Attainment of Sexual Maturity and Gonadotropin Priming in Gilts Determine Follicular Development, Endocrine Milieu and Response to Ovulatory Triggers.

The routine procedure of estrous cycle synchronization in pigs allows for the use of gonadotropins to stimulate ovarian activity. The applied protocols of eCG and hFSH priming similarly affected development of ovarian follicles in two classes 3−6 mm and >6 mm of diameter, however, the number of small follicles (<3 mm) was 2-fold higher in hFSH- than in eCG-primed prepubertal gilts. The attainment of sexual maturity increased concentration of estradiol, testosterone and androstenedione in the follicular fluid of hFSH/eCG-primed gilts, however, prostaglandin E2 and F2α metabolite increased in mature hFSH- and eCG-primed gilts, respectively. The maturity increased mRNA and/or protein expression of key steroidogenic enzymes, prostaglandin synthases or luteinizing hormone receptors in follicular walls. Both hormonal primers played a moderate role in affecting expression of steroidogenic enzymes in follicular walls. In vitro studies showed higher estradiol production in r-hLH (p = 0.04)- and r-hCG (p = 0.049)-stimulated follicular walls of mature gilts than in prepubertal hFSH-primed gilts. Both ovulatory triggers decreased the abundance of LHCG/FSH mRNA receptors in follicular walls, which mimic downregulation of these receptors by a preovulatory LH surge, confirmed in vivo. These data revealed the importance of sexual maturity in the protection of the estrogenic environment, and the selective, moderate role of eCG and FSH in the activation of steroidogenic enzymes in preovulatory follicles.

Trends in the Incidence of Acute Hepatitis B in the Polish Population and Their Determinants.

Introduction: The World Health Assembly adopted the Global Health Strategy and aims to reduce the incidence of Hepatitis from up to 10 million cases per year to 0.9 million cases and to reduce deaths from 1.4 million to 0.5 million per year by 2030. However, given the prevalence of chronic Hepatitis B in many countries and the incidence of new cases of acute Hepatitis B, the task is not easy. This study investigates the trends and determinants of the incidence of acute Hepatitis B in Poland in 2005-2019. Materials and Methods: Data on the incidence of acute hepatitis B (AHBV) were obtained from the National Institute of Public Health. A case definition for AHBV was consistent with the EU definition. The incidence trends were determined by considering the sex, age and place of residence. Due to the exponential dependence model, the computations were based on the logarithm of the incidence rate. This allowed for the transformation to linear form and analysis could be conducted using linear models. Pearson's correlation was used to determine the linear trend of incidence in general and according to sex and place of residence. The values of incidence rates (independent proportions test) and the coefficients illustrating the trends under study were also compared among males and females as well as urban and rural residents. Results: The incidence of AHBV in the Polish population decreased with similar slopes in both sexes. The newly reported cases of AHBV were more frequent in the male population. The incidence of acute Hepatitis B in the urban population was significantly higher than in the rural population. The significant decreasing trends in incidence were observed in all age ranges, with the exception of two age ranges 0-4 and 10-14, where the total incidence during the whole study period was negligible. Conclusion: Despite the significant decrease in the incidence of AHBV in Poland and its position among the European countries with the lowest hepatitis B (HBV) incidence, the alarmingly high proportion of iatrogenic infections requires further improvement in the sanitary condition of health care facilities. It is also necessary to decrease the number of unvaccinated individuals.

Altrenogest affects the development and endocrine milieu of ovarian follicles in prepubertal and mature gilts†.

Altrenogest with gonadotropins is commonly used to synchronize the estrous cycle, but it can also lead to follicular cyst formation, especially in prepubertal gilts. Here, we aimed to investigate how maturity and altrenogest treatment affect the development, endocrine milieu, and molecular control of ovarian follicles. Crossbred prepubertal and mature gilts were challenged or not (control) with altrenogest, and ovaries were collected in the morning on the first day of behavioral estrus. In prepubertal gilts, altrenogest decreased the percentage of primordial and atretic small follicles, but increased large antral follicles when compared with controls. In mature gilts, altrenogest reduced the percentage of primary follicles and elevated the total number of antral follicles. Maturity affected the estradiol level in the follicular fluid of preovulatory follicles, luteinizing hormone (LH)-stimulated cyclic adenosine monophosphate (cAMP) generation, and LH receptor messenger RNA (mRNA) expression in granulosa. Moreover, cytochrome P45017A1 (CYP17A1) mRNA levels in the theca layer were affected and correlated with follicular androstendione and estradiol concentration. Altrenogest negatively affected follicular fluid progesterone concentration and decreased levels of prostaglandin (PG) E2 in prepubertal gilts and PGF2alpha metabolite in mature gilts. LH-stimulated cAMP release in granulosa cells of mature gilts as well as human chorionic gonadotropin- and forskolin-induced cAMP were also affected. In addition, altrenogest downregulated CYP17A1 mRNA in the prepubertal theca layer and PGF2alpha synthase expression in the granulosa and theca layer of mature gilts. To the best of our knowledge, this is the first study to report multiple effects of maturity and altrenogest on the endocrine milieu and molecular regulations governing ovarian follicle development in gilts.

Is Primary Poorly Differentiated Sarcomatoid Malignancy of the Parotid Gland Sarcomatoid Undifferentiated/Dedifferentiated Melanoma? Report of Three Unusual Cases Diagnosed by Fine-Needle Aspiration Combined with Histological, Immunohistochemical, and Molecular Analyses.

INTRODUCTION: Poorly differentiated primary sarcomatoid parotid malignancies are extremely rare. These tumors have not been consistently studied by morphology, immunohistochemistry, or molecular techniques. CASE PRESENTATION: We report three unusual cases of parotid gland poorly-differentiated sarcomatoid malignancy investigated by fine-needle aspiration and studied histologically, by immunohistochemistry and molecular investigations. Aspirates showed poorly specific polymorphous sarcomatoid malignancy in all cases. Histologically, all cases were polymorphous high-grade malignancies, and additionally, one case showed epithelial structures and was finally classified as salivary carcinosarcoma. Immunohistochemistry showed classical melanocytic markers negativity but positivity for PRAME, CD10, and WT1 in all three tumors and for CD56 in two tumors, which can potentially be supportive of melanocytic origin. Although not entirely specific, molecular characterization also suggested the melanocytic lineage of these tumors. CONCLUSION: Although rare, primary malignant melanoma of salivary gland was already described, but undifferentiated/dedifferentiated amelanotic forms are unknown in this localization up today. Further case reports of similar presentations are required to confirm the unequivocal primary origin of these obscure neoplasms in the parotid gland.

Prognostic comparison of the proliferation markers (mitotic activity index, phosphohistone H3, Ki67), steroid receptors, HER2, high molecular weight cytokeratins and classical prognostic factors in T1₋2N0M0 breast cancer.

The proliferation factors: mitotic activity index (MAI), phosphohistone H3 (PPH3) and Ki67 have strong prognostic value in early breast cancer but their independent value to each other and other prognostic factors has not been evaluated. In 237 T1₋2N0M0 breast cancers without systemic adjuvant treatment, formalized MAI assessment and strictly standardized, fully automated quantitative immunohistochemistry (IHC) for Ki67, PPH3, estrogen (ER) and progesterone receptor (PR), HER2, cytokeratins-5/6 and -14, and automated digital image analysis (DIA) for measuring PPH3 and Ki67 were performed. Section thickness was measured to further control IHC measurements. All features were measured in the periphery of tumors. The different proliferation assessments and other well-established clinicopathological and biomarker prognostic factors were compared. DIA-Ki67 added prognostically to PPH3. None of the other biomarkers or clinicopathological variables added prognostically to this PPH3/Ki67 combination. However, when PPH3 is replaced by MAI the prognostic value is nearly the same. In early operable node negative breast cancer without adjuvant systemic treatment, Ki67 with a threshold of 6.5% assessed by digital image analysis in the periphery of the tumor is prognostically strong. The combination of either PPH3/Ki67 or MAI/Ki67 overshadowed the prognostic value of all other features including Ki67 alone.

Atretic preovulatory follicles could be precursors of ovarian lutein cysts in the pig.

Ovarian cysts contribute to reduced reproductive performance in pigs. Unfortunately, the mechanism of lutein cysts formation remains unknown. Here, we compared the endocrine and molecular milieus of intact, healthy preovulatory follicles (PF), gonadotropin (eCG/hCG)-induced healthy and atretic-like PF, as well as gonadotropin-provoked and spontaneous ovarian cysts in gilts. Several endocrine and molecular indicators and microRNA were compared in walls of PF and cysts. Intact and healthy PF, showed high estradiol/androstendione and low progesterone levels associated with CYP17A1, HSD17B1, and CYP19A1 elevation and reduced StAR/HSD3B1 protein expression. In contrast, low estradiol/androstendione and high progesterone concentrations, accompanied by decreased CYP17A1, HSD17B1, CYP19A1 and increased HSD3B1 protein abundance, appeared in atretic-like PF, gonadotropin-induced and spontaneous cysts. High progesterone receptor (PGR) protein abundance was maintained in intact and healthy PF, while it dropped in atretic-like PF, gonadotropins-induced and spontaneous cysts. The atretic PF showed high level of TNFα compared to healthy PF. In conclusion, follicular lutein cysts could be recruited from atretic-like PF with lost estrogenic milieu and inability to ovulate. Ovulatory cascade was presumably disrupted by a low PGR and high TNFα levels associated with earlier luteinization of follicular walls. These results suggest a novel mechanism of lutein ovarian cysts development in pigs and, perhaps, other species.

[Tobacco and alcohol use among the unemployed]. / Palenie papierosów i picie alkoholu wsród bezrobotnych.

There is no doubt today, that any amount of tobacco products use and excessive alcohol consumption are among the fundamental causes of diseases. The health situation of the unemployed is worse than employed. One of the consequences of unemployment and also ways of coping with it can be unhealthy behaviors. The aim of this paper is to present the prevalence of smoking and alcohol consumption, and to identify their causes among the unemployed, and also to show possible changes in these behaviors as a result of finding themselves in a situation of employment deprivation. The results of this study have demonstrated that the unemployed often have anti-health behaviors such as smoking and alcohol consumption with high frequency and single intake exceeding health standards. One of the important factors of smoking and drinking alcohol is a desire to reduce the emotional tension. Being outside the labor market affects the start of the consumption of alcohol and tobacco, but does not result in the cessation of consumption. It happens that the unemployment influence the reduction of consumption of alcohol and tobacco, and the key role is played by the economic factor.

The Role of Reduced Oxygen Supply and Transcription Factors cJUN and CREB in Progesterone Production during the Corpus Luteum Rescue in Gilts.

The corpus luteum plays a fundamental role in regulating reproduction via progesterone production. Still, there is little data on factors regulating the maintenance of luteal function during early pregnancy in gilts. Previous studies emphasize the role of hypoxia and HIF-1 in the regulation of steroidogenic and angiogenic genes expression and progesterone production by ovarian cells. Using the corpus luteum of cyclic and early pregnant gilts we analyzed: (1) the in vitro effects of reduced oxygen tension on progesterone production and mRNA expression of HIF1A and luteal function regulators, STAR and VEGFA; (2) the ex vivo profiles of mRNA and protein expression of HIF-1α, STAR, VEGFA and transcription factors-cJUN and CREB, regulating STAR expression, in the corpus luteum of cyclic and pregnant gilts. The synthesis of progesterone was gradually inhibited in cyclic or pregnant gilt luteal tissue (on day 13 of cycle or pregnancy) incubated in a decreasing concentration−20%, 10%, and 3% of oxygen (O2). Luteal tissues of pregnant gilts produced trace amounts of progesterone in 10% O2, which was similar to cyclic gilts in 3% O2. HIF1A expression increased after 24 h of incubation in tissues of cyclic gilts in 3% vs. 20% O2 (p < 0.01), whereas levels of STAR and VEGFA increased significantly in cyclic and pregnant gilt tissues incubated in 10% and 3% vs. 20% O2. The ex vivo mRNA expression of HIF1A and VEGFA was elevated (p < 0.001) on day 14 vs. day 12 of pregnancy. The protein expression of HIF-1 and VEGFA increased (p < 0.001), whereas the level of STAR (mRNA and protein) and progesterone dropped (p < 0.001) on day 14 of the estrous cycle vs. a parallel day of pregnancy and/or day 12 of the estrous cycle. The content of phosphorylated cJUN and CREB was elevated (p < 0.01) in the luteal tissue on day 12 or 14 of pregnancy vs. parallel days of the estrous cycle. These increases of phosphorylated cJUN and CREB may be involved in STAR expression in the luteal tissue during early pregnancy in gilts.

Endocrine and molecular milieus of ovarian follicles are diversely affected by human chorionic gonadotropin and gonadotropin-releasing hormone in prepubertal and mature gilts.

Different strategies are used to meet optimal reproductive performance or manage reproductive health. Although exogenous human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonists (A) are commonly used to trigger ovulation in estrous cycle synchronization, little is known about their effect on the ovarian follicle. Here, we explored whether hCG- and GnRH-A-induced native luteinizing hormone (LH) can affect the endocrine and molecular milieus of ovarian preovulatory follicles in pigs at different stages of sexual development. We collected ovaries 30 h after hCG/GnRH-A administration from altrenogest and pregnant mare serum gonadotropin (eCG)-primed prepubertal and sexually mature gilts. Several endocrine and molecular alternations were indicated, including broad hormonal trigger-induced changes in follicular fluid steroid hormones and prostaglandin levels. However, sexual maturity affected only estradiol levels. Trigger- and/or maturity-dependent changes in the abundance of hormone receptors (FSHR and LHCGR) and proteins associated with lipid metabolism and steroidogenesis (e.g., STAR, HSD3B1, and CYP11A1), prostaglandin synthesis (PTGS2 and PTGFS), extracellular matrix remodeling (MMP1 and TIMP1), protein folding (HSPs), molecular transport (TF), and cell function and survival (e.g., VIM) were observed. These data revealed different endocrine properties of exogenous and endogenous gonadotropins, with a potent progestational/androgenic role of hCG and estrogenic/pro-developmental function of LH.

[Cigarette smoking among children and adolescents on probation and their family and peer group]. / Palenie tytoniu wsród dzieci i mlodziezy objetej nadzorami kuratorskimi a rodzina i grupa rówiesnicza.

Smoking is one of the most prevalent and also one of the most unhealthy lifestyle elements. The aim of this paper is to present the incidence and causes of smoking among children and adolescents on probation, and examine how immediate social environment reacts to their smoking. The analysis was based on the results of 190 structured interviews taken from february to may 2010 among persons who are aged 11 to 17 years, living in the city of Poznan. It was found that cigarette smoking in the study population is common phenomenon, primarily correlated with age, but also to gender. Family and peer environment, not only does not constitute a buffer against smoking, but sometimes it reinforces the unhealthy behaviors.

Validating the prognostic value of proliferation measured by Phosphohistone H3 (PPH3) in invasive lymph node-negative breast cancer patients less than 71 years of age.

We validated and compared the prognostic value of the proliferation marker phosphohistone H3 (PPH3) with classical variables in 241 T(1-2)N(0)M(0) breast cancer patients less than 71 years old with long-term follow-up (median 117 months) and without adjuvant treatment. PPH3 was measured by automated digital image analysis. Thirty-seven patients (15%) developed distant metastases and 29 (12%) died. The previously established PPH3 prognostic threshold H3 <13 (n = 157; 65% of all cases) vs. >or=13 (n = 84; 35% of all cases) was the strongest prognostic threshold exceeding all other characteristics, with 10-year recurrence-free survival of distant metastases of 96 and 64%, respectively (P = < 0.0001, hazard ratio = 7.8, 95% confidence interval = 3.4-17.9). PPH3 is robust as it showed high inter-observer reproducibility and was prognostic over wide range of thresholds around 13 and is the strongest prognostic variable in invasive node-negative breast cancer patients less than 71 years old.

Proliferation is the strongest prognosticator in node-negative breast cancer: significance, error sources, alternatives and comparison with molecular prognostic markers.

Independent studies have shown that in node negative breast cancer patients less than 71 years, the proliferation marker mitotic activity index (MAI) is the strongest, most well reproducible prognosticator and chemotherapy success predictor. The MAI overshadows the prognostic value of tubule formation, nuclear atypia and thereby grade. An often used crude mitotic impression is much less prognostic than the MAI; strict adherence to the MAI protocol is therefore important. The prognostic value of the MAI is age dependent: although patients with a MAI > or = 10 always have a poor prognosis irrespective of age, a low MAI (<10) loses its favourable prognostic association in women >70 years. PPH3 counts are prognostically stronger than the MAI, and markers such as Cyclin-B and E2FR are promising, but must be validated. Compared with commercial prognostic gene expression signatures, the MAI is at least as strong prognostically, has far fewer false positive results and as such should be included as an independent feature in any node negative breast cancer pathology report.

The prognostic value of molecular biomarkers in tissue removed by curettage from FIGO stage 1 and 2 endometrioid type endometrial cancer.

OBJECTIVE: To analyze the prognostic value of molecular biomarkers in curettages of endometrioid endometrial cancer pathologic FIGO stages 1 and 2. STUDY DESIGN: Population-based survival analysis in 258 patients of classical prognostic features and molecular biomarkers of cell cycle regulation, (anti)apoptosis, proliferation, squamous differentiation, and PTEN/Akt pathway. RESULTS: With 74 months median follow-up (range, 1-209), 24 (9.3%) patients had metastases develop. Pathologic FIGO stage 2B (6% of all cases) and age > 68 years had independent multivariate prognostic value. Many molecular biomarkers were prognostic, particularly cell-cycle regulators p16, p21, p27, p53, p63, and the antiapoptosis marker survivin (which mostly stains mitoses). The strong prognostic value of a multivariate model with survivin, p21, and p53 overshadowed all other prognosticators in pathologic FIGO 1 and 2A. CONCLUSION: In pathologic FIGO stage 1 and 2A endometrioid endometrial cancer curettages, combined biomarkers survivin, p21, and p53 expression patterns are prognostically stronger than classical feature combinations.

[Smoking among the unemployed: impact of structural factors on lifestyle]. / Palenie tytoniu przez bezrobotnych: strukturalne zaleznosci stylu zycia.

In times of economic crisis, questions arise about its relationship to the state of public health. One of the responses might be to investigate health behaviors of people who suffer most from the crisis, which is the unemployed. This study focuses on the many links between smoking among the jobless and other aspects of their lifestyle as well as selected social factors. In our research, we used statistical methods and a questionnaire. based survey. The research was conducted in 2007 and it covered 1,068 unemployed persons registered with the District Employment Office in Poznan. The prevalence of smoking among the unemployed is higher than the national average and is associated with their socio-economic status, gender and such lifestyle aspects as the amount of alcohol consumed, the amount of free time, body mass index, the number of meals consumed, the number of persons the unemployed can rely on, and the amount of time devoted to exercise.

[Cigarette smoking among the unemployed registered with Poznan District Employment Office]. / Palenie tytoniu przez bezrobotnych zarejestrowanych w Powiatowym Urzedzie Pracy w Poznaniu.

The aim of this paper was to present the incidence and causes of smoking among those currently unemployed, and to show changes, if any, resulting from their continued joblessness. The analysis was based on the results of 1,068 surveys taken in 2007 among the unemployed registered with the District Employment Office in Poznan. It was found that cigarette smoking among the unemployed remains high and is associated with the respondents' gender, educational background, economic status and duration of unemployment. Severity of smoking increased more often for those unemployed on a short-term basis, with a number of smoked cigarettes per day more likely to decrease for those in medium- and long-term unemployment. Respondents quoted two equivalent reasons for smoking: wanting to have a cigarette and frustration.

Digital image analysis improves the quality of subjective HER-2 expression scoring in breast cancer.

AIM: To compare HER-2 scoring reproducibility by subjective and digital image analysis (DIA) scores with each other and with fluorescence in situ hybridization (FISH) assessed HER-2 amplification. METHODS: Herceptest-stained Tissue Micro Arrays of 219 breast carcinomas were scored (DAKO protocol) by 3 observers (both independent and as consensus), scored by DIA and both scores were compared with FISH amplification results. RESULTS: Interobserver subjective scores reproducibility was good (kappa 0.82 to 0.86) but therapeutically important 3+/2+discrepancies occurred in 11% to 16% of all 3+ cases. Subjective scores and FISH results differed considerably. Consensus scores by 3 pathologists correlated better with FISH, reducing the number of both Immunohistochemical (IHC) negative/FISH positives and IHC 3+/FISH negatives. DIA scores were well reproducible and correlated better with FISH amplification than did subjective scores. CONCLUSIONS: DIA scores were comparable with consensus scores between 3 expert pathologists, were very well reproducible and performed better in classifying IHC 3+/FISH+ cases than did subjective scores.

[Smoking as an aspect of lifestyle among 18-year-old secondary school students in Poznan]. / Palenie papierosów jako aspekt stylu zycia wsród 18-letnich uczniów poznanskich szkól.

Smoking remains a serious health threat in Poland. The age of 18 years is set as a conventional and symbolic boundary when young people enter adulthood and, at the same time, gain legal access to cigarettes and alcohol. At this age, however, most smokers have already developed smoking habits. This study seeks to identify how prevalent is smoking among 18-year old learning adolescents, and what is its relation to certain social factors and students' lifestyle. In our research, we used statistical methods and a questionnaire-based survey. The research was conducted in 2007 and it covered 400 third-year secondary school students in Poznan. Smoking among adolescents remains at a relatively high level and is related to the type of school, fulfilment of material needs, subjective perception of a state of health, use of other drugs, and a chosen lifestyle.

Consolidative Radiotherapy to Residual Masses After Chemotherapy Is Associated With Improved Outcome in Diffuse Large B-Cell Lymphoma. A Retrospective, Population-Based Study.

BACKGROUND: The role of consolidative radiotherapy (RT) in advanced diffuse large B-cell lymphoma (DLBCL) is not established. PATIENTS AND METHODS: In a population-based retrospective analysis of patients with DLBCL in Western Norway during 2003 to 2008, 170 consecutive patients admitted to Haukeland University Hospital (HUS) and 94 to Stavanger University Hospital (SUS) were included. The mean age was 64 years (range, 17-95 years), 147 patients (56%) were male, 80 patients (30%) had stage I/II, 126 patients (48%) stage III/IV, and 57 patients (22%) had primary extranodal disease. RESULTS: There were no differences between hospitals in patient characteristics, use of rituximab, number of chemotherapy courses or cumulative doses, or in distribution of response categories after chemotherapy. The use of RT was significantly different: 17 patients (23%) received RT at SUS and 92 patients (65%) at HUS (P < .001). For 219 patients with International Prognostic Index (IPI) score of 0 to 3, 5-year cancer-specific survival (CSS) was 67% at SUS and 81% at HUS (P = .012). For 73 patients with complete response after chemotherapy there were no differences in survival between patients with and without RT. For 138 patients with any residual mass after chemotherapy, there were highly significant differences in favor of receiving RT (n = 81) versus no RT (n = 57): 5-year CSS 89% versus 69% (P < .001), and 5-year overall survival 82% versus 59% (P = .005). The effect of RT on residual mass was evident in most subgroups, mainly in low to intermediate risk, but not in high-risk (IPI 4-5) patients. CONCLUSION: With the limitations of a retrospective study, these data suggest that consolidative RT might improve survival in DLBCL patients with a residual mass after chemotherapy, also in advanced disease.

Adult ocular medulloepithelioma diagnosed by transscleral fine needle aspiration: A case report.

Ocular medulloepithelioma (ME) is a rare congenital tumor which occurs usually during childhood but is also reported in adults. They have seen an intraocular tumor in an 89 years-old female with a history of small cell lung carcinoma. Transscleral fine needle aspiration was performed. Aspirates were rich and composed of two distinctive populations of cells. The first consisted of epithelioid large cohesive cells with rare rosettes. Nuclei were oval and chromatin was delicate with small nucleoli. The second population consisted of smaller and dispersed cells with regular nuclei and dusty chromatin. Immunohistochemistry performed on paraffin-embedded cell block sections showed that the larger cells and rosettes were cytokeratin AE1/AE3, Synaptophysin, Chromogranin A, CD56, NSE, and EMA positive, whereas the smaller cells were always negative. Interestingly smaller cells expressed only weak nuclear positivity for TTF1, whereas larger cells were TTF1 negative. Melanocytic markers were negative in both populations. Morphological patterns and immunohistochemical staining confirmed ocular ME and allowed to exclude pulmonary metastasis or primary malignant melanoma. The patient was successfully treated by brachytherapy alone and is alive and well 10 months after treatment. Diagn. Cytopathol. 2017;45:561-564. © 2017 Wiley Periodicals, Inc.