Publications by authors named "Muhammad Younus"

80 Publications

Exploring Rabies Endemicity in Pakistan: Major Constraints & Possible Solutions.

Acta Trop 2021 Jun 15:106011. Epub 2021 Jun 15.

Department of Pathobiology, KBCMA University College of Veterinary and Animal Sciences, Narowal, 51600, Pakistan.

Rabies, the oldest recorded viral zoonosis in the Indo-Pakistan subcontinent, is a neglected and lingering endemic disease in Pakistan. The review of online available rabies-related journals, papers and reports through platforms and electronic databases have provided the basis for a detailed analysis of the rabies situation in Pakistan. Only published materials related to various research areas of rabies in Pakistan were included and meaningful conclusions were developed to identify major constraints and generate an intellectual discussion on possible solutions. Results revealed 52 studies representing major issues concerning rabies prevention related to topics including, but not limited to: epidemiological investigations (40.38%), prophylactic measures (21.15%), population of wandering dogs (13.46%), public awareness and government interventions (17.30%) and diagnostic surveillance (7.69%). In order to minimize these problems and reduce the prevalence of dog bites or rabies in significant manners, the country direly needs to apply the following actions: a maintained supply of rabies prophylactic measures in public hospitals at subsidized rates, mass dog vaccination at regional levels, enforced responsible animal ownerships, implementing a systematic One Health approach, and diagnostic labs equipped with surveillance mechanisms established in coordination with the livestock and medical departments. This review, which presents up-to-date information on the risk factors and epidemiological features of rabies in Pakistan, provides useful information for scientists, policy makers, and administrative health officials wishing to understand how this deadly disease persists in the absence of effective control measures.
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http://dx.doi.org/10.1016/j.actatropica.2021.106011DOI Listing
June 2021

Phytochemical profiling, in vitro and in vivo anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides (Fenzl) Verdc. (Aizoaceae).

Inflammopharmacology 2021 Jun 1. Epub 2021 Jun 1.

Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.

Sesuvium sesuvioides (Fenzl) Verdc is traditionally used in the treatment of inflammatory diseases such as arthritis and gout The aim of present study was to assess the possible anti-inflammatory, analgesic and antipyretic potential of the methanol extract of Sesuvium sesuvioides (SsCr) to prove scientifically its folklore use in the inflammatory diseases and to screen its total antioxidant capacity by multiple methods and phytocompounds by GC-MS. The preliminary phytochemical studies showed the presence of phenols, flavonoids, glycosides, coumarin, terpenoids, saponins, fats and carbohydrates in crude extract. The total phenolic contents (27.31 ± 0.28 mg GAE/g) and total flavonoids (3.58 ± 0.12 mgRE/g) values were observed. The antioxidant capacity of SsCr showed significant DPPH, ABTS, CUPRAC, FRAP, PBD and metal chelating results. GC-MS analysis displayed the phytoconstituents with anti-inflammatory potentials such as 2-methoxy-4-vinylphenol, vanillin, umbelliferone, methyl ferulate, palmitoleic acid, methyl palmitate and phytol. SsCr presented noteworthy HRBC membrane stability with maximum inhibition of cell hemolysis (47.79%). In carrageenan-induced hind paw edema assay result showed dose-dependent anti-inflammatory action. SsCr presented significant (p < 0.05) analgesic activity in hot-plate and tail flicking tests similarly it also showed the noteworthy inhibition in pain latency against formalin induced analgesia at 1st and 2nd phases. SsCr reduced the acetic acid-induced writhes at different doses (250, 500 and 750 mg). Results of antipyretic activity of SsCr extract were significant at 500 and 750 mg. The results of in vitro and in vivo experimental studies verified the anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides and supported the folklore uses of this plant.
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http://dx.doi.org/10.1007/s10787-021-00824-9DOI Listing
June 2021

Biallelic variant in DACH1, encoding Dachshund Homolog 1, defines a novel candidate locus for recessive postaxial polydactyly type A.

Genomics 2021 May 20;113(4):2495-2502. Epub 2021 May 20.

Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; Division of Genetics, Department of Pediatrics, King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Polydactyly or hexadactyly is characterized by an extra digit/toe with or without a bone. Currently, variants in ten genes have been implicated in the non-syndromic form of polydactyly. DNA from a single affected individual having bilateral postaxial polydactyly was subjected to whole exome sequencing (WES), followed by Sanger sequencing. Homology modeling was performed for the identified variant and advance microscopy imaging approaches were used to reveal the localization of the DACH1 protein at the base of primary cilia. A disease-causing biallelic missense variant (c.563G > A; p.Cys188Tyr; NM_080760.5) was identified in the DACH1 gene segregating perfectly within the family. Structural analysis using homology modeling of the DACH1 protein revealed secondary structure change that might result in loss of function or influence downstream interactions. Moreover, siRNA-mediated depletion of DACH1 showed a key role of DACH1 in ciliogenesis and cilia function. This study provides the first evidence of involvement of the DACH1 gene in digits development in humans and its role in primary cilia. This signifies the importance and yet unexplored role of DACH1.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.015DOI Listing
May 2021

Extracts of Euphorbia nivulia Buch.-Ham. showed both phytotoxic and insecticidal capacities against Lemna minor L. and Oxycarenus hyalinipennis Costa.

PLoS One 2021 30;16(4):e0250118. Epub 2021 Apr 30.

Department of Biotechnology, College of Sciences, Taif University, Taif, Saudi Arabia.

Many phytochemicals can affect the growth and development of plants and insects which can be used as biological control agents. In this study, different concentrations of crude, hexane, chloroform, butanol, and aqueous extracts of Euphorbia nivulia Buch.-Ham., an endemic plant of the Cholistan desert in South Punjab of Pakistan, were analysed for their chemical constituents. Their various concentrations were also tested for their phytotoxic and insecticidal potential against duckweed, Lemna minor L., and the dusky cotton bug, Oxycarenus hyalinipennis Costa. various polyphenols, i.e., quercetin, gallic acid, caffeic acid, syringic acid, coumaric acid, ferulic acid, and cinnamic acid were detected in different concentrations with different solvents during the phytochemical screening of E. nivulia. In the phytotoxicity test, except for 100 μg/mL of the butanol extract gave 4.5% growth regulation, no phytotoxic lethality could be found at 10 and 100 μg/mL of all the extracts. The highest concentration, 1000 μg/mL, of the chloroform, crude, and butanol extracts showed 100, 63.1, and 27.1% of growth inhibition in duckweed, respectively. In the insecticidal bioassay, the highest O. hyalinipennis mortalities (87 and 75%) were recorded at 15% concentration of the chloroform and butanol extracts of E. nivulia. In contrast, the lower concentrations of the E. nivulia extracts caused the lower mortalities. Altogether, these findings revealed that E. nivulia chloroform extracts showed significant phytotoxicity while all the extracts showed insecticidal potential. This potential can be, further, refined to be developed for bio-control agents.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250118PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087071PMC
April 2021

Phytochemical, antimicrobial and time-kill kinetics potentials of Euphorbia nivulia Buch.-Ham.: A Cholistan desert medicinal plant.

Pak J Pharm Sci 2020 Sep;33(5(Special)):2461-2469

Department of Pharmacognosy, Faculty of Pharmacy, Gomal University, Dera Ismail Khan, Pakistan.

Euphorbia nivulia a locally occurring plant species possesses antiseptic, analgesic and anti-inflammatory properties and is ethnopharmacologically used in various ailments like skin, ear disorders, boils, and worm infestation. Preliminary phytochemical screening showed presence of flavonoids, polyphenolics, glycosides, alkaloids, tannins and triterpenoids in (70% aqueous-ethanolic) Euphorbia nivulia crude extract (En cr) and its four fractions, i.e., hexane fraction (En hex), butanol fraction (En bt), chloroform fraction (En ch), and aqueous fraction (En aq). In current study, Agar well diffusion and time-kill kinetic assays were performed for antimicrobial activity. 300 mg/ml concentration showed maximum inhibitory zone. Highest zone of inhibition (15.5mm) was demonstrated by En ch fraction against Proteus mirabilis. Staphyllococcus aureus was the most sensitive bacteria against whom all fractions except En aq fraction were active. Maximum MIC (15.3 mg/ml) was shown by En ch fraction against Proteus mirabilis. Similarly, En ch fraction showed (15.1 mg/ml) remarkable MIC against Candida albicans. Significant higher antibacterial and antifungal activity was revealed in high concentration. Time-kill kinetics studies revealed bacteriostatic action. Noteworthy antimicrobial activity may be due to bioactive compounds of extract which may be a potential antibacterial and antifungal agent.
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September 2020

Automated multi-class classification of skin lesions through deep convolutional neural network with dermoscopic images.

Comput Med Imaging Graph 2021 Mar 24;88:101843. Epub 2020 Dec 24.

Department of Information and Computational Sciences, School of Mathematical Sciences and LMAM, Peking University, Beijing, 100871, People's Republic of China. Electronic address:

As an analytic tool in medicine, deep learning has gained great attention and opened new ways for disease diagnosis. Recent studies validate the effectiveness of deep learning algorithms for binary classification of skin lesions (i.e., melanomas and nevi classes) with dermoscopic images. Nonetheless, those binary classification methods cannot be applied to the general clinical situation of skin cancer screening in which multi-class classification must be taken into account. The main objective of this research is to develop, implement, and calibrate an advanced deep learning model in the context of automated multi-class classification of skin lesions. The proposed Deep Convolutional Neural Network (DCNN) model is carefully designed with several layers, and multiple filter sizes, but fewer filters and parameters to improve efficacy and performance. Dermoscopic images are acquired from the International Skin Imaging Collaboration databases (ISIC-17, ISIC-18, and ISIC-19) for experiments. The experimental results of the proposed DCNN approach are presented in terms of precision, sensitivity, specificity, and other metrics. Specifically, it attains 94 % precision, 93 % sensitivity, and 91 % specificity in ISIC-17. It is demonstrated by the experimental results that this proposed DCNN approach outperforms state-of-the-art algorithms, exhibiting 0.964 area under the receiver operating characteristics (AUROC) in ISIC-17 for the classification of skin lesions and can be used to assist dermatologists in classifying skin lesions. As a result, this proposed approach provides a novel and feasible way for automating and expediting the skin lesion classification task as well as saving effort, time, and human life.
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http://dx.doi.org/10.1016/j.compmedimag.2020.101843DOI Listing
March 2021

Seroprevalence and Molecular Identification of spp. in Bovines in Pakistan-Investigating Association With Risk Factors Using Machine Learning.

Front Vet Sci 2020 2;7:594498. Epub 2020 Dec 2.

Friedrich-Loeffler-Institut, Institute of Bacterial Infections and Zoonoses, Jena, Germany.

