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Steroidogenesis of gonadal cells is tightly regulated by gonadotropins. However, certain polycyclic aromatic hydrocarbons, including Benzo[a]pyrene (BaP), induce reproductive toxicity. Several existing studies have considered higher than environmentally relevant concentrations of BaP on male and female steroidogenesis following long-term exposure. Also, the impact of short-term exposure to BaP on gonadotropin-stimulated cells is understudied. Therefore, we evaluated the effect of 1 nM and 1 µM BaP on luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e. the mouse tumor Leydig cell line mLTC1, and the human primary granulosa lutein cells (hGLC) post 8- and 24-h exposure. Cell signalling studies were performed by homogeneous time-resolved fluorescence (HTRF) assay, bioluminescence energy transfer (BRET) and Western blotting, while immunostainings and immunoassays were used for intracellular protein expression and steroidogenesis analyses, respectively. BaP decreased cAMP production in gonadotropin-stimulated mLTC1 interfering with Gαs activation. Therefore, decrease in gonadotropin-mediated CREB phosphorylation in mLTC1 treated with 1 μM BaP was observed, while StAR protein levels in gonadotropin-stimulated mLTC1 cells were unaffected by BaP. Further, BaP decreased LH- and hCG-mediated progesterone production in mLTC1. Contrastingly, BaP failed to mediate any change in cAMP, genes and proteins of steroidogenic machinery and steroidogenesis of gonadotropin-treated hGLC. Our results indicate that short-term exposure to BaP significantly impairs steroidogenic signalling in mLTC1 interfering with Gαs. These findings could have a significant impact on our understanding of the mechanism of reproductive toxicity by endocrine disruptors., (© 2024. The Author(s).)

Bisphenol A (BPA) is a ubiquitous, synthetic chemical proven to induce reproductive disorders in both men and women. The available studies investigated the effects of BPA on male and female steroidogenesis following long-term exposure to the compound at relatively high environmental concentrations. However, the impact of short-term exposure to BPA on reproduction is poorly studied. We evaluated if 8 and 24 h exposure to 1 nM and 1 µM BPA perturbs luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e., the mouse tumour Leydig cell line mLTC1, and human primary granulosa lutein cells (hGLC). Cell signalling studies were performed using a homogeneous time-resolved fluorescence (HTRF) assay and Western blotting, while gene expression analysis was carried out using real-time PCR. Immunostainings and an immunoassay were used for intracellular protein expression and steroidogenesis analyses, respectively. The presence of BPA leads to no significant changes in gonadotropin-induced cAMP accumulation, alongside phosphorylation of downstream molecules, such as ERK1/2, CREB and p38 MAPK, in both the cell models. BPA did not impact STARD1 , CYP11A1 and CYP19A1 gene expression in hGLC, nor Stard1 and Cyp17a1 expression in mLTC1 treated with LH/hCG. Additionally, the StAR protein expression was unchanged upon exposure to BPA. Progesterone and oestradiol levels in the culture medium, measured by hGLC, as well as the testosterone and progesterone levels in the culture medium, measured by mLTC1, did not change in the presence of BPA combined with LH/hCG. These data suggest that short-term exposure to environmental concentrations of BPA does not compromise the LH/hCG-induced steroidogenic potential of either human granulosa or mouse Leydig cells.

Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma ofthe FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed. [ABSTRACT FROM AUTHOR]

We recently described a solid phase immunoradiometric assay (IRMA) for anti-thyroglobulin and anti-thyroid microsomal antibodies. In the present study a similar IRMA for gastric parietal cell antibodies (PCA) has been developed. Samples to be tested are incubated within wells of polyvinyl microtitre plates coated with solubilized gastric microsomal antigen. After removal of unbound material, PCA is detected by adding purified 125I-anti-human IgG antibody. A good correlation was found with the results of PCA assays obtained by indirect immunofluorescence. In contrast, negative PCA by IRMA were consistently obtained in sera containing high titres of several other organ specific and non-organ specific autoantibodies. PCA determinations by IRMA were than carried out in a series of normal controls and patients with autoimmune or non-autoimmune thyroid disorders. Positive results were obtained in three of 70 (4.3%) apparently normal subjects, in 16 of 87 (18.4%) patients with Hashimoto's thyroiditis, in 10 of 48 (20.8%) with idiopathic myxoedema. in 25 of 95 (25.6%) with Graves' disease and in five of 64 (7.8%) with other non-autoimmune thyroid disorders. Preliminary results showed that quantitative measurements of PCA by IRMA could be performed using a serum containing high levels of PCA as standard reference. In conclusion, PCA may be easily and specifically detected using the same IRMA procedure previously developed for anti-thyroid antibodies. We therefore suggest that the present IRMA may be proposed as a general technique for the detection of different organ specific autoantibodies. [ABSTRACT FROM AUTHOR]

Classified as endocrine disrupting chemicals (EDCs), perchlorate, nitrate, and thiocyanate have been implicated with obesity and reproductive disorders. This study used three cycles of the National Health and Nutrition Examination Survey (NHANES 2013–2018); 813 women of reproductive age were finally included. We used multivariable logistic regression to analyze the associations between the three anions and obesity and infertility. Subsequently, we performed mediation analysis to explore the potential mediating effect of obesity on infertility in association with anion exposure. Increased concentrations of perchlorate and nitrate showed inverse correlations with the risk of obesity (OR = 0.73, 95% CI: 0.55–0.96; OR = 0.59, 95% CI: 0.40–0.87). Perchlorate was negatively associated with infertility (OR = 0.68, 95% CI: 0.51–0.91), and obesity was a mediator in association between perchlorate and infertility. These findings suggest that women of reproductive age may be protected from obesity and infertility by exposure to perchlorate and nitrate, with obesity acting as a moderating factor in the observed association. This study provides a valuable understanding of the complex links between environmental contaminants, obesity, and reproductive health, and identifies potential strategies to reduce the risk of infertility and improve women's health. [ABSTRACT FROM AUTHOR]

Background: Few studies are reported on interventions that have been carried out in children and adolescents using diaphragmatic breathing (DB) together with methods like counseling, muscle relaxation, therapeutic exercise, and music therapy. Objective: The goal of the review is to evaluate the effectiveness of DB as complementary therapy in the stress of the pediatric population (6–18 years old). Methods: Detailed research was carried out in the current literature to find relevant studies published from 2010 to October 2024 in PubMed and Cochrane Library. Thirteen studies that fulfilled the inclusion criteria were included in the study. Nine studies involved obese and overweight pediatric populations and the other four involved pediatric patients. Results: The interventions comprised two 8-week studies in an obese pediatric population, seven studies in healthy children and adolescents with normal weight. The studies were based on DB, muscle relaxation, nutrition, counseling, music therapy, and slow breathing exercises. The participants in the intervention group improved in comparison to those in the control group in terms of stress and depression in most included studies, in terms of school performance in two studies, in terms of better family relationships in one study, and showed improvement in anthropometric indicators in two studies. In four studies that involved pediatric patients, stress and fear of medical procedures were reduced. Conclusions: DB can effectively contribute on its own or in combination with other therapeutic methods to improving physiological and psychological indicators in the pediatric population. It is useful to integrate stress management programs that include DB training as clinical practice in primary healthcare and in school schedules for elementary and high-school students. [ABSTRACT FROM AUTHOR]

Thyroid function plays a seminal role in the growth and development of children, and alterations in signaling pathways which interfere with the biosynthesis, transport, and metabolism of thyroid hormones might impact on the skin of such patients: this review explores the relationship between different thyroid disorders and dermatological manifestations with a particular focus on the pediatric population. Common cutaneous conditions associated with thyroid dysfunction may include chronic urticaria, vitiligo, and alopecia, which can be early harbingers of an underlying endocrine disruption. This review also highlights the growing cognizance of a "thyroid–skin axis", with thyroid hormones influencing many physiologic processes within the skin such as keratinocyte proliferation, hair growth, and epidermal differentiation. A precocious recognition of abnormal dermatological signs can be crucial in pediatric patients for a timely diagnosis before any development of complications and for personalized treatments of an underlying thyroid disorder, which can even be symptomless at an initial phase. Despite the lack of standardized guidelines for managing dermatologic manifestations occurring in thyroid diseases, a regular screening to identify endocrine dysfunction is recommended in those children who present chronic urticaria, vitiligo, or alopecia, though further research is needed to decipher mechanisms involved in the thyroid-skin partnership and develop more targeted management approaches. [ABSTRACT FROM AUTHOR]

Parallel measurements of circulating anti-thyroid microsomal (anti-M) antibodies by radioassay and haemagglutinatinn were performed on subjects with or without thyroid disorders. Three quarters (75.4%) of control subjects had undetectable antibody levels (< 10 u/ml) by radioassay and only 3.1% had concentrations of &ges; 75 u/ml. Abnormally elevated levels (&ges; 75 u/ml) were found in most of the patients with Hashimoto's thyroiditis (94.1%) or idiopathic myxoedema (86.7%), in the majority (75.0%) of those with Graves' disease and only in a minority of those with other thyroid disorders. The percentage of positive sera by haemagglutination was verisimilar in all groups to that of abnormal values observed in the radioassay. Direct comparison of parallel tests on a total of 631 sera revealed a highly significant correlation (r = 0.91, P < 0.001) between the two methods, but elevated antibody titres by haemaegglutination were found in some sera with negative radioassays. All these sera were from a single patient with thyroid carcinoma associated with Hashimoto's thyroiditis and had elevated levels of anti-thyroglobulin (anti-Tg) antibodies. Evidence that such discrepancies were due to anti-Tg antibodies reacting with microsomal-bound Tg was provided by the demonstration that the haemagglutination produced by these sera could be completely inhibited by the addition of Tg. A similar inhibition was observed with two rabbit antisera to human Tg, but not with sera from patients with thyroid autoimmune disorders containing high levels of anti-microsomal anti-bodies. [ABSTRACT FROM AUTHOR]

Objectives: To examine, by ultrasonography the prevalence of thyroid nodules in a cross sectional study of male medical workers occupationally exposed to chi radiation at the Pisa hospital, in comparison with controls matched for age and sex.Methods: 50 male medical workers exposed to radiation were randomly matched for age (+/- 2 years) with 100 male workers not occupationally exposed to ionising radiation who lived in a slightly iodine deficient area of Tuscany (Lunigiana) (control group 1), and with 100 male workers not exposed to radiation who lived in the same area (Pisa) (control group 2).Results: Of the occupationally exposed subjects, thyroid nodules were detected in 19/50 (38.0%). Among controls, thyroid nodules were detected in 19/100 subjects of control group 1 and in 13/100 of control group 2. Comparison of exposed and control groups, stratified into 30-39, 40-49, and 50-59 year old age subgroups, showed a higher significant relative risk for thyroid nodules in the exposed subjects.Conclusion: The results suggest that occupational exposure to radiation may be a risk factor for thyroid nodules. [ABSTRACT FROM AUTHOR]

(1) Background: Exploring the relationship between spontaneous breathing patterns and aerobic and anerobic running exercise performance can greatly improve our understanding of optimizing physical fitness. Spontaneous breathing patterns refer to how the rhythm and depth of breathing affect performance and physical adaptation during exercise. (2) Methods: This study aimed to investigate this relationship by enrolling 240 college students (120 males and 120 females, aged 18–22). We evaluated their resting respiratory rate (RR), the combined total of abdominal and thoracic movements (AM+TM), the proportion of abdominal movement to the overall respiratory movement (AM/(AM+TM)), and the inhalation to exhalation ratio (I/E ratio). Additionally, their performance in a 50 m sprint (measuring anerobic capability), an 800- or 1000 m run (assessing mixed aerobic and anerobic capacity), and a 12 min distance run (evaluating aerobic capacity) was recorded. (3) Results: Our findings, through both correlational and comparative analyses, indicate that a larger AM+TM is predictive of a greater distance covered in the 12 min run, suggesting enhanced aerobic capacity. Interestingly, among female participants, a lower body mass index (BMI) coupled with a higher proportion of abdominal movement (AM/(AM+TM)) was linked to better performance in the 800 m run, indicative of superior mixed aerobic and anerobic capacities. These results imply that women with a larger tidal volume and those with a lower BMI but higher abdominal contribution to breathing at rest may exhibit better aerobic and mixed exercise capacities, respectively. (4) Conclusions: Based on these findings, we recommend that healthcare professionals and physical education instructors incorporate respiratory pattern assessments into their practices to potentially improve the physical health of their clients and students, with a particular emphasis on female populations. This study underscores the importance of understanding the intricate relationship between spontaneous respiratory patterns and exercise capabilities in enhancing overall physical fitness and health. [ABSTRACT FROM AUTHOR]

The lungs of 50 symptom free workers exposed to amosite and with normal pulmonary function tests were examined by high resolution computed tomography (HRCT). Twenty five had normal standard chest radiographs whereas the other 25 had radiographs interpreted as near normal (International Labour Office profusion score < 0/1 or suspected pleural plaques). In 13 of the workers the results of HRCT were negative; in 22 pleural plaques were found, in five there was only parenchymal involvement, and 10 had both pleural and parenchymal changes. The mean duration of exposure to amosite was significantly longer for the subjects with parenchymal signs than for those with normal parenchyma and for the workers with pleural plaques than for those with normal pleura and lung parenchyma. The prevalence of identified pleural and parenchymal abnormalities in the 50 workers was also significantly higher than in a reference group without exposure to asbestos. It is concluded that HRCT may detect initial lung and pleural involvement in symptom free workers exposed to amosite and the mean duration of exposure is longer for subjects with parenchymal or pleural involvement.

Inositols have demonstrated a role in cancer prevention and treatment in many kinds of neoplasms. Their molecular mechanisms vary from the regulation of survival and proliferative pathways to the modulation of immunity and oxidative stress. The dysregulation of many pathways and mechanisms regulated by inositols has been demonstrated in endocrine and neuroendocrine tumors but the role of inositol supplementation in this context has not been clarified. The aim of this review is to summarize the molecular basis of the possible role of inositols in endocrine and neuroendocrine tumors, proposing it as an adjuvant therapy. [ABSTRACT FROM AUTHOR]

(1) Background: Subclinical hypothyroidism (SHT) is a condition that has been a subject of controversy in the literature due to its association with psychological and psychiatric symptoms as well as autonomic imbalances. To gain a better understanding of the effects of SHT on patients, a research study has been undertaken to investigate the presence of psychological symptoms and autonomic imbalances in a group of individuals diagnosed with SHT. (2) Methods: In this case–control study, 50 patients diagnosed with SHT who accessed the Department of Endocrinology of the University of Pisa were consecutively recruited. Psychological symptoms were measured through the Crown–Crisp Experiential Index (CCEI), whereas autonomic imbalance was described using the Psychophysiological Stress Profile (PSP), with simultaneous recording of the following psychophysiological parameters: Surface Electromyogram (sEMG), Skin Conductance Level (SCL), heart rate (HR), and peripheral temperature (PT). The patients' values were compared to those of 50 healthy control subjects. (3) Results: The comparison between groups highlighted significant differences in the CCEI and PSP. In particular, patients reported higher rates of psychological symptoms (anxiety, depression, somatic complaints, and hysteria behavior). Significantly higher levels of autonomic arousal were also recorded. More specifically, the sEMG, SCL, HR, and PT values were different between the two groups. (4) Conclusions: The study has confirmed the presence of autonomic hyperarousal in patients diagnosed with subclinical hypothyroidism. This is likely due to the body's attempt to compensate for a general lack of energy by accelerating the autonomic activity. The findings also underline the significance of a comprehensive assessment approach that takes into account various dimensions such as psychological and psychophysical well-being. Such an approach helps in evaluating the impact of subclinical diseases on overall health and well-being. [ABSTRACT FROM AUTHOR]

(1) Background: After thyroid malignancy is ruled out, treatment options for multinodular goiter patients include surgery, levothyroxine suppressive therapy, and 131-I therapy. Surgery effectively reduces goiter size but carries risks of surgical and anesthetic complications. 131-I therapy is the only nonsurgical alternative, but its effectiveness diminishes with goiter size and depends on iodine sufficiency. This study aimed to assess the efficacy and safety of 0.1 mg rhTSH as an adjuvant to a fixed dose of 131-I therapy in patients with a recurrence of large multinodular goiter, several years after the initial thyroidectomy. (2) Methods: 14 patients (13 females and 1 male), aged 59.14 ± 15.44 (range, 35–78 years) received 11mciu of 131-I, 24 h after the administration of 0.1 mg rhTSH. The primary endpoint was the change in thyroid volume (by ultrasound measurements) as well as in the diameter of the predominant nodule during a follow-up period of 10 years. Secondary endpoints were the alterations in thyroid function and potential adverse effects. (3) Results: A significant decrease in the volume of initial thyroid remnants (32.16 ± 16.66 mL) was observed from the first reevaluation (at 4 months, 23.12 ± 11.59 mL) as well as at the end of the follow-up period (10 years, 12.62 ± 8.76 mL), p < 0.01. A significant reduction in the dominant nodule was also observed (from 31.71 ± 10.46 mm in the beginning to 26.67 ± 11.05 mm). (4) Conclusions: Further investigation is needed since this approach could be attractive in terms of minimizing the potential risks of reoperation in these patients. [ABSTRACT FROM AUTHOR]

The organs of the male reproductive tract, including the testis, epididymis, prostate, seminal vesicles, and semen, must provide an immunoregulatory environment conducive to germ cell viability and successful fertilization. Many immune components, such as immune cells, have been investigated regarding reproductive immunology and function; however, the investigation of the role of complement in this system has only more recently been gaining traction in research. This review focuses on complement in the male reproductive tract, with the goal of compiling information currently known about complement components detected in male reproductive organs and identifying areas in need of further research. Considering the recent and upcoming research about the noncanonical functions of complement, this information is relevant and applicable in the fields of reproductive immunology, fertility, and immune regulation. [ABSTRACT FROM AUTHOR]

Autoimmune polyglandular syndromes (APS) are classified into four main categories, APS1–APS4. APS1 is caused by AIRE gene loss of function mutations, while the genetic background of the other APS remains to be clarified. Here, we investigated the potential association between AIRE gene promoter Single Nucleotide Polymorphisms (SNPs) and susceptibility to APS. We sequenced the AIRE gene promoter of 74 APS patients, also analyzing their clinical and autoantibody profile, and we further conducted molecular modeling studies on the identified SNPs. Overall, we found 6 SNPs (-230Y, -655R, -261M, -380S, -191M, -402S) of the AIRE promoter in patients' DNA. Interestingly, folding free energy calculations highlighted that all identified SNPs, except for -261M, modify the stability of the nucleic acid structure. A rather similar percentage of APS3 and APS4 patients had polymorphisms in the AIRE promoter. Conversely, there was no association between APS2 and AIRE promoter polymorphisms. Further AIRE promoter SNPs were found in 4 out of 5 patients with APS1 clinical diagnosis that did not harbor AIRE loss of function mutations. We hypothesize that AIRE promoter polymorphisms could contribute to APS predisposition, although this should be validated through genetic screening in larger patient cohorts and in vitro and in vivo functional studies. [ABSTRACT FROM AUTHOR]

Herbal extraction residues (HERs) cause serious environmental pollution and resource waste. In this study, a novel green route was designed for the comprehensive reutilization of all components in HERs, taking Magnolia officinalis residues (MOR) as an example. The reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients (magnolol and honokiol) originally remaining in MOR and to make MOR more accessible for hydrolysis. A metal--organic frame material MIL-101(Cr) with a maximum absorption capacity of 255.64 mg g-1 was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions, and 40 g L-1 reducing sugars were obtained with 81.8% enzymatic hydrolysis rate at 10% MOR solid loading. Finally, 382 mg L-1 β-amyrin was produced from MOR hydrolysates by an engineered yeast strain. In total, 1 kg honokiol, 8 kg magnolol, and 7.64 kg b-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB. [ABSTRACT FROM AUTHOR]

Serum myoglobin (Mb) concentrations have been measured by radioimmunoassay in normal subjects, in hypothyroid patients examined 20 days after withdrawal of thyroid hormone therapy ("short-term" hypothyroidism), and in untreated hypothyroids ("long-term" hypothyroidism). In "short-term" hypothyroids, serum Mb levels were significantly higher (p less than 0.01) than those observed in normal controls, although only a minority or patients showed elevated Mb levels. In "long-term" hypothyroids, serum Mb concentrations were significantly higher than that found in normal controls (p less than 0.0001) and in "short-term" hypothyroids (p less than 0.001). In "long-term" hypothyroidism a significant inverse correlation was found between serum thyroid hormones and Mb, whereas no similar correlation was observed in "short-term" hypothyroidism. The administration of progressively increasing doses of L-T4 untreated hypothyroids was followed by normalization of serum Mb, but serum TSH levels still remained elevated. These data indicate that the duration and the severity of hypothyroidism are important factors in the rise of serum Mb, and that the normalization of serum Mb is faster than that of serum TSH and requires less L-T4 than that needed for normal TSH secretion.

We recently described a solid phase immunoradiometric assay (IRMA) for anti-thyroglobulin and anti-thyroid microsomal antibodies. In the present study a similar IRMA for gastric parietal cell antibodies (PCA) has been developed. Samples to be tested are incubated within wells of polyvinyl microtitre plates coated with solubilized gastric microsomal antigen. After removal of unbound material, PCA is detected by adding purified 125I-anti-human IgG antibody. A good correlation was found with the results of PCA assays obtained by indirect immunofluorescence. In contrast, negative PCA by IRMA were consistently obtained in sera containing high titres of several other organ specific and non-organ specific autoantibodies. PCA determinations by IRMA were than carried out in a series of normal controls and patients with autoimmune or non-autoimmune thyroid disorders. Positive results were obtained in three of 70 (4.3%) apparently normal subjects, in 16 of 87 (18.4%) patients with Hashimoto's thyroiditis, in 10 of 48 (20.8%) with idiopathic myxoedema, in 25 of 95 (25.6%) with Graves' disease and in five of 64 (7.8%) with other non-autoimmune thyroid disorders. Preliminary results showed that quantitative measurements of PCA by IRMA could be performed using a serum containing high levels of PCA as standard reference. In conclusion, PCA may be easily and specifically detected using the same IRMA procedure previously developed for anti-thyroid antibodies. We therefore suggest that the present IRMA may be proposed as a general technique for the detection of different organ specific autoantibodies.

Amiodarone associated thyrotoxicosis (AAT) occurs in approximately 10% of patients treated with this iodine rich drug in areas of mild iodine deficiency. The thyroid radioactive iodine uptake (RAIU) is usually undetectable or very low in iodine-induced thyrotoxicosis. In the present study, 35 patients with AAT were evaluated. Twelve patients had no thyroid abnormalities by physical exam and all had 24-hr RAIU less than or equal to 4%. In contrast, nine of 11 patients with AAT and diffuse goiters and eight of 12 patients with AAT and nodular goiters had RAIU values greater than 8%. In patients with AAT and goiter it appears possible that the thyroid fails to adapt normally to the excess iodide load, resulting in an inappropriately high RAIU in the presence of excess plasma iodine.

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Backgrounds: The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking. We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs. Methods: To identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase, Cochrane Library, CBM, CNKI, Wan-Fang and ICTRP databases. The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies. The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS), the improvement of proptosis and diplopia improvement, and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses. Results: A total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab). TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX. TCZ was the highest probability of safety, followed by RTX and TMB. Conclusions: Based on the best available evidence, TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials, indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition, the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established, and it is encouraging that the treatment paradigm for GO may change in the future. This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA) (27). [ABSTRACT FROM AUTHOR]

Baseline biodiversity data are key for ecological and evolutionary studies and are especially relevant for areas such as the Maldivian Archipelago in the Indian Ocean, which can act as a stepping-stone for the transport of widely distributed marine species. We surveyed the islands and reefs of the Faafu and Malé Atolls with snorkeling and scuba diving, collecting the two gastropod subclasses, Heterobranchia and Vetigastropoda. Our inventory comprises 104 species photographed alive to create an identification guide. We also provide COI barcodes for most species, adding novel sequence data for the Maldivian malacofauna. Half of our species represent new records for the Maldives, emphasizing how much diversity remains to be discovered. Species distributions reflect ecological rarity, with almost 60% of taxa only found in one site. We also compiled a comprehensive checklist of heterobranchs and vetigastropods of the Maldives based on literature records, resulting in 320 species, which, together with barcoding data, indicate several potential cryptic species in the Indo-Pacific. Six new species are described, the nudibranchs Limenandra evanescenti n. sp., Eubranchus putnami n. sp., Sakuraeolis marhe n. sp., Moridilla maldivensis n. sp., Tergiposacca perspicua n. sp., and the sacoglossan Costasiella fridae n. sp. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid cancer (ATC) is a rare and rapidly fatal human cancer. Its usual treatment includes the combination of surgery, external hyperfractionated radiation therapy, and chemotherapy. These treatments permit achieving about 6–10 months of median survival. For this reason, it is challenging to predict the ATC patient clinical therapy responsiveness. Pazopanib is a multitarget tyrosine kinase inhibitor of VEGF receptors, PDGF, and c-Kit. Until now, the effect of pazopanib in primary human ATC cells (pATC) has not been reported in the literature. The aim of our study was to evaluate in vitro the antineoplastic effect of pazopanib in pATC. Surgical thyroidal tissues were collected from five patients with ATC, from thyroid biopsy at the moment of first surgical operation. An inhibition of proliferation, migration, and invasion, and an increase in apoptosis were demonstrated upon treating pATC cells with pazopanib (p < 0.05). Moreover, pazopanib was able to significantly decrease the VEGF expression in pATC cells (p < 0.05). To conclude, in this study, we demonstrate the antineoplastic activity of the antiangiogenic inhibitor, pazopanib, in human pATC in vitro. [ABSTRACT FROM AUTHOR]

Chitons (Polyplacophora) are marine molluscs that mostly inhabit rocky intertidal shores. Their biological and phylogenetic studies are comparatively sparse in the western Indo-Pacific regions. In addition, chitons belonging to the subfamily Acanthopleurinae Dall, 1889, collected from the Andaman Sea of the northeastern Indian Ocean and the Jizan coast of Saudi Arabia were sequenced and analyzed to study the phylogenetic affinities. The analysis was carried out using a single locus dataset (cytochrome oxidase 1) generated during the present study and integrated with sequences retrieved from GenBank. Acanthopleura gemmata (Blainville, 1825) from India was linked to Acanthopleura vaillantii Rochebrune, 1882, from the Saudi Arabia coast. Squamopleura miles (Carpenter in Pilsbry, 1893) from the Indian coast forms a separate clade representing the genus. Furthermore, the results illustrate several significant instances of misplacement of several species under the wrong genus and the existence of cryptic species within the genera Acanthopleura and Squamopleura. An integrated approach is required to better understand these important intertidal groups' taxonomy, systematics, and biogeography. [ABSTRACT FROM AUTHOR]

A new 2-(5,9-dioxa-13b-boranaphtho[3,2,1-de]anthracene-8-yl)-4-(trimethylsilyl)pyridine-based iridium complex was synthesized for efficient solution-processed sky-blue phosphorescent organic light-emitting diodes (PhOLEDs). The effect of dioxaboranaphthoanthracene instead of phenyl with the electron-accepting group, as well as the bulky pyridine with the trimethylsilyl group, on the ligand was investigated. The new dopant was found to have an extremely high photoluminescence quantum yield of 94% when doped in an emissive layer. As a result, the solution-processed blue PhOLED consisting of a simple structure without any interlayer exhibited remarkable light-emitting performance with an external quantum efficiency of 8.93% and a current efficiency of 23.56 cd/A. [ABSTRACT FROM AUTHOR]

Background: Thyroid-associated ophthalmopathy (TAO) is a common orbital inflammatory disease, but the abnormal expression of proteins in tears of TAO patients has not been systematically studied. The purpose of this study is to compare and analyze the total tear protein profile of TAO patients and to provide protein cues for TAO pathogenesis. Methods: Tear samples were isolated from 30 TAO patients with obvious ocular surface damage and 30 healthy control subjects. Tear samples from 30 individuals were mixed and divided into three sample pools. Easy nano-scale LC-MS/MS based on labeling-free quantitative technology was utilized to profile tear proteome. Results: Here, electrospray ionization mass spectra and SDS-PAGE results confirmed the good parallelisms among samples. A total of 313 proteins were obtained from six tear pools, among them, 103 differential abundance proteins (DAPs) were identified, including 99 up-regulated DAPs (including APOA1, HV103, IGH, and Transferrin variant) and four down-regulated DAPs (including FABA, VCC1, NUCB2, and E-cadherin) in the TAO group compared with the control group. GO analysis showed that up-regulated DAPs were mainly enriched in lipid metabolism and platelet molecular function, and down-regulated DAPs were involved in binding, cell junction, and cellular process. KEGG results indicated that DAPs were involved in 117 kinds of signal transduction pathways, among which the immune-related pathway of complement and coagulation cascades had the greatest relevance. Methods: Tear samples were isolated from 30 TAO patients with obvious ocular surface damage and 30 healthy control subjects. Tear samples from 30 individuals were mixed and divided into three sample pools. Easy nano-scale LC-MS/MS based on labeling-free quantitative technology was utilized to profile tear proteome. Results: Here, electrospray ionization mass spectra and SDS-PAGE results confirmed the good parallelisms among samples. A total of 313 proteins were obtained from six tear pools, among them, 103 differential abundance proteins (DAPs) were identified, including 99 up-regulated DAPs (including APOA1, HV103, IGH, and Transferrin variant) and four down-regulated DAPs (including FABA, VCC1, NUCB2, and E-cadherin) in the TAO group compared with the control group. GO analysis showed that up-regulated DAPs were mainly enriched in lipid metabolism and platelet molecular function, and down-regulated DAPs were involved in binding, cell junction, and cellular process. KEGG results indicated that DAPs were involved in 117 kinds of signal transduction pathways, among which the immune-related pathway of complement and coagulation cascades had the greatest relevance. [ABSTRACT FROM AUTHOR]

Myoinositol (Myo) is an isoform of inositol, a cyclic polyol with 6 hydroxyl groups. Myo is mainly derived from dietary intake while its endogenous production is generated from glucose by enzymatic reactions. Moreover, Myo is also synthesized de novo by catabolism of phosphatidylinositol (PI), phosphoinositides (PIP), and inositol phosphates (IP). Myo has a determinant role in thyroid function and autoimmune diseases as it regulates iodine organification and thyroid hormone biosynthesis by the formation of hydrogen peroxide (H2O2) in thyrocytes. Depletion of Myo that is involved in the thyroid stimulating hormone (TSH) signaling pathway, may cause the development of thyroid diseases such as hypothyroidism. TSH levels significantly decreased in patients with subclinical hypothyroidism, with or without autoimmune thyroiditis, after treatment with Myo plus Selenium (Myo+Se). In addition to TSH, antithyroid autoantibodies are reduced. This review summarizes the role of Myo in the thyroidal physiology and its role in the management of some thyroid diseases. [ABSTRACT FROM AUTHOR]

This article describes a novel experimental study considering a multiband fibre–wireless system for constructing the transport network for fifth-generation (5G) networks. This study describes the development and testing of a 5G new radio (NR) multi-input multi-output (MIMO) hybrid fibre–wireless (FiWi) system for enhanced mobile broadband (eMBB) using digital pre-distortion (DPD). Analog radio over fibre (A-RoF) technology was used to create the optical fronthaul (OFH) that includes a 3 GHz supercell in a long-range scenario as well as a femtocell scenario using the 20 GHz band. As a proof of concept, a Mach Zehnder modulator with two independent radio frequency waveforms modifies a 1310 nm optical carrier using a distributed feedback laser across 10 km of conventional standard single-mode fibre. It may be inferred that a hybrid FiWi-based MIMO-enabled 5G NR system based on OFH could be a strong competitor for future mobile haul applications. Moreover, a convolutional neural network (CNN)-based DPD is used to improve the performance of the link. The error vector magnitude (EVM) performance for 5G NR bands is predicted to fulfil the Third Generation Partnership Project's (3GPP) Release 17 standards. [ABSTRACT FROM AUTHOR]

Thyroid hormones play an essential role in brain functioning not only during development, but also in adult life. A link between visuospatial abilities and thyroid hormones has already been established. However, it is unclear whether this link is related to the changes in visual information processing, whether the ventral or the dorsal streams are more affected, or the interaction of the two pathways is impaired. The present study aimed to evaluate the effect of hypothyroidism on the visuospatial abilities related to the ventral and dorsal visual pathways using behavioral tasks. Twenty-six newly diagnosed hypothyroid patients and 26 euthyroid controls took part in the study. They had to determine whether the virtual center of radial Glass patterns (GPs) was shifted to the left or right of the screen center, or to discriminate between radial and concentric GPs with varying coherence. Three different conditions were applied: static and two dynamic flicker conditions with a limited lifetime of the dot pairs. The results show that the coherence thresholds were higher in the static condition and the center location task for both groups. The hypothyroid group had higher thresholds in discriminating the radial from the concentric patterns in the dynamic flicker conditions. The proportion of correct responses was lower in the hypothyroid group for patterns with the centers shifted to the right and for concentric compared to the radial patterns. The control group showed decreased performance in localizing the pattern centers shifted to the left. The findings imply that hypothyroidism leads to subtle changes in integrating spatiotemporal information that might be related to deficient processing in the ventral system and the reallocation of spatial attention under cognitive load. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common (~90%) type of endocrine-system tumor, accounting for 70% of the deaths from endocrine cancers. In the last years, the high-throughput genomics has been able to identify pathways/molecular targets involved in survival and tumor progression. Targeted therapy and immunotherapy individually have many limitations. Regarding the first one, although it greatly reduces the size of the cancer, clinical responses are generally transient and often lead to cancer relapse after initial treatment. For the second one, although it induces longer-lasting responses in cancer patients than targeted therapy, its response rate is lower. The individual limitations of these two different types of therapies can be overcome by combining them. Here, we discuss MAPK pathway inhibitors, i.e., BRAF and MEK inhibitors, combined with checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4. Several mutations make tumors resistant to treatments. Therefore, more studies are needed to investigate the patient's individual tumor mutation burden in order to overcome the problem of resistance to therapy and to develop new combination therapies. [ABSTRACT FROM AUTHOR]

Background: The biological behavior of thyroid cancer in children has been known to be different from that in adults. We sought to understand the differences between DTC presentation in pediatric (<16 years) and adult patients, to guide better prognosis and clinical treatments. Methods: This retrospective study included 48 pediatric patients younger than 16 years who underwent initial thyroid surgery and were diagnosed with DTC between January 1992 and December 2014 at Yonsei University in Seoul, South Korea. For a 1:4 propensity score-matched analysis, adult patients with matched sex and cancer size were included. Results: The mean age was 12.54 ± 3.01 years. Total thyroidectomy (70.8%) without lateral lymph node dissection (47.9%) was the most commonly performed surgery. Central (73.9%) and lateral neck node metastases (62.5%) were common; distant metastasis was observed in 2 (4.2%) patients and recurrence occurred in 11 (22.9%). In propensity score-matched analysis, central lymph node metastasis and lateral neck node metastasis were significantly more frequent in pediatric patients. Symptoms were more common in the pediatric group than in the adult group (p < 0.001). In stratified cox regression, pediatric patients were more likely to experience recurrence [HR 5.339 (1.239–23.007)]. In stratified log-rank analysis, recurrence-free survival was significantly different between the adult and pediatric groups (p = 0.0209). Conclusion: DTC in the pediatric group revealed more aggressive patterns than in the adult group with the same cancer size. Central lymph node metastasis and lateral neck node metastasis were more frequent. Stratified log-rank analysis revealed that recurrence was significantly higher in pediatric patients than in matched adult patients. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) is often complicated with some other autoimmune disorders. The complication of various autoimmune disorders is known as autoimmune polyglandular syndrome (APS). Once autoimmune thyroid disease develops, various autoimmune diseases can also occur. Such phenomena are classified as APS types 3A to 3D. In this report, we show the onset of T1DM in a patient with ulcerative colitis (UC) and Sjogren's syndrome. The most important and interesting point in this case is that, if we did not check her thyroid-associated antibodies, we could not have diagnosed her as APS. From the data of this case, we assumed that the patient suffered from APS type 3A, 3B, and 3D variants. This case pointed out very clearly the importance of testing for thyroid-associated antibodies under various autoimmune disease conditions even if the thyroid hormone levels are euthyroid. Moreover, based on the strong linkage between inflammatory bowel disease and T1DM and the compatibility with both T1DM and APS type 3, we think it is possible that Hashimoto's disease is present under complicated conditions together with UC and T1DM. It would be important to repeatedly check for thyroid-associated antibodies even in euthyroid patients, especially under various autoimmune disease conditions. [ABSTRACT FROM AUTHOR]

This study describes an experimental realization using digital predistortion (DPD) for a fifth generation (5G) multiband new radio (NR) optical front haul (OFH) based Radio over Fiber (RoF) link. For the performance enhancement and complexity reduction of RoF links, a novel Convolutional Neural Network (CNN) based DPD technique is proposed, followed by comparisons with the generalised memory polynomial (GMP) based DPD method. To support enhanced mobile broad band scenario, the experimental testbed uses the 5G NR waveforms at 10 GHz with 20 MHz bandwidth and a flexible-waveform signal at 3 GHz with 20 MHz bandwidth. For 10 km of typical single mode fiber, a Mach Zehnder Modulator with two distinct radio frequency waveforms modulates a 1310 nm optical carrier utilizing distributed feedback laser. The error vector magnitude and number of estimated coefficients, and multiplications are all used to describe the experimental outcomes. The goal of the research is to see if CNN-based DPD improves performance while lowering complexity levels to meet 3GPP Release 17 criteria. [ABSTRACT FROM AUTHOR]

Autoimmune polyglandular syndromes (APS) are rare disorders characterized by auto‐destruction of endocrine and non‐endocrine organs by organ‐specific antibody‐directed T‐lymphocytic infiltration. This case highlights a 29‐year‐old Caucasian man with vitiligo found to have significant neurological abnormalities in the setting of newly diagnosed pernicious anemia and thyroid autoimmune disease. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITD) are T-cell-mediated organ specific autoimmune disorders, deriving from an altered response of the immune system that leads to the immune attack to the thyroid. Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the two principal AITD clinical presentations. Hypothyroidism and thyrotoxicosis are, respectively, the clinical hallmarks of HT and GD. Patients with autoimmune thyroiditis are treated daily with synthetic L-thyroxine (L-T4) at the dose of 1.5–1.7 μg/kg. Various L-T4 formulations are commercially available (tablet, liquid solution, or soft gel capsule). L-T4 in tablets is generally prescribed to treat hypothyroidism, whereas the liquid formulation, or soft gel capsules, can be administered in hypothyroid patients in case of malabsorption or in patients in therapy with drugs interfering with L-T4 absorption. Furthermore, myoinositol has a crucial role in thyroid autoimmunity and function. Clinical studies reported a significant decline in TSH and antithyroid autoantibodies levels after treatment with myoinositol + selenium in patients with subclinical hypothyroidism and autoimmune thyroiditis. Moreover, thyroidectomy can be rarely recommended in patients with autoimmune thyroiditis, with cosmetic reasons for a goiter, or with important signs or symptoms of local compression, or nodular disease with a "suspicious" cytology for malignancy. Furthermore, a recent randomized trial suggested that total thyroidectomy can improve quality of life and fatigue, while medical therapy did not. In this review, we overview currently available evidence in personalized medicine in patients with autoimmune thyroiditis and hypothyroidism. Further research is needed in larger population to investigate the effect of these new treatments on quality of life. [ABSTRACT FROM AUTHOR]

Graves' disease (GD) is a condition caused by an autoimmune process involving the thyroid gland, whose main outcome is hyperthyroidism. TSAb start the autoimmune process stimulating the overproduction of thyroid hormones. In addition, TSAb can stimulate TSH-R expressed in fibroblasts and orbital pre-adipocytes leading to the manifestation of Graves' ophtalmopathy (GO). Also, autoantibodies directed against IGF-1R have an important role in immune-pathogenesis of GO. Fundamental is the role played by cytokines (IFN-γ, TNF-α, Il-6), and Th1 chemokines in the immune-pathogenesis of both disorders, particularly in the active phase. Novel discoveries in the field led to the investigation of promising therapies, such as immune-therapies towards specific antigens (for example against TSH-R), aiming in restoring the immune tolerance versus the immune dominant epitopes associated with autoimmunity in GD. Moreover, Etanercept (that blocks the TNF-mediated inflammatory responses), TCZ (that acts against the IL-6 receptor), and RTX (that acts against CD20) have proven to be useful and safe therapeutic options in refractory GO treatment. Furthermore, teprotumumab (a human monoclonal anti-IGF-1R blocking antibody), have been revealed effective in the treatment of patients with moderate-severe GO and it is now approved for GO therapy in United States. Molecules able to act as antagonists of CXCR3, or to block CXCL10, are also under study. More extensive researches are needed to deepen out these drugs as well as to identify new targeted and effective therapies, that will permit a more precise identification of GD, or GO, patients able to respond to specific targeted therapies. [ABSTRACT FROM AUTHOR]