Circulating levels of irisin and Meteorin-like protein in PCOS and its correlation with metabolic parameters.

INTRODUCTION: Research on obesity, which results from excessive food consumption and sedentary lifestyle, has focused on increasing energy expenditure. Recently, muscle tissue is being investigated as an endocrine active organ, secreting molecules called myokines. Multiple studies have been performed to assess myokine levels in various disorders, including polycystic ovary syndrome (PCOS) and metabolic syndrome. Irisin and Meteorin-like protein (Metrnl) are particles which, among others, are suggested to play an important role in adipose tissue browning and improving insulin sensitivity. MATERIAL AND METHODS: The study population consisted of 31 women with PCOS and 18 healthy individuals. PCOS was diagnosed based on revised 2003 Rotterdam criteria. Multiple anthropometrical, hormonal, and biochemical parameters were assessed, including oral glucose tolerance test and body composition with dual energy X-ray absorptiometry. Serum levels of irisin and Metrnl were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were no differences between the PCOS and control groups according to age, body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), or body mass composition. Assessment of Metrnl and irisin concentrations revealed no significant differences between PCOS and healthy women. The irisin level was negatively correlated with BMI, body fat mass, fasting glucose, and insulin concentrations. No relationship between Metrnl level and metabolic parameters was found. CONCLUSIONS: Although irisin seems to be a promising biomarker, inconsistent research limits its value in clinical use in the assessment or treatment of obesity. Metrnl level was not affected in the study population, but it might be connected to the severity of metabolic disturbances.

Alteration of Branched-Chain and Aromatic Amino Acid Profile as a Novel Approach in Studying Polycystic Ovary Syndrome Pathogenesis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive-age women and predisposes them to the development of metabolic disturbances. Recent research has shown that several metabolic factors may play a role in PCOS pathogenesis, and it has been suggested that an alteration in the amino acid profile might be a predictive sign of metabolic disorders. Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are concepts that have attracted scientific attention; however, a universal definition has not been established yet for these terms. Already existing definitions of MHO involve the coexistence of obesity with the absence or minimal presence of other metabolic syndrome parameters. A group of 326 women, 209 diagnosed with PCOS and 117 healthy individuals, participated in this study. Multiple parameters were assessed, including anthropometrical, biochemical, and hormonal ones, and gas-liquid chromatography, combined with tandem mass spectrometry, was used to investigate the amino acid profile. Statistical analysis revealed noticeably higher levels of all aromatic amino acids in PCOS women compared to the control group: phenylalanine 47.37 ± 7.0 vs. 45.4 ± 6.09 nmol/mL (p = 0.01), tyrosine 61.69 ± 9.56 vs. 58.08 ± 8.89 nmol/mL (p < 0.01), and tryptophan 53.66 ± 11.42 vs. 49.81 ± 11.18 nmol/mL (p < 0.01); however, there was no significant difference in the "tryptophan ratio" between the PCOS and control group (p = 0.88). A comparison of MHO and MUO PCOS women revealed that LAP, leucine, and isoleucine concentrations were significantly higher among the MUO subgroup: respectively, 101.98 ± 34.74 vs. 55.80 ± 24.33 (p < 0.001); 153.26 ± 22.26 vs. 137.25 ± 25.76 nmol/mL (p = 0.04); and 92.92 ± 16.09 vs. 82.60 ± 18.70 nmol/mL (p = 0.02). No significant differences in BMI, fasting glucose, and HOMA-IR between MHO and MUO were found: respectively, 35.0 ± 4.8 vs. 36.1 ± 4.6 kg/m2 (p = 0.59); 88.0 ± 6.0 vs. 87.73 ± 6.28 mg/dL (p = 0.67); and 3.36 ± 1.70 vs. 4.17 ± 1.77 (p = 0.1). The identification of altered amino acid profiles in PCOS holds potential clinical implications. Amino acids may serve as biomarkers for diagnosing and monitoring the metabolic status of individuals with PCOS. The alteration of BCAAs and AAAs may be involved in PCOS pathogenesis, but the underlying mechanism should be further investigated.

Specific Alteration of Branched-Chain Amino Acid Profile in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive age women; it is a complex health issue with numerous comorbidities. Attention has recently been drawn to amino acids as they are molecules essential to maintain homeostasis. The aim of the study was to investigate the branch chain amino acid (BCAA) profile in women with PCOS. A total of 326 women, 208 diagnosed with PCOS and 118 healthy controls, participated in the study; all the patients were between 18 and 40 years old. Anthropometrical, biochemical and hormonal parameters were assessed. Gas-liquid chromatography combined with tandem mass spectrometry was used to investigate BCAA levels. Statistical analysis showed significantly higher plasma levels of BCAAs (540.59 ± 97.23 nmol/mL vs. 501.09 ± 85.33 nmol/mL; p < 0.001) in women with PCOS. Significant correlations (p < 0.05) were found between BCAA and BMI, HOMA-IR, waist circumference and total testosterone levels. In the analysis of individuals with abdominal obesity, there were significant differences between PCOS and controls in BCAA (558.13 ± 100.51 vs. 514.22 ± 79.76 nmol/mL) and the concentrations of all the analyzed amino acids were higher in the PCOS patients. Hyperandrogenemia in PCOS patients was associated with significantly higher leucine, isoleucine and total BCAA levels. The increase of BCAA levels among PCOS patients in comparison to healthy controls might be an early sign of metabolic alteration and a predictive factor for other disturbances.

Does predelivery body mass index really matter in pregnancy?

OBJECTIVES: The aim of the study was to compare the perinatal outcome between the normal weight, overweight and obese pregnant women who delivered in the third-level center of reference. Moreover, the objective was to analyze the usefulness of predelivery body mass index (BMI) in prediction of preterm delivery, prolonged second stage of labor, instrumental vaginal delivery, cesarean section, fetal macrosomia, dystocia and newborn acidosis. MATERIAL AND METHODS: The retrospective study included 2104 patients, divided into three groups, with BMI between 18.5 and 24.9; 25.0 and 29.9; higher than or equal 30.0 kg/m2, respectively. The data were assessed from the medical history. RESULTS: The predelivery obesity increases the risk of cesarean section (aOR 1.63), macrosomia (aOR 8.89) and dystocia (aOR 3.40) in comparison to normal weight women. Moreover, the obese females had three times greater risk of having a macrosomic child (aOR 3.57) and 1.5 times greater risk of cesarean section (aOR 1.52) than overweight group. The role of predelivery BMI in the prediction of cesarean delivery (AUC 0.550; sensitivity 0.39; specificity 0.71, p < 0.001, cut-off value 28.7 kg/m2), macrosomia (AUC 0.714; sensitivity 0.66; specificity 0.70; p < 0.001, cut-off value 29.0 kg/m2) and dystocia (AUC 0.658; sensitivity 0.77; specificity 0.53, p < 0.001, cut-off value 27.0 kg/m2) was significant. CONCLUSIONS: The predelivery obesity increases the risk of cesarean section, macrosomia and shoulder dystocia and is a useful parameter in the prediction of perinatal outcomes. The establishing cut-off value for predelivery BMI was the lowest in prediction of shoulder dystocia.

Laboratory interference in the thyroid function test.

Thyroid hormones and thyroid-stimulating hormone (TSH) laboratory tests are commonly used worldwide, and their results have an important influence on decisions about treatment and further diagnostic processes. Any discrepancies between symptoms and laboratory results or between results of different tests should be closely investigated to avoid misdiagnosis and unnecessary treatment. Inconsistencies in hormone tests might be a result of physiological changes in hormonal balance, a disease, drug intake, or laboratory interference. Major factors that interfere with thyroid function tests are: heterophilic antibodies, macro TSH, biotin, thyroid hormones autoantibodies, anti-streptavidin, and anti-ruthenium antibodies. In this paper we discuss the influence of different factors on the procedures of hormonal immunoassays, as well as methods to minimise the risk of false results and misdiagnoses.

Nutritional behavior in pregnancy.

OBJECTIVES: The aim of the study was to characterize nutritional behavior in pregnancy. MATERIAL AND METHODS: The survey study included 250 pregnant women. The survey concerned dietary behavior refferedto the type of diet, the number of meals per day, snacking between meals, consumption of meat, fish, dairy products,bread, fruits and vegetables. RESULTS: 88.8% of the respondents were not on a special diet. The most of the women ate more than three times a day.The women usually ate fruits and vegetables, yogurt and sweets as snacks between meals. The majority of respondentsconsumed meat and sliced meats twice or once a day with the preference of poultry. Only 17.6% of them ate fish with therecommended frequency and as much as 21.2% chose not-recommended species. Almost 29.6% of patients consumed3 to 4 servings of milk or milk products a day and 16.8% of them excluded milk. Half of the respondents declared eatingwheat bread and 24% of them chose wheat roll during pregnancy. Despite the large number of women who consumedwheat baking, a considerable amount of women chose wholemeal bread and wholemeal rolls. Nutritional behaviors werecorrelated with on education level and weight gain during pregnancy. CONCLUSIONS: The frequency of meals was adequate for the most of pregnant women as well as recommended consumptionof meat with poultry preference. However, the inappropriate nutrition was also observed in a low consumption of fishand dairy products, a high consumption of wheat breadstuff and sweets, as well as in a small intake of milk. Education leveland weight gain during pregnancy were associated with nutritional behaviors.

Molecular Signature of Prospero Homeobox 1 (PROX1) in Follicular Thyroid Carcinoma Cells.

The prospero homeobox 1 (PROX1) transcription factor is a product of one of the lymphangiogenesis master genes. It has also been suggested to play a role in carcinogenesis, although its precise role in tumour development and metastasis remains unclear. The aim of this study was to gain more knowledge on the PROX1 function in thyroid tumorigenesis. Follicular thyroid cancer-derived cells-CGTH-W-1-were transfected with PROX1-siRNA (small interfering RNA) and their proliferation, cell cycle, apoptosis and motility were then analysed. The transcriptional signature of PROX1 depletion was determined using RNA-Sequencing (RNA-Seq) and the expression of relevant genes was further validated using reverse transcriptase quantitative PCR (RT-qPCR), Western blot and immunocytochemistry. PROX1 depletion resulted in a decreased cell motility, with both migratory and invasive potential being significantly reduced. The cell morphology was also affected, while the other studied cancer-related cell characteristics were not significantly altered. RNA-seq analysis revealed significant changes in the expression of transcripts encoding genes involved in both motility and cytoskeleton organization. Our transcriptional analysis of PROX1-depleted follicular thyroid carcinoma cells followed by functional and phenotypical analyses provide, for the first time, evidence that PROX1 plays an important role in the metastasis of thyroid cancer cells by regulating genes involved in focal adhesion and cytoskeleton organization in tumour cells.

Exome scale map of genetic alterations promoting metastasis in colorectal cancer.

BACKGROUND: Approximately 90% of colorectal cancer (CRC) deaths are caused by tumors ability to migrate into the adjacent tissues and metastase into distant organs. More than 40 genes have been causally linked to the development of CRC but no mutations have been associated with metastasis yet. To identify molecular basis of CRC metastasis we performed whole-exome and genome-scale transcriptome sequencing of 7 liver metastases along with their matched primary tumours and normal tissue. Multiple, spatially separated fragments of primary tumours were analyzed in each case. Uniformly malignant tissue specimen were selected with macrodissection, for three samples followed with laser microdissection. RESULTS: > 100 sequencing coverage allowed for detection of genetic alterations in subpopulation of tumour cells. Mutations in KRAS, APC, POLE, and PTPRT, previously associated with CRC development, were detected in most patients. Several new associations were identified, including PLXND1, CELSR3, BAHD1 and PNPLA6. CONCLUSIONS: We confirm the essential role of inflammation in CRC progression but question the mechanism of matrix metalloproteinases activation described in other work. Comprehensive sequencing data made it possible to associate genome-scale mutation distribution with gene expression patterns. To our knowledge, this is the first work to report such link in CRC metastasis context.

Anaplastic thyroid carcinoma with rapid thyrotoxicosis - a case report and the literature review.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies and constitutes approximately 1.6-5% of the malignant neoplasms of the thyroid gland. ATC usually manifests itself with the local symptoms due to a rapidly enlarging thyroid mass, and as other thyroid cancers, has only seldom been reported to cause thyrotoxicosis. Up to now only 9 cases of ATC with concomitant thyrotoxicosis have been described. CASE REPORT: We report a rare case of a 66-year-old woman, who had had the preexisting large, euthyroid multinodular goiter for almost 50 years. She was consulted by a doctor because of a 4-week history of thyrotoxicosis, symptoms of the congestive heart failure and a rapid increase in the size of the goiter. Thyroid hormone levels were consistent with a hyperthyroid state. The fine-needle aspiration biopsy confirmed a diagnosis of the anaplastic thyroid carcinoma, the small cells variant. The 99m Tc-pertechnetate scintigraphy visualized non-homogenous tracer distribution with hot nodules. She was given a doxorubicin (20 mg/week) and required the continuous antithyroid treatment. The patient died a one year after the first symptoms of the disease occurred. DISCUSSION: The association between ATC and a thyrotoxic state is very rare. In most cases, thyrotoxicosis concomitant with ATC was thought to be a result of the destruction of the thyroid follicles by the rapid infiltration with malignant cells, resulting in the leakage of preformed hormones to the circulation. In that case the most probable cause of thyrotoxicosis was the multinodular goiter coexisting with ATC. A simultaneous onset of tumor growth, thyrotoxicosis and a relatively long survival time of our patient is worth to notice and discuss.

Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts.

Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death worldwide. Patient-derived xenograft (PDX) models maintain complex intratumoral biology and heterogeneity and therefore remain the platform of choice for translational drug discovery. In this study, we implanted 37 primary CRC tumors and five CRC cell lines into NU/J mice to develop xenograft models. Primary tumors and established xenografts were histologically assessed and surveyed for genetic variants and gene expression using a panel of 409 cancer-related genes and RNA-seq, respectively. More than half of CRC tumors (20 out of 37, 54%) developed into a PDX. Histological assessment confirmed that PDX grading, stromal components, inflammation, and budding were consistent with those of the primary tumors. DNA sequencing identified an average of 0.14 variants per gene per sample. The percentage of mutated variants in PDXs increased with successive passages, indicating a decrease in clonal heterogeneity. Gene Ontology analyses of 4180 differentially expressed transcripts (adj. p value < 0.05) revealed overrepresentation of genes involved in cell division and catabolic processes among the transcripts upregulated in PDXs; downregulated transcripts were associated with GO terms related to extracellular matrix organization, immune responses, and angiogenesis. Neither a transcriptome-based consensus molecular subtype (CMS) classifier nor three other predictors reliably matched PDX molecular subtypes with those of the primary tumors. In sum, both genetic and transcriptomic profiles differed between donor tumors and PDXs, likely as a consequence of subclonal evolution at the early phase of xenograft development, making molecular stratification of PDXs challenging.

Clinical and hormonal features of women with polycystic ovary syndrome living in rural and urban areas.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies among women at reproductive age, but its pathology remains unknown. From epidemiological studies it is known that endogenous, mainly genetic and exogenous, environmental factors are of importance. OBJECTIVE: The aim of the study was to compare the phenotype of women diagnosed with PCOS from urban and rural areas of Poland. According to the knowledge of the authors, this is first such study. MATERIAL AND METHODS: The retrospective study included 3,877 PCOS patients: 2511 women living in cities and 1,366 village inhabitants, aged between 18 - 45 years. Clinical data, including medical history, body mass, height and hirsutism severity was obtained from each patient. Hormones were also tested in each patient: follicle stimulating hormone, luteinizing hormone, prolactin, estradiol [E2], testosterone, dehydroepiandrosterone sulphate [DHEAS], thyroid stimulating hormone, free thyroxin, insulin [INS], 17 hydroxyprogesterone, cortisol [CORT]) and metabolic (75g oral glucose tolerance test, Chol - total cholesterol, HDL-C - high density lipoprotein cholesterol, LDL-C low density lipoprotein cholesterol, and the TG (triglicerides) profile. RESULTS: PCOS women from urban areas had a higher mean serum concentration of E2 in comparison to the inhabitants of rural areas. Women from cities had a lower mean level of DHEAS, CORT, and INS measured in the morning than rural residents. Insulin-resistance, using homeostasis model assessment, was more pronounced among women from villages. The prevalence of menstrual disorders, in general, was higher in PCOS women living in rural comparing to urban areas. CONCLUSIONS: The clinical and biochemical indices differed significantly between women diagnosed with PCOS living in cities and villages. In general in Poland, the PCOS phenotype is more severe in women living in rural areas. This study shows that different living conditions significantly affect the PCOS phenotype.

PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland.

BACKGROUND: The PALB2 gene encodes a protein that plays a crucial role in maintaining genomic integrity. Germline inactivating mutations in PALB2 are associated with an increased risk of breast and ovarian cancer. The prevalence and spectrum of recurrent PALB2 germline mutations in breast and ovarian cancer patients from Poland is not clearly defined. METHODS: PALB2 exons were amplified from 460 BRCA1/2-mutation negative women with familial breast and/or ovarian cancer and early-onset breast cancer using AmpliSeq technology and sequenced on an Ion Torrent PGM sequencer. In addition, eight selected variants were genotyped using TaqMan assays in 807 BRCA1/2-mutation negative breast cancer patients and 1690 healthy women. RESULTS: Two recurrent PALB2 mutations, c.172_175delTTGT and c.509_510delGA, were identified, along with one novel mutation, c.347insT. In total, PALB2 pathogenic mutations were detected in 7/460 (1.5%) patients. Furthermore, in breast and/or ovarian cancer patients, several single nucleotide variants (SNVs) were detected in the PALB2 coding region. In an additional group of 807 patients, eight (1%) carriers of two pathogenic mutations, c.172_175delTTGT (0.5%) and c.509_510delGA (0.5%), were identified. The c.509_510delGA mutation was not identified in healthy controls, while c.172_175delTTGT was identified in 4/1690 (0.24%) of control women. CONCLUSIONS: Germline mutations in the PALB2 gene were observed at a frequency of approximately 1.5% in Polish breast and/or ovarian cancer patients. Our study confirms two recurrent PALB2 mutations; c.172_175delGA and c.509_510delGA.

Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.

Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn's disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10-11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.

Sonoelastography in the evaluation of capsule formation after breast augmentation - preliminary results from a follow-up study.

INTRODUCTION: There are many indications for breast augmentation, including reconstruction after mastectomy, correction of congenital disorders and cosmetic procedures. The most frequent local complication of this surgery is capsule formation due to fibrosis. The aim of the study was to assess the usefulness of sonoelastography in the evaluation of capsule formation around silicone implants. MATERIAL AND METHODS: The study group included 13 patients aged 20 to 41, who underwent breast augmentation with silicone implants. Their 26 breasts were examined before surgery, 7 and 14 days and a minimum of 8.5 months after surgery. The breast stiffness was assessed with tonometry and shear wave elastography to evaluate elasticity of the breast tissue and capsule formation after surgery. RESULTS: We assessed the correlation between capsular elasticity measured at successive visits and the Baker scale. There were no significant relationships between any pairs of variables (p > 0.05). We also analyzed the correlation between the time of the follow-up and changes in the tissue elasticity of every region - no significant relationship was found. The greatest decrease in pericapsular elasticity was established in lower and inner quadrants. Moreover, there was a significant difference between the elasticity of the tissue before and 1 week after surgery (p < 0.05) and no significant changes in the elasticity before surgery and at the end of the follow-up. CONCLUSIONS: Sonoelastography is precise in evaluation of capsule formation after breast augmentation. It may show changes that cannot be assessed using palpation.