Surgical management of intracranial aneurysms (IAs) remains one of the most challenging and dynamic tasks for neurosurgeons. The rivalry between modern time microsurgery and progress in endovascular intervention has provided a great arena for advancement and lead to redefine training concept and referral pattern. Both approaches has its own merits, risks and complications and the best outcome is achieved by case individualization and complimentary multidisciplinary approach.The recent innovation in microscopic and endoscopic tailored skull base approaches, intraoperative 3D and ICG video-angiography, design of high quality aneurysm clips, and refinement of cerebral bypass techniques enhance IAs neurosurgical management and their clinical outcome. The command of tailored skull base approaches should be part of the training curriculum of young generation of neurosurgeons to compliment the emerging treatment options of endovascular intervention.

MicroRNAs (miRNAs), miR-9/9*, and miR-124 (miR-9/9*-124) display fate-reprogramming activities when ectopically expressed in human fibroblasts by erasing the fibroblast identity and evoking a pan-neuronal state. In contrast to induced pluripotent stem cell-derived neurons, miRNA-induced neurons (miNs) retain the biological age of the starting fibroblasts through direct fate conversion and thus provide a human neuron-based platform to study cellular properties inherent in aged neurons and model adult-onset neurodegenerative disorders using patient-derived cells. Furthermore, expression of neuronal subtype-specific transcription factors in conjunction with miR-9/9*-124 guides the miNs to distinct neuronal fates, a feature critical for modeling disorders that affect specific neuronal subtypes. Here, we describe the miR-9/9*-124-based neuronal reprogramming protocols for the generation of several disease-relevant neuronal subtypes: striatal medium spiny neurons, cortical neurons, and spinal cord motor neurons.

BACKGROUND: Colorectal cancer (CRC) is a multifactorial disease resