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  • 1
    Online Resource
    Online Resource
    The Effect of Thyrotropin-Releasing Hormone and Antithyroid Drugs on Fetal Thyroid Function
    MDPI AG ; 2021
    In:  Children Vol. 8, No. 6 ( 2021-05-28), p. 454-
    Details
    In: Children, MDPI AG, Vol. 8, No. 6 ( 2021-05-28), p. 454-
    Abstract: A euthyroid pregnant woman will normally have a fetus that displays normal fetal development. However, studies have long demonstrated the role of T3 (Triiodothyronine), T4 (Thyroxine), and TSH (Thyroid Stimulating Hormone) and their degree of penetrability into the fetal circulation. Maternal thyrotropin-releasing hormone (TRH) crosses the placental site and, from mid-gestation onward, is able to promote fetal TSH secretion. Its origin is not only hypothalamic, as was believed until recently. The maternal pancreas, and other extraneural and extrahypothalamic organs, can produce TRH variants, which are transported through the placenta affecting, to a degree, fetal thyroid function. Antithyroid drugs (ATDs) also cross the placenta and, because of their therapeutic actions, can affect fetal thyroid development, leading in some cases to adverse outcomes. Furthermore, there are a number of TRH analogues that share the same properties as the endogenous hormone. Thus, in this narrative review, we highlight the interaction of all the above with fetal growth in uncomplicated pregnancies.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    URL: Article
    DOI: 10.3390/children8060454
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2732685-8
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  • 2
    Online Resource
    Online Resource
    A Novel Variant in the TP53 Gene Causing Li–Fraumeni Syndrome
    MDPI AG ; 2023
    In:  Children Vol. 10, No. 7 ( 2023-06-30), p. 1150-
    Details
    In: Children, MDPI AG, Vol. 10, No. 7 ( 2023-06-30), p. 1150-
    Abstract: Li–Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline pathogenic variants in the tumor protein p53 (TP53) gene and elevated risk of a broad range of early-onset malignancies. Patients with LFS are at risk of a second and third primary tumor. A 15-month-old girl consulted for clitoromegaly and pubic hair. Adrenal ultrasound detected a large left adrenal tumor. Left total adrenalectomy confirmed adrenocortical carcinoma. Family history revealed multiple highly malignant neoplasms at an early age across five generations, and a genetic dominant trait seemed probable. Whole-genome sequencing was performed. Multiple members of the family were found positive for a novel likely pathogenic variant (c. 892delGinsTTT, p. Glu298PhefsX48, NM_000546.6) in the TP53 gene, causing the loss of normal protein function through non-sense-mediated mRNA decay. According to the PSV1 supporting criteria and the Auto PVS1 online tool this frameshift variant: hg19/17-7577045-TC-TAAA:NM_000546.6 has a very strong, definitive clinical validity for LFS with autosomal dominant inheritance. Proper guidance resulted in timely diagnosis of a second tumor (primary osteosarcoma) in the index case and in the early detection of breast and cervical cancer in her young mother. Patients with cancer predisposition syndromes like LFS require close multidisciplinary cancer surveillance and appropriate referral to expert centers.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    URL: Article
    DOI: 10.3390/children10071150
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2732685-8
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  • 3
    Online Resource
    Online Resource
    TGF-β Physiology as a Novel Therapeutic Target Regarding Autoimmune Thyroid Diseases: Where Do We Stand and What to Expect
    MDPI AG ; 2021
    In:  Medicina Vol. 57, No. 6 ( 2021-06-14), p. 621-
    Details
    In: Medicina, MDPI AG, Vol. 57, No. 6 ( 2021-06-14), p. 621-
    Abstract: Transforming growth factor beta (TGF-β), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases. Based on the close interplay between thyroid autoimmunity and TGF-β, scientific interest was shifted to the understanding of the possible role of this molecule regarding the diagnosis, prognosis, and therapy of these diseases. The main aim of this review is to present research data about possible treatment options based on the role of TGF-β in thyroid autoimmunity. Suggested TGF-β-mediated therapeutic strategies regarding autoimmune thyroid diseases include either the enhancement of its immunosuppressive role or inhibition of its facilitatory role in thyroid autoimmunity. For example, the application of hr-TGF-β can be used to bolster the inhibitory role of TGF-β regarding the development of thyroid diseases, whereas anti-TGF-β antibodies and similar molecules could impede its immune-promoting effects by blocking different levels of TGF-β biosynthesis and activation pathways. In conclusion, TGF-β could evolve to a promising, novel therapeutic tool for thyroid autoimmunity.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    URL: Article
    DOI: 10.3390/medicina57060621
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2088820-X
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  • 4
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    Online Resource
    The Effect of Dietary Supplements on Oxidative Stress in Pregnant Women with Gestational Diabetes Mellitus: A Network Meta-Analysis
    MDPI AG ; 2021
    In:  Nutrients Vol. 13, No. 7 ( 2021-06-30), p. 2284-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 7 ( 2021-06-30), p. 2284-
    Abstract: Background: Gestational diabetes mellitus (GDM) exacerbates the oxidative stress status of the pregnant women. Τo improve the oxidative stress status, several therapeutic interventions have been suggested. The aim of this network meta-analysis is to assess the effect of different dietary supplements on the oxidative stress status in pregnant women with GDM. Methods: A network meta-analysis of randomized control trials was performed comparing the changes delta (Δ) in total antioxidant capacity (TAC) and concentration of malondialdehyde (MDA) as primary outcomes, following different therapeutic interventions with dietary supplements in pregnant women with GDM. Four electronic databases and grey literature sources were searched. The secondary outcomes were other markers of oxidative stress. Results: The meta-analysis included 16 studies of 1173 women with GDM. Regarding ΔTAC: probiotics and omega-3 with vitamin E were superior to placebo/no intervention. Regarding ΔMDA: vitamin D with calcium, omega-3, vitamin D, omega-3 with vitamin E, magnesium with zinc and calcium, and probiotics were superior to placebo/no intervention. Conclusions: Administration of dietary supplements in women with GDM can be helpful in limiting the oxidative stress which develop in these pregnancies.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13072284
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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  • 5
    Online Resource
    Online Resource
    Circulating Neuroendocrine Tumor Biomarkers: Past, Present and Future
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 19 ( 2022-09-21), p. 5542-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 19 ( 2022-09-21), p. 5542-
    Abstract: Neuroendocrine tumors are a heterogeneous group of neoplasms originating from the diffuse endocrine system. Depending on primary location and hormonal status, they range in terms of clinical presentation, prognosis and treatment. Functional tumors often develop symptoms indicating an excess of hormones produced by the neoplasm (exempli gratia insulinoma, glucagonoma and VIPoma) and can be diagnosed using monoanalytes. For non-functional tumors (inactive or producing insignificant amounts of hormones), universal biomarkers have not been established. The matter remains an important unmet need in the field of neuroendocrine tumors. Substances researched over the years, such as chromogranin A and neuron-specific enolase, lack the desired sensitivity and specificity. In recent years, the potential use of Circulating Tumor Cells or multianalytes such as a circulating microRNA and NETest have been widely discussed. They offer superior diagnostic parameters in comparison to traditional biomarkers and depict disease status in a more comprehensive way. Despite a lot of promise, no international standards have yet been developed regarding their routine use and clinical application. In this literature review, we describe the analytes used over the years and cover novel biomarkers that could find a use in the future. We discuss their pros and cons while showcasing recent advances in the field of neuroendocrine tumor biomarkers.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11195542
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 6
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    Online Resource
    Liquid Biopsy in Type 2 Diabetes Mellitus Management: Building Specific Biosignatures via Machine Learning
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 4 ( 2022-02-17), p. 1045-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 4 ( 2022-02-17), p. 1045-
    Abstract: Background: The need for minimally invasive biomarkers for the early diagnosis of type 2 diabetes (T2DM) prior to the clinical onset and monitoring of β-pancreatic cell loss is emerging. Here, we focused on studying circulating cell-free DNA (ccfDNA) as a liquid biopsy biomaterial for accurate diagnosis/monitoring of T2DM. Methods: ccfDNA levels were directly quantified in sera from 96 T2DM patients and 71 healthy individuals via fluorometry, and then fragment DNA size profiling was performed by capillary electrophoresis. Following this, ccfDNA methylation levels of five β-cell-related genes were measured via qPCR. Data were analyzed by automated machine learning to build classifying predictive models. Results: ccfDNA levels were found to be similar between groups but indicative of apoptosis in T2DM. INS (Insulin), IAPP (Islet Amyloid Polypeptide-Amylin), GCK (Glucokinase), and KCNJ11 (Potassium Inwardly Rectifying Channel Subfamily J member 11) levels differed significantly between groups. AutoML analysis delivered biosignatures including GCK, IAPP and KCNJ11 methylation, with the highest ever reported discriminating performance of T2DM from healthy individuals (AUC 0.927). Conclusions: Our data unravel the value of ccfDNA as a minimally invasive biomaterial carrying important clinical information for T2DM. Upon prospective clinical evaluation, the built biosignature can be disruptive for T2DM clinical management.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11041045
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 7
    Online Resource
    Online Resource
    Exercise-Induced Oxidative Stress Responses in the Pediatric Population
    MDPI AG ; 2017
    In:  Antioxidants Vol. 6, No. 1 ( 2017-01-17), p. 6-
    Details
    In: Antioxidants, MDPI AG, Vol. 6, No. 1 ( 2017-01-17), p. 6-
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox6010006
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 8
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    Online Resource
    Assessment of Type 2 Diabetes Risk in Young Women with Polycystic Ovary Syndrome
    MDPI AG ; 2023
    In:  Diagnostics Vol. 13, No. 12 ( 2023-06-14), p. 2067-
    Details
    In: Diagnostics, MDPI AG, Vol. 13, No. 12 ( 2023-06-14), p. 2067-
    Abstract: Women with polycystic ovary syndrome (PCOS) are at increased risk for dysglycemia and type 2 diabetes compared to healthy BMI-matched women of reproductive age: robust evidence exists supporting this notion. The presence of altered glycemic status in young women with the syndrome presents a distinct challenge for the clinician for several reasons. Firstly, the reported incidence of this disorder varies among the limited available studies. Furthermore, there is a lack of consensus on the best screening method, which women to screen, at what frequency, and which strategies need to be implemented to reduce the above risk. We provide data regarding the prevalence of dysglycemia in young women suffering from PCOS and the pathophysiological mechanisms underlying the disorder. In addition, we present evidence suggesting universal screening with the oral glucose tolerance test in young women with the syndrome, irrespective of age or BMI status, to identify and manage glycemic abnormalities in a timely manner. Regarding follow-up, oral glucose testing should be carried out at regular intervals if there are initial abnormal findings or predisposing factors. Finally, the efficacy of a well-balanced diet in conjunction with regular exercise and the use of non-pharmacologic agents in this specific population is discussed.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics13122067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662336-5
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  • 9
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    Online Resource
    Identification of the Rare Ala871Glu Mutation in the Androgen Receptor Gene Leading to Complete Androgen Insensitivity Syndrome in an Adolescent Girl with Primary Amenorrhea
    MDPI AG ; 2022
    In:  Children Vol. 9, No. 12 ( 2022-12-03), p. 1900-
    Details
    In: Children, MDPI AG, Vol. 9, No. 12 ( 2022-12-03), p. 1900-
    Abstract: Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C 〉 A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    URL: Article
    DOI: 10.3390/children9121900
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2732685-8
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  • 10
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    Online Resource
    Effects of Two Workload-Matched High-Intensity Interval Training Protocols on Regional Body Composition and Fat Oxidation in Obese Men
    MDPI AG ; 2021
    In:  Nutrients Vol. 13, No. 4 ( 2021-03-27), p. 1096-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 4 ( 2021-03-27), p. 1096-
    Abstract: The effects of two high-intensity interval training (HIIT) protocols on regional body composition and fat oxidation in men with obesity were compared using a parallel randomized design. Sixteen inactive males (age, 38.9 ± 7.3 years; body fat, 31.8 ± 3.9%; peak oxygen uptake, VO2peak, 30.9 ± 4.1 mL/kg/min; all mean ± SD) were randomly assigned to either HIIT10 (48 × 10 s bouts at 100% of peak power [Wpeak] with 15 s of recovery) or HIIT60 group (8 × 60 s bouts at 100% Wpeak with 90 s of recovery), and subsequently completed eight weeks of training, while maintaining the same diet. Analyses of variance (ANOVA) showed only a main effect of time (p 〈 0.01) and no group or interaction effects (p 〉 0.05) in the examined parameters. Total and trunk fat mass decreased by 1.81 kg (90%CI: −2.63 to −0.99 kg; p = 0.002) and 1.45 kg (90%CI: −1.95 to −0.94 kg; p 〈 0.001), respectively, while leg lean mass increased by 0.86 kg (90%CI: 0.63 to 1.08 kg; p 〈 0.001), following both HIIT protocols. HIIT increased peak fat oxidation (PFO) (from 0.20 ± 0.05 to 0.33 ± 0.08 g/min, p = 0.001), as well as fat oxidation over a wide range of submaximal exercise intensities, and shifted PFO to higher intensity (from 33.6 ± 4.6 to 37.6 ± 6.7% VO2peak, p = 0.039). HIIT, irrespective of protocol, improved VO2peak by 20.0 ± 7.2% (p 〈 0.001), while blood lactate at various submaximal intensities decreased by 20.6% (p = 0.001). In conclusion, both HIIT protocols were equally effective in improving regional body composition and fat oxidation during exercise in obese men.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13041096
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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