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Saeed Mohammadi Nasr,1 Navid Rabiee,2 Sakineh Hajebi,3,4 Sepideh Ahmadi,5 Yousef Fatahi,6– 8 Masoumehossadat Hosseini,9,10 Mojtaba Bagherzadeh,2 Amir Mohammad Ghadiri,2 Mohammad Rabiee,11 Vahid Jajarmi,12,13 Thomas J Webster14 1Faculty of Chemical Engineering, Sahand University of Technology, Tabriz, Iran; 2Department of Chemistry, Sharif University of Technology, Tehran, Iran; 3Faculty of Polymer Engineering, Sahand University of Technology, Tabriz, Iran; 4Institute of Polymeric Materials, Sahand University of Technology, Tabriz, Iran; 5Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 6Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 7Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 8Universal Scientific Education and Research Network (USERN), Tehran, Iran; 9Department of Chemistry, Faculty of Chemistry and Petroleum Sciences, Shahid Beheshti University, Tehran, Iran; 10Soroush Mana Pharmed, Pharmaceutical Holding, Golrang Industrial Group, Tehran, Iran; 11Biomaterial Group, Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran; 12Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 13Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 14Department of Chemical Engineering, Northeastern University, Boston, MA 02115, United StatesCorrespondence: Thomas J Webster Email th.webster@neu.eduAbstract: Cardiovascular diseases are the number one cause of heart failure and death in the world, and the transplantation of the heart is an effective and viable choice for treatment despite presenting many disadvantages (most notably, transplant heart availability). To overcome this problem, cardiac tissue engineering is considered a promising approach by using implantable artificial blood vessels, injectable gels, and cardiac patches (to name a few) made from biodegradable polymers. Biodegradable polymers are classified into two main categories: natural and synthetic polymers. Natural biodegradable polymers have some distinct advantages such as biodegradability, abundant availability, and renewability but have some significant drawbacks such as rapid degradation, insufficient electrical conductivity, immunological reaction, and poor mechanical properties for cardiac tissue engineering. Synthetic biodegradable polymers have some advantages such as strong mechanical properties, controlled structure, great processing flexibility, and usually no immunological concerns; however, they have some drawbacks such as a lack of cell attachment and possible low biocompatibility. Some applications have combined the best of both and exciting new natural/synthetic composites have been utilized. Recently, the use of nanostructured polymers and polymer nanocomposites has revolutionized the field of cardiac tissue engineering due to their enhanced mechanical, electrical, and surface properties promoting tissue growth. In this review, recent research on the use of biodegradable natural/synthetic nanocomposite polymers in cardiac tissue engineering is presented with forward looking thoughts provided for what is needed for the field to mature.Keywords: biodegradable polymer, tissue engineering, cardiac cell, composite, natural, synthetic

Background and Aims: Different adhesives with different solvents may have different solvent evaporation rates. The purpose of this study was to evaluate the solvent evaporation in the self etch and total etch adhesive in different air drying times. Materials and Methods: Five adhesives were used in this study: Excite, Prime & Bond NT, UNO, Single Bond, SE Bond Primer. Twelve drops of each adhesive were used for each period of air drying (5, 15, 30 sec). The percentage of mass loss was measured during each test. Data were analized using two-way ANOVA and Tukey. Results: Acetone base adhesives showed more loss of mass than other adhesives (P

We investigated the vasodilatory effect of isoprenaline at large vessels (aorta, renal ans saphenous arteries, vena cava, renal and saphenous veins) in doxorbicin-induced model of heart failure. Thirty saline-treated (normal group) and thirty doxorubicin treated rabbits (1 mg/kg administered intravenously twice weekly for 8 weeks) were studied after 16 weeks of treatment. Chronic heart failure was confirmed by histopathology. Arteries and veins were cut as rings and so bathed in Krebs maintained at 37°C and gassed with 95% O2 and 5% CO2. Then all tissues were placed under different resting tensions and allowed to equilibrate for 1 hour. Then all the tissues were contracted with U-46619 (0.1 µM) nearly ten minutes before initial applications of isoprenaline. When the U-46619 (0.1 µM). induced contraction reached a plateau, concentration-response curves to isoprenaline were obtained. Isoprenaline was chosen as vasodilator resulting from stimulating beta-receptors in blood vessels. Maximum effect (Ema) and median effective concentration (EC50) were determined from each concentration-response curve and pD2 was calculatd as-log (EC50). Isoprenaline induced relaxations in all vessels. Aorta and renal artery were the most sensitive ones and had the maximum relaxations (15-20%). In relaxation due to β-adrencoeptor agonist isoproterenaol, the aorta and renal artery were the most sensitive vessels. Compared with control, in doxorubicin treated rabbits, Emax of isoprenalin was not modified in all the studied vessles. Relaxation responses were negligible and maximum responses in vena cava, and renal vein were only-5-10 percent. Of all vessels there was no significant difference between control and doxorubicin induced of heart failure in response to isoprenaline.

We investigated contraction to noradrenaline (NA) and KC1 and sensitivity of NA at the level of larger vessels (thoracic aorta and vena cava; left renal artery and left renal vein; lateral saphenous artery and lateral saphenous vein and finally central ear artery and marginal ear vein) in a model devised to mimic heart failure. The model presented here is the rabbit coronary ligation model in which myocardial infarction was produced ligation model in which myocardial infarction was produced in male New Zeeland white myocardial infarction was produced in male New Zeeland white rabbits (2.6 kg-3.0 Kg) by ligation of the marginal branch of the left descending coronary artery. The development of chronic heart failure was allowed to proceed over eight weeks. Animals were killed by overdose with pentobarbitone sodium (IV injection). Arteries and veins were carefully removed with as little connective tissue as possible and placed in cold physiological salt solution (PSS). The arterial and venous rings were mounted in 10 ml isolated organ baths, bathed in Kerbs maintained at 37 °c with 95% O2 plus 5% CO2. The rings were then placed under different resting tensions. After initial application of tension, tissues were left to equilibrate for a 60 min period. Then all tissues were exposed to cumulative concentration of NA (1nM-300µM). Following complete washout, the preparations were left for 45 minutes to re-equilibrate. Then all preparations were contracted with KCl (Krebs solution, sodium free and high KCl, 125 mM) and allowed to contract for 5-10 min. Following complete washout with normal Krebs an additional 30 minutes equilibration period was allowed. Then cumulative concentration-response curves (CCRS) to NA obtained by increasing the concentration-response curves (CCRC) to NA obtained by increasing the concentration of the agonist in half-log increments. In contraction responses to NA aorta, ear artery and ear vein were the most sensitive preparations (pD2 values: 9.96, 7.04 and 7.8 respectively). Renal artery and aorta had relatively very large maximum responses to NA among the arteries (6.7 and 4.3 g respectively) and saphenous vein had greated maximum responses to NA among the arteries (6.7 and 4.3g respectively) and saphenous vein had greatest maximum response among the veins (2.9g). The results led to two major conclusions with respect to the model. First, vasoconstrictions to noradrenaline were unaltered. Second, contractions to KCl (125 mM) were preserved in large vessels (arteries and veins) in coronary ligated rabbits after 8 weeks compared with a normal control population.

Recent discoveries have revealed that genetic variants in γ-aminobutyric acid type A (GABA A ) receptor subunits can lead to both gain-of-function (GOF) and loss-of-function (LOF) receptors. GABA A receptors, however, have a pseudosymmetrical pentameric assembly, and curiously diverse functional outcomes have been reported for certain homologous variants in paralogous genes (paralogous variants). To investigate this, we assembled a cohort of 11 individuals harboring paralogous M1 proline missense variants in GABRA1 , GABRB2 , GABRB3, and GABRG2. Seven mutations (α1 P260L , α1 P260S , β2 P252L , β3 P253L , β3 P253S , γ2 P282A , and γ2 P282S ) in α1β2/3γ2 receptors were analyzed using electrophysiological examinations and molecular dynamics simulations. All individuals in the cohort were diagnosed with developmental and epileptic encephalopathy, with a median seizure onset age of 3.5 mo, and all exhibited global developmental delay. The clinical data for this cohort aligned with established GABA A receptor GOF but not LOF cohorts. Electrophysiological assessments revealed that all variants caused GOF by increasing GABA sensitivity by 3- to 23-fold. In some cases, this was accompanied by LOF traits such as reduced maximal current amplitude and enhanced receptor desensitization. The specific subunit mutated and whether the mutation occurred in one or two subunits within the pentamer influenced the overall effects. Molecular dynamics simulations confirmed similar structural changes from all mutations, but with position-dependent asymmetry. These findings establish that paralogous variants affecting the 100% conserved proline residue in the M1 transmembrane helix of GABA A R subunits all lead to overall GOF traits. The unexpected asymmetric and mixed effects on receptor function have broader implications for interpreting functional analyses for multimeric ion-channel proteins., Competing Interests: Competing interests statement:P.C. is Executive Vice President, Research at the company Saniona in Denmark. The remaining authors declare no competing interests.

Background: Variants in GABRB2, encoding the β2 subunit of the γ-aminobutyric acid type A (GABA A ) receptor, can result in a diverse range of conditions, ranging from febrile seizures to severe developmental and epileptic encephalopathies. However, the mechanisms underlying the risk of developing milder vs more severe forms of disorder remain unclear. In this study, we conducted a comprehensive genotype-phenotype correlation analysis in a cohort of individuals with GABRB2 variants., Methods: Genetic and electroclinical data of 42 individuals harbouring 26 different GABRB2 variants were collected and accompanied by electrophysiological analysis of the effects of the variants on receptor function., Findings: Electrophysiological assessments of α1β2γ2 receptors revealed that 25/26 variants caused dysfunction to core receptor properties such as GABA sensitivity. Of these, 17 resulted in gain-of-function (GOF) while eight yielded loss-of-function traits (LOF). Genotype-phenotype correlation analysis revealed that individuals harbouring GOF variants suffered from severe developmental delay/intellectual disability (DD/ID, 74%), movement disorders such as dystonia or dyskinesia (59%), microcephaly (50%) and high risk of early mortality (26%). Conversely, LOF variants were associated with milder disease manifestations. Individuals with these variants typically exhibited fever-triggered seizures (92%), milder degrees of DD/ID (85%), and maintained ambulatory function (85%). Notably, severe movement disorders or microcephaly were not reported in individuals with loss-of-function variants., Interpretation: The data reveals that genetic variants in GABRB2 can lead to both gain and loss-of-function, and this divergence is correlated with distinct disease manifestations. Utilising this information, we constructed a diagnostic flowchart that aids in predicting the pathogenicity of recently identified variants by considering clinical phenotypes., Funding: This work was funded by the Australian National Health & Medical Research Council, the Novo Nordisk Foundation and The Lundbeck Foundation., Competing Interests: Declaration of interests SOR is the chair of the Young Epilepsy Section, ILAE, and has received consulting fees from Biopas-UCB, support for attending meetings and/or travel from Mythotherapies, and speaker fees from Abbott, LivaNova, Sanofi, Biopas-UCB and Nutricia. MT has received consulting fees from Biomarin, support for attending meetings and/or travel from Biomarin and Jazz Pharmaceuticals, and participated in Data Safety Monitoring Boards or Advisory Boards for Biocodex. SA is the deputy editor of Epilepsia, and has received consulting fees from UCB, Xenon, Encoded Therapeutics, EISAI, Stoke, Proveca, speaker fees from Biocodex, EISAI, Jazz Pharmaceuticals, Neuraxpharm, Nutricia and UCB and participated in Data Safety Monitoring Boards or Advisory Boards for GRIN Therapeutics. JK has received consulting fees from Biomarin, support for attending meetings and/or travel from Biomarin and Jazz Pharmaceuticals, and participated in Data Safety Monitoring Boards or Advisory Boards for Biocodex. SW has received consulting fees from UCB, Knopp Biosciences, Encoded Therapeutics, Roche, support for attending meetings and/or travel from Angelini Pharma, and participated in Data Safety Monitoring Boards or Advisory Boards for Angelini Pharma and Xenon Pharmaceuticals. NS has received consulting fees from Biomarin, support for attending meetings and/or travel from Biomarin and Jazz Pharmaceuticals, and participated in Data Safety Monitoring Boards or Advisory Boards for Biocodex. PB has received consulting fees from LivaNova, EISAI, Jazz Pharmaceuticals, Angelini Pharma and support for attending meetings and/or travel from Angelini Pharma and EISAI. RSM has received consulting fees from UCB, Orion, Saniona, Immedica and Atalanta, and speaker fees from EISAI, Angelini Pharma, Jazz Pharmaceuticals, Orion and UCB. PC is Executive Vice President, Research at the company Saniona in Denmark. The remaining authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders., (© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Purpose: Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype-phenotype correlations., Methods: Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3, and we reviewed previously published cases. All missense variants were mapped onto the 3-dimensional structure of the GABRB3 subunit, and clinical phenotypes associated with the different key structural domains were investigated., Results: We characterized 71 individuals with GABRB3 variants, including 22 novel subjects, expressing a wide spectrum of phenotypes. Interestingly, phenotypes correlated with structural locations of the variants. Generalized epilepsy, with a median age at onset of 12 months, and mild-to-moderate ID were associated with variants in the extracellular domain. Focal epilepsy with earlier onset (median: age 4 months) and severe ID were associated with variants in both the pore-lining helical transmembrane domain and the extracellular domain., Conclusion: These genotype-phenotype correlations will aid the genetic counseling and treatment of individuals affected by GABRB3-related disorders. Future studies may reveal whether functional differences underlie the phenotypic differences., Competing Interests: Conflicts of Interest The authors of declare no conflicts of interest., (Copyright © 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: A significant correlation exists between type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), where up to 40% of diabetic patients suffer from CKD as a direct result of diabetic complications. The management of diabetes in CKD patients can be challenging due to their need for disease-specific diets, as well as increased risks of complications due to malnutrition, which is why their dietary needs and nutritional requirements require attention to detail, and have to be assessed and tailored according to the patient's needs., Objectives: This systematic review aimed to assess nutritional requirements for type 2 diabetes mellitus patients with chronic renal failure., Methods: In this review, 85 articles were screened, and 22 articles were then analyzed and selected as per the study criteria. PRISMA guidelines were used to select and screen the articles. Data search included a PubMed search using MeSH terms, and a literature review through the Cochrane library and the British Medical Journal., Results: The study highlighted the important nutrients and minerals needed to be maintained within a specified range in accordance with the patient's needs and conditions. In addition, dietary restrictions must be set to prevent disease progression and deterioration. Dietary intake in hemodialysis patients must be carefully calculated based on their needs, with tight monitoring of their blood glucose. Protein intake in hemodialysis patients should be determined based on risk-to-benefit ratios., Conclusion: Dietary requirements should be individualized based on the patient's disease severity and progression. Assessment of the patient's previous and current diet, as well as matching it with their dietary requirements and preferences is crucial., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Injury resulting from contaminated sharp devices among health care workers (HCWs) is one of the most important concerns in medical centers. This can lead to dangerous infections such as human immunodeficiency virus, hepatitis B virus and hepatitis C virus among such people. The documentation of needle stick injuries started in Sadi Hospital, Isfahan, Iran in 2003, and our objective was to study cases of injuries by sharp devices before and after the implementation of intervention methods., Methods: In an intervention survey of the type of before and after study, we studied injuries by needle and other sharp devices among 87 HCWs in Sadi Hospital, a private hospital in Isfahan, Iran, during the years 2003-2004. The groups under study were workers and paramedical staff; and the wards under study included surgery, internal, lab, x-ray and laundry. We entered and evaluated the data in SPSS software., Results: In the first phase of the study in 2003, 55.2% of those injured had been injured by sharp devices. After intervention in 2004, this percentage was reduced to 19.5% (p < 0.05). At the beginning of the study, 26.4% of the injured had been injured by sharp devices more than twice, and at the end of the study this number was reduced to 2.3% (p < 0.05). Also, injuries resulting from recapping were 45.8% at the beginning of the study, which was reduced to 5.9% at the end (p < 0.05)., Discussion: With regard to this study and other studies carried out in other countries, a large number of injuries by contaminated sharp devices can be prevented by implementing suitable educational programs regarding disposal of sharp devices, and by using safe needle devices.