BACKGROUND: Stress and negative mood in pregnancy have been linked to less favorable birth outcomes, but the mechanisms underlying this effect remain largely unknown. We examined associations between emotions in pregnancy, pro- and anti-inflammatory cytokines (IFN-γ, IL-6, IL-8, IL-10, IL-12, IL-17, MCP-1, MIP-1β, TNF-α) and birth outcomes (gestational age at birth and birth weight) in a low-risk sample. METHODS: At each trimester of pregnancy, participants (N = 74) completed the Positive and Negative Affect Schedule, Perceived Stress Scale, Edinburgh Postnatal Depression Scale, and State-Trait Anxiety Inventory. They provided blood samples in the third trimester. Multivariate regression with a reduction of dimensionality (orthogonal projection to latent structures) was used to assess associations between maternal emotions, cytokine levels, and birth outcomes. RESULTS: We found significant positive associations between negative mood (depressive symptoms in the second and third trimesters and negative affect in the third trimester) and anti-inflammatory cytokine IL-10 levels, and negative associations between maternal distress in the second and third trimesters and pro-/anti-inflammatory cytokine ratios (IFN-γ/IL-10, TNF-α/IL-10 and IL-6/IL-10). Higher levels of pro-inflammatory cytokines IFN-γ, IL-12, IL-17, and TNF-α were associated with younger gestational age at birth and lower birth weight. LIMITATIONS: We did not control for relevant factors such as social support, health-related behaviors, or cortisol levels. CONCLUSIONS: Negative mood in mid- and late pregnancy may shift cytokine balance toward the anti-inflammatory cytokine dominance. Our results provide further evidence for the negative association between pro-inflammatory cytokines in late pregnancy and gestational age at birth/birth weight, which we observed even in a low-risk population.

• Klíčová slova
• Anxiety, Birth outcomes, Cytokines, Depressive symptoms, Pregnancy, Stress,
• MeSH
• afekt fyziologie   MeSH
• cytokiny * krev   MeSH
• deprese krev   psychologie   MeSH
• dospělí MeSH
• gestační stáří MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• porodní hmotnost MeSH
• prospektivní studie MeSH
• psychický stres krev   MeSH
• těhotenství MeSH
• třetí trimestr těhotenství krev   MeSH
• výsledek těhotenství * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny * MeSH

Background: Recent studies have suggested that pathogenic variants of the DICER1 gene could be a driver of alterations in some pediatric thyroid nodules, but data are still limited. The aim of this study was to detect variants in the DICER1 gene in a large cohort of pediatric thyroid nodules and then correlate them with clinicopathological data, with a focus on the disease prognosis in patients with thyroid carcinoma. Methods: This retrospective cohort study consisted of 350 pediatric and young adult patients (aged 2-21 years) with thyroid nodules, from whom 275 fresh-frozen thyroid nodule samples and 92 fine-needle aspiration biopsy (FNAB) samples were collected. After an analysis of variants in major genetic alterations of thyroid tumors, variants in the DICER1 gene were identified using next-generation sequencing and multiplex ligation-dependent probe amplification methods. Peripheral blood was analyzed from patients with DICER1-positive tumors. The results of genetic analysis were then correlated with clinicopathological data. Results: Variants in the DICER1 gene were detected in a total of 24/350 (6.9%; 95%CI [4.4;10.0]) pediatric and young adult patients, respectively, in 10/119 (8.4%; [4.1;14.9]) patients with benign fresh-frozen tissue, in 8/141 (5.7%; [1.9;9.5]) with papillary thyroid carcinoma (PTC) and in 6/86 (7.0%; [4.1;14.6]) patients with FNAB. No other gene alteration was found in DICER1-positive samples. Germline DICER1 variants were identified in 11/24 (45.8%; [25.6;67.2]) patients. Two somatic (biallelic) variants in the DICER1 gene were found in 9/24 (37.5%; [18.8;59.4]) thyroid nodules. Somatic deletions of at least 3 Mbp long were revealed in 2/24 (8.3%; [1.0;27.0]) cases. DICER1-positive PTCs were significantly associated with the follicular subtype of PTC (p = 0.001), encapsulation (p = 0.006) and were larger in size (p = 0.035), but with no extrathyroidal extension (p = 0.039), and less frequent lymph node metastases (p = 0.003) compared with DICER1-negative PTCs. Patients with DICER1-positive PTC had an excellent response to treatment in 75% of cases. Conclusions: Variants of the DICER1 gene are frequently found in the thyroid nodules of pediatric and young adult patients. In our patients, DICER1-positive PTCs showed low invasiveness. Our findings support considering more conservative management for DICER1-positive low-risk PTCs.

• Klíčová slova
• DICER1 gene, DICER1 syndrome, papillary thyroid carcinoma, pediatric, thyroid nodules,
• MeSH
• DEAD-box RNA-helikasy * genetika   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory štítné žlázy * genetika   patologie   MeSH
• papilární karcinom štítné žlázy genetika   patologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• ribonukleasa III * genetika   MeSH
• tenkojehlová biopsie MeSH
• uzle štítné žlázy * genetika   patologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DEAD-box RNA-helikasy * MeSH
• DICER1 protein, human MeSH Prohlížeč
• ribonukleasa III * MeSH

Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients. Samples were analyzed for known driver mutations occurring in thyroid cancer. Negative samples were subjected to extensive RET fusion gene analyses using next-generation sequencing and real-time PCR. RET fusion genes were not detected in any low-risk neoplasm or benign thyroid tissue and were detected only in papillary thyroid carcinomas (PTCs), in 113/993 (11.4%) patients, three times more frequently in pediatric and adolescent patients (29.8%) than in adult patients (8.7%). A total of 20 types of RET fusions were identified. RET fusion-positive carcinomas were associated with aggressive tumor behavior, including high rates of lymph node (75.2%) and distant metastases (18.6%), significantly higher than in NTRK fusion, BRAF V600E and RAS-positive carcinomas. Local and distant metastases were also frequently found in patients with microcarcinomas positive for the RET fusions. 'True recurrences' occurred rarely (2.4%) and only in adult patients. The 2-, 5-, 10-year disease-specific survival rates were 99%, 96%, and 95%, respectively. RET fusion-positive carcinomas were associated with high invasiveness and metastatic activity, but probably due to intensive treatment with low patient mortality.

• Klíčová slova
• RET, fusion gene, outcome, papillary thyroid carcinoma, rearrangement,
• MeSH
• dítě MeSH
• dospělí MeSH
• karcinom * MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• nádory štítné žlázy * genetika   patologie   MeSH
• papilární karcinom štítné žlázy MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• protoonkogenní proteiny c-ret genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protoonkogenní proteiny B-Raf MeSH
• protoonkogenní proteiny c-ret MeSH
• RET protein, human MeSH Prohlížeč

BACKGROUND: We describe early and typical nonendocrine symptoms of Multiple Endocrine Neoplasia type 2B (MEN2B) presented in our patients with de novo M918T mutation in the RET proto-oncogene in early childhood, however, the diagnosis of MEN2B and medullary thyroid carcinoma (MTC) was confirmed late, in the second decade of life. In this paper, we emphasize the possibility of growth retardation, growth hormone (GH) deficiency and ovarian teratoma as a new symptom of MEN2B. CASE REPORTS: Advanced MTC with palpable mass on the neck and nonendocrine symptoms such as marfanoid habitus, thickened lips, mucosal neuromas led to the diagnosis in case 1 at the age of 13 years and GH deficiency and nonendocrine symptoms in case 2 at the age of 11 years. The earliest feature of MEN2B was alacrima and constipation. Patient 1 was operated on for a slipped femoral capital epiphysis and for a cystic ovarian teratoma. CONCLUSIONS: Improved awareness of nonendocrine signs of MEN2B could lead to earlier diagnosis, when surgical cure of MTC is possible. Alacrima is the first sign of MEN2B. We confirmed the possibility of growth retardation and GH deficiency in MEN2B, which had been previously rarely described. We suggest that patients with MEN2B may develop cystic ovarian teratoma, to the best of our knowledge, which has never been described so far in the literature. The results of this study could be used to guide further diagnosing of MENB2 at the early stage for better clinical outcome. We emphasize that MEN2B carries a risk for development of cystic ovarian teratoma as a novel tumor in this disease.

