (11%) had the Carney complex, and 2 had neurofibromatosis type 1. All tumors showed nodular growth with frequent lymphoid aggregates at the periphery. Within the nodules, there were nests and trabeculae of pale to eosinophilic epithelioid tumor cells with frequent cytoplasmic vacuolization interspersed with hypocellular, often myxoid stroma with conspicuous neutrophils. Spindled tumor cells were a minor component (<5%) in the clinically benign, ambiguous, and malignant tumors, except in 1 malignant tumor where they comprised 50% to 60% of the cellularity. Calcifications were noted in all but 2 benign tumors that were otherwise of typical appearance. Six tumors (3 in the clinically benign, 1 in the clinically ambiguous, and 2 in the malignant groups) were considered potentially malignant based on the presence of ≥1 adverse pathologic features previously recognized (see reference 1)-that is, size>4 cm, extratesticular growth, necrosis, significant atypia, vascular invasion, and >3 mitotic figures/10 HPFs. Of these, 3 tumors had ≥2 adverse features. One in a 7-year-old was clinically benign despite 5 "malignant" features; the remaining 2 in 27- and 30-year-olds, were clinically malignant, with both fulfilling previously suggested criteria for pathologically malignant tumors (age above 25 y and ≥2 adverse pathologic features). No clinically benign or ambiguous tumor met those same criteria. Of the adverse features, each of the 2 clinically malignant tumors showed tumor necrosis and lymphovascular invasion. All patients, except 1 with a clinically malignant tumor, were alive at a median follow-up of 33 months. In addition, in our literature review of 97 additional LCCSCTs, we identified 2 clinically malignant tumors in 42- and 45-year-old men that lacked any documented adverse pathologic criterion and 2 clinically malignant cases in patients with either the Carney complex or Peutz-Jeghers syndrome. In summary, our study and literature review support that all LCCSCTs in patients above 25 years old should be considered potentially malignant, and those in this age group with ≥2 adverse pathologic features warrant aggressive clinical management; furthermore, syndrome-associated cases are not uniformly benign. Tumor necrosis and lymphovascular invasion likely should receive greater adverse prognostic weight. LCCSCTs in young children may show benign outcomes despite several adverse pathologic features.
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http://dx.doi.org/10.1097/PAS.0000000000001849DOI Listing
December 2021

Impact of Role Conflict on Intention to Leave Job With the Moderating Role of Job Embeddedness in Banking Sector Employees.

Front Psychol 2021 19;12:719449. Epub 2021 Nov 19.

School of Economics and Management, North China Electric Power University, Beijing, China.

This study investigates why some employees intend to leave their jobs when facing conflict between family responsibilities and job routines. The present study also reveals the moderating role of on-the-job embeddedness between role conflict and intention to leave the job. Drawing on conservation of resources theory, the paper investigates the buffering effect of the three on-the-job embeddedness components (fit, links, and sacrifice). Data were collected from banking officers because most of the employees have to face role conflict between family and job responsibilities, as banking is considered among the most stressful jobs. Collected data were analyzed by applying structural equation modeling. Results indicate that the role conflict significantly influences intention to leave the job. Furthermore, the study shows that on-the-job embeddedness moderates the relationship between role conflict and intention to leave. The results suggest that organizations can reduce turnover intention during times of work and life conflict by developing employee on-the-job embeddedness. This study provides some insights to managers on why many employees leave their jobs and how to overcome this problem. Management should also offer extra and available resources in periods of greater tension to minimize early thinking regarding quitting.
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http://dx.doi.org/10.3389/fpsyg.2021.719449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639511PMC
November 2021

New Parameterized Inequalities for -Quasiconvex Functions via (, )-Calculus.

Entropy (Basel) 2021 Nov 16;23(11). Epub 2021 Nov 16.

Department of Mathematics, Anand International College of Engineering, Jaipur 302001, India.

In this work, first, we consider novel parameterized identities for the left and right part of the (p,q)-analogue of Hermite-Hadamard inequality. Second, using these new parameterized identities, we give new parameterized (p,q)-trapezoid and parameterized (p,q)-midpoint type integral inequalities via η-quasiconvex function. By changing values of parameter μ∈[0,1], some new special cases from the main results are obtained and some known results are recaptured as well. Finally, at the end, an application to special means is given as well. This new research has the potential to establish new boundaries in comparative literature and some well-known implications. From an application perspective, the proposed research on the η-quasiconvex function has interesting results that illustrate the applicability and superiority of the results obtained.
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http://dx.doi.org/10.3390/e23111523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621369PMC
November 2021

Large cell calcifying Sertoli cell tumour: a contemporary multi-institutional case series highlighting the diagnostic utility of PRKAR1A immunohistochemistry.

Histopathology 2021 Nov 15. Epub 2021 Nov 15.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Aims: Large cell calcifying Sertoli cell tumour (LCCSCT) is a rare testicular sex cord-stromal tumour that primarily affects young patients and is associated with Carney complex. We sought to characterise the clinicopathological features of a series of LCCSCT and evaluate the diagnostic utility of PRKAR1A immunohistochemistry (IHC).

Methods And Results: The LCCSCT cohort (n = 15) had a median age of 16 years (range = 2-30 years). Four patients were known to have Carney complex. PRKAR1A IHC was performed in each case. For comparison, PRKAR1A IHC was also assessed in other sex cord-stromal tumours, including Sertoli cell tumour, not otherwise specified (SCT, NOS; n = 10), intratubular large cell hyalinising Sertoli cell tumour (n = 1) and Leydig cell tumour (n = 23). Loss of cytoplasmic PRKAR1A expression was observed in all but one LCCSCT (14 of 15; 93%). PRKAR1A expression was retained in all SCTs, NOS (10 of 10; 100%), the majority of Leydig cell tumours (22 of 23; 96%) and an intratubular large cell hyalinising Sertoli cell tumour (1 of 1; 100%). One Leydig cell tumour showed equivocal staining (multifocal weak expression).

Conclusions: Overall, PRKAR1A loss is both sensitive (93%) and highly specific (97%) for the diagnosis of LCCSCT. PRKAR1A loss may aid its diagnosis, particularly in sporadic cases and those that are the first presentation of Carney complex.
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http://dx.doi.org/10.1111/his.14599DOI Listing
November 2021

Current status of therapeutic approaches and vaccines for SARS-CoV-2.

Future Microbiol 2021 Nov 11. Epub 2021 Nov 11.

Centre of Excellence in Molecular Biology, University of The Punjab, Lahore, Pakistan.

SARS-CoV-2, declared a pandemic in March 2020, is the current global health challenge. The global bioburden of this virus is increasing at a rapid pace. Many antiviral drugs and vaccines have been registered for clinical trials because of their inhibitory activity observed . Currently, five types of vaccines have successfully passed Phase IV clinical trial and are being administered in populations worldwide. A plethora of experimental designs have been proposed worldwide in order to find a safe and efficacious treatment option. Therefore, it is necessary to provide baseline data and information to clinicians and researchers so that they can review the current status of therapeutics and efficacy of already developed vaccines. This review article summarizes all therapeutic options that may help to combat SARS-CoV-2.
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http://dx.doi.org/10.2217/fmb-2020-0147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582592PMC
November 2021

Eosinophilic Esophagitis Symptom Scores Are High in Children Without Eosinophilic Disease.

J Pediatr Gastroenterol Nutr 2021 Oct 11. Epub 2021 Oct 11.

Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine/Riley Hospital for Children Department of Pathology Department of Biostatistics, Indiana University School of Medicine Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine/Riley Hospital for Children Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Community Health Network, Indiana University School of Medicine/Riley Hospital for Children Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine/Riley Hospital for Children (at the time of contribution), Eli Lilly and Company, Indianapolis, IN (current).

Objectives: The Pediatric Eosinophilic Esophagitis (EoE) Symptom Score version 2 (PEESSv2.0) is an EoE-specific validated metric for disease monitoring, but its use has not been explored outside of EoE. Our aim was to determine if PEESSv2.0 scores differentiate between children with EoE and non-EoE esophageal dysfunction undergoing initial esophagogastroduodenoscopy (EGD).

Methods: A prospective cohort study of pediatric subjects was conducted. Children ages 1-18 undergoing initial EGD for esophageal dysfunction were enrolled. Demographics, clinical history, and child self-report and parent-proxy report PEESSv2.0 symptom scores were collected at the time of EGD. Esophageal biopsies were reviewed, and EoE was defined as >15 eosinophils/high powered field (hpf) seen in any level of the esophagus. Non-EoE was defined as <15 eosinophils/hpf.

Results: Seventy-one children were included in the study from 2015 to 2018 [59% (42/71) males; mean age 9.2 years; range 1-17 years]. Fifty-eight percent (41/71) met criteria for EoE, and 42% (30/71) were labeled non-EoE. Non-EoE children and their parents had higher/worse median PEESSv2.0 total scores than those with EoE [47.0 vs 28.0 (P = 0.001) and 40.5 vs 26.5 (P = 0.012), respectively]. Non-EoE children reported higher median GERD [9.0 vs 4.0 (P = 0.003)], nausea/vomiting [9.0 vs 4.0 (P = 0.003)], and pain [11.0 vs 6.0 (P = 0.001)] subdomain scores compared to those with EoE. PEESSv2.0 dysphagia subdomain scores (child and parent-proxy) did not differ between EoE and non-EoE groups [22.0 vs 15.0 (P = 0.184) and 18.5 vs 17.4 (P = 0.330), respectively].

Discussion: Total PEESSv2.0 scores were worse in non-EoE group compared to EoE group. Although PEESSv2.0 is validated for use in monitoring EoE therapy, it does not distinguish children with EoE from non-EoE esophageal dysfunction at the time of diagnostic EGD.
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http://dx.doi.org/10.1097/MPG.0000000000003324DOI Listing
October 2021

Dengue Vaccines: Ongoing Challenges and Current Status in the Advancement of Different Candidates.

Crit Rev Eukaryot Gene Expr 2021 ;31(5):7-19

Center of Excellence in Molecular Biology (CEMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan.

Dengue is a vector-borne highly systemic infectious disease of the tropical and subtropical countries and is devastating millions of lives worldwide. It may be self-eliminated like a mild fever or may cause life-threatening fatal complications as dengue hemorrhagic fever and dengue shock syndrome. The lack of specific and effective antiviral drugs and vaccines amplify its transmission rate across the world. The development of the dengue vaccine has been an ambitious task due to the presence of four different dengue serotypes capable of carrying antibody enhancement complex mechanisms. In this review, we have summarized the ongoing challenges in the construction of a dengue vaccine and the current status of the vaccine development. Limited knowledge of immune responses against dengue infection, lack of human or animal model of disease, and suboptimal assay strategies to detect immune responses after infection or vaccination, are some barriers to vaccine and drug development. A tetravalent vaccine with low cost, high efficiency, and capable of eliciting immune responses against all four serotypes is needed to minimize the epidemics. Currently, only one live attenuated chimeric dengue vaccine, the CYD Dengue Vaccine, has completed its third phase and has been licensed. DENVax and TetraVax-DV-TV003 (TV003) are in the third phase while others are still in the first trial phase.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2021038839DOI Listing
January 2021

Enhanced ultraviolet-visible photocatalysis of RGO/equaixial geometry TiO composites on degradation of organic dyes in water.

Environ Sci Pollut Res Int 2021 Sep 25. Epub 2021 Sep 25.

Shaanxi Key Laboratory of Polymer Science and Technology, Ministry of Education Key Laboratory of Supernormal Material Physics and Chemistry, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an, 710129, People's Republic of China.

The reduced graphene oxide dopped equaixial geometry TiO (rGO/egTiO) composite as photocatalyst was synthesized hydrothermally with various mass ratios of tetrabutyl titanate. The photocatalyst is considered to be rGO/equaixial geometry TiO in terms of modifying the combined reduced graphene Oxide and TiO. The rGO plays a vital role in rGO/egTiO composite as photocatalysts were analyzed in methylene blue (MB) and rhodamine B (RhB) photocatalytic degradation under UV and simulated solar light irradiation. This synthesized catalyst was characterized by various analytical techniques such as XPS, XRD, SEM, BET, and TEM. The rGO/egTiO composite exhibits enhanced photocatalytic performance with degradation rates of 97.5 and 97% on RhB and MB for 60 min under UV radiation respectively, while the degradation rate of 94 and 92 % was observed on the same dyes for 6 h under the simulated sunlight radiation. The enhanced photocatalytic performance of the rGO/egTiO composite under ultraviolet irradiation source was owing to a high separation efficiency of the photo-induced electron-hole pairs, while the photocatalytic performance under simulated sunlight radiation was due to the photosensitive and charge separator behavior of rGO. This offers us an excellent potential of significant photocatalytic activity for the removal of organic contaminants from wastewater.
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http://dx.doi.org/10.1007/s11356-021-16605-4DOI Listing
September 2021

Exploration of ethnomedicinal plants and their practices in human and livestock healthcare in Haripur District, Khyber Pakhtunkhwa, Pakistan.

J Ethnobiol Ethnomed 2021 Sep 8;17(1):55. Epub 2021 Sep 8.

Department of Mathematics, College of Science Al-Zulfi, Majmaah University, Al-Majmaah, 11952, Saudi Arabia.

Background: The utilization of plants and plant resources for various ethnobotanical purposes is a common practice in local towns and villages of developing countries, especially in regard to human and veterinary healthcare. For this reason, it is important to unveil and document ethnomedicinal plants and their traditional/folk usage for human and livestock healthcare from unexplored areas. Here we advance our findings on ethnomedicinal plants from Haripur District, Pakistan, not only for conservation purposes, but also for further pharmacological screenings and applied research.

Methodology: Information of ethnomedicinal plants was obtained using a carefully planned questionnaire and interviews from 80 local people and traditional healers (Hakims) in Haripur District, Pakistan, from 2015 to 2017. Informed consent was obtained from each participant before conducting the interview process. Quantitative ethnobotanical indices, such as relative frequency of citation (RFC), use value (UV) and Jaccard index (JI), were calculated for each recorded species. Correlation analysis between the RFC and UV was tested by Pearson's correlation, SPSS (ver. 16).

Results: A total of 80 plant species (33 herbs, 24 trees, 21 shrubs and 2 climbers) belonging to 50 families were being used in the study area to treat livestock and human diseases. Lamiaceae was the most dominant family with 7 species (8.7%), followed by Fabaceae with 6 species (7.5%), and Moraceae with 5 species (6.2%). Local people used different methods of preparation for different plant parts; among them, decoction/tea (22 species) was the popular method, followed by powder/grained (20 species) and paste/poultice (14 species). It was observed that most of the species (~ 12 to 16 species) were utilized to treat human and livestock digestive system-related problems, respectively. The Jaccard index found that plant usage in two studies (District Abbottabad and Sulaiman Range) was more comparable. Local people mainly relied on folk medicines due to their rich accessibility, low cost and higher efficacy against diseases. Unfortunately, this important traditional knowledge is vanishing fast, and many medicinal plants are under severe threat. The most threats associated to species observed in the study area include Dehri, Garmthun, Baghpur, Najafpur and Pharala.

Conclusion: The study has indicated that local people have higher confidence in the usage of ethnomedicinal plants and are still using them for the treatment of various ailments. Comparative analysis with other studies may strongly reflected the novel use of these plants, which may be due to the deep-rooted and unique socio-cultural setup of the study area. However, awareness campaigns, conservation efforts and pharmacological and applied research are required for further exploration and may be a step in the right direction to unveil prospective pharmaceuticals.
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http://dx.doi.org/10.1186/s13002-021-00480-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424965PMC
September 2021

Macular Vascular Density Analysis Using Adobe Photoshop Software In Diabetic Eyes: Optical Coherence Tomography Angiography Study.

J Ayub Med Coll Abbottabad 2021 Jul-Sep;33(3):441-446

Department of Biotechnology and Genetic Engineering, University of Agriculture, Peshawar, Pakistan.

Background: Optical Coherence Tomography Angiography (OCTA) is dye less microvascular visualizing technique. In study we binaries OCTA images of macular vessels in healthy and diabetic subjects without macular oedema using Adobe Photoshop CS3 extended version.

Methods: Prospective, single centered, observational study total of 58 eyes of 108 Diabetic Retinopathy (DR) subjects and 20 eyes of 40 normal subjects with mean age of 58.3±10.5 range (40-82) were included in our study. Ten eyes with Non-Diabetic Retinopathy (NDR), twenty-nine eyes with Non-Proliferative Diabetic Retinopathy (NPDR) (mild-10, moderate-7 and severe-12) and nineteen eyes with Proliferative Diabetic Retinopathy (PDR)are studied with images obtained using OCTA between September 2016 to June 2017. Scan area of 6×6 mm was selected to find morphological changes in the superficial retinal layers and deep retinal layers. Captured OCTA images were binarized using automated thresholding algorithm. Macular Vessel Density (MVD) (%) and Foveal Avascular Zone area (mm2) measured for superficial and deep retinal vessel arcade. For comparison, analysis of variance and Kruskal-Wallis test are applied.

Results: Diabetic eyes were grouped according to their severity level. MVD and FAZ are compared in all groups. Results are significantly lower in all groups except in controls and NDR. Significant decrease is observed in vascular density of most layers with progress in retinopathy.

Conclusions: Adobe Photoshop CS3 extended version is an excellent tool for image binarization. Calculating FAZ area and MVD using OCTA images agreed closely with clinical grading system. Application of this method can be helpful in monitoring disease progression.
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November 2021

Analysis Of Consultation Length In Khyber Pakhtunkhwa, Pakistan.

J Ayub Med Coll Abbottabad 2021 Jul-Sep;33(3):424-430

Punjab University College of Information Technology, University of the Punjab, Lahore, Pakistan.

Background: Consultation length is considered as direct measure of quality healthcare service and patient satisfaction. We analysed data collected from five different hospitals to inference the effects of sub-factors on consultation length. These factors have positive contribution in predicting the behaviour of consultation length.

Methods: We performed cross-sectional study on first hand data collected from 386 participants using snow ball sampling method. The survey instrument was questionnaire and face to face interviews. We considered null hypothesis (H0=0) as means are equal against alternative hypothesis (H1 ≠ 0) for factors of time consumed by overall consultation, patient's history, physical examination, and prescription writing. Data was also analysed by nonparametric univariate tests and multiple linear regression model.

Results: Mean of consultation length is 22.466 minutes [CI: 21.420-23.512 and α=0.01]. Null hypothesis (H0=0) was rejected in favour of alternative hypothesis (H1≠0) by all factors due to sufficient evidence in data except prescription writing which failed to reject H0.

Conclusions: We found factors had high spread in mean values and rejected null hypothesis indicating the duration of health workforces' consultation is varying in different setups. Multiple factors contributed in formation of consultation length of doctors. Similar studies related to conservation of variation in consultation length must consider these factors. Eventually, such studies reporting this variation and its factors will add up in its efficacy and provisioning of appropriate consultation time totting up in patient's satisfaction positively.
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November 2021

Next-generation sequencing studies on the E1-HVR1 region of hepatitis C virus (HCV) from non-high-risk HCV patients living in Punjab and Khyber Pakhtunkhwa, Pakistan.

Arch Virol 2021 Nov 27;166(11):3049-3059. Epub 2021 Aug 27.

Divison of Molecular Virology, Center of Excellence in Molecular Biology (CEMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore, Pakistan.

The incidence rate of hepatitis C virus (HCV) infection in Pakistan is very high. In this study, we evaluated the genetic heterogeneity of HCV hypervariable region 1 (HVR1) from the HCV-infected Pakistani population and compare the isolated genotypes with representative sequences from internationally diverse geographic regions. We also investigated potential transmission events in non-high-risk HCV patients. Next-generation sequencing (NGS) data from the E1-HVR1 region from 30 HCV patients were used for phylogenetic analysis. Reference sequences were retrieved from the Los Alamos HCV and GenBank databases. NGS data were analyzed to examine HCV HVR1 sequence diversity and identify transmission links among HCV-infected individuals using Global Hepatitis Outbreak and Surveillance Technology (GHOST). Phylogenetic analysis showed the predominance of HCV genotype 3a (86.6%), followed by 1a (6.6%), 1b (3.3%), and 3b (3.3%). NGS of HVR1 displayed significant genetic heterogeneity of HCV populations within each patient. The average nucleotide sequence diversity for HVR1 was 0.055. JR781281 was found to be the most diverse (0.14) of the specimens. Phylogenetic analysis demonstrated that all HCV specimens sequenced in this study were more similar to each other and showed variations from the representative sequences. The GHOST results suggested genetic relatedness between two (6.6%) HCV cases, possibly defining an incipient outbreak in a non-high-risk population. We urge rigorous countrywide investigation of outbreaks to identify transmission clusters and their sources to incorporate preventive measures for disease control.
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http://dx.doi.org/10.1007/s00705-021-05203-xDOI Listing
November 2021

Cytokine storm syndrome in SARS-CoV-2: a review.

Z Naturforsch C J Biosci 2022 Jan 24;77(1-2):65-69. Epub 2021 Aug 24.

Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.

After wreaking havoc on a global level with a total of 5,488,825 confirmed cases and 349,095 deaths as of May 2020, severe acute respiratory syndrome coronavirus 2 is truly living up to the expectations of a 21st-century pandemic. Since the major cause of mortality is a respiratory failure from acute respiratory distress syndrome, the only present-day management option is supportive as the transmission relies solely on human-to-human contact. Patients suffering from coronavirus disease 2019 (COVID-19) should be tested for hyper inflammation to screen those for whom immunosuppression can increases chances of survival. As more and more clinical data surfaces, it suggests patients with mild or severe cytokine storms are at greater risk of failing fatally and hence these cytokine storms should be targets for treatment in salvaging COVID-19 patients.
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http://dx.doi.org/10.1515/znc-2021-0062DOI Listing
January 2022

Seroepidemiology and associated risk factors of hepatitis B and C virus infections among pregnant women attending maternity wards at two hospitals in Swabi, Khyber Pakhtunkhwa, Pakistan.

PLoS One 2021 20;16(8):e0255189. Epub 2021 Aug 20.

Department of Agronomy, Faculty of Agriculture and Environment, Islamia University Bahawalpur, Bahawalpur, Pakistan.

Background & Aim: Hepatitis B and C infections are global issues that are associated with a massive financial burden in developing countries where vertical transmission is the major mode and remains high. This cross-sectional study was designed to investigate the seroepidemiology and associated risk factors of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among 375 pregnant women attending antenatal care health facilities at Bacha Khan Medical Complex (BKMC) Shahmansoor and District Head Quarter (DHQ) Hospital Swabi, Khyber Pakhtunkhwa, Pakistan.

Methodology: From a total of 375 pregnant women selected using systematic random sampling from both hospitals, 10 ml of blood samples were collected and alienated serum was examined for indicators identification through the Immuno-Chromatographic Test (ICT) and 3rd Generation Enzyme-Linked Immunosorbent Assay (ELISA). A pre-structured questionnaire was used to collect the socio-demographic data and possible risk factors. The data was analyzed via SPSS 23.0 statistical software. A chi-square analysis was performed to determine the association between variables. P-value < 0.05 was set statistically significant.

Results: The overall frequency of HBV and HCV among 375 pregnant women involved in the study was 3.7% and 2.1% respectively. None of the pregnant women were co-infected with HBV and HCV. Dental extraction (P = 0.001) and blood transfusion (P = 0.0005) were significantly allied with HBV infection while surgical procedure (P = 0.0001) was significantly associated with HCV infection. Moreover the sociodemographic characteristics: residential status (P = 0.017) and educational level (P = 0.048) were found significant risk factors of HBsAg and maternal age (P = 0.033) of anti-HCV, respectively.

Conclusion & Recommendation: HBV and HCV infections are intermediary endemic in the study area. A higher prevalence of HBV was detected among pregnant mothers with a history of dental extraction, history of blood transfusion, resident to the urban area and low educational level. The age and surgical procedures were the potential risk factors found significantly associated with HCV positivity among pregnant mothers in our setup. Future negotiations to control vertical transmission should include routine antenatal screening for these infections early in pregnancy and the requirement of efficient preventive tools including the birth dose of the hepatitis B vaccine in combination with hepatitis B immune globulins to the neonate.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255189PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384242PMC
November 2021

Early detection of MDR Mycobacterium tuberculosis mutations in Pakistan.

Sci Rep 2021 08 18;11(1):16736. Epub 2021 Aug 18.

Division of Molecular Virology and Infectious Diseases, Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, 87-West Canal Bank Road, Thokar Niaz Baig, Lahore, Pakistan.

The result of improper treatment has led to the rise of Multidrug-resistant (MDR) strains. This concern still exists in Pakistan. In order to save energy, time and resources an early detection of resistant cases is imperative. Thus, a treated group of 100 isolates and a control group of 56 untreated isolates were studied. PCR and gene sequencing showed mutations at codon 531 and 513 in the rpoB gene. 12% of cases showed a double mutation in the rpoB gene. katG gene showed mutations at codon 315 and 299. 28.6% of the control group cases were positive for MDR whereas 100% of the treated group were positive for MDR. This study explores the significantly increasing ratio of MDR-TB among Pakistani population. This study provides prevalent MDR mutations among Pakistanis and suggests developing such molecular assays that are time and cost effective. Importance: Pakistan is a developing country and has fourth highest incidence rate of MDR-TB. The treatment of MDR-TB is the use of second line drugs that has severe side effects as well as it requires long time span. One of the strategies to control the spread of MDR-TB is to decipher the aberrations at molecular level in order to formulate potent drugs that can treat the patients within short span of time. Determining the mutation profile of MDR in Pakistani populations will open new horizons for the improvement of drug treatment regimens to make it more effective or for the development of novel potent drugs and vaccines to better treat the drug-resistant TB. Moreover, this study will be help in disease control program.
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http://dx.doi.org/10.1038/s41598-021-96116-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373971PMC
August 2021

Health risk assessment of heavy metals via consumption of dietary vegetables using wastewater for irrigation in Swabi, Khyber Pakhtunkhwa, Pakistan.

PLoS One 2021 11;16(8):e0255853. Epub 2021 Aug 11.

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

Health assumptions to the population due to the utilization of contaminated vegetables have been a great concern all over the world. In this study, an investigation has been conducted to ascertain metal concentrations in the wastewater, soil and commonly consumed vegetables from the vicinity of Gadoon Industrial Estate Swabi, Khyber Pakhtunkhwa Pakistan. Physicochemical parameters such as pH, electrical conductivity (EC), total dissolved solids (TDS), total suspended solids (TSS) and total solids (TS) and heavy metals such as Pb, Cr, Cd, Ni, Zn, Cu, Fe, Mn were determined using Atomic Absorption Spectrophotometer (AAS). Moreover, possible health risks due to the consumption of vegetables have also been estimated. pH and TSS in wastewater were found to be higher than the permissible limit set by WHO (1996). These results revealed that Cr concentration in the wastewater was above the permissible limits of United States Environmental Protection Agency (USEPA) which may lead to a detrimental effect on soil quality deterioration, ultimately leading to food contamination. ANOVA analysis demonstrated a significant difference in soil samples for Pb, Cr, Cd, Ni, Zn and Cu at p ≤ 0.001, for Mn at p ≤ 0.05 while no significant difference was observed for Fe respectively. ANOVA analysis also exhibited the highest mean value for Pb, Cr, Cd and Zn in vegetables. A substantial positive correlation was found among the soil and vegetable contamination. The transfer factor for Cr, Pb, Zn, Mn, Ni, Cd and Cu was greater than 0.5 due to contamination caused by domestic discharges and industrial effluents. Health assessment via consumption of dietary vegetables revealed a higher level than the permissible limit (HRI > 1) for Pb and Cd in children and adults. Enrichment factor (EF) due to consumption of vegetables was found higher for Pb and Cr respectively. Based on the findings of this study, there would be a significant risk to the consumers associated with consumptions of vegetables being cultivated in Gadoon Industrial Estate area of district Swabi. Therefore, strict regulatory control measures are highly recommended for the safety of vegetables originated from the study area.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255853PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357160PMC
December 2021

Novel Coronavirus: A Review from Origin to Current Status of Therapeutic Strategies.

Crit Rev Eukaryot Gene Expr 2021 ;31(3):21-34

Center of Excellence in Molecular Biology (CEMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan.

Coronaviruses (CoVs) are continuously emerging, highly transmissible, and pathogenic agents that primarily target the human respiratory system. Previous outbreaks of severe acute respiratory syndrome-CoV and Middle East respiratory syndrome-CoV remain life-threatening and global public health concerns. A novel CoV outbreak that occurred in December 2019 in Wuhan, China was declared a pandemic outbreak that has since killed millions of individuals worldwide. Rapid transmission, genetic variations, and unavailability of specific therapeutic drugs are major factors that led to this alarming and deadly situation. Currently, > 200 clinical vaccine trials are underway to combat infection. This review summarizes reports related to CoV origin, genetic variations, drug options, status of nine vaccines that were in phase III trials, and novel therapies including convalescent plasma and stem cell treatment.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2021038075DOI Listing
August 2021

Effect of exogenous alpha-tocopherol on physio-biochemical attributes and agronomic performance of lentil (Lens culinaris Medik.) under drought stress.

PLoS One 2021 6;16(8):e0248200. Epub 2021 Aug 6.

Centre of Interdisciplinary Research in Basic Sciences, International Islamic University, Islamabad, Pakistan.

Water being a vital part of cell protoplasm plays a significant role in sustaining life on earth; however, drastic changes in climatic conditions lead to limiting the availability of water and causing other environmental adversities. α-tocopherol being a powerful antioxidant, protects lipid membranes from the drastic effects of oxidative stress by deactivating singlet oxygen, reducing superoxide radicals, and terminating lipid peroxidation by reducing fatty acyl peroxy radicals under drought stress conditions. A pot experiment was conducted and two groups of lentil cultivar (Punjab-2009) were exposed to 20 and 25 days of drought induced stress by restricting the availability of water after 60th day of germination. Both of the groups were sprinkled with α-tocopherol 100, 200 and 300 mg/L. Induced water deficit stress conditions caused a pronounced decline in growth parameters including absolute growth rate (AGR), leaf area index (LAI), leaf area ratio (LAR), root shoot ratio (RSR), relative growth rate (RGR), chlorophyll a, b, total chlorophyll content, carotenoids, and soluble protein content (SPC) which were significantly enhanced by exogenously applied α-tocopherol. Moreover, a significant increase was reported in total proline content (TPC), soluble sugar content (SSC), glycine betaine (GB) content, endogenous tocopherol levels, ascorbate peroxidase (APX), catalase (CAT) peroxidase (POD) and superoxide dismutase (SOD) activities. On the contrary, exogenously applied α-tocopherol significantly reduced the concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2). In conclusion, it was confirmed that exogenous application of α-tocopherol under drought induced stress regimes resulted in membrane protection by inhibiting lipid peroxidation, enhancing the activities of antioxidative enzymes (APX, CAT, POD, and SOD) and accumulation of osmolytes such as glycine betaine, proline and sugar. Consequently, modulating different growth, physiological and biochemical attributes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248200PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345888PMC
November 2021

Comparative Profiling of Button Mushroom, Agaricus bisporus (Agaricomycetes), Possessing Textural, Antibacterial, Elemental, and Antioxidant Properties in Diverse Collections from China.

Int J Med Mushrooms 2021 ;23(5):79-90

Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, People's Republic of China.

Button mushroom (Agaricus bisporus) is cultured commercially and consumed worldwide for its unique flavor, texture, and culinary qualities. The objective of this study was to assess the textural profile together with the phenolic content and antioxidant, antibacterial, and elemental composition of wild and commercially cultivated A. bisporus from China. Of the six mushroom strains studied, both cultivated strains CCMJ1013 (fresh: 85.8 N/m2; stored: 57.9 N/m2) and CCMJ1343 (fresh: 94.7 N/m2; stored: 52.9 N/m2) recorded elevated hardness. Our results revealed that wild A. bisporus strain CCMJ1363 contained the highest phenolic content (7.840 mg gallic acid equivalents [GAE]/g), followed by CCMJ1361 (7.125 mg GAE/g) and CCMJ1351 (6.709 mg GAE/g). Antioxidant activity was elevated in CCMJ1351 (inhibition concentration at 50% inhibition [IC50] = 1.04 mg/mL) followed by CCMJ1361 (IC50 = 1.67 mg/mL) in the 1,1-diphenyl-2-picrylhydrazyl assay, whereas CCMJ1351 showed the maximum antioxidant activity (353.54 mg Trolox equivalents/g) in the ferric reducing antioxidant power assay. The maximum 2,2'-azobis(2-amidinopropane) di-hydrochloride-induced erythrocyte hemolysis inhibition was found in wild A. bisporus CCMJ1363 (86.09% inhibition) followed by CCMJ1351 (84.45% inhibition). In terms of antibacterial activity, only a wild A. bisporus strain (CCMJ1361) showed antibacterial activity against pathogenic bacteria (Bacillus coli and Staphylococcus aureus). Wild strain CCMJ1110 contained the highest level of zinc and magnesium; CCMJ1361 showed higher levels of calcium and iron, and CCMJ1363 contained a comparatively higher composition of nitrogen, sodium, and aluminum. Therefore, the current study lays a foundation for creating high-performance, culinary-quality, and stress-resistant germplasms in breeding for A. bisporus strains.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2021038270DOI Listing
November 2021

Biofilm: Morphology, Genetics, Pathogenesis and Treatment Strategies.

Int J Environ Res Public Health 2021 07 16;18(14). Epub 2021 Jul 16.

Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.

is a nosocomial bacterium causing different infectious diseases, ranging from skin and soft tissue infections to more serious and life-threatening infections such as septicaemia. forms a complex structure of extracellular polymeric biofilm that provides a fully secured and functional environment for the formation of microcolonies, their sustenance and recolonization of sessile cells after its dispersal. biofilm protects the cells against hostile conditions, i.e., changes in temperature, limitations or deprivation of nutrients and dehydration, and, more importantly, protects the cells against antibacterial drugs. Drugs are increasingly becoming partially or fully inactive against as they are either less penetrable or totally impenetrable due to the presence of biofilms surrounding the bacterial cells. Other factors, such as evasion of innate host immune system, genome plasticity and adaptability through gene evolution and exchange of genetic material, also contribute to the ineffectiveness of antibacterial drugs. This increasing tolerance to antibiotics has contributed to the emergence and rise of antimicrobial resistance (AMR), a serious problem that has resulted in increased morbidity and mortality of human and animal populations globally, in addition to causing huge financial losses to the global economy. The purpose of this review is to highlight different aspects of biofilm formation and its overall architecture, individual biofilm constituents, clinical implications and role in pathogenesis and drug resistance. The review also discusses different techniques used in the qualitative and quantitative investigation of biofilm and various strategies that can be employed to inhibit and eradicate biofilm.
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http://dx.doi.org/10.3390/ijerph18147602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304105PMC
July 2021

Distribution of High-risk Human Papillomavirus Genotypes in Cervical Secretions in Punjab.

J Coll Physicians Surg Pak 2021 Jul;30(7):786-791

Institute of Molecular Biology & Biotechnology (IMBB), University of Lahore, Lahore, Pakistan.

Objective: To determine the high risk-human papillomavirus (HR-HPV) prevalence, genotype distribution, and associated risk factors in women with general gynaecological problems.

Study Design: Descriptive, cross-sectional study.

Place And Duration Of Study: Lady Wallingdon Hospital, Lahore from August 2018 to May 2019.

Methodology: One hundred females with general gynaecological problems constituted the sample. Real-time polymerase chain reaction and liquid base cytology were performed for HR-HPV detection, genotyping, and cytological changes in cervical samples.

Results: The overall prevalence of HR-HPV was found to be 57%, with the most frequent HR-HPV genotypes HPV 16 (18%), HPV 18 (6%), and HPV 45 (1%). The total prevalence of single HR-HPV infection was 25%; whereas, multiple co-infection of HR-HPV was seen in 32% of cases. In total, 81% of these women had normal cytology and 19% had cytologic abnormalities. A significant association was observed between HR-HPV infection and general gynaecological complaints and between HR-HPV infection and cytological abnormalities (p < 0.001).

Conclusion: The HR-HPV prevalence was 57% with the most prevalent genotypes were HPV 16 and HPV 18. The results will also aid the identification of HR-HPV 51 and 31 genotypes, which should be added in the multi-type HPV vaccines. Key Words: Cancer of cervix, Human papillomavirus, Papanicolaou test, Pakistan.
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http://dx.doi.org/10.29271/jcpsp.2021.07.786DOI Listing
July 2021

Somatic-Type Yolk Sac Tumor Arising as a Predominant Component of Bladder Urothelial Carcinoma.

Int J Surg Pathol 2021 Jul 13:10668969211030688. Epub 2021 Jul 13.

12250Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.

Germ cell differentiation has been described in association with somatic tumors arising from several organ systems; rare cases arising from urothelium have been reported. Here we present a 62-year-old male with a remote history of lung cancer, a left adrenal gland mass, and a 5.6 cm left bladder wall mass; cystoscopy demonstrated a large papillary mass on the left anterior bladder wall. A transurethral resection specimen was sent for review in consultation and showed extensive papillary structures with thin fibrovascular cores lined by neoplastic cells with clear cytoplasm. These neoplastic cells were diffusely positive for pancytokeratin, CDX2 (caudal-type homebox 2), SALL4 (sal-like transcription factor 4), glypican-3, AFP (alpha-fetoprotein), while negative for PAX-8 (paired box gene 8), NKX3.1 (NK3 homeobox 1), PSA (prostate specific antigen), TTF-1 (thyroid transcription factor 1), Napsin A, inhibin, and OCT4 (octamer-binding transcription factor 4). Conventional urothelial conventional carcinoma and focal squamous differentiation were also identified as minor components. Urothelial carcinoma was focally positive for GATA3 (GATA-binding protein 3) and p63; SALL4 and glypican-3 were negative. Overall findings supported a yolk sac tumor with a smaller component of squamous cell carcinoma (<1%). Subsequent cystectomy showed similar morphologic features and immunoprofile in addition to foci of urothelial carcinoma and urothelial carcinoma in situ. No chromosome 12p abnormalities were identified by fluorescent in-situ hybridization study. A diagnosis of yolk sac tumor derived from urothelial carcinoma was made. Yolk sac tumor should be considered in the differential diagnosis of a high-grade urothelial carcinoma, particularly when glandular or other unusual architectural patterns are present. A somatic origin with underlying genomic instability similar to what has been described in the uterus and ovaries is suggested.
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http://dx.doi.org/10.1177/10668969211030688DOI Listing
July 2021

Immunohistochemical Characterization of 120 Testicular Sex Cord-Stromal Tumors With an Emphasis on the Diagnostic Utility of SOX9, FOXL2, and SF-1.

Am J Surg Pathol 2021 10;45(10):1303-1313

Department of Pathology, Indiana University School of Medicine, Indianapolis, IN.

Sex cord-stromal tumors (SCSTs) account for the second most common category of testicular neoplasms and include several entities that may show overlapping morphologies and present diagnostic challenges. We analyzed a cohort of 120 testicular SCSTs and investigated the diagnostic utility of SRY-box transcription factor 9 (SOX9), forkhead box protein L2 (FOXL2), and steroidogenic factor 1 (SF-1) immunohistochemical stains. The results were compared with the more commonly used SCST markers, inhibin α, calretinin, and Wilms' tumor 1 (WT1). SF-1 was overall the most sensitive stain (91%), followed by inhibin α (70%), calretinin (52%), FOXL2 (50%), SOX9 (47%), and WT1 (37%), but sensitivities varied by tumor type. SOX9 and calretinin were more commonly positive in sex cord elements versus stromal elements (62% vs. 27% and 47% vs. 9%, respectively), whereas FOXL2 was more commonly positive in stromal elements versus sex cord elements (100% vs. 55%) when excluding Leydig cell tumors from the stromal category. Although no individual stain was diagnostically specific, some immunophenotypic patterns were noted that may help in the subclassification of SCSTs. We conclude that SOX9, FOXL2, and SF-1 are useful immunohistochemical stains for confirming sex cord-stromal differentiation in testicular tumors and provide increased sensitivity as well as additional diagnostic information, especially when combined with the more commonly used inhibin α, calretinin, and WT1 immunostains. Although morphology is paramount for subclassification of SCSTs, knowledge of certain immunohistochemical patterns may be helpful for diagnostically challenging cases.
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http://dx.doi.org/10.1097/PAS.0000000000001704DOI Listing
October 2021

Adenocarcinoma of the Rete Testis: Seven Additional Cases, Including Exclusively and Predominantly Intrarete Tumors.

Am J Surg Pathol 2021 12;45(12):1720-1724

Department of Pathology & Laboratory Medicine, Indiana University School of Medicine and Indiana University Health Partners Indianapolis, IN.

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http://dx.doi.org/10.1097/PAS.0000000000001771DOI Listing
December 2021

Low-grade oncocytic tumour expands the spectrum of renal oncocytic tumours and deserves separate classification: a review of 23 cases from a single tertiary institute.

J Clin Pathol 2021 Jun 24. Epub 2021 Jun 24.

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

Aims: Low-grade oncocytic tumour (LOT) has recently been introduced as a potential distinct entity.

Methods: At the Indiana University department of pathology, primary renal epithelial neoplasms between 2005 and 2020 were searched after appropriate institutional review board permissions.

Results: Twenty-three cases (male/female ratio 14/9) with a median age of 66 (23-84 years) were identified. The majority of patients underwent partial nephrectomy (15/23, 65%), with a median tumour size of 4.0 cm (2.2-10.5 cm). Only one case had infiltration beyond the kidney (perinephric fat). Solid/diffuse proliferation of tightly packed oncocytic tumour cells and occasional tubule formations, with an abrupt edematous change in the stroma with loosely connected small clusters of tumour cells. Along with diffuse CK7 expression with lack of CD117 in all cases, vimentin was positive in 8/23 cases (35%, 5 focal). CD10 was expressed in 6/13 (46%, 4 focal). Alpha-Methylacyl-CoA Racemase (AMACR) was positive in 5/8 (63%) cases. Focal but intense cytoplasmic colloidal iron stain was present in 3/20 (15%) cases. Luminal or cytoplasmic/perinuclear precipitation was observed in 8/20 (40%) cases. Succinate Dehydrogenase B (SDHB) was performed in 6 cases, with all retained expression.

Conclusions: LOT is a clinically indolent and potentially benign entity with distinguishable morphology and immunohistochemical profile that can be performed and be easily interpreted in most of surgical pathology settings. Additional studies with larger cohorts, comprehensive molecular evaluation and longer follow-up are needed to definitively recognise these tumours as a separate entity and to further address the possibility of active surveillance options in eligible patients.
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http://dx.doi.org/10.1136/jclinpath-2021-207478DOI Listing
June 2021
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