Intrauterine Exposure to Biologics in Inflammatory Autoimmune Diseases: A Systematic Review

Background: Inflammatory autoimmune diseases are chronic diseases that often affect women of childbearing age. Therefore, detailed knowledge of the safety profile of medications used for management of inflammatory autoimmune diseases during pregnancy is important. However, in many cases the potential harmful effects of medications (especially biologics) during pregnancy (and lactation) on mother and child have not been fully identified. Objective: Our aim was to update the data on the occurrence of miscarriages and (major) congenital malformations when using biologics during pregnancy based on newly published articles. Additionally, we selected several different secondary outcomes that may be of interest for clinicians, especially information on adverse events in the use of a specific biologic during pregnancy. Material and Methods: A search was conducted from 1 January 2015 until 4 July 2019 in Embase.com, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar with specific search terms for each database. Selection of publications was based on title/abstract and followed by full text (double blinded, two researchers). An overview was made based on outcomes of interest. References of the included publications were reviewed to include and minimize the missing publications. Results: A total of 143 publications were included. The total number of cases ranged from nine for canakinumab to 4276 for infliximab. The rates of miscarriages and major congenital malformations did not show relevant differences from those rates in the general population. Conclusion: Despite limitations to our study, no major safety issues were reported and no trend could be identified in the reported malformations

The in silico insight into carbon nanotube and nucleic acid bases interaction

Background: To explore practical applications of carbon nanotubes (CNTs) in biomedical fields the properties of their interaction with biomolecules must be revealed. Recent years, the interaction of CNTs with biomolecules is a subject of research interest for practical applications so that previous research explored that CNTs have complementary structure properties with single strand DNA (ssDNA). Objectives: Hence, the quantum mechanics (QM) method based on ab initio was used for this purpose. Therefore values of binding energy, charge distribution, electronic energy and other physical properties of interaction were studied for interaction of nucleic acid bases and SCNT. Materials and Methods: In this study, the interaction between nucleic acid bases and a (4, 4) single-walled carbon nanotube (SCNT) were investigated through calculations within quantum mechanics (QM) method at theoretical level of Hartree-Fock (HF) method using 6-31G basis set. Hence, the physical properties such as electronic energy, total dipole moment, charge distributions and binding energy of nucleic acid bases interaction with SCNT were investigated based on HF method. Results: It has been found that the guanine base adsorption is bound stronger to the outer surface of nanotube in comparison to the other bases, consistent with the recent theoretical studies. In the other words, the results explored that guanine interaction with SCNT has optimum level of electronic energy so that their interaction is stable. Also, the calculations illustrated that SCNT interact to nucleic acid bases by noncovalent interaction because of charge distribution an electrostatic area is created in place of interaction. Conclusions: Consequently, small diameter SCNT interaction with nucleic acid bases is noncovalent. Also, the results revealed that small diameter SCNT interaction especially SCNT (4, 4) with nucleic acid bases can be useful in practical application area of biomedical fields such detection and drug delivery. © 2016, Iranian Red Crescent Medical Journal

INCREASED RADIORESISTANCE TO LETHAL DOSES OF GAMMA RAYS IN MICE AND RATS AFTER EXPOSURE TO MICROWAVE RADIATION EMITTED BY A GSM MOBILE PHONE SIMULATOR

The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1st phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2nd phase, 30 male rats were divided into 2 groups of 15 animals. The 1st group received microwave exposure. The 2nd group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response

Reported congenital malformations after exposure to non-tumour necrosis factor inhibitor biologics:A retrospective comparative study in EudraVigilance

AIM: To evaluate the number and nature of reported congenital malformations (CMs) after intrauterine exposure to non-tumour necrosis factor inhibitor biologics (non-TNFi biologics) compared to certolizumab pegol (CZP) MATERIAL AND METHODS: A retrospective comparative study was conducted in the EudraVigilance (EV) database. A safe biologic (CZP) was considered as the reference group. Odds ratios (ORs) for CMs were calculated for each non-TNFi biologics (including abatacept, anakinra, belimumab, ixekizumab, rituximab, secukinumab, tocilizumab, ustekinumab and vedolizumab), versus CZP (quantitative assessment). Then, CM patterns were reviewed in consultation with a clinical geneticist (qualitative assessment). RESULTS: ORs were not statistically significant except for belimumab and vedolizumab (similar in magnitude). Except for vedolizumab, no specific CM patterns were observed for the included non-TNFi biologics. Three cases of corpus callosum agenesis (CCA) were identified for vedolizumab (versus null in CZP and other investigated non-TNFi biologics). Two of the CCA cases were associated with other neurological CMs (one cerebral ventriculomegaly with microcephaly and one polymicrogyria). This may indicate that these CCAs are related to undiagnosed genetic alterations or are associated with the underlying maternal disease, although a definite relationship with vedolizumab exposure cannot be ruled out. CONCLUSION: No special safety signal was identified regarding the occurrence of CMs after exposure to abatacept (n= 64), anakinra (n= 20), belimumab (n= 93), ixekizumab (n= 29), rituximab (n=57), secukinumab (n= 128), tocilizumab (n= 124) and ustekinumab (n= 215). Regarding observed CCAs in the vedolizumab group (n= 113) no firm conclusions can be made based on available information

Modelling Temperature Variation of Mushroom Growing Hall Using Artificial Neural Networks

The recent developments of computer and electronic systems have made the use of intelligent systems for the automation of agricultural industries. In this study, the temperature variation of the mushroom growing room was modeled by multi-layered perceptron and radial basis function networks based on independent parameters including ambient temperature, water temperature, fresh air and circulation air dampers, and water tap. According to the obtained results from the networks, the best network for MLP was in the second repetition with 12 neurons in the hidden layer and in 20 neurons in the hidden layer for radial basis function network. The obtained results from comparative parameters for two networks showed the highest correlation coefficient (0.966), the lowest root mean square error (RMSE) (0.787) and the lowest mean absolute error (MAE) (0.02746) for radial basis function. Therefore, the neural network with radial basis function was selected as a predictor of the behavior of the system for the temperature of mushroom growing halls controlling system

The pre- and post-authorisation data published by the European Medicines Agency on the use of Biologics during pregnancy and lactation

Aims: The effects of biologics on reproduction/lactation are mostly unknown although many patients that receive biologics are women of reproductive age. The first objective of this study was to investigate the publicly available data on pregnancy/lactation before and after marketing authorization in Europe of biologics for the indications of rheumatologic inflammatory autoimmune diseases and inflammatory bowel disease. Secondary objectives included the assessment of the clinical relevance of the provided data and comparison of initial and post-authorization data. Methods: Initial and post-authorization data were extracted from the European Public Assessment Reports and the latest versions of Summary of Product Characteristics using publicly available documents on the European Medicines Agency's website. Four sections were categorized regarding pregnancy outcomes: pre-clinical/animal studies, human female fertility, pregnancy-related outcomes and congenital malformations in the human fetus. Three sections were categorized regarding lactation outcomes: pre-clinical/animal studies, excretion in human breast milk and absorption in children through breastfeeding. The clinical applicability of each category was scored by specified criteria, based on scientific literature, and further as defined by the authors. Results: For the 16 included biologics, post-authorization data were delivered only for adalimumab, certolizumab pegol, etanercept and infliximab. For the 12 remaining biologics limited data on pregnancy and lactation during the post-marketing period of 2–21 years were available. Conclusions: In this article several suggestions are provided for improving a multidisciplinary approach to these issues. The initiation of suitable registries by marketing authorization holders and data transparency for clinicians and academics are highly endorsed

Acceptance of shari?ah-compliant precious metal-backed cryptocurrency as an alternative currency: an empirical validation of adoption of innovation theory

In the crypto world, there is a proverbial (and literal) gold rush now occurring. Currently, more than 37 gold-backed cryptocurrency companies have now emerged. Interestingly, some of them also claim to be Sharīʿah-compliant. Introducing precious metal-backed cryptocurrencies is perceived to be an innovation among global payment systems, hampered in part by lack of supporting empirical evidence. Therefore, this research investigates potential users' tendency to adopt a Sharīʿah-compliant precious metal-backed cryptocurrency. As such, this study adopts an extended adoption model, which consists of eight factors. Partial least squares structural equation modeling (PLS-SEM) analysis was conducted on data elicited from economic active residents in Klang Valley from questionnaires. Overall, it was found six out of the eight constructs specified to influence the adoption of precious metal-backed cryptocurrency were statistically significant where 54.5% of the variation in adoption of PMBC can be explained by the structure model provided by this research. It was also found 63.55% of the respondents are willing to adopt precious metal-backed cryptocurrency in their future transactions

Maternal and neonatal antibody levels on pertussis vaccination in pregnant women on immune-modulating therapy for rheumatic disease

OBJECTIVES: While protection against pertussis following maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination was demonstrated in healthy term-born infants, no evidence is available on Tdap vaccination in combination with immune-modulating therapy during pregnancy. In this pilot study, we explored whether treatment with tumour necrosis factor alpha inhibitors (TNFis) in pregnant patients with rheumatic disease interferes with Tdap vaccine responses and affects maternal anti-pertussis IgG antibody levels in newborns. METHODS: Patients were included by a rheumatologist during pregnancy in case they received maternal Tdap vaccination in the late-second or early-third trimester of pregnancy. Blood samples were obtained from mothers during the first pregnancy trimester, 3 months after delivery and from the umbilical cord. IgG antibody levels against Tdap-included antigens were measured using a bead-based multiplex immunoassay. Findings on patients exposed to TNFis were compared with those from TNFi-unexposed patients and with data from a historical comparator study among healthy Tdap vaccinated mother-infant pairs (n=53). RESULTS: 66 patients (46 exposed and 20 unexposed to TNFIs) were enrolled. No major differences in IgG antibody levels were observed between TNFi-exposed and unexposed mothers before maternal Tdap vaccination and 3 months after delivery. In cord sera, however, antibody levels against pertussis toxin were significantly lower after TNFi-treatment (35.94 IU/mL, 95% CI 20.68 to 62.45) compared with no TNFi-treatment of mothers with rheumatic disease (94.61 IU/mL, 95% CI 48.89 to 183.07) and lower compared with a cohort of healthy mothers (125.12 IU/mL, 95% CI 90.75 to 172.50). We observed similar differences for filamentous haemagglutinin, pertactin, tetanus toxoid and diphtheria toxoid. CONCLUSION: These preliminary data indicate no major differences in IgG antibody levels on maternal Tdap vaccination in pregnant women with or without immune-modulating treatment, although our findings suggest that TNFis during pregnancy induce lower maternal anti-pertussis-specific protective antibody levels in newborns

Effect of Plant Density on Growth and Yield of Three Sunflower Hybrids (Helianthus annuus L.) as a Second Crop

In order to study the effects of plant density on growth, yield and oil percentage of three sunflower hybrids (Azargol, Alistar, Eroflor) an experiment was conducted at Agriculture Research Station of Myandoab in 2004. These hybrids were sown at four densities of 6, 8, 10 and 12 plants m-2 as factorial based on randomized complete block design with three replications. The results showed that dry matter accumulation (DM), crop growth rate (CGR) and relative growth rate (RGR) were increased with increasing plant density. By increment plant density, leaf area index (LAI) was slowly increased in early stages of growth but with beginning of plant rapid growth, increased dramatically. DM and CGR in Azargol and Eroflor were greater than Alistar. Analysis of variance showed that all traits were significantly affected by plant density. Yield per unit area, oil percentage and oil yield per unit area were increased, with increasing plant density. Although seed yield per plant at low densities was greater than that of high densities, but this increment was not enough for compensating the reduction of yield due to low density

Numerical simulation of nanofluid flow inside a root canal

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