• Klíčová slova
• growth hormone deficiency, medullary thyroid carcinoma, multiple endocrine neoplasia type 2B, ovarian teratoma,
• MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mnohočetná endokrinní neoplazie typ 2B * diagnóza   genetika   patologie   MeSH
• nádory štítné žlázy * komplikace   chirurgie   MeSH
• protoonkogenní proteiny c-ret genetika   MeSH
• růstový hormon MeSH
• teratom * komplikace   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• protoonkogenní proteiny c-ret MeSH
• růstový hormon MeSH

CONTEXT: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined. OBJECTIVE: To study whether BRAF V600E affected LNM-associated mortality in PTC. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months. RESULTS: Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism. CONCLUSIONS: LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.

• Klíčová slova
• BRAF mutation, lymph node metastasis, mortality, prognostic molecular marker, risk stratification, thyroid cancer,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   mortalita   patologie   MeSH
• lymfatické metastázy MeSH
• míra přežití MeSH
• mutace * MeSH
• nádorové biomarkery genetika   MeSH
• nádory štítné žlázy genetika   mortalita   patologie   MeSH
• následné studie MeSH
• papilární karcinom štítné žlázy genetika   mortalita   sekundární   MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny B-Raf MeSH

Alzheimer's disease (AD) is the most common type of dementia, but it is very difficult to diagnose with certainty, so many AD studies have attempted to find early and relevant diagnostic markers. Regulated upon activation, normal T cell expressed and secreted (RANTES, also known as C-C chemokine ligand) is a chemokine involved in the migration of T cells and other lymphoid cells. Changes in RANTES levels and its expression in blood or in cerebrospinal fluid have been reported in some neurodegenerative diseases, such as Parkinson's disease and multiple sclerosis, but also in metabolic diseases in which inflammation plays a role. The aim of this observational study was to assess RANTES levels in peripheral blood as clinical indicators of AD. Plasma levels of RANTES were investigated in 85 AD patients in a relatively early phase of AD (median 8.5 months after diagnosis; 39 men and 46 women; average age 75.7 years), and in 78 control subjects (24 men and 54 women; average age 66 years). We found much higher plasma levels of RANTES in AD patients compared to controls. A negative correlation of RANTES levels with age, disease duration, Fazekas scale score, and the medial temporal lobe atrophy (MTA) score (Scheltens's scale) was found in AD patients, i.e., the higher levels corresponded to earlier stages of the disease. Plasma RANTES levels were not correlated with cognitive scores. In AD patients, RANTES levels were positively correlated with the levels of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α, which is consistent with the well-known fact that AD is associated with inflammatory processes. RANTES levels were also positively correlated with insulin levels in AD patients, with insulin resistance (HOMA-R) and pancreatic beta cell function (HOMA-F). This study evaluated several clinical and metabolic factors that may affect plasma levels of RANTES, but these factors could not explain the increases in RANTES levels observed in AD patients. Plasma levels of RANTES appear to be an interesting peripheral marker for early stages of AD. The study was approved by the Ethics Committee of Institute of Endocrinology, Prague, Czech Republic on July 22, 2011.

• Klíčová slova
• Alzheimer’s disease, RANTES, biomarker, central nervous system, cognitive impairment, inflammation,
• Publikační typ
• časopisecké články MeSH

In August 2017, an increased incidence of Salmonella Bareilly was detected in the Czech Republic. An investigation was conducted with Slovakia to confirm the outbreak and identify the source. Probable outbreak cases were defined as cases with laboratory-confirmed S. Bareilly reported in either of the national surveillance systems, and/or the Czech and Slovak National Reference Laboratory databases from July 2017. Confirmed cases had the pulsed-field gel electrophoresis (PFGE) outbreak pulsotype or up to 5 alleles difference from outbreak cluster members by core genome multilocus sequence typing (cgMLST). PFGE and whole genome sequencing were used for isolate comparison. The same trawling questionnaire was used in both countries. By the end of October 2018, 325 cases were identified. Among 88 human S. Bareilly isolates analysed by PFGE, 82 (93%) shared an identical pulsotype; cgMLST of 17 S. Bareilly human isolates showed 1-2 allele difference. The trawling questionnaire excluded consumption of unusual or imported foods. In September 2018, an isolate closely related to the outbreak isolates was identified in a powdered egg product. A spray dryer was recognised as the contamination source and the production plant was closed. Using molecular typing methods, we detected a diffuse cross-border outbreak caused by S. Bareilly.

• Klíčová slova
• Salmonella Bareilly, WGS, food- and water-borne diseases, outbreak, powdered egg product, spray dryer,
• MeSH
• epidemický výskyt choroby * MeSH
• genom bakteriální MeSH
• lidé MeSH
• multilokusová sekvenční typizace MeSH
• pulzní gelová elektroforéza MeSH
• Salmonella * genetika   MeSH
• sekvenování celého genomu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Slovenská republika epidemiologie   MeSH

Background: Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods: The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results: A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF, and MET fusions were found, of which five novel, TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, and EML4/MET, rearrangements were identified and a CUL1/BRAF rearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions, followed by NTRK3 fusions. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies, and NTRK3 fusions were associated with the follicular variant of PTC. Conclusions: Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.

• Klíčová slova
• RNA targeted sequencing, fusion genes, papillary thyroid carcinoma, pediatric, rearrangements,
• MeSH
• bodová mutace MeSH
• dítě MeSH
• fenotyp MeSH
• fúze genů * MeSH
• genetická predispozice k nemoci MeSH
• genová přestavba MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   MeSH
• nádory štítné žlázy genetika   patologie   terapie   MeSH
• papilární karcinom štítné žlázy genetika   patologie   terapie   MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• protoonkogenní proteiny c-met genetika   MeSH
• protoonkogenní proteiny c-ret genetika   MeSH
• receptor trkA genetika   MeSH
• receptor trkC genetika   MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• MET protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• NTRK1 protein, human MeSH Prohlížeč
• NTRK3 protein, human MeSH Prohlížeč
• protoonkogenní proteiny B-Raf MeSH
• protoonkogenní proteiny c-met MeSH
• protoonkogenní proteiny c-ret MeSH
• receptor trkA MeSH
• receptor trkC MeSH
• RET protein, human MeSH Prohlížeč

Peripheral insulin resistance is associated with decreasing adiponectin and increasing leptin plasma levels, and also with cognitive decline. The effects of adipokines on brain function have been published from both animal and human studies. In particular, the influence of leptin and adiponectin on the development of Alzheimer's disease (AD) has been extensively investigated. However, the association between adipsin and AD is as yet unknown. In 37 patients with AD and 65 controls that followed the same study protocol, we tested whether adiponectin, leptin, and adipsin could be used as biomarkers in the early stages of AD. In contrast with conclusions of cognition studies in insulin resistant states, our study found a correlation of impaired neuropsychological performance with increasing adiponectin and decreasing leptin in AD patients. Nevertheless, no significant differences between patients and controls were found. AD women had significantly increased adipsin compared to controls, and there was a positive correlation of adipsin with age and disease duration. Although adipokines do not appear to be suitable biomarkers for early AD diagnosis, they certainly play a role in the pathogenesis of AD. Further studies will be needed to explain the cause of the adipokine "breaking point" that leads to the pathogenesis of overt AD.

• MeSH
• adiponektin krev   MeSH
• Alzheimerova nemoc krev   patologie   MeSH
• biologické markery krev   MeSH
• komplement - faktor D analýza   MeSH
• leptin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adiponektin MeSH
• ADIPOQ protein, human MeSH Prohlížeč
• biologické markery MeSH
• CFD protein, human MeSH Prohlížeč
• komplement - faktor D MeSH
• leptin MeSH

Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue.

• MeSH
• C-peptid aplikace a dávkování   fyziologie   MeSH
• diabetes mellitus 2. typu komplikace   farmakoterapie   patologie   MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• nemoci cév etiologie   metabolismus   patologie   prevence a kontrola   MeSH
• nemoci nervového systému etiologie   metabolismus   patologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• C-peptid MeSH