Bovine brucellosis is a global zoonosis of public health importance. It is an endemic disease in many developing countries including Pakistan. This study aimed to estimate the seroprevalence and molecular detection of bovine brucellosis and to assess the association of potential risk factors with test results. A total of 176 milk and 402 serum samples were collected from cattle and buffaloes in three districts of upper Punjab, Pakistan. Milk samples were investigated using milk ring test (MRT), while sera were tested by Rose-Bengal plate agglutination test (RBPT) and indirect enzyme-linked immunosorbent assay (i-ELISA). Real-time PCR was used for detection of DNA in investigated samples. Anti- antibodies were detected in 37 (21.02%) bovine milk samples using MRT and in 66 (16.4%) and 71 (17.7%) bovine sera using RBPT and i-ELISA, respectively. Real-time PCR detected DNA in 31 (7.71%) from a total of 402 bovine sera and identified as . Seroprevalence and molecular identification of bovine brucellosis varied in some regions in Pakistan. With the use of machine learning, the association of test results with risk factors including age, animal species/type, herd size, history of abortion, pregnancy status, lactation status, and geographical location was analyzed. Machine learning confirmed a real observation that lactation status was found to be the highest significant factor, while abortion, age, and pregnancy came second in terms of significance. To the authors' best knowledge, this is the first time to use machine learning to assess brucellosis in Pakistan; this is a model that can be applied for other developing countries in the future. The development of control strategies for bovine brucellosis through the implementation of uninterrupted surveillance and interactive extension programs in Pakistan is highly recommended.
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http://dx.doi.org/10.3389/fvets.2020.594498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738322PMC
December 2020

Stealth Strategies of for Immune Evasion.

Curr Issues Mol Biol 2021 17;41:597-616. Epub 2020 Oct 17.

Department of Hand Surgery, China Japan Union Hospital, Jilin University, 126 XianTai Street, Changchun, China.

Tuberculosis is a devastating disease causing high mortality all over the world, especially in the developing countries. () is the causative agent of tuberculosis which replicates in the intracellular environment of host macrophages. Although the host immune system is capable of completely eliminating the pathogen, co-evolution of with humans has resulted in its ability to hijack the host innate and adaptive immune systems in numerous ways. Limited recent progress has been made in the understanding of immune escape mechanisms, hence exploration of survival strategies of has been critically reviewed with an insight into understanding its pathogenesis. We summarized the recent studies regarding the modulation of innate immune response, adaptive immune response, epigenetics and the role of miRNA. All of these advancements suggest that is well-familiarize with the host immune system and possess the ability to hijack it for intracellular survival.
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http://dx.doi.org/10.21775/cimb.041.597DOI Listing
October 2020

Regulating quantal size of neurotransmitter release through a GPCR voltage sensor.

Proc Natl Acad Sci U S A 2020 10 12;117(43):26985-26995. Epub 2020 Oct 12.

State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, 100871 Beijing, China

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Giβγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y receptors. D76 and D127 in P2Y were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y(D76/D127) → Giβγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.
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http://dx.doi.org/10.1073/pnas.2005274117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604499PMC
October 2020

Retraction notice to "Mycoplasma synoviae vaccine modifies virus shedding and immune responses of avian influenza (H9N2) infection in commercial layers" [Poult. Sci. 96 (2017) 3086-3095].

Poult Sci 2020 Aug 15;99(8):R4102. Epub 2020 Jul 15.

Department of Pathobiology, PMAS Arid Agriculture University, Rawalpindi, Pakistan.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The authors retract the above paper due to: 1) conflict of interest among the authors; and 2) addition of co-author Dr. Muhammad Younus without his knowledge or permission. The authors apologize for these two grave mistakes.
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http://dx.doi.org/10.1016/j.psj.2020.07.002DOI Listing
August 2020

α-Glucosidase Inhibitory, Anti-Oxidant, and Anti-Hyperglycemic Effects of -Ham. in STZ-Induced Diabetic Rats.

Dose Response 2020 Jul-Sep;18(3):1559325820939429. Epub 2020 Jul 7.

Department of Food Science and Technology, University College of Agriculture and Environmental Sciences, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.

In this study, we aimed to investigate the antidiabetic effects of , native to Cholistan Desert area of Bahawalpur, Pakistan. First, we performed high-performance liquid chromatography analysis and found that this plant contains ferulic acid, gallic acid, quercetin, benzoic acid, polyphenols, and flavonoids. Then, we performed in vitro and in vivo studies to assess its effects on diabetic Wistar rat model. The experiments were performed and compared with control drug glibenclamide. The 70% hydroalcoholic extract of exhibited 97.8% in vitro α-glucosidase inhibitory effect at a dose of 1.0 mg/mL. We orally administered the extract of and control drug to the streptozotocin (STZ)-induced diabetic rats and analyzed its antidiabetic effects. We found that the extract of with a dose of 500 mg/kg/body weight exhibited significant effect to reduce blood glucose in STZ-induced rats as compared with the control group ( < .001). Our histological data also showed that the extract significantly improved the histopathology of pancreas. Collectively, both in vitro and in vivo studies revealed that possesses α-glucosidase inhibitory, antioxidant, and anti-hyperglycemic effect in STZ-induced diabetic rats.
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http://dx.doi.org/10.1177/1559325820939429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343366PMC
July 2020

Enhanced Efficacy of Direct-Acting Antivirals in Hepatitis C Patients by Coadministration of Black Cumin and Ascorbate as Antioxidant Adjuvants.

Oxid Med Cell Longev 2020 3;2020:7087921. Epub 2020 Jun 3.

Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.

The widespread adaptation of a new generation of direct-acting antiviral agents (DAAs) unveils a superlative effect in the eradication of the hepatitis C virus (HCV). However, this therapy has been reported to exhibit vigorous side effects that pose a risk in fleet recovery. This study was conducted to investigate the efficacy of DAAs: sofosbuvir (SOF) and ribavirin (RBV), along with black cumin (BLC) and ascorbate (ASC), as adjuvants on hematological parameters; oxidative stress markers such as total antioxidant status (TAS), superoxide dismutase (SOD), reduced (GSH) and oxidized (GSSG) glutathione (GSH), gamma-glutamyl transferase (GGT), and malondialdehyde (MDA); liver function markers such as aspartate transaminase (AST), alanine aminotransferase (ALT), bilirubin, and alkaline phosphatase (ALP); and viral load with determined genotypes. HCV-infected patients ( = 30) were randomly divided into two equal groups: control group ( = 15) and treatment group ( = 15). The control group was subjected only to SOF and RBV (400 mg each/day). Synergistically, the treatment group was administered with adjuvant therapy of BLC (250 mg/day) and ASC (1000 mg/day) along with DAAs (400 mg each/day) for 8 weeks. All selected patients were subjected to sampling at pre- and posttreatment stages for the assessment of defined parameters. The data revealed that the BLC/ASC adjuvant therapy boosted the efficacy of DAAs by reducing the elevated levels of liver markers such as AST, ALT, ALP, and bilirubin in the treatment group compared with those in the control group ( > 0.05). The adjuvant therapy synchronously showed an ameliorating effect on hematological parameters. The SOF/RBV with adjuvant therapy also demonstrated an increasing effect in the activity of SOD, TAS, and GSH and a decreasing effect for GSSG, GGT, and malondialdehyde (MDA; > 0.05) followed by curtailing a RT-PCR-quantified viral load. Our findings provide evidence that systemic administration of BLC/ASC efficiently alleviates hematological, serological, and antioxidant markers as well as the viral load in hepatitis C patients. This highlights a potentially novel role of BLC and ASC in palliating hepatitis C.
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http://dx.doi.org/10.1155/2020/7087921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290872PMC
January 2021

Reply to "TRPA1-dependent calcium transients and CGRP release in DRG neurons require extracellular calcium".

J Cell Biol 2020 06;219(6)

State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.

In this issue, Gebhardt et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.201702151) express interest in our recently published work (Shang et al. 2016. J. Cell Biol.https://doi.org/10.1083/jcb.201603081). Here, we would like to address their concerns regarding the lysosomal TRPA1-mediated intracellular calcium transients in dorsal root ganglion neurons.
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http://dx.doi.org/10.1083/jcb.202004017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265323PMC
June 2020

Evaluation of the Effectiveness of Additional Risk Minimization Measures for Voriconazole in the EU: Findings and Lessons Learned from a Healthcare Professional Survey.

Pharmaceut Med 2019 04;33(2):121-133

Epidemiology, Worldwide Safety and Regulatory, Pfizer Inc, New York, NY, USA.

Background: Voriconazole is an extended-spectrum antifungal agent approved for the treatment and prophylaxis of invasive aspergillosis and other serious fungal infections. In 2014, additional risk minimization measures (aRMM) consisting of a Healthcare Professional (HCP) Question and Answer (Q&A) Brochure, HCP Checklist, and Patient Alert Card were implemented on a rolling basis across the European Union (EU) to mitigate three key risks with voriconazole: phototoxicity, squamous cell carcinoma (SCC) of the skin, and hepatotoxicity. The risks of phototoxicity and hepatotoxicity have been documented in the Summary of Product Characteristics (SmPC) since voriconazole was first approved in the EU in 2002. However, the risk of SCC of the skin was a more recent addition to the SmPC (added in 2010).

Objectives: We evaluated the effectiveness of the aRMM, as per EU Good Pharmacovigilance Practices Module XVI, via a survey of HCPs.

Methods: An online survey was conducted among specialty care HCPs in 10 EU countries who had received by mail aRMM tools 12 months previously. Survey questions evaluated HCPs' receipt and utilization of aRMM tools, and knowledge of the three risks.

Results: Of 27,396 HCPs invited to participate, 332 eligible respondents completed the survey (response rate: 447/26,735; 1.7%). In total, 19.6% of respondents recalled receiving the HCP Q&A Brochure, 22.6% the HCP Checklist, and 25.9% the Patient Alert Card. HCPs had a high level of knowledge of phototoxicity and hepatotoxicity; however, knowledge of SCC was lower. Knowledge of the three risks and self-reported risk minimization behavior was slightly improved in those who had read the HCP Q&A Brochure compared with those who had not.

Conclusion: The effectiveness of the voriconazole aRMM cannot be meaningfully inferred from the results due to the low survey response rate. The assessment indirectly points to the SmPC or other resources being the main source of risk information for HCPs. Engaging HCPs before designing and implementing an aRMM program is crucial to ensure an effective and focused program. (EU PAS registration number: EUPAS12624).
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http://dx.doi.org/10.1007/s40290-019-00273-4DOI Listing
April 2019

A method for recording the two phases of dopamine release in mammalian brain striatum slices.

Analyst 2020 Jan;145(2):453-459

State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.

Striatal dopamine (DA) release plays an essential role in many physiological functions including motor and non-motor behaviors (such as reward, motivation, and cognition). We have previously reported that, following a single electrical field stimulation, the amperometric recording of DA release from presynaptic terminals in striatal slices (both ventral and dorsal) contains two temporally separated phases. The first phase (direct DA transmission, direct DT) arises from DA terminal release following autologous action potentials (APs), while the second phase (cholinergic transmission-induced DA transmission, CTDT) arises from delayed DA release triggered by the activation of cholinergic interneurons to DA terminals (axon-axon transmission). The millisecond time-resolution of amperometry permits separation of an ∼7 ms latency difference from the single synapse (axon-axon) within the two-phase DA-release (2pDA) signal, and thus the 2pDA signal provides a novel method to study either direct DT, or CTDT, or both. Here, we describe the 2pDA method, including signal recording, processing, analysis, and troubleshooting (anti-artifact). Compared with other DA assays using different stimuli, recording methods, and preparations (such as high performance liquid chromatography or fast scan cyclic voltammetry), 2pDA recording is a novel and powerful physiological recording method for the study of DA transmissions in situ.
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http://dx.doi.org/10.1039/c9an01941cDOI Listing
January 2020

Superparamagnetic nanoarchitectures for disease-specific biomarker detection.

Chem Soc Rev 2019 Dec;48(24):5717-5751

Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia.

The detection of clinically relevant disease-specific biomolecules, including nucleic acids, circulating tumor cells, proteins, antibodies, and extracellular vesicles, has been indispensable to understand their functions in disease diagnosis and prognosis. Therefore, a biosensor for the robust, ultrasensitive, and selective detection of these low-abundant biomolecules in body fluids (blood, urine, and saliva) is emerging in current clinical research. In recent years, nanomaterials, especially superparamagnetic nanomaterials, have played essential roles in biosensing due to their intrinsic magnetic, electrochemical, and optical properties. However, engineered multicomponent magnetic nanoparticle-based current biosensors that offer the advantages of excellent stability in a complex biomatrix; easy and alterable biorecognition of ligands, antibodies, and receptor molecules; and unified point-of-care integration have yet to be achieved. This review introduces the recent advances in superparamagnetic nanostructures for electrochemical and optical biosensing for disease-specific biomarkers. This review emphasizes the synthesis, biofunctionalization, and intrinsic properties of nanomaterials essential for robust, ultrasensitive biosensing. With a particular emphasis on nanostructure-based electrochemical and optical detection of disease-specific biomarkers such as nucleic acids (DNA and RNA), proteins, autoantibodies, and cells, this review also chronicles the needs and challenges of nanoarchitecture-based detection. These summaries provide further insights for researchers to inspire their future work on the development of nanostructures for integrating into biosensing and devices for a broad field of applications in analytical sensing and in clinic.
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http://dx.doi.org/10.1039/c9cs00174cDOI Listing
December 2019

Stereochemical Effects on Platinum Acetylide Two-Photon Chromophores.

J Phys Chem A 2019 Oct 17;123(43):9382-9393. Epub 2019 Oct 17.

Department of Chemistry , University of Texas at San Antonio , San Antonio , Texas 78249 , United States.

A series of -platinum(II) acetylide complexes containing two-photon-absorbing chromophores have been synthesized and characterized to explore the effects of stereochemistry on the nonlinear absorption properties. The molecules feature 4-(phenylethynyl)phenylethynylene (PE2), diphenylaminofluorene (DPAF), and benzothiazolylfluorene (BTF) ligands. The photophysical properties were investigated under one- and two-photon conditions and compared to the known analogues via UV-visible absorption, photoluminescence, femtosecond and nanosecond transient absorption (TA), nanosecond z-scan, and femtosecond two-photon absorption (2PA). The bent complexes exhibit blue shifts in the absorption, emission, femtosecond, and nanosecond TA spectra along with lower molar extinction coefficients and lower phosphorescence yields relative to the complexes suggesting less efficient Pt-induced spin-orbit coupling and intersystem crossing in the configuration. The chromophores are noncentrosymmetric and therefore show dipolar behavior with a pronounced 2PA in the 0-0 transition of the S → S band, while the complexes show quadrupolar behavior with a forbidden 0-0 transition. In the S → S region, both and complexes show intense two-photon-absorption bands (up to 3700 GM by the peak cross section for -BTF) which contain a significant contribution from the excited state absorption (S → S). All six complexes exhibit comparable nonlinear absorption response with a significant contribution from triplet-triplet absorption that slightly favors complexes but is more strongly dependent upon the structure of the π-conjugated chromophore.
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http://dx.doi.org/10.1021/acs.jpca.9b07823DOI Listing
October 2019

Biallelic Missense Mutation in the Underlies Distal Arthrogryposis Type 5 (DA5D).

Front Pediatr 2019 28;7:343. Epub 2019 Aug 28.

Department of Chemistry, Women University Swabi, Swabi, Pakistan.

Distal arthrogryposis (DA) is a heterogeneous sub-group of arthrogryposis multiplex congenita (AMC), mostly characterized by having congenital contractures affecting hands, wrists, feet, and ankles. Distal arthrogryposis is mostly autosomal dominantly inherited, while only one sub-type DA type 5D is inherited in an autosomal recessive manner. Clinically, DA5D is described having knee extension contractures, micrognathia, distal joint contractures, clubfoot, ptosis, contractures (shoulders, elbows, and wrists), and scoliosis. Using whole exome sequencing (WES) followed by Sanger sequencing, we report on a first familial case of DA5D from Pakistani population having a novel biallelic missense mutation (c.158C>A, p.Pro53Leu) in the gene. Our result support that homozygous mutations in causes DA5D and expands the clinical and allelic spectrum of related contracture syndromes.
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http://dx.doi.org/10.3389/fped.2019.00343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724761PMC
August 2019

Managing plastic waste disposal by assessing consumers' recycling behavior: the case of a densely populated developing country.

Environ Sci Pollut Res Int 2019 Nov 12;26(32):33054-33066. Epub 2019 Sep 12.

Centre for English, IQRA University, Karachi, 75300, Pakistan.

The rapid increase in urbanization has given rise to the need of proper waste management. Within municipal waste, the plastic waste is a growing concern which is causing severe harm to our ecosystem. If ignored, this problem will have harmful effects on both human and wildlife. Therefore, this study aims to find out the factors that influence the recycling behavior patterns of consumers regarding plastic waste. The variables from the theory of planned behavior were adopted to study the behavior of consumers toward recycling plastic waste. The data was collected from 243 residents of Karachi-metropolitan city of Pakistan. The partial least square-structural equation modelling was applied to analyze the data. The findings of the current study reveal that different consumers' attributes and attitudes trigger different types of recycling behavior when it comes to waste disposal. Pressure from family and friends and perceived behavioral control trigger the behavior of reselling the waste plastic products while consumer's awareness of consequences and personal attitude toward proper waste disposal leads to reuse or donating that product to someone who can use that plastic product. The understanding of these consumer attributes may help to shape the behavioral outcomes in order to manage waste disposal. This study will be beneficial for business managers looking to improve reverse logistics as well as government/municipal policy makers and academics/researchers who are interested in a solution-oriented study.
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http://dx.doi.org/10.1007/s11356-019-06411-4DOI Listing
November 2019

Impaired D2 receptor-dependent dopaminergic transmission in prefrontal cortex of awake mouse model of Parkinson's disease.

Brain 2019 10;142(10):3099-3115

State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.

The loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson's disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Parkinson's disease remain largely unexplored. Using two-photon microscopic Ca2+ imaging in awake PARK7-/- and PARK7+/+ mice, we found that (i) PARK7-/- neurons in the frontal association cortex showed substantially higher circuit activity recorded as spontaneous somatic Ca2+ signals; (ii) both basal and evoked dopamine release remained intact, as determined by both electrochemical dopamine recordings and high performance liquid chromatography in vivo; (iii) D2 receptor expression was significantly decreased in postsynaptic frontal association cortical neurons, and the hyper-neuronal activity were rescued by D2 receptor intervention using either local pharmacology or viral D2 receptor over-expression; and (iv) PARK7-/- mice showed anxiety-like behaviours that were rescued by either local D2 receptor pharmacology or overexpression. Thus, for first time, we demonstrated a robust D2 receptor-dependent phenotype of individual neurons within the prefrontal cortex circuit in awake parkinsonian mice that linked with anxiety. Our work sheds light on early-onset phenotypes and the mechanisms underlying Parkinson's disease by imaging brain circuits in an awake mouse model.
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http://dx.doi.org/10.1093/brain/awz243DOI Listing
October 2019

Simple Fabrication of PVA-ZnS Composite Films with Superior Photocatalytic Performance: Enhanced Luminescence Property, Morphology, and Thermal Stability.

ACS Omega 2019 Apr 2;4(4):6144-6153. Epub 2019 Apr 2.

International Center for Materials Nanoarchitectonics, National Institute for Materials Science (NIMS), 1-2-1, Sengen, Tsukuba, Ibaraki 305-0047, Japan.

Poly(vinyl alcohol) (PVA)-ZnS composite films were prepared by varying the composition of PVA ranging from 1-5 wt % through a simple solvent casting method. The photocatalytic enactment of the composites was evaluated along with the investigations of their photoluminescence (PL), optical transparency, morphology, and thermal properties. The firm interaction between the ZnS and PVA was confirmed by Fourier transform infrared, UV-vis, and PL spectroscopies. PVA-ZnS composites showed enhanced luminescence property than PVA. The composites exhibited very good optical transparency regardless of the amount of PVA addition. The thermogravimetric analysis data indeed exhibited better thermal stability of the composites. The glass transition temperature (), melting temperature (), enthalpy of melting (Δ), and crystallinity were evaluated for such composites. The composites demonstrated morphological variations depending on the amount of PVA addition, although the particle size of ZnS remained similar in the nanometer range (50-120 nm) for all composite samples. The prepared composite films exhibited superior photocatalytic performance in the degradation of methylene blue compared with the bare ZnS and PVA. This study may give a new insight into the fabrication of PVA-ZnS photocatalysts for the treatment of organic pollutants.
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http://dx.doi.org/10.1021/acsomega.8b02807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648807PMC
April 2019

Lack of association of Aspergillus colonization with the development of bronchiolitis obliterans syndrome in lung transplant recipients: An international cohort study.

J Heart Lung Transplant 2019 09 19;38(9):963-971. Epub 2019 Jun 19.

Division of Infectious Diseases, Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada. Electronic address:

Background: Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTRs). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of LTRs to assess whether Aspergillus colonization with large or small conidia is a risk factor for the development of BOS.

Methods: Consecutive LTRs from January 2005 to December 2008 were evaluated. Rates of BOS and associated risk factors were recorded at 4 years. International Society of Heart and Lung Transplantation criteria were used to define fungal and other infections. A Cox proportional-hazards-model was constructed to assess the association between Aspergillus colonization and the development of BOS controlling for confounders.

Results: A total of 747 LTRs were included. The cumulative incidence of BOS at 4 years after transplant was 33% (250 of 747). Additionally, 22% of LTRs experienced Aspergillus colonization after transplantation. Aspergillus colonization with either large (hazard ratio [HR] = 0.6, 95% confidence interval [CI] = 0.3-1.2, p = 0.12) or small conidia (HR = 0.9, 95% CI = 0.6-1.4, p = 0.74) was not associated with the development of BOS. Factors associated with increased risk of development of BOS were the male gender (HR = 1.4, 95% CI = 1.1-1.8, p = 0.02) and episodes of acute rejection (1-2 episodes, HR = 1.5, 95% CI = 1.1-2.1, p = 0.014; 3-4 episodes, HR = 1.6, 95% CI = 1.0-2.6, p = 0.036; >4 episodes, HR = 2.2, 95% CI = 1.1-4.3, p = 0.02), whereas tacrolimus use was associated with reduced risk of BOS (HR = 0.6, 95% CI = 0.5-0.9, p = 0.007).

Conclusions: We conclude from this large multicenter cohort of lung transplant patients, that Aspergillus colonization with large or small conidia did not show an association with the development of BOS.
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http://dx.doi.org/10.1016/j.healun.2019.06.007DOI Listing
September 2019

Report: Pharmacognostic and physicochemical screening of Euphorbia nivulia Buch.-Ham.

Pak J Pharm Sci 2019 May;32(3):1111-1119

Department of Botany, Faculty of Sciences, The Islamia University of Bahawalpur, Pakistan.

Euphorbia nivulia Buch.-Ham. (Euphorbiaceae) is commonly known as Indian Spurge Tree in English, and "Saj Thor" or "Jhanami booti" in local language. The plant is used traditionally in the treatment of various diseases like inflammation, fever, worm infection, asthma, cough, wounds and diabetes. In current study fresh as well as dried aerial parts of the plant and cut sections were examined, both macroscopically and microscopically. The study also deals with fluorescence analysis and phytochemical characteristics and other WHO recommended methods for standardization. WHO guidelines on quality control for medicinal plants materials were used for pharmacognostical evaluation of E. nivulia, phytochemical screening helps in determining the predominant classes of active constituents responsible for the activity. The present work will be helpful in identification of the fresh and dried samples of aerial parts pharmacognostically and anatomically. These studies will serve as a reference for correct identification and may be helpful in checking any type of adulteration. These observations will also help in differentiating this species from closely related species of the same genus and family.
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May 2019

Proposition and Real-Time Implementation of an Energy-Aware Routing Protocol for a Software Defined Wireless Sensor Network.

Sensors (Basel) 2019 Jun 18;19(12). Epub 2019 Jun 18.

Department of Information and Communication Engineering, Yeungnam University, Gyeongsan 38542, Korea.

A wireless sensor network (WSN) has achieved significant importance in tracking different physical or environmental conditions using wireless sensor nodes. Such types of networks are used in various applications including smart cities, smart building, military target tracking and surveillance, natural disaster relief, and smart homes. However, the limited power capacity of sensor nodes is considered a major issue that hampers the performance of a WSN. A plethora of research has been conducted to reduce the energy consumption of sensor nodes in traditional WSN, however the limited functional capability of such networks is the main constraint in designing sophisticated and dynamic solutions. Given this, software defined networking (SDN) has revolutionized traditional networks by providing a programmable and flexible framework. Therefore, SDN concepts can be utilized in designing energy-efficient WSN solutions. In this paper, we exploit SDN capabilities to conserve energy consumption in a traditional WSN. To achieve this, an energy-aware multihop routing protocol (named EASDN) is proposed for software defined wireless sensor network (SDWSN). The proposed protocol is evaluated in a real environment. For this purpose, a test bed is developed using Raspberry Pi. The experimental results show that the proposed algorithm exhibits promising results in terms of network lifetime, average energy consumption, the packet delivery ratio, and average delay in comparison to an existing energy efficient routing protocol for SDWSN and a traditional source routing algorithm.
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http://dx.doi.org/10.3390/s19122739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631970PMC
June 2019

Homozygous Nonsense Mutation (p.Arg97) Causing Limb-Girdle Muscular Dystrophy Type 2F (LGMD2F) in a Consanguineous Family, a Case Report.

Front Genet 2018 23;9:727. Epub 2019 Jan 23.

Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Limb-girdle muscular dystrophy (LGMD) is an increasingly heterogeneous category of inherited muscle diseases, mainly affecting the muscles of shoulder areas and the hip, segregating in both autosomal recessive and dominant manner. To-date, thirty-one loci have been identified for LGMD including seven autosomal dominant (LGMD type 1) and twenty four autosomal recessive (LGMD type 2) inherited loci. The present report describes a consanguineous family segregating LGMD2F in an autosomal recessive pattern. The affected individual is an 11-year-old boy having two brothers and a sister. Direct targeted next generation sequencing was performed for the single affected individual (VI-1) followed by Sanger sequencing. Targeted next generation sequencing revealed a novel homozygous nonsense mutation (c.289C>T; p.Arg97) in the exon 3 of the delta-sarcoglycan () gene, that introduces a premature stop codon (TCA), resulting in a nonsense mediated decay or a truncated protein product. This is the first report of LGMD2F caused by an variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene in causing LGMD2F and might help in genetic counseling, which is more important to deliver the risk of carrier or affected in the future pregnancies.
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http://dx.doi.org/10.3389/fgene.2018.00727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354032PMC
January 2019

A Long-term Safety Study of Latanoprost in Pediatric Patients With Glaucoma and Ocular Hypertension: A Prospective Cohort Study.

Am J Ophthalmol 2018 12 5;196:101-111. Epub 2018 Sep 5.

Pediatric Ophthalmology and Strabismus Service, Duke Eye Center, Duke University School of Medicine, Durham, North Carolina, USA.

Purpose: The objective was to assess the long-term effect of treatment with latanoprost on ocular development and safety in pediatric patients with glaucoma and ocular hypertension.

Design: Prospective cohort study.

Methods: This was a prospective 3-year cohort study conducted in 14 countries in Europe and South America. Patients aged < 18 years with glaucoma or ocular hypertension were enrolled into either the latanoprost or non-prostaglandin (non-PG) group in this observational study. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline to 3 years. Several secondary endpoints were evaluated, including corneal thickness and ocular hyperpigmentation. For treatment comparison, analysis of covariance (ANCOVA) was used for continuous endpoints and Fisher exact test was applied for proportion of participants with clinically significant deterioration events.

Results: A total of 175 patients were enrolled: 102 in the latanoprost group (median follow-up: 36.7 months) and 73 in the non-PG group (median follow-up: 36.1 months). There was no statistically significant difference between the latanoprost and the non-PG groups (aged 5 to <18 years) in BCVA change from baseline (least square mean logMAR difference -0.03 [95% confidence interval: -0.12, 0.06]), corneal thickness, or ocular hyperpigmentation.

Conclusions: Latanoprost had an acceptable safety profile with no evidence of inducing clinically meaningful or statistically significant changes in ocular development or ocular hyperpigmentation in pediatric patients with glaucoma and ocular hypertension.
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http://dx.doi.org/10.1016/j.ajo.2018.08.039DOI Listing
December 2018

Real-time Loop-mediated Isothermal Amplification (LAMP) of Gene of .

J Vet Res 2017 Dec 27;61(4):439-444. Epub 2017 Dec 27.

Department of Pathobiology, University of Veterinary and Animal Sciences, Lahore Sub-Campus, Jhang-35200, Pakistan.

Introduction: is considered the most pathogenic and economically significant avian spp. for the worldwide poultry industry. The aim of this study was to develop a novel and sensitive real-time loop-mediated isothermal amplification (LAMP) assay based on the amplification of its gene sequence for its rapid molecular detection in poultry.

Material And Methods: Blood samples from 300 broiler and layer chickens were screened using a rapid serum agglutination (RSA) test. A real-time LAMP reaction was conducted with seropositive swab samples at 60ºC for 90 min in an ESEQuant tube scanner using 6-carboxyfluorescein as the reporting dye.

Results: The sensitivity of the developed assay was 10 fg/µL of DNA. The assay was found 100% specific, showing no cross-reactivity with other avian species. The proportion found of the positive samples by the real-time LAMP was 58%. In comparison, the RSA was found to detect 52% of positive cases.

Conclusion: The real-time LAMP emerged as a more sensitive and accurate method for molecular detection of than RSA. Robustness and precision give it applicability as a potential field diagnostic tool for control. The study will be beneficial in reducing economic losses that inflicts on the poultry industry. This is the first reported development of a real-time LAMP assay based on the amplification of the gene sequence using an ESEQuant tube scanner for galline detection.
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http://dx.doi.org/10.1515/jvetres-2017-0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937342PMC
December 2017

Pathological Alterations in Respiratory System During Co-infection with Low Pathogenic Avian Influenza Virus (H9N2) and in Broiler Chickens.

J Vet Res 2017 Sep 19;61(3):253-258. Epub 2017 Sep 19.

Pir Mehr Ali Shah Arid Agriculture University, 46000, Rawalpindi, Pakistan.

Introduction: Despite the advancements in the field, there is a lack of data when it comes to co-infections in poultry. Therefore, this study was designed to address this issue.

Material And Methods: Broiler birds were experimentally infected with (O78) and low pathogenic avian influenza (LPAI) strain, alone or in combination. The experimental groups were negative control.

Results: The infected birds showed most severe clinical signs in +LPAI group along with a significant decrease in weight and enhanced macroscopic and microscopic pathological lesions. The survival rate was 60%, 84%, and 100% in birds inoculated with +LPAI, , and LPAI virus alone, respectively. The results showed that experimental co-infection with and H9N2 strain of LPAI virus increased the severity of clinical signs, mortality rate, and gross lesions. The HI titre against LPAI virus infection in the co-infected group was significantly higher than the HI titre of LPAI group, which may indicate that may promote propagation of H9N2 LPAI virus by alteration of immune response.

Conclusion: The present study revealed that co-infection with and H9N2 LPAI virus caused more serious synergistic pathogenic effects and indicates the role of both pathogens as complicating factors in poultry infections.
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http://dx.doi.org/10.1515/jvetres-2017-0035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894427PMC
September 2017

Assessment of Risk Evaluation and Mitigation Strategies (REMS) for varenicline (Chantix): A multistage patient survey.

Pharmacoepidemiol Drug Saf 2018 03 6;27(3):253-262. Epub 2018 Feb 6.

Epidemiology, Optum, Boston, MA, USA.

Purpose: To evaluate the Risk Evaluation and Mitigation Strategies (REMS) for varenicline by assessing patients' understanding of the varenicline medication guide (MG) at pre-specified time points: 18 months, 3 years, and 7 years after the REMS approval.

Methods: Self-administered surveys were mailed to people who received varenicline based on a pharmacy dispensing. Survey questions assessed understanding of potential risks outlined in the MG: neuropsychiatric symptoms, skin reactions, allergic reactions, and cardiovascular risks. Crude and weighted analyses were conducted.

Results: The response to the survey overall was between 18% and 19%. Among responders, approximately 90% recalled receiving the MG, and at least 80% read all or part of it. At least 88% correctly identified neuropsychiatric symptoms as potential medication effects, while 41% did so for skin reactions, 53% for allergic reactions, and 82% for cardiovascular risks. Patients who read the MG had a high proportion of correct responses to the risk comprehension questions.

Conclusions: A large majority of patients who were dispensed varenicline recalled receiving the MG and were able to correctly recall neuropsychiatric and cardiovascular risks in all 3 surveys. The varenicline MG may be an effective tool for patient education.
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http://dx.doi.org/10.1002/pds.4373DOI Listing
March 2018

Safety of fenbendazole in common peafowl (Pavo cristatus).

Pak J Pharm Sci 2018 Jan;31(1):159-167

Pir Mehr Ali Shah, Arid Agriculture University, Rawalpindi, Pakistan.

The present study was undertaken to find out the safety levels of fenbendazole in common peafowl. This bird, raised on aviaries and zoos, can be severely parasitized with Ascaridia galli (enteric worms) and Syngamus trachea (gapeworm) along with other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic in animals. The objective of this work was to provide target animal safety data in young peafowl and to demonstrate reproductive safety in adult birds. During the experimental study, diets containing fenbendazole at 0, 100, 200 and 300 ppm were fed for 21 days (three times the normal treatment duration). Data for feed consumption, feed conversion rate, and body weights were recorded for each bird in each group. Drug concentrations in different tissues of birds were determined to correlate concentrations with clinical observations, clinical pathology, and histologic findings. There were no morbidities or mortalities after study day 21. Additionally, there were no statistically significant treatment-related differences among above mentioned parameters. Analysis of fenbendazole concentrations in kidney, liver, leg/thigh, and breast muscle and skin with associated fat revealed that, even at the highest dose level used and with no feed withdrawal, fenbendazole concentrations were relatively low in these tissues. These findings indicate that fenbendazole has a relatively wide margin of safety in young peafowl and that the proposed dose of 100 ppm in the feed for 7 consecutive days is well within the margin of safety. In the reproductive safety study, five breeder peafowl farms fed fendbendazole at 100ppm for 7 days and collected data on hatching percentage of peahen eggs before and after treatment. Reproductive performance in peahen was not adversely affected.
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January 2018