Wpływ starzenia się społeczeństwa na strukturę chorobowości w ginekologii

Objectives: The aim of the study was to assess the impact of demographic changes of the population, mainly the process of aging, on the structure of morbidity in gynaecology, and also to determine the direction of emerging changes. Material and methods: Medical documentation was analysed for all patients of the Gynaecological Department of the Clinical Hospital in Białystok, who were hospitalized in the years 1996, 2000 and 2004. A database containing information about 8428 patients was created. Results and conclusions: There is an increase in the number of women at the retirement age treated at a gynaecological ward. The average age of patients hospitalized due to endometrial cancer has increased by about 12 years. The age of patients treated due to uterine fibroids increased by four years, while the average age of women treated due to static disorder increased by 8 years. Population aging is a process of progressive and significant impact on changing the structure of morbidity of gynaecological wards

Wyższe stężenie betatrofiny u pacjentów z noworozpoznaną cukrzycą

Introduction. Betatrophin is primarily produced in the liver and regulates the metabolism of triglycerides. Its elevated concentration might be associated with an increased risk of type 2 diabetes. The aim of the study was to evaluate the impact of betatrophin on beta cell function and to compare the concentration of betatrophin in patients newly diagnosed with type 1 diabetes mellitus (T1DM including LADA), type 2 diabetes mellitus (T2DM) and a control group (CG) of healthy volunteers. Patients and methods. The study included 210 patients with newly diagnosed diabetes (70 with T1DM, 140 with T2DM) and 70 CG. To evaluate the relationship between betatrophin and insulin secretion, a glucagon stimulation test was conducted. Results. Serum betatrophin concentrations were signi­ficantly elevated in T1DM and T2DM in comparison to the control group (3.47 [Q1 = 2.28, Q3 = 4.54] in T1DM vs. 1.81 [Q1 = 1.04, Q3 = 2.67] ng/ml in CG, p < 0.001; 3.12 [Q1 = 1.89, Q3 = 4.48] in T2DM vs. 1.81 [Q1 = 1.04, Q3 = 2.67] ng/ml in CG, p < 0.001). No statistically significant differences in betatrophin concentration were observed between the T1DM and T2DM groups. Significant correlations were established between betatrophin, triglyceride (TG) and high-density lipopro­tein (HDL) levels in all study participants, and C-peptide in the T1DM group. Conclusions. Betatrophin concentration was signi­ficantly elevated in patients with newly diagnosed T1DM and T2DM, compared to the control group and could be a biomarker of diabetes. Our study provided evidence which supports the impact of betatrophin on lipid metabolism. The positive correlation between betatrophin and C-peptide in the T1DM group suggests that betatrophin is associated with insulin secretion in T1DM.Wstęp: Betatrofina jest produkowana głównie w wątrobie i reguluje metabolizm triglicerydów. Podwyższone stężenie betatrofiny może być związane ze zwiększonym ryzykiem rozwoju cukrzycy typu 2. Cel: Celem naszej pracy była ocena wpływu betatrofiny na funkcję komórek beta trzustki i porównanie stężenia betatrofiny u pacjentów z noworozpoznaną cukrzycą typu 1 (CT1 w tym LADA), typu 2 (CT2) oraz w grupie kontrolnej (GK). Metody: Do badania włączono 210 pacjentów ze świeżo rozpoznaną cukrzycą (70 CT1, 140 CT2) oraz 70 GK. W celu oceny związku pomiędzy stężeniem betatrofiny a wydzielaniem insuliny wykonywany był test z glukagonem. Wyniki: Stężenie betatrofiny było istotnie statystycznie wyższe w grupie CT1 i CT2 w porównaniu do grupy kontrolnej (CT1vs.GK: 3.47 (Q1=2.28, Q3=4.54) vs. 1.81 (Q1=1.04, Q3=2.67) ng/ml, odpowiednio,

Wyższe stężenie betatrofiny u chorych z nowo rozpoznaną cukrzycą

Wstęp. Betatrofina jest produkowana głównie w wątrobie i reguluje metabolizm triglicerydów. Pod­wyższone stężenie betatrofiny może być związane ze zwiększonym ryzykiem rozwoju cukrzycy typu 2. Celem niniejszej pracy była ocena wpływu betatrofiny na funkcję komórek beta trzustki i porównanie jej stężeń u chorych z nowo rozpoznaną cukrzycą typu 1 (T1DM; w tym LADA), typu 2 (T2DM) oraz w grupie kontrolnej. Metody. Do badania włączono 210 chorych z nowo rozpoznaną cukrzycą (70 — T1DM, 140 — T2DM) oraz 70 osób stanowiących grupę kontrolną. W celu oceny związku pomiędzy stężeniem betatrofiny a wydzielaniem insuliny wykonywano test z gluka­gonem. Wyniki. Stężenia betatrofiny były istotnie statystycznie wyższe w grupie T1DM i T2DM w porównaniu z grupą kontrolną [T1DM vs. grupa kontrolna: odpowied­nio 3,47 (Q1 = 2,28; Q3 = 4,54) vs. 1,81 (Q1 = 1,04; Q3 = 2,67) ng/ml; p < 0,001; T2DM vs. grupa kontrol­na: odpowiednio 3,12 (Q1 = 1,89; Q3 = 4,48) vs. 1,81 (Q1 = 1,04; Q3 = 2,67) ng/ml; p < 0,001]. Nie stwierdzo­no istotnych statystycznie różnic w stężeniach betatro­finy pomiędzy T1DM a T2DM. Betatrofina korelowała istotnie statystycznie ze stężeniem triglicerydów (TG) i lipoprotein wysokiej gęstości (HDL) w całej badanej grupie oraz ze stężeniem peptydu C w grupie T1DM. Wnioski. Stężenie betatrofiny jest istotnie wyższe u chorych z nowo rozpoznaną T1DM i T2DM w po­równaniu z grupą kontrolną i prawdopodobnie może być biomarkerem cukrzycy. Nasze badanie potwierdza istotny wpływ betatrofiny na metabolizm lipidów. Dodatnia korelacja betatrofiny z peptydem C w grupie T1DM sugeruje, że betatrofina jest związana z wydzie­laniem insuliny w T1DM

Elastography of Endometrium in Women Taking Tamoxifen: A New Approach to an Old Diagnostic Problem

Tamoxifen is a commonly used selective estrogen receptor modulator applied in the treatment for breast cancer. However, in the endometrium, Tamoxifen stimulates tissue growth, cellular transformation, the migration of the cells, and metastatic potential in endometrial cancer. Considering that uterine cancer is the most common neoplasm of the reproductive tract and the third most common neoplastic disease in women, the aim of this study was to investigate if applying elastography in examining the endometrium was beneficial for uterine cancer screening protocols in women on selective estrogen receptor modulator therapy. This study was based on the execution of a classic assessment of the endometrium that included the evaluation of the following: echogenicity, central endometrial stripe, presence of fluid in the uterine lumen, myometrium–endometrium interface, intensity of vascularization and vascular pattern. An ultrasound presentation was then processed and analyzed with elastography. The values of the elastography parameters demonstrated good consistency for the measurement of the softest endometrial layer thickness in elastography. A strong positive correlation (R = 0.56) was demonstrated between the endometrial thickness, as determined by ultrasound examination, and the softest endometrial layer in elastography (p < 0.001). The research showed that the elastography measurements of the width of the softest endometrium layer, based on a population of women taking Tamoxifen, appeared to be a promising option for endometrial cancer screening

Human coronavirus HKU1 spike protein uses O-acetylated sialic acid as an attachment receptor determinant and employs hemagglutinin-esterase protein as a receptor-destroying enzyme

Human coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9-O-acetylated sialic acid (9-O-Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9-O-Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate-O-acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas the O-acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the only in vitro replication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploits O-Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate-O-acetylesterase RDE activity. IMPORTANCE Human coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is an O-acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types of O-acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate-O-acetylesterase RDE activity

Predictive modelling of response to neoadjuvant therapy in HER2+ breast cancer

Abstract HER2-positive (HER2+) breast cancer accounts for 20–25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10–05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients. Here we report predictive modelling of neoadjuvant therapy response using clinicopathological and genomic features of pre-treatment tumour biopsies identified age, estrogen receptor (ER) status and level of immune cell infiltration may together be important for predicting response. Clonal evolution analysis of longitudinally collected tumour samples show subclonal diversity and dynamics are evident with potential therapy resistant subclones detected. The sources of greater pre-treatment immunogenicity associated with a pathological complete response is largely unexplored in HER2+ tumours. However, here we point to the possibility of APOBEC associated mutagenesis, specifically in the ER-neg/HER2+ subtype as a potential mediator of this immunogenic phenotype