OBJECTIVE: This study aimed to evaluate the accuracy and effectiveness of different strategies for the diagnosis of acute myocardial infarction (AMI) in the elderly in real-life clinical practice. METHODS: Patients older than 70 years presenting to the emergency department with chest pain were included. The performance of six decision aid rules (T-MACS, HEART, EDACS, TIMI, GRACE, and ADAPT) and solo troponin T strategy for diagnosing AMI was evaluated by calculating sensitivity, specificity, odds ratios, negative and positive predictive values. RESULTS: A total of 250 patients, with a mean age of 78.5 years, were enrolled. Forty-eight patients (19.2 %) had an acute myocardial infarction in a 30 day follow-up period. The sensitivity for ruling-out AMI was 100 % for T-MACS, HEART, and ADAPT; 97.9 % for EDACS, 93.8 % for TIMI, and 81.3 % for GRACE and solo TnT strategy. For ruling-in AMI, the specificity was 97.5 % for T-MACS, 95 % for TIMI, 83.2 % for HEART, 81.7 % for GRACE, and 46 % for ADAPT. CONCLUSION: T-MACS decision aid had the best performance for rule-out and rule-in diagnostics of AMI. Risk stratification of patients with suspected acute coronary syndrome based on decision aid rules can be used in real-life practice, even in the population of the elderly (Tab. 6, Fig. 1, Ref. 17).

• MeSH
• Chest Pain etiology   MeSH
• Myocardial Infarction * diagnosis   epidemiology   MeSH
• Humans MeSH
• Clinical Decision Rules * MeSH
• Risk MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Statistics as Topic MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Publication type
• Clinical Study MeSH
• Research Support, Non-U.S. Gov't MeSH

Publikace se zaměřuje na různé etické, antropologické a historické aspekty estetické medicíny a chirurgie. Určeno odborné i široké veřejnosti.; Publikace si klade za cíl zasadit fenomén estetické chirurgie do širšího rámce.Kromě lékařského hlediska seznamuje čtenáře s historií tohoto medicínského oboru, poukazuje na to, jak se v dějinách lidstva měnil ideál tělesné krásy, zkoumá antropologický profil pacienta a věnuje se osobnosti estetického chirurga. Na základě těchto souvislostí se snaží dospět k určitému etickému zhodnocení. V závěru prezentuje krátkou kazuistiku a autorův pohled na věc.

• MeSH
• History of Medicine MeSH
• Beauty MeSH
• Christianity MeSH
• Anthropology, Cultural MeSH
• Interdisciplinary Communication MeSH
• Surgery, Plastic MeSH
• Physician-Patient Relations ethics   MeSH
• Publication type
• Monograph MeSH
• Popular Work MeSH

• Conspectus
• Ortopedie. Chirurgie. Oftalmologie
• NML Fields
• estetická medicína
• plastická chirurgie
• antropologie

• MeSH
• Emergencies MeSH
• Critical Care MeSH
• Wounds and Injuries MeSH
• Emergency Treatment MeSH
• Publication type
• Atlas MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• urgentní lékařství
• NML Publication type
• kolektivní monografie

The long-term feeding of a high-concentrate diet (the concentrate ratio is greater than 60 %) leads to mammary gland inflammatory response in ruminants and decreased quality in dairy cows and affects the robust development of the dairy industry. The main reason is closely related to elevated lipopolysaccharide (LPS) in the body. In this experiment, a bovine mammary epithelial cell line (MAC-T) was used as a model, and LPS at different concentrations (0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, 10000 ng/ml) was added to the cells. The cell survival rate, oxidative stress indicators, total lipid droplet area, triglyceride content and key genes regulating lipid metabolism were detected by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT), assay kit, microscope observation and RT-PCR methods to explore the regulatory mechanism of mammary health and milk fat synthesis. The results showed that compared with those of the control group, the survival rates of cells were significantly decreased after 9 h of stimulation with 1000 ng/ml and 10000 ng/ml LPS (P<0.01). The contents of superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) in cells were significantly decreased (P<0.05). Compared with that of the control group, the content of malondialdehyde (MDA) in cells was significantly increased (P<0.05) after stimulation with 10000 ng/ml LPS for 9 h. After 9 h of stimulation with 100 ng/ml, 1000 ng/ml and 10000 ng/ml LPS, the total lipid drop area and triglyceride (TG) content of MAC-T cells were significantly decreased (P<0.05). The expression levels of fatty acid synthesis-related genes Acetyl-CoA carboxylase (ACC) and Stearoyl-CoA desaturase 1 (SCD-1) were significantly decreased after 9 h of stimulation with 100 ng/ml, 1000 ng/ml and 10000 ng/ml LPS (P<0.05), while the expression levels of Fatty Acid synthetase (FAS) were significantly decreased after stimulation with 1000 ng/ml and 10000 ng/ml LPS (P<0.05). TG synthesis by the related gene Diacylglycerol acyltransferase-1 (DGAT1) was significantly lower than that of the control group after stimulation with 1000 ng/ml and 10000 ng/ml LPS for 9 h (P<0.05), and Diacylglycerol acyltransferase-2 (DGAT2) also showed a significant decrease after 10000 ng/ml LPS stimulation (P<0.05). In conclusion, adding different concentrations of LPS to MAC-T cells not only led to a decrease in cell activity, resulting in oxidative damage, but also affected fatty acid and TG synthesis, which may ultimately be closely related to the decrease in milk fat synthesis.

• MeSH
• Cell Line MeSH
• Epithelial Cells metabolism   MeSH
• Lipopolysaccharides MeSH
• Mastitis, Bovine etiology   metabolism   MeSH
• Lipid Metabolism * MeSH
• Oxidative Stress * MeSH
• Cattle MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Allogeneic HSCT represents the only potentially curative treatment for very high risk (VHR) ALL. Two consecutive international prospective studies, ALL-SCT-(I)BFM 2003 and 2007 were conducted in 1150 pediatric patients. 569 presented with VHR disease leading to any kind of HSCT. All patients >2 year old were transplanted after TBI-based MAC. The median follow-up was 5 years. 463 patients were transplanted from matched donor (MD) and 106 from mismatched donor (MMD). 214 were in CR1. Stem cell source was unmanipulated BM for 330 patients, unmanipulated PBSC for 135, ex vivo T-cell depleted PBSC for 62 and cord-blood for 26. There were more advanced disease, more ex vivo T-cell depletion, and more chemotherapy based conditioning regimen for patients transplanted from MMD as compared to those transplanted from MSD or MD. Median follow up (reversed Kaplan Meier estimator) was 4.99 years, median follow up of survivals was 4.88, range (0.01-11.72) years. The 4-year CI of extensive cGvHD was 13 ± 2% and 17 ± 4% (p = NS) for the patients transplanted from MD and MMD, respectively. 4-year EFS was statistically better for patients transplanted from MD (60 ± 2% vs. 42 ± 5%, p < 0.001) for the whole cohort. This difference does not exist if considering separately patients treated in the most recent study. There was no difference in 4-year CI of relapse. The 4-year NRM was lower for patients transplanted from MD (9 ± 1% vs. 23 ± 4%, p < 0.001). In multivariate analysis, donor-type appears as a negative risk-factor for OS, EFS, and NRM. This paper demonstrates the impact of donor type on overall results of allogeneic stem cell transplantation for very-high risk pediatric acute lymphoblastic leukemia with worse results when using MMD stem cell source.

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * therapy   MeSH
• Tissue Donors MeSH
• Child MeSH
• Humans MeSH
• Graft vs Host Disease * MeSH
• Child, Preschool MeSH
• Transplantation Conditioning MeSH
• Prospective Studies MeSH
• Retrospective Studies MeSH
• Hematopoietic Stem Cell Transplantation * MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Child, Preschool MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Úvod: Bolesti na hrudi patří mezi nejčastější důvody pro akutní vyšetření. Pacienti ve vysokém věku se často prezentují atypickými symptomy a nejednoznačnými laboratorními a elektrokardiografickými nálezy, což znesnadňuje rychlou diagnostiku. K efektivní rizikové stratifikaci byly vyvinuty diagnostické algoritmy, které mohou dále nasměrovat další vyšetřovací a léčebný postup.

Introduction: Chest pain is one of the leading causes for visit at the emergency department. Atypical symptoms, ambiguous laboratory and electrocardiographical findings in elderly make the rapid diagnostics difficult. Diagnostic algorithms were developed for effective risk stratification and they can direct us towards the right diagnosis and correct treatment. Objective: The aim of this study is to evaluate the effectiveness of T-MACS algorithm in very old patients presenting with acute chest pain. Methods: Retrospective analysis of 104 patients older than 80 years which were examined at emergency department for acute chest pain. Primary composite endpoint was combination of acute myocardial infarction, percutaneous coronary intervention (PCI) and all-cause death in 30 day and 12 months follow-up. Results: Mean age of study population is 84.9 years. Risk stratification according to T-MACS model: very low risk 1 %, low risk 24 %, intermediate risk 69.2 % and high risk 5.8 % patients. In 30 days follow-up, the incidence of primary composite endpoint (MACE) was 26.9 %, acute myocardial infarction 26 %, PCI 7.7% and all-cause mortality was 1.9 %. Estimated risk of major adverse cardiac events in 30 days was 28 % (average T-MACS score). T-MACS < 2 % has 100 % sensitivity and 100 % negative predictive value for absence of MACE, T-MACS > 95 % has 98.7 % specificity and 83.3 % positive predictive value for occurrence of MACE respectively. Patients with MACE had significantly different T-MACS score (p value < 0.01) compared to patients without MACE, difference in levels of hs-TnT was not statistically significance (p value > 0.05). Conclusion: We found good correlation between estimated and real incidence of selected cardiac events in our population. For the prediction of MACE the single value of hs-TnT is not good enough, more convenient is to use combination of more parameters. T-MACS has very high sensitivity and negative predictive value for absence of MACE and can be used in real world practice even in population of very old patients.

• Keywords
• T-MACS,
• MeSH
• Algorithms * MeSH
• Chest Pain diagnosis   etiology   MeSH
• Cardiovascular Diseases * diagnosis   epidemiology   MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Risk MeSH
• Heart Disease Risk Factors MeSH
• Aged, 80 and over MeSH
• Statistics as Topic MeSH
• Check Tag
• Humans MeSH
• Aged, 80 and over MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Chromatin remodeling, including histone post-translational modifications, during spermatogenesis can affect sperm quality and fertility, and epigenetic marks may therefore be useful for clinical evaluations of sperm. Together with histone hyperacetylation, the dimethylation of histone H3 on lysine K4 (H3K4me2) is also required during protamination. Accordingly, we evaluated the utilization of this epigenetic mark for the identification of sperm with decrease quality and immature chromatin. In this study, 99 semen samples, including 22 normozoospermic (N), 63 asthenozoospermic (A), and 14 oligoasthenozoospermic (OA) samples, were comprehensively analyzed with respect to H3K4me2 levels, DNA damage (DNA fragmentation index, DFI), and sperm immaturity (high DNA stainability, %HDS), as determined by a sperm chromatin structure assay using flow cytometry. We detected a significant relationship between H3K4me2 and %HDS (r = 0.47; p < 0.001). Furthermore, we observed negative correlations between H3K4me2 and sperm concentration, motility, and mitochondrial activity (p < 0.05). The increase in immaturity as semen quality decreased (N > A > OA) indicates the importance of chromatin immaturity and histone code deviations in sperm evaluations. Using various approaches, our study elucidated H3K4me2 as a molecular marker of sperm quality with potential use in reproductive medicine.Abbreviations: A: asthenozoospermic; AO: acridine orange; ART: assisted reproductive therapy; BWW: Biggers-Whitten Whittingham; DAPI: 4',6' -diamidino-2-phenylindole; DFI: DNA fragmentation index; H3K4me2: dimethylation of lysine K4 on histones H3; HDS: high DNA stainability; HRP: horseradish peroxidase; MACS: magnetic-activated cell sorting; N: normospermic; NGS: normal goat serum; OA: oligoasthenozoospermic; PTM: post-translational modification; SCSA: sperm chromatin structure assay; SUTI: sperm ubiquitin tag assay; TBS-T: TBS with 0.5% Tween-20.

• MeSH
• Semen Analysis MeSH
• Asthenozoospermia metabolism   MeSH
• Biomarkers metabolism   MeSH
• Adult MeSH
• Histone Code * MeSH
• Histones metabolism   MeSH
• Humans MeSH
• Methylation MeSH
• Oligospermia metabolism   MeSH
• Chromatin Assembly and Disassembly * MeSH
• Spermatozoa metabolism   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

The development of efficient galectin-3 (Gal-3) inhibitors draws attention in the field of anti-cancer therapy, especially due to the prominent role of extra- and intracellular Gal-3 in vital processes of cancerogenesis, such as immunosuppression, stimulation of tumor cells proliferation, survival, invasion, apoptotic resistance, and metastasis formation and progression. Here, by combining poly-LacNAc (Galβ4GlcNAc)-derived oligosaccharides with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers, we synthesized multivalent glycopolymer inhibitors with a high potential to target extracellular and intracellular Gal-3. The inhibitory capabilities of the best conjugate in the studied series were in the nanomolar range proving the excellent Gal-3 inhibitory potential. Moreover, thorough investigation of the inhibitory effect in the biological conditions showed that the glycopolymers strongly inhibited Gal-3-induced apoptosis of T lymphocytes and suppressed migration and spreading of colorectal, breast, melanoma, and prostate cancer cells. In sum, the strong inhibitory activity toward Gal-3, combined with favorable pharmacokinetics of HPMA copolymers ensuring enhanced tumor accumulation via the enhanced permeability and retention effect, nominate the glycopolymers containing LacdiNAc-LacNAc (GalNAcβ4GlcNAcβ3Galβ4GlcNAc) tetrasaccharide as promising tools for preclinical in anti-cancer therapy evaluation.

• MeSH
• Apoptosis * MeSH
• Galectin 3 * MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Cell Movement MeSH
• Polymers MeSH
• T-Lymphocytes MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and immunohistochemical features with the more common mesonephric adenocarcinoma (MAC), which mostly arises the uterine cervix. Despite the similarities between these tumors, the histogenesis of M-LAC is still disputable. CASE PRESENTATION: Sixty-one-year-old woman presented with an advanced tumor of the left ovary with intraabdominal spread and liver metastases. After receiving 5 cycles of neoadjuvant chemotherapy, she underwent a hysterectomy with bilateral salpingo-oophorectomy, and resection of the liver metastasis, omentum, and appendix. Histologically, the ovarian tumor consisted of two components, whose morphology and immunohistochemical results were typical of either a serous borderline tumor (immunohistochemical positivity for PAX8, WT1, ER and PR) or a mesonephric-like carcinoma (immunohistochemical positivity for PAX8, TTF1 and GATA3). Only the component of the mesonephric-like adenocarcinoma metastasized to the omentum and liver. A molecular analysis with a panel of 271 genes (size 1020 kbp) was performed separately on samples from the borderline tumor, primary ovarian mesonephric-like adenocarcinoma, and liver metastasis. The results showed the clonal origin of all samples, which shared the same KRAS (NM_004985.3:c.34G > T, p.(G12C)) and PIK3CA (NM_006218.2:c.1633G > A, p.(E545K)) somatic mutations. Moreover, in the sample from the primary mesonephric-like carcinoma and its liver metastasis a likely pathogenic somatic MYCN mutation (NM_005378.4:c.131C > T, p.(P44L) was found. In all samples, the deletion of exons 9-10 in the CHEK2 gene was present, which is in concordance with the previously performed genetic testing of the blood specimen which revealed the hereditary CHEK2 mutation in this patient. CONCLUSIONS: Our result support the theory that at least some mesonephric-like ovarian adenocarcinomas are of Müllerian origin. The serous borderline tumor seems to be a precursor of mesonephric-like adenocarcinoma, which has been proven in our case by both tumors sharing the same mutations, and the presence of cumulative molecular aberrations in the mesonephric-like adenocarcinoma.

• MeSH
• Adenocarcinoma diagnosis   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mesonephroma pathology   MeSH
• Biomarkers, Tumor analysis   MeSH
• Uterine Neoplasms diagnosis   pathology   MeSH
• Ovarian Neoplasms diagnosis   pathology   MeSH
• Ovary pathology   MeSH
• Precancerous Conditions pathology   MeSH
• Cystadenoma, Serous diagnosis   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

The Bordetella adenylate cyclase toxin-hemolysin (CyaA) and the α-hemolysin (HlyA) of Escherichia coli belong to the family of cytolytic pore-forming Repeats in ToXin (RTX) cytotoxins. HlyA preferentially binds the αLβ2 integrin LFA-1 (CD11a/CD18) of leukocytes and can promiscuously bind and also permeabilize many other cells. CyaA bears an N-terminal adenylyl cyclase (AC) domain linked to a pore-forming RTX cytolysin (Hly) moiety, binds the complement receptor 3 (CR3, αMβ2, CD11b/CD18, or Mac-1) of myeloid phagocytes, penetrates their plasma membrane, and delivers the AC enzyme into the cytosol. We constructed a set of CyaA/HlyA chimeras and show that the CyaC-acylated segment and the CR3-binding RTX domain of CyaA can be functionally replaced by the HlyC-acylated segment and the much shorter RTX domain of HlyA. Instead of binding CR3, a CyaA1-710/HlyA411-1024 chimera bound the LFA-1 receptor and effectively delivered AC into Jurkat T cells. At high chimera concentrations (25 nm), the interaction with LFA-1 was not required for CyaA1-710/HlyA411-1024 binding to CHO cells. However, interaction with the LFA-1 receptor strongly enhanced the specific capacity of the bound CyaA1-710/HlyA411-1024 chimera to penetrate cells and deliver the AC enzyme into their cytosol. Hence, interaction of the acylated segment and/or the RTX domain of HlyA with LFA-1 promoted a productive membrane interaction of the chimera. These results help delimit residues 400-710 of CyaA as an "AC translocon" sufficient for translocation of the AC polypeptide across the plasma membrane of target cells.

• MeSH
• Adenylate Cyclase Toxin metabolism   MeSH
• Lymphocyte Function-Associated Antigen-1 metabolism   MeSH
• Bordetella * MeSH
• CHO Cells MeSH
• Cricetulus MeSH
• Cytosol metabolism   MeSH
• Jurkat Cells MeSH
• Humans MeSH
• Macrophage-1 Antigen metabolism   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• THP-1 Cells MeSH
• Protein Transport MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH