Introduction: The introduction of BRAF inhibitor vemurafenib significantly improvedoverall survival (OS) in metastatic melanoma patients.Aim of the Study: The purpose of this study was to determine OS and progressionfree survival (PFS) in patients with advanced metastatic melanoma treated withvemurafenib in the Oncology Clinic, University Clinical Centre of the Republic ofSrpska (UKC RS). The secondary goal is to determine the effect of elevated serumlactate dehydrogenase (LDH) on OS.Patients and Methods: We analysed patients that received vemurafenib in theApril 2015. until March 2018. They had pathohistologically confirmed B-RAF positivemetastatic melanoma. LDH values were measured at the start of the treatment.Results: A total of 16 patients were analyzed, with an average age of 53 years(37-78). A large number of patients at the start had multiple sites of metastases.Calculated OS in patients who received vemurafenib is 11.8 months (p=0,23), withstandard deviation (SD) 9.18. The calculated PFS is 9.5, SD 7,57. OS in patients withnormal LDH is 14.4 months, SD 10.73, and with elevated LDH is 8.4 months, SD4.9 (p=0.079).Conclusion: Use of vemurafenib resulted in an improvement in PFS, with improvedOS in patients with advanced BRAF-mutated melanoma. In patients with elevatedLDH OS was reduced. This shows that LDH is a good prognostic marker and thatwe should do it routinely for all patients with melanoma. This study has indicatedthe need for new diagnostic and therapeutic options for melanoma in Republic ofSrpska.

For a young researcher, the best way to improve his skills and develop his research capabilities is to work in established research laboratories where he is enabled to learn modern techniques and how to attack the scientific problems. Today, we have easy communications, including computers and the internet, but direct interactions with the most experienced scientists are the best way for young scientist to advance his research capabilities. Ulf Svante von Euler, Swedish pharmacologist and physiologist presents the best example that illustrates how interaction of a young researcher with established scientists develop his research capabilities and become a well-known scientist1.When Ulf was seventeen (1922), he came in Stockholm to study medicine. As a student, he became interested in research, and in 1926 he attended the Twelfth International Congress of Physiologists in Stockholm where he heard lectures by I. P. Pavlov, E. H. Starling and other great scientists of the time. He also observed a historic demonstration by Otto Loewi on the existence of Vagusstoff in the frog’s heart, which would stimulate his own interest and research on mediators of nerve transmission. Prior to this demonstration, Loewi had published several papers on the nature of this chemical substance that slowed the heart, but not all of his research contemporaries were convinced. However, a successful demonstration at the Congress (repeated eighteen times) convinced all critics. Von Euler recalled that these experiments inspired his enduring interest in neurohumoral transmission.Initially, von Euler was influenced by several well-known Swedish scientists: G. Liljestrand (pharmacologist/physiologist), R. Fåraeus (a hematologist) and H. Theorell (a biochemist, who received the Nobel Prize for Medicine and Physiology in 1955). Ulf defended his doctoral dissertation in 1930 and became a professor of pharmacology. Then, he received a two-year scholarship for postdoctoral studies abroad that enabled him to improve his skills by working with several famous foreign researchers.The young Ulf von Euler made the most of this opportunity. He spent six months in Hampstead at Sir Henry Dale’s laboratory, two months in Birmingham with I. de Burgh Daly, eight months in Ghent with C. Heymans, and three months in Frankfurt with G. Embden. Later, in 1934, he returned to London for six months to work with A. Hill, primarily because Liljestrand advised him instead of pharmacology, rather to devote to physiology because at that time in Sweden this scientific discipline was more appreciated. Towards the end of 1937, he went back to Hampstead for five months to work again with Sir Henry Dale.

Introduction: Gastrectomy is one of the most common surgical methods for the treatment of gastric cancer, which basically destroys the mechanism and digestion chemistry. Reconstruction after gastrectomy attempts to optimize the antireflux and nutritive component of the postgastrectomic syndrome.Objective: To determine which reconstructive method after gastrectomy has the optimal synthesis of antireflux and nutritional components.Patients and Methods: 111 patients were treated for gastric malignancies at the Surgical Clinic of the University Clinical Center in Banja Luka, which were operated with the intention of achieving curability.Results: Based on Fisher’s exact probability test there is no statistically significant difference (p> 0.05) in mortality compared to the restoration of digestive continuity after gastrectomy. Reflux oesophagitis is the dominant modality of morbidity in omega-loop reconstruction (p <0.05). There is no statistically significant difference (p> 0.05) in late dumping syndrome in patients relative to individual gastric substitution options. In the Hunt-Lawrence-Rodino pouch reconstruction option, there is no statistically significant difference (p> 0.05) in the participation of individual modalities of meal quantity in relation to the condition before the disease or the modality of the nutritional status. .Conclusion: The results indicate the antireflux component of reconstruction Roux en Y and the advantage of the nutritive component in the loop modification (the creation of the Hunt-Lawrence-Rodino pouch).

During the field investigation of wetland flora and vegetation conducted on carstic terrains of Nevesinjsko polje (Bosnia & Herzegovina) we discovered numerous individuals of Carex limosa L. This Arctic–boreal relic species is remarkably rare in Southeastern Europe with only several known records across Balkans and few recent records for Bosnia & Herzegovina. Its habitat in Nevesinjsko polje can be described as an transitional mire with pronounced Sphagnum turfs on top of which C. limosa forms almost homogenous, species–poor stands of community Caricetum limosae Br.–Bl. In this article is presented the short account of this first confirmed record of C. limosa for Nevesinjsko polje (Bosnia & Herzegovina).

Summary The second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) stimulates gene expression via the cAMP-regulated transcriptional coactivator (CRTC) family of cAMP response element-binding protein coactivators. In the basal state, CRTCs are phosphorylated by salt-inducible kinases (SIKs) and sequestered in the cytoplasm by 14-3-3 proteins. cAMP signaling inhibits the SIKs, leading to CRTC dephosphorylation and nuclear translocation. Here we show that although all CRTCs are regulated by SIKs, their interactions with Ser/Thr-specific protein phosphatases are distinct. CRTC1 and CRTC2 associate selectively with the calcium-dependent phosphatase calcineurin, whereas CRTC3 interacts with B55 PP2A holoenzymes via a conserved PP2A-binding region (amino acids 380–401). CRTC3-PP2A complex formation was induced by phosphorylation of CRTC3 at S391, facilitating the subsequent activation of CRTC3 by dephosphorylation at 14-3-3 binding sites. As stimulation of mitogenic pathways promoted S391 phosphorylation via the activation of ERKs and CDKs, our results demonstrate how a ubiquitous phosphatase enables cross talk between growth factor and cAMP signaling pathways at the level of a transcriptional coactivator.

Abstract This video demonstrates microsurgical resection of low-grade (Grade I) thoracic spinal cord astrocytoma. Astrocytomas are the most common pediatric intramedullary tumors and occur secondary to ependymomas in adults.1,2 The treatment goal should be radical gross total resection while preserving neurological function with intraoperative neuromonitoring.2-4 To our knowledge, this is the first video report on microsurgical resection of low-grade spinal cord astrocytoma.  A 58-yr-old female presented with gait disturbances has been featured in this video. A spinal MRI revealed T1/T2 hyperintense intramedullary tumor at T4, suggesting spinal cord astrocytoma versus ependymoma. Dura was opened in the midline and tacked to the surrounding muscle tissue with tacking sutures. The arachnoid was opened separately with microscissors, keeping it intact for closure at the end of surgery. Liga clips were applied to hold the arachnoid to the dura. Myelotomy was done in the midline,5 opening the posterior median sulcus over the length of the tumor and extending proximally and distally a few millimeters beyond the tumor.3,5 The tumor reduction was achieved by coagulation or debulking. Once sufficient debulking was achieved, dissection of the tumor margins toward surrounding cord was performed. Preoperative recording of motor-evoked potentials (MEPs) compared with continuous intraoperative MEPs were essential for preserving the neurological function and quality of life. The intraoperative finding of a clear tumor plane of resection carries positive prognostic significance and reduces the risk of complications.2,3,6  A pathohistological diagnosis showed a low-grade (Grade I) spinal cord astrocytoma (pilocytic). Follow-up MRI showed no sign of tumor or recurrence. The patient recovered fully and was neurologically intact. Written consent was obtained directly from the patient.

We correct the exponent in the error term of the prime geodesic theorem for hyperbolic 3‐manifolds and in Park's theorem for higher dimensions [ , ].

Differences in gut microbiota composition and function were observed between patients with inflammatory bowel disease or irritable bowel syndrome. Distinguishing two similar gut disorders Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are two of the most common diseases of the gastrointestinal tract. In new work, Vich Vila and colleagues have characterized the gut microbiota composition of both disorders using shotgun metagenomic sequencing of stool samples from 1792 individuals. Analyses involving bacterial taxonomy, metabolic functions, antibiotic resistance genes, virulence factors, and bacterial growth rates showed key differences between these two gut disorders. On the basis of gut microbiota composition differences, patients with IBD could be distinguished from those with IBS. Changes in the gut microbiota have been associated with two of the most common gastrointestinal diseases, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Here, we performed a case-control analysis using shotgun metagenomic sequencing of stool samples from 1792 individuals with IBD and IBS compared with control individuals in the general population. Despite substantial overlap between the gut microbiome of patients with IBD and IBS compared with control individuals, we were able to use gut microbiota composition differences to distinguish patients with IBD from those with IBS. By combining species-level profiles and strain-level profiles with bacterial growth rates, metabolic functions, antibiotic resistance, and virulence factor analyses, we identified key bacterial species that may be involved in two common gastrointestinal diseases.

Concentrations of phosphorus (P), the main limiting nutrient in freshwater ecosystems, need to be reduced, but this is difficult due to high spatial and temporal variations and limited resources. Reliable targeting of critical source areas, such as erosion-prone fields and parts of fields, is necessary to improve the cost efficiency of mitigation measures. We used high-resolution (2 m × 2 m) distributed modelling to calculate erosion risk for a large area (202 279 km2) covering > 90% of Swedish arable land. Comparison of model results with independent farmers’ observations in a pilot catchment showed high spatial agreement. The modelled worst case scenario produced reasonable quantitative results comparable to measured 90th percentile values of suspended sediment (SS) loads at both field and small catchment scale (R2 = 0.81, p < 0.001). Overall, loads of SS, especially during extreme episodes, strongly governed losses of unreactive P and total P at both field and catchment scale.