Trombosis del stent 10 años después de la intervención coronaria percutánea con stents nuevos frente a stents de la primera generación. Observaciones del metanálisis DECADE / Ten-year patterns of stent thrombosis after percutaneous coronary intervention with new- versus early-generation drug-eluting stents: insights from the DECADE cooperation

Introducción y objetivos El metanálisis DECADE es un análisis de datos de pacientes individuales de ensayos de stents liberadores de fármacos (SLF) con un seguimiento de 10 años. El objetivo del estudio es analizar el riesgo de trombosis definitiva del stent (TS) hasta 10 años después de la intervención coronaria percutánea (ICP) en pacientes tratados con DES de primera y de nueva generación. Métodos Se agruparon los datos de pacientes individuales de cinco ensayos de SLF con un seguimiento de 10 años. El objetivo primario fue la TS hasta 10 años después de la ICP. Los pacientes se dividieron en 2 grupos según la generación de stent implantada (primera y nueva). El análisis de los datos de los participantes individuales se realizó mediante el enfoque de una etapa. Resultados Se incluyeron 9.700 pacientes, 6.866 en el grupo de SLF nuevos y 2.834 en el grupo de SLF de primera generación. A los 10 años, la TS se produjo en 69 de los 6.866 pacientes tratados con SLF de nueva generación y en 91 de los 2.834 pacientes tratados con la SLF de primera generación (1,0% frente a 3,5%, razón de tasas 0,32; IC95%, 0,23-0,45). La tasa de TS fue menor en el grupo de SLF de nueva generación en comparación con el grupo de SLF de primera, de 1-5 años (razón de tasas 0,14; IC95%, 0,08-0,26) y de 5-10 años (razón de tasas 0,23; IC95%, 0,08-0,61) después de la ICP. Conclusiones La incidencia de TS hasta 10 años después de la ICP con los SLF de nueva generación es del 1%. Los SLF de nueva generación se asocian a una menor incidencia de TS a 10 años comparados con los SLF de primera generación, especialmente después de 1 año de la ICP (AU)

Introduction and objectives The DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES. Methods Individual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach. Results We included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI. Conclusions The incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PC (AU)

[miR-485-3p and miR-4728-5p as Tumor Suppressors in Pathogenesis of Colorectal Cancer].

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have major functions in the development and progression of colorectal cancer (CRC) as tumor suppressors or oncogenes. The aim of the current research was to assess the role of miR-485-3p and miR-4728-5p in the pathogenesis of CRC. In this study, fresh tumor and adjacent non-tumor tissue samples were obtained from a total of 59 CRC patients, 37 from colon and 22 from rectum. The expression profiles of miR-485-3p and miR-4728-5p were determined using qRT-PCR. miRNA-related transcription factor (TF) regulatory networks were constructed using the TransmiR v2.0, TF-regulated target genes were determined using the Human.mirFFL.DB and TRRUST v2.0, functional annotation and pathway enrichment analyses were performed using DIANA-mir-Path v3.0 and -Tarbase v7.0. The results demonstrated that the expression levels of both miR-485-3p and miR-4728-5p were very significantly downregulated in CRC tissues (fold changes = 0.42 ± 0.70 and 0.59 ± 1.06, respectively; both p = 0.000). On the other hand, lower expression levels of miR-485-3p were detected in the both rectum and colon. Moreover, the decrease in the expression levels of miR-4728-5p was correlated with increasing age. However, these differences were not statistically significant according to the FDR-related p-values (0.126 and 0.168, respectively). By bioinformatics analyses, miR-485-3p and miR-4728-5p-related TFs were identified. Some of these TFs, namely, AR, CREB1, CEBPB, FOXA1, GTF2I, MAZ, NCOR2, NFIC, NRF1, SIN3A, SREBF1, SREBF2, p53 and YY1, appeared to be associated with CRC and were, therefore, selected to construct miRNA-TF-gene networks of potential targets for the early diagnosis and treatment of CRC. Pathway enrichment analysis indicated Hippo signaling pathway as heavily regulated by miR-485-3p. It seems that the decrease in expression levels of miR-485-3p and miR-4728-5p might be associated with development of colorectal cancer.

The Effects of O6-methyl Guanine DNA-methyl Transferase Promotor Methylation and CpG1, CpG2, CpG3 and CpG4 Methylation on Treatment Response and their Prognostic Significance in Patients with Glioblastoma.

This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O6- methyl guanine methyl transferase (MGMT) and meth-ylation of CpG 1, CpG2, CpG3 and CpG4 in glioblastoma (GB) patients received postoperative radiotherapy (PORT), with or without adjuvant temozolomide (TMZ). One hundred patients with GB who received PORT with concomitant TMZ plus adjuvant TMZ or PORT alone, were included. The MGMT promoter methylation of CpG1, CpG2, CpG3 and CpG4 islands were examined. Overall, MGMT-methylation emerged as a significant prognostic factor for better overall survival (OS) and progression-free survival (PFS) [odds ratio (OR): 0.609, 95% confidence interval (95% CI): 0.395-0.939, p = 0.02; OR: 0.662,95% CI: 0.430-1019, p = 0.5, respectively]. The methylation of each CpG1, CpG2, CpG3 and CpG4 islands was found to have no significant effects on OS and the methylation of each CpGl, CpG2 and CpG4 islands had no significant effect on PFS (p <0.05 for all). On the other hand, the methylation of CpG3 had a positive prognostic effect on PFS (OR: 2.1, 95% CI: 0.99-4.67, p = 0.04). In the group that only received radiotherapy (RT), CpG1 and CpC3 methylations were found to have a positive prognostic significance in terms of PFS (OR: 266, 95% CI: 1.05-6.75, p -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, p = 0.04 for CpG3). The MGMT promoter methylation represents an important biomarker for predicting response to therapy. Individual islands, particularly CpG3, deserves further investigation as a prognostic marker. Further studies need to be done with larger sample sizes to clarify the results.

Morphometric analysis of fossil bumble bees (Hymenoptera, Apidae, Bombini) reveals their taxonomic affinities.

Bumble bees (Bombus spp.) are a widespread corbiculate lineage (Apinae: Corbiculata: Bombini), mostly found among temperate and alpine ecosystems. Approximately 260 species have been recognized and grouped recently into a simplified system of 15 subgenera. Most of the species are nest-building and primitively eusocial. Species of Bombus have been more intensely studied than any other lineages of bees with the exception of the honey bees. However, most bumble bee fossils are poorly described and documented, making their placement relative to other Bombus uncertain. A large portion of the known and presumed bumble bee fossils were re-examined in an attempt to better understand their affinities with extant Bombini. The taxonomic affinities of fossil specimens were re-assessed based on morphological features and previous descriptions, and for 13 specimens based on geometric morphometrics of forewing shape. None of the specimens coming from Eocene and Oligocene deposits were assigned within the contemporary shape space of any subgenus of Bombus. It is shown that Calyptapis florissantensis Cockerell, 1906 (Eocene-Oligocene boundary, Florissant shale, Colorado, USA) and Oligobombus cuspidatus Antropov, 2014 (Late Eocene, Bembridge Marls) likely belong to stem-group Bombini. Bombus anacolus Zhang, 1994, B. dilectus Zhang, 1994, B. luianus Zhang, 1990 (Middle Miocene, Shanwang Formation), as well as B. vetustus Rasnitsyn & Michener, 1991 (Miocene, Botchi Formation) are considered as species inquirenda. In the Miocene, affinities of fossils with derived subgenera of Bombus s. l. increased, and some are included in the shape space of contemporary subgenera: Cullumanobombus (i.e., B. pristinus Unger, 1867, B. randeckensis Wappler & Engel, 2012, and B. trophonius Prokop, Dehon, Michez & Engel, 2017), Melanobombus (i.e., B. cerdanyensis Dehon, De Meulemeester & Engel, 2014), and Mendacibombus (i.e., B. beskonakensis (Nel & Petrulevicius, 2003), new combination), agreeing with previous estimates of diversification.

Krukenberg tumor presenting with amenorrhea as the sole initial symptom: Case report and review of the literature.

Krukenberg tumor (KT), mostly originates from gastric cancer, is the metastatic tumor of ovaries accounting for 1-2% of all ovarian cancer. Common presenting symptoms include abdominal pain, distension, and ascites. Rests of the patients have non-specific gastrointestinal symptoms including dyspepsia, weight loss, nausea and vomiting. Gynecologic symptoms such as virilization, menstrual bleeding or irregularity and amenorrhea are much less frequent in the literature cases. Here, we present an unusual case of KT presented with amenorrhea as the sole initial symptom.

Improvement production of bacterial cellulose by semi-continuous process in molasses medium.

Bacterial cellulose (BC) has unique properties such as structural, functional, physical and chemical. The mass production of BC for industrial application has recently become attractive to produce more economical and high productive cellulose. In this study, to improve the productivity of bacterial cellulose (BC), BC production by Gluconacetobacter xylinus FC01 was investigated in molasses medium with static semi-continuous operation mode. Cell dry weight, polysaccharide, sugar and cellulose concentrations were monitored and cellulose was characterized by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The highest cellulose yield (1.637 g/L) was obtained in SCP50-7d, which molasses of 1/2 ratio for 7 days by static semi-continuous operation mode. The results show that BC can be highly produced by G. xylinus in molasses with static semi-continuous process than batch process. We claimed that low-cost medium with semi-continuous operation mode in static culture is a good candidate for industrial scale BC productions.

Systematical studies on the species of the subgenus Bombus (Thoracobombus) (Hymenoptera: Apidae, Bombus Latreille) in Turkey.

The aim of this study was to analyze the 12 species which belong to the subgenus Bombus (Thoracobombus) by identifying, collating and testing the applicability of geometrics morphometrics for distinguishing the species. This was carried out on 133 females and 42 males which were collected from various localities in Turkey. After digitizing landmarks on the right fore wings, 2-dimensional Cartesian coordinates were calculated and by Procrustes analysis the coordinates were standardized and superimposed. Principal Components Analysis (PCA) and Canonical Variates Analysis (CVA) were performed to show the distribution of all species. Then, deformations which appeared in thin-plate splines were observed. Mean values of all the specimens were calculated and Sequential, Agglomerative, Hierarchical, and Nesting clustering method (SAHN) was performed with these data to obtain the dissimilarity trees. It can be concluded that all species were found to have consistently different wing shapes from each other. In females, the species B. armeniacus, B. mesomelas and B. pomorum which resemble each other, were also found to be similar based on their wing morphometry. Both in females and males, the subspecies B. sylvarum citrinofasciatus and B. sylvarum daghestanicus and the species B. humilis and B. laesus exposed high similarity in wing morphometry. In males, results showed that the species B. armeniacus and B. mesomelas and the species B. humilis and B. zonatus have very similar wing shape.

Metastatic malignant peripheral nerve sheath tumor in neurofibromatosis type 1: a geriatric patient report.

Neurofibromatosis type 1 (NF1) (von Recklinghausen disease) is an autosomal dominantly inherited neurocutaneous disorder which affects many systems like ocular, cutaneous and nervous systems and seen in 1:3500 births. Cardinal diagnostic criteria of NF1 were established in 1987 by National Institutes of Health Consensus.Early diagnosis and the findings of NF1 are unclear in childhood, but with age the clinical symptoms become apparent. NF1 is occasionally associated with mental retardation.In this report, together a review of the literature, we present a quite elderly patient, 79-year-old-man, with NF1 suffering from metastatic malignant peripheral nerve sheath tumor in the axillary lymph node invading the brachial plexus and pleura. Moreover, this enormous metastatic mass had restricted movement of the extremity. He had multiple neurofibromas of different sizes almost covering his entire body, massively. To the best of our knowledge, our patient's malignant peripheral nerve sheath tumor and massive neurofibromatosis is a rare case to present in the eighth decade of life.

An alternative micrographic method for decreasing bleeding and recurrence in the treatment of rhinophyma.

Rhinophyma is a subtype of rosacea which develops at the advanced stage of rosacea and is characterized by an excessive enlargement of the sebaceous glands. Its etiology is not well-defined beyond the following usual suspects: vitamin deficiencies, stress, hormonal factors and the Demodex folliculorum mite. Carcinoma may develop in rhinophyma patients. The first surgical process for rhinophyma was applied by Daniel Sennert in 1629. The ideal surgical method for treatment of rhinophyma is still unclear and controversial. Massive bleeding makes a controlled excision of the mass impossible, which contributes to the recurrence of rhinophyma. In this case, we combined trichloroacetic acid (TCA 45%) with dermabrasion, a treatment which hasn't been reported previously. Our method was suggested by the Mohs micrographic surgery technique, which employs serial excisions.

Intraspecific variability of natural populations of Phlebotomus sergenti, the main vector of Leishmania tropica.

An intraspecific study of Phlebotomus sergenti was performed on populations from Turkey, Syria, Israel, and Uzbekistan by four different approaches: geometric morphometrics, RAPD analysis, internal transcribed spacer 2 (ITS2) sequencing (nuclear marker), and cytochrome B sequencing (mitochondrial marker). In RAPD analysis, distinct clades were formed in accordance with the geographical origin of the specimens. There was no distinct grouping according to place of origin within the Turkish samples from various localities in south-eastern Anatolia, which suggests a gene flow between populations separated spatially by the Amanos mountains, a mountain range of a considerable altitude. The results of ITS2 rDNA sequencing complied with the previously published intraspecific division of P. sergenti into two branches, northeastern and southwestern. However, mtDNA haplotypes formed three lineages with specimens from Turkey and Israel, sharing a common clade. A previously postulated hypothesis about a complex of sibling species within P. sergenti is therefore questionable. Cytochrome B seems to be a more discriminative marker for intraspecific variability assessment.

Effect of different larval rearing temperatures on the productivity (R o) and morphology of the malaria vector Anopheles superpictus Grassi (Diptera: Culicidae) using geometric morphometrics.

Temperature affects both the biology and morphology of mosquito vectors. Geometric morphometrics is a useful new tool for capturing and analyzing differences in shape and size in many morphological parameters, including wings. We have used this technique for capturing the differences in the wings of the malaria vector Anopheles superpictus, using cohorts reared at six different constant temperatures (15°, 20°, 25°, 27°, 30°, and 35° C) and also searched for potential correlations with the life tables of the species. We studied wing shape in both male and female adults, using 22 landmarks on the wing in relation to ecological parameters, including the development rate. The ecological zero was calculated as 9.93° C and the thermal constant as 296.34 day-degrees. The rearing temperature affects egg, larval, and pupal development and also the total time from egg to adult. As rearing temperatures increased, longevity decreased in both sexes. In An. superpictus, R(o) value and productivity correlated with the statistically significant gradual deformations in the wing shape related to size in both sexes. These deformations directly linked to differences in immature rearing temperatures. Analysis using PCA and UPGMA phenograms showed that although wings of females became narrower dorsoventrally as the temperature increased, they became broader in males. Comparisons of the wing landmarks indicated the medial part of the wing was most affected by larval rearing temperatures, showing relatively more deformations. Algorithmic values of the life tables were determined in correlation with the results of geometric morphometrics. Comparisons of centroid sizes in the cohorts showed that overall wing size became smaller in both sexes in response to higher rearing temperatures.

Phenotypic variation among local populations of phlebotomine sand flies (Diptera: Psychodidae) in southern Turkey.

The wing-shape morphology of local populations of the medically important phlebotomine sand flies, Phlebotomus sergenti, P. papatasi, P. tobbi, and P. similis, were examined in both sexes by using geometric morphometrics. There are three major mountain ranges that may serve as geographical barriers for species distribution in the study area and four main gaps were recognized among these barriers. We found no statistically important differences in wing morphology in all examined species in both sexes for all local populations. These results show that the barriers are not sufficient to stop gene flow among local populations of sand flies. The graphical depiction of PCA, CVA, and F-test confirmed our morphometric study suggesting that the difference in wing morphology between P. similis and P. sergenti indicates that these are clearly different species. These two show sympatric distribution in the Konya Plain of Anatolia.

Distribution and altitudinal structuring of phlebotomine sand flies (Diptera: Psychodidae) in southern Anatolia, Turkey: their relation to human cutaneous leishmaniasis.

The two Old World genera, Phlebotomus and Sergentomyia, were both recorded in southern Anatolia in Turkey. Phlebotomus species predominated and comprised about 93% of the entire collection (3,172 specimens). Out of the sixteen species identified, two belonged to the genus Sergentomyia: S. dentata and S. theodori. The remaining fourteen species in the genus Phlebotomus were grouped under four subgenera including some species that are elsewhere known to act as vectors of human cutaneous leishmaniasis. Most of the Phlebotomus were P. tobbi (32.5%), but P. papatasi, P. transcaucasicus, P. halepensis, P. galilaeus, P. sergenti, P. syriacus, P. neglectus, P. simici, P. alexandri, P. similis, P jacusieli, P. perfiliewi, and P. brevis were also identified. There were two associations of sand fly fauna with altitudinal gradient; the first one at relatively higher altitudes and the second one at lower altitudes. The transition between these two assemblages was within the range of 800-1,000 m. It is likely that Adana and Hatay provinces are transitional areas between western and eastern Anatolia. Mountains do not appear to be important geographical barriers for sand fly distribution. We also found that the proven vector P. sergenti is a widely distributed species throughout southern Anatolia and this species, together with its closely related species P. similis, shows sympatry in Konya Province.

A comparison of the intraspecific variability of Phlebotomus sergenti Parrot, 1917 (Diptera: Psychodidae).

Phlebotomus sergenti populations from different areas of the Mediterranean basin are known to exhibit high intraspecific variability. Previous studies of ITS2 revealed the presence of two branches that may represent sibling species. To corroborate this finding by other tools, two colonies of P. sergenti originating from Turkey and Israel, each belonging to a different ITS2 branch, were compared by three different methods: geometric morphometric analysis of wing shape, RAPD (random amplified polymorphic DNA), and cross-mating study. For geometric morphometric analysis, two-dimensional Cartesian coordinates of 16 landmarks from the wings were digitized and analyzed. Significant shape differences were found between colonies but not between sexes within each colony. RAPD results formed two distinctive clades corresponding to the origin of the colony but also showed heterogenity among members of both colonies. In cross-mating studies, viable hybrid F1 and F2 progeny were obtained when both Turkish males/Israeli females and Israeli males/Turkish females were crossed. F1 progeny was included in RAPD analysis and these hybrids formed a distinctive clade with an intermediate position between the two parental clades. No significant differences were found in egg production of crossed sand flies. The cross-mating study showed that there is no reproductive barrier between P. sergenti from different geographical areas. On the other hand, RAPD and geometric morphometric analysis revealed a significant difference between colonies and confirmed the suitability of previous ITS2 analysis for discrimination among sand fly populations. Further development of molecular markers should resolve a possible existence of sibling species within Phlebotomus sergenti.

Variability in natural populations of Anopheles sacharovi (Diptera: Culicidae) from southeast Anatolia, revealed by morphometric and allozymic analyses.

Four populations of Anopheles sacharovi Favre occurring in different ecological subregions at altitudes between 353-1,126 m in the Sanliurfa Province of southeast Turkey were compared using morphometric and allozyme analyses. Four allozyme loci were assessed for genetic differentiation among samples from four localities. The similarity phenogram obtained from the allozyme data showed that populations at Birecik and Sandi branched as a separate group from the Pamuklu and Gedik populations. The Gedik population at the highest altitude (1,126 m) was clustered as a separate branch when linear measurements of 63 morphological characteristics were examined. The UPGMA phenogram also showed that Pamuklu and Sandi formed a cluster while Birecik and Gedik formed separate groups.

Altitudinal variation in morphometric and molecular characteristics of Phlebotomus papatasi populations.

Four populations of the phlebotomine sandfly Phlebotomus (Phlebotomus) papatasi (Scopoli) (Diptera: Psychodidae), in different ecoregions at altitudes between 368 and 1117 m in the Sanliurfa Province of Turkey, were compared using morphometric and isoenzyme analyses. A similarity phenogram obtained from allozyme data showed that heterozygosity was extremely low, particularly for the alleles which were found to be completely fixed in populations at Hamdun (HMD) and Alitas (ALT). Populations at Akcakale (AKL) and ALT branched as a separate group from populations at Hayatiharrani (HHR) and HMD. The ALT population at the highest altitude (1117 m), and the HHR population (488 m) were clustered distinctly when linear measurements of 46 morphological characteristics were examined. A UPGMA (unweighted pair-group method using arithmetic averages) phenogram also showed that ALT and HHR clustered separately, whereas AKL and HMD formed another group.

The prevalence of neurological disorders among children in Gemlik (Turkey).

With a descriptive survey, the authors tried to ascertain the prevalence of certain neurological disorders among children aged up to five years. Questionnaires were administered to mothers and their children were divided into two groups (559 children): neurologically healthy and suspect. Suspect children were examined by a paediatrician, who assigned a diagnosis where appropriate (361 children). A control group was selected from the healthy children (420 children), and they were neurologically examined with the suspect children. Cases and controls were compared for family history, and pregnancy and delivery risks. The most frequent condition found was febrile convulsions (0.45 per cent), followed by epilepsy (0.9 per cent) and cerebral palsy (0.5 per cent).