Fabricating Multiphasic Angiogenic Scaffolds Using Amyloid/Roxadustat-Assisted High-Temperature Protein Printing.

Repairing multiphasic defects is cumbersome. This study presents new soft and hard scaffold designs aimed at facilitating the regeneration of multiphasic defects by enhancing angiogenesis and improving cell attachment. Here, the nonimmunogenic, nontoxic, and cost-effective human serum albumin (HSA) fibril (HSA-F) was used to fabricate thermostable (up to 90 °C) and hard printable polymers. Additionally, using a 10.0 mg/mL HSA-F, an innovative hydrogel was synthesized in a mixture with 2.0% chitosan-conjugated arginine, which can gel in a cell-friendly and pH physiological environment (pH 7.4). The presence of HSA-F in both hard and soft scaffolds led to an increase in significant attachment of the scaffolds to the human periodontal ligament fibroblast (PDLF), human umbilical vein endothelial cell (HUVEC), and human osteoblast. Further studies showed that migration (up to 157%), proliferation (up to 400%), and metabolism (up to 210%) of these cells have also improved in the direction of tissue repair. By examining different in vitro and ex ovo experiments, we observed that the final multiphasic scaffold can increase blood vessel density in the process of per-vascularization as well as angiogenesis. By providing a coculture environment including PDLF and HUVEC, important cross-talk between these two cells prevails in the presence of roxadustat drug, a proangiogenic in this study. In vitro and ex ovo results demonstrated significant enhancements in the angiogenic response and cell attachment, indicating the effectiveness of the proposed design. This approach holds promise for the regeneration of complex tissue defects by providing a conducive environment for vascularization and cellular integration, thus promoting tissue healing.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Metabolic Syndrome and Assisted Reproductive Techniques.

Objective: Metabolic syndrome is a risk factor affecting reproductive health and pregnant outcomes. So far, the effect of this syndrome on the success rate of assisted reproduction techniques (ART) has not been investigated. The aim of this study was to investigate the relationship between metabolic syndrome and the success rate of ART in infertile women in Isfahan. Materials and methods: A prospective cohort study performed on 147 women candidates using in-vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) and/or ICSI methods referred to Isfahan Infertility Center in two groups with metabolic syndrome(n=49) without metabolic syndrome(n=98), by convenience sampling methods in Isfahan, Iran in 2018. Body mass index (BMI) and waist, abdominal circumference, Serum triglyceride (TG), cholesterol and FBS were measured. If ßHCG test was positive (day 15-16 after ART), transvaginal sonography (TVS) was done 15 days later. Pregnant women were followed up to the 20th week of pregnancy. To analyze, t-test, chi-square and logistic regression tests were used. Results: The frequency of metabolic syndrome was 33.4% (n=49). The frequency of ART was not significantly different between women with and without metabolic syndrome (p=0.321). The relative frequency of pregnancy (p=0.907) and abortion (p=0.896) did not show a significant difference between the two groups. Independent t-test showed that the mean FBS, HDL, TG, systolic and diastolic BP, abdominal circumference and BMI in the studied units did not differ significantly based on the occurrence of pregnancy and abortion. Conclusion: According to the results of this study, there was no significant difference between the indicators of metabolic syndrome and the success rate of ART in achieving, pregnancy and pregnant outcomes in the first twenty weeks of pregnancy.

Aptamer/doxorubicin-conjugated nanoparticles target membranous CEMIP2 in colorectal cancer.

The objectives were to identify the functional domains of a potential oncoprotein, cell migration inducing hyaluronidase 2 (CEMIP2), evaluate its expression levels and roles in colorectal cancer (CRC), and develop an aptamer-based nanoparticle for targeted therapy. Data mining on TCGA identified that CEMIP2 might play oncogenic roles in CRC. In a local cohort, CEMIP2 mRNA levels significantly stepwise increase in CRC patients with higher stages, and high CEMIP2 confers worse disease-free survival. In addition, CEMIP2 mRNA levels significantly correlated to hyaluronan levels in sera from CRC patients. Deletion mapping identified that CEMIP2 containing G8 and PANDER-like domains preserved hyaluronidase activity and oncogenic roles, including cell proliferation, anchorage-independent cell growth, cell migration and invasion, and human umbilical vein endothelial cell (HUVEC) tube formation in CRC-derived cells. A customized monoclonal mouse anti-human CEMIP2 antibody probing the PANDER-like domain (anti-289307) counteracted CEMIP2-mediated carcinogenesis in vitro. Cell-SELEX pinpointed an aptamer, aptCEMIP2(101), specifically interacted with the full-length CEMIP2, potentially involving its 3D structure. Treatments with aptCEMIP2(101) significantly reduced CEMIP2-mediated tumorigenesis in vitro. Mesoporous silica nanoparticles (MSN) carrying atpCEMIP2(101) and Dox were fabricated. Dox@MSN, MSN-aptCEMIP2(101), and Dox@MSN-aptCEMIP2(101) significantly suppressed tumorigenesis in vitro compared to the Mock, while Dox@MSN-aptCEMIP2(101) showed substantially higher effects compared to Dox@MSN and MSN-aptCEMIP2(101) in CRC-derived cells. Our study identified a novel oncogene and developed an effective aptamer-based targeted therapeutic strategy.

Evaluation of the Therapeutic Effect of 15 ppm Silver Nanoparticle Spray Compared to Clotrimazole 1% on Candida Vaginitis: A Randomized Controlled Clinical Trial.

Objective: In vitro and in vivo researches have shown that silver nanoparticles have more antimicrobial properties with a lower concentration than antifungal agents against candida vaginitis. Therefore, this study evaluated the therapeutic effect of silver nanoparticles (Nivasha spray15ppm) compared to clotrimazole 1% vaginal cream on candida vaginitis. Materials and methods: In this clinical trial study, 110 women with confirmed candida vaginitis randomly were divided into test (n=58) and control (n=52) groups. Silver nanoparticles spray with an applicator (Nivasha 15 ppm), and clotrimazole 1% were administered to test and control groups, respectively. Then, within ten days, post-intervention checkup and patient self-reported for treatment results were recorded in checklists and the data were analyzed statistically. Results: The improvement rate in test group (98.0%) was 1.44 times higher than in control (67.9%). Moreover, disease symptoms after the intervention (including unusual secretions, itching and burning, redness) in test group were significantly less than in the control, but there was no significant difference in the ratio of edema in two groups (p=0.071). Furthermore, the average recovery time (days) of all symptoms in test group was lower than control (p<0.05). Finally, the rate of patients' satisfaction with the treatment process in the test group (76.9%) was more than control (46.6%) (p=0.004). Conclusion: Nivasha spray had more effectiveness compared to the clotrimazole 1%. Therefore, it can be used as an alternative drug in the treatment of Candida vaginitis.

Design, development, and evaluation of a self-care program for women with osteoporosis: The protocol of a mixed-method study.

BACKGROUND: Osteoporosis, the fourth most common disease in the world, affects the elderly and postmenopausal women and imposes a great financial and social burden on individuals and society. Furthermore, it has a significant impact on the quality of patients' life. This study tries to take an effective step toward improving the quality of patients' life by developing and evaluating the self-care program of women with osteoporosis. MATERIALS AND METHODS: In this research, a hybrid sequential design of quantitative and qualitative type consisting of three phases is used. This mixed-method study aimed to develop and evaluate a self-care program for women with osteoporosis. CONCLUSION: Familiarity with the needs of these patients and the use of self-care programs and considering social, cultural, and psychological factors could be effective steps to improve the health of women with osteoporosis. These steps can improve the quality of life and reduce the costs of treatment for this group of women.

A review on biofilms and the currently available antibiofilm approaches: Matrix-destabilizing hydrolases and anti-bacterial peptides as promising candidates for the food industries.

Biofilms are communities of microorganisms that can be harmful and/or beneficial, depending on location and cell content. Since in most cases (such as the formation of biofilms in laboratory/medicinal equipment, water pipes, high humidity-placed structures, and the food packaging machinery) these bacterial and fungal communities are troublesome, researchers in various fields are trying to find a promising strategy to destroy or slow down their formation. In general, anti-biofilm strategies are divided into the plant-based and non-plant categories, with the latter including nanoparticles, bacteriophages, enzymes, surfactants, active peptides and free fatty acids. In most cases, using a single strategy will not be sufficient to eliminate biofilm, and consequently, two or more strategies will inevitably be used to deal with this unwanted phenomenon. According to the analysis of potential biofilm inhibition strategies, the best option for the food industry would be the use of hydrolase enzymes and peptides extracted from natural sources. This article represents a systematic review of the previous efforts made in these directions.

Design, implementation, and evaluation of self-care program in the prevention of breast cancer among women in Isfahan: a community-based participatory action research protocol.

INTRODUCTION: Breast cancer is one of the most prevalent cancers among women in Isfahan, Iran; however, its prevention is not desirable in this city. This disease poses several health, social and economic challenges for women. To promote women's self-care in breast cancer prevention, this study aims to design, implement and evaluate a self-care program among women in Isfahan through using a community-based participatory action research method. METHODS: The present study is based on a community-based participatory action research approach. In this study, the participatory action research includes four general phases of organizing, action planning, action, and rethinking. These phases are summarized as follows: In the organizing phase, the needs of the participants and the action research settings are examined. This means that the current situation is identified and the views of the process owners are assessed. In the action planning phase, using the results of the first phase, some strategies are designed to promote self-care behaviors in the prevention of breast cancer among women in Isfahan. In the implementation phase, the selected strategies are implemented with the help of the process owners. Finally, in the rethinking phase, the results of the implementation of the strategies are monitored and evaluated. This cycle continues until the intended results are achieved. DISCUSSION: Changing the role of individuals from a passive status to an aware and active status in the care process requires motivation, responsibility, and active participation of individuals in the disease control process. Moreover, many cultural and social factors affect the active participation of Iranian women. Therefore, individuals can be involved in promoting their health using a community-based participatory action research approach.

TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis.

CONTEXT: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. OBJECTIVE: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. METHODS: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. RESULTS: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. CONCLUSION: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

Nanoparticles for Coronavirus Control.

More than 2 years have passed since the SARS-CoV-2 outbreak began, and many challenges that existed at the beginning of this pandemic have been solved. Some countries have been able to overcome this global challenge by relying on vaccines against the virus, and vaccination has begun in many countries. Many of the proposed vaccines have nanoparticles as carriers, and there are different nano-based diagnostic approaches for rapid detection of the virus. In this review article, we briefly examine the biology of SARS-CoV-2, including the structure of the virus and what makes it pathogenic, as well as describe biotechnological methods of vaccine production, and types of the available and published nano-based ideas for overcoming the virus pandemic. Among these issues, various physical and chemical properties of nanoparticles are discussed to evaluate the optimal conditions for the production of the nano-mediated vaccines. At the end, challenges facing the international community and biotechnological answers for future viral attacks are reviewed.

The effectiveness of simulation training in obstetric emergencies: A meta-analysis.

Role of clinical skill training in the formation of skills and professional competencies of midwifery students is important. Hence, the use of "training new methods are essential in clinical settings." This study aimed at determining the effectiveness of simulation training in obstetric emergencies. In this meta-analysis study, international databases of Web of Science, Scopous, Proquest, and PubMed and Iranian databases such as Irandoc, Magiran, and SID were searched for studies published between 2000 and 2020 using related keywords. Based on the consortium checklist, the full text of the selected articles was reviewed and in case of a specific score, the article was analyzed. The results show that, out of 420 studies after applying the inclusion and exclusion criteria, only nine clinical trial articles were reviewed. Studies were conducted in Iran, the United States, France, China, and Chicago. The results of meta-analysis showed that the simulation training method can be effective in managing midwifery emergencies. Hence, the use of simulation training method can be effective in various areas of learning related to obstetric emergencies.

High glycosyltransferase 8 domain containing two protein levels contribute to poor prognosis in urothelial carcinoma.

OBJECTIVE: To examine the expression levels of the glycosyltransferase 8 domain containing protein 2 and its clinical implications in urothelial carcinoma patients. METHODS: Data mining, immunohistochemistry together with H-score calculation was carried out to evaluate the glycosyltransferase 8 domain containing protein 2 levels on tissue specimens from urothelial carcinoma patients, retrospectively. Correlations between glycosyltransferase 8 domain containing protein 2 H-score and imperative clinicopathological factors were measured. The indication of glycosyltransferase 8 domain containing protein 2 level on disease-specific and metastasis-free survivals were next analyzed. RESULTS: In upper tract urothelial carcinomas (n = 340) and bladder urothelial carcinomas (n = 295), 170 (50%) and 148 (50%) patients, respectively, were identified to have high glycosyltransferase 8 domain containing protein 2 expression. The glycosyltransferase 8 domain containing protein 2 levels were correlated to several clinicopathological characteristics and patient survival. Upregulation of the glycosyltransferase 8 domain containing protein 2 was correlated to primary tumor (P < 0.001), nodal metastasis (P < 0.001), histological grade (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.05) and mitotic rate (P < 0.001). High glycosyltransferase 8 domain containing protein 2 levels independently predicted poor disease-specific survival (P = 0.049) and metastasis-free survival (P = 0.008) in upper tract urothelial carcinoma and urinary bladder urothelial carcinoma, respectively. Gene Ontology enrichment analysis additionally showed that multiple biological processes were enriched including "ECM organization" (Gene Ontology:0030198), "extracellular structure organization" (Gene Ontology:0043062), "biological adhesion" (Gene Ontology:0022610), "cell adhesion" (Gene Ontology:0007155), "collagen fibril organization" (Gene Ontology:0030199) and "vasculature development" (Gene Ontology:0001944). CONCLUSIONS: The present findings suggest that upregulation of the glycosyltransferase 8 domain containing protein 2 is an independent and disadvantageous prognosticator in urothelial carcinoma. High glycosyltransferase 8 domain containing protein 2 level might play a crucial role in progression of urothelial carcinoma.

Reference Intervals for Thyroid Hormones During the First Trimester of Gestation: A Report from an Area with a Sufficient Iodine Level.

A concern was raised 1 regarding the number of pregnant women in the analysis of reference range for the thyroid hormones in pregnancy 2, where we reported 185 cases and it was believed to be 145 cases.

The Effect of Type of Delivery on the Nitric Oxide Metabolites and Endothelial Dysfunction in Pregnant Women.

BACKGROUND: Since endothelial dysfunction is related to atherosclerosis, this study was planned to determine the effect of type of delivery on Nitric Oxide (NO) metabolites and endothelial function. MATERIALS AND METHODS: This Cohort study was conducted in 2015 in selected hospitals of Isfahan. 88 nulliparous women with gestational age of 39 weeks and above were enrolled in this study using convenience sampling method and finally, after giving birth, 51 mothers with vaginal delivery, 21 with urgent C-section and 13 with elective C-section were considered for data analysis. The serum levels of NO metabolites were measured in the laboratory with standard kits and data was analyzed using student and paired t-test, one-way ANOVA, and Chi-square test. The significance level was considered less than 0.05 for all tests. RESULTS: The NO metabolites levels in mothers who had vaginal delivery or urgent C-section showed a significant difference before and after delivery (normal vaginal delivery (NVD): t50 = 5.61, p < 0.001, Urgent C-section: t23 = 5.38, p < 0.001). But those with elective C-section showed no significant difference in the nitrate and total nitrite levels before and after delivery (p > 0.05). CONCLUSIONS: Since reduction in serum levels of NO metabolites may possibly indicate endothelial dysfunction and predict cardiovascular disease, especially atherosclerosis in the future, it could be concluded that, childbirth, regardless of the type of delivery, could damage the endothelial cells but C-section (urgent or elective) could cause more disruption than vaginal delivery.

Thyroid volume and nodular and diffuse thyroid diseases by ultrasonography in pregnant women: A case-control study.

BACKGROUND: Currently, it is shown that pregnancy may have an impact on the thyroid that can be leading to pregnancy complications such as abortion, preeclampsia, and preterm delivery. The objective was to compare the thyroid volume, number and characteristics of thyroid nodules, and prevalence of diffuse thyroid diseases in a sample of Iranian pregnant women in the first trimester to nonpregnant women. MATERIALS AND METHODS: This case-control study was conducted on 298 pregnant and 290 nonpregnant women. Thyroid volume, maximum diameter of thyroid nodules and prevalence of moderate to highly suspicious thyroid nodules, Hashimoto's appearance and goiter were assessed using thyroid ultrasonography. Antithyroperoxidase (TPO) antibodies were measured if the sonographic features were highly suggested for Hashimoto's thyroiditis. RESULTS: The mean of total thyroid volume in pregnant and nonpregnant women was 6 and 6.5 ml, respectively (P = 0.053), and the median (interquartile range) was 6.2 and 5.5, respectively. Nodules were observed in 16.4% of pregnant and 16.6% of nonpregnant women (P = 0.845). Hashimoto's thyroiditis was detected in 6.7% of pregnant and 12.4% of nonpregnant women (P = 0.013). Anti-TPO antibodies were detected in 5% of pregnant and 9.3% of nonpregnant women (P = 0.034). CONCLUSION: The thyroid volume and nodule characteristics in the first trimester of pregnancy were similar to nonpregnant women. Hashimoto's thyroiditis and anti-TPO antibodies in pregnant women were significantly lower than in nonpregnant women.

Characterization of insulin cross-seeding: the underlying mechanism reveals seeding and denaturant-induced insulin fibrillation proceeds through structurally similar intermediates.

Insulin rapidly fibrillates in the presence of amyloid seeds from different sources. To address its cross-reactivity we chose the seeds of seven model proteins and peptides along with the seeds of insulin itself. Model candidates were selected/designed according to their size, amino acid sequence, and hydrophobicity. We found while some seeds provided catalytic ends for inducing the formation of non-native insulin conformers and increase fibrillation, others attenuated insulin fibrillation kinetics. We also observed competition between the intermediate insulin conformers which formed with urea and amyloid seeds in entering the fibrillogenic pathway. Simultaneous incubation of insulin with urea and amyloid seeds resulted in the formation of nearly similar insulin intermediate conformers which synergistically enhance insulin fibrillation kinetics. Given these results, it is highly likely that, structurally, there is a specific intermediate in different pathways of insulin fibrillation that governs fibrillation kinetics and morphology of the final mature fibril. Overall, this study provides a novel mechanistic insight into insulin fibrillation and gives new information on how seeds of different proteins are capable of altering insulin fibrillation kinetics and morphology. This report, for the first time, tries to answer an important question that why fibrillation of insulin is either accelerated or attenuated in the presence of amyloid fibril seeds from different sources.