Histološko i histomorfometrijsko istraživanje kore malog mozga i srebrom obojenih regija nukleolusne organizacije Purkinjeovih neurona u štakora kronično tretiranim morfinom

The effects of chronic morphine administration on the rat cerebellum and silver stained nucleolus organizer regions in Purkinje cells were investigated by means of histological, histochemical and histometrical techniques. Thirty-two young (30-32 days of age) Wistar rats (equal numbers of both genders) were randomly divided into 2 groups, as control and morphine-treated, each having equal numbers of both genders, a total of 16 animals. The control animals were injected subcutaneously with 1mL/kg physiological saline, and the morphine-treated rats received 5 mg/kg morphine hydrochloride subcutaneously at daily intervals for 30 days. The thickness of the molecular and granular layers of the cerebellum, the diameters of the nuclei and nucleoli of cerebellar Purkinje neurones, and the number and size of the silver staining nucleolus organizer regions of the Purkinje cell nuclei were determined histomorphometrically. The morphine administration caused slight histological changes in the cerebellum. The molecular layer thickness of the cerebellum was significantly (P<0.05) reduced, and the decrease was mainly in the male animals. In contrast, the layer thickened insignificantly in the morphine-treated females. The granular layer thickened slightly but insignificantly in both genders of the morphine-treated group. The Purkinje cell count significantly decreased with morphine treatment. Nucleus size did not change with morphine treatment. However, morphine-treated animals had smaller nucleoli. It was concluded that morphine treatment caused significant histomorphological changes in the cerebellar cortex in a sexually dimorphic manner.Učinci kronične primjene morfina na mali mozak štakora i na srebrom obojene regije nukleolusne organizacije Purkinjeovih neurona istraživani su histološkim, histokemijskim i histometrijskim tehnikama. Trideset i dva mlada Wistar štakora (dob 30 - 32 dana), u jednakom omjeru spolova, metodom slučajnog izbora podijeljena su u dvije skupine s po 16 jedinki u svakoj skupini. Životinjama u kontrolnoj skupini potkožno je primijenjen 1 mL/kg fiziološke otopine, dok su životinje u pokusnoj skupini dobile 5 mg/kg morfin hidroklorida, potkožno, svaki dan tijekom 30 dana. Za određivanje zadebljanja molekularnih i granulacijskih slojeva maloga mozga, promjera jezgre i nukleolusa Purkinjeovih neurona u malom mozgu te broja i veličine srebrom obojenih regija nukleolusne organizacije Purkinjeovih neurona primijenjena je histomorfometrijska metoda. Davanje morfina izazvalo je blage histološke promjene u malom mozgu. Debljina molekularnog sloja maloga mozga značajno je smanjena (P<0,05). To je ponajprije bilo izraženo kod životinja muškoga spola, dok je molekularni sloj kod ženki tretiranih morfinom bio tek neznatno zadebljan. Granulirani sloj bio je blago i nesignifikantno zadebljan u oba spola unutar skupine tretirane morfinom. Broj Purkinjeovih stanica značajno je smanjen nakon primjene morfina, dok to nije bio slučaj s veličinom jezgre koja se nije mijenjala. No, životinje koje su dobivale morfin imale su manje nukleole. Zaključeno je da liječenje morfinom uzrokuje značajne histomorfološke promjene u kori maloga mozga, pri čemu važnu ulogu ima spol jedinke

La integración de los refugiados en el mercado laboral turco

La concesión en Turquía del derecho de acceso al trabajo formal a los refugiados sirios fue un primer paso hacia su integración económica, pero sigue habiendo retos. Con el apoyo de la comunidad internacional, el Gobierno turco está tomando medidas para superar algunos de ellos

Incidence of coronary bifurcation lesion as a culprit lesion in patients with acute myocardial infarction: impact of treatment strategy on short- and long-term outcomes

Background: Although, there are several studies comparing single and two-stent techniques in patients with bifurcation lesions, evidence in patients presenting with myocardial infarction (MI) is still insufficient.1-3 We aimed to assess the short- and long-term outcomes of provisional and two-stent techniques of bifurcation lesions in patients with acute coronary syndromes (ACS). Patients and Methods: 2992 patients with MI who underwent percutaneous coronary intervention (PCI) were enrolled in the present study. Of 2992 patients, 385 patients with MI had bifurcation lesions. The Synergy between PCI with TAXUS™ and Cardiac Surgery (SYNTAX) score, pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow, post-PCI TIMI flow, duration of procedure, angiographic features, post-PCI side branch loss, 1- and 12-month mortality rates were noted. Results: 169 (43.9%) patients had ST-segment elevation MI, whereas 216 (56.1%) patients had non-STsegment elevation MI. 355 (92.2%) patients underwent provisional stenting and 30 (7.8%) patients underwent two-stent technique. Side branch loss was observed in 40 patients (11.2%) in the provisional group and 1 patient (3.3%) in the two-stent group (p=0.2). Compared to provisional group, durations of angiography and revascularization in two-stent group were significantly longer (p<0.001 and p<0.001). Both 1-month and 12-month mortality rates were similar in provisional and two-stent groups (4.2% vs. 3.3%, p=0.8 and 11.5% and 13.3%, p=0.7; respectively). Conclusion: In patients presenting with ACS and bifurcation lesions, procedural success, side branch loss, as well as short- and long-term mortality were similar in both provisional and two-stent techniques

Novel Dynamic Partial Reconfiguration Implementation of K-Means Clustering on FPGAs: Comparative Results with GPPs and GPUs

K-means clustering has been widely used in processing large datasets in many fields of studies. Advancement in many data collection techniques has been generating enormous amounts of data, leaving scientists with the challenging task of processing them. Using General Purpose Processors (GPPs) to process large datasets may take a long time; therefore many acceleration methods have been proposed in the literature to speed up the processing of such large datasets. In this work, a parameterized implementation of the K-means clustering algorithm in Field Programmable Gate Array (FPGA) is presented and compared with previous FPGA implementation as well as recent implementations on Graphics Processing Units (GPUs) and GPPs. The proposed FPGA has higher performance in terms of speedup over previous GPP and GPU implementations (two orders and one order of magnitude, resp.). In addition, the FPGA implementation is more energy efficient than GPP and GPU (615x and 31x, resp.). Furthermore, three novel implementations of the K-means clustering based on dynamic partial reconfiguration (DPR) are presented offering high degree of flexibility to dynamically reconfigure the FPGA. The DPR implementations achieved speedups in reconfiguration time between 4x to 15x

Recurrent Intestinal Intussuseption in Adult: A Case Report

Intussusseption is an usually incident that may present in pediatric patients but we encounter rarely in adults. It leads to obstruction of the gastrointestinal tract. In pediatric patients, etiological factors are due to benign incidents usually, but in adults, often depends on tumors. Etiological factors should be investigated after obtaining the reduction of intussusception and intraluminal pathologies should be excluded. It will cause to intussusseption recurrence after years if reduction perform without treating etiological factors

Are the single-step resection and primary anastomosis suitable for obstructıve colorectal patients in older cases?

Aim To investigate the efficacy and safety of the single-step surgery in elderly patients with obstructive colorectal cancer. Methods All patients who underwent single-step surgery and primary anastomosis for obstructive colorectal cancer in the period between January 2012 December 2017 were evaluated in this study. The patients were divided into two groups: younger than 65 (Group Young) and older than 65 (Group Old). Demographic data, American Society of Anesthesiologists scores (ASA) scores, comorbidities, preoperative albumin levels, type of surgery, postoperative morbidity and mortality, pathological stages, and overall survival rates were investigated. Results A total of 89 patients were included: 49 (54%) were older than 65 (Group Old). In Group Old, the mean age was 75 (65-97), of which 28 (58.3%) were males. There were 41 patients younger than 65 (Group Young) with the mean age of 52.6 (41-64 years of age), of which 21 (51.2%) were males. There was no difference between groups according to albumin level. There was no statistical difference between two groups according to tumour localization, pathological stage and type of surgery, as well as according to surgical complications. The median overall survival rate was 11 months in both groups (0-66) (p=0.320). Conclusion Meticulous preparation of older patients (correction of anaemia, electrolyte levels and pH ) paves the road for successful surgeries, including single-step resection and primary anastomosis

Epigenetic-focused CRISPR/Cas9 screen identifies (absent, small, or homeotic)2-like protein (ASH2L) as a regulator of glioblastoma cell survival

Background: Glioblastoma is the most common and aggressive primary brain tumor with extremely poor prognosis, highlighting an urgent need for developing novel treatment options. Identifying epigenetic vulnerabilities of cancer cells can provide excellent therapeutic intervention points for various types of cancers. Method: In this study, we investigated epigenetic regulators of glioblastoma cell survival through CRISPR/Cas9 based genetic ablation screens using a customized sgRNA library EpiDoKOL, which targets critical functional domains of chromatin modifiers. Results: Screens conducted in multiple cell lines revealed ASH2L, a histone lysine methyltransferase complex subunit, as a major regulator of glioblastoma cell viability. ASH2L depletion led to cell cycle arrest and apoptosis. RNA sequencing and greenCUT&RUN together identified a set of cell cycle regulatory genes, such as TRA2B, BARD1, KIF20B, ARID4A and SMARCC1 that were downregulated upon ASH2L depletion. Mass spectrometry analysis revealed the interaction partners of ASH2L in glioblastoma cell lines as SET1/MLL family members including SETD1A, SETD1B, MLL1 and MLL2. We further showed that glioblastoma cells had a differential dependency on expression of SET1/MLL family members for survival. The growth of ASH2L-depleted glioblastoma cells was markedly slower than controls in orthotopic in vivo models. TCGA analysis showed high ASH2L expression in glioblastoma compared to low grade gliomas and immunohistochemical analysis revealed significant ASH2L expression in glioblastoma tissues, attesting to its clinical relevance. Therefore, high throughput, robust and affordable screens with focused libraries, such as EpiDoKOL, holds great promise to enable rapid discovery of novel epigenetic regulators of cancer cell survival, such as ASH2L. Conclusion: Together, we suggest that targeting ASH2L could serve as a new therapeutic opportunity for glioblastoma

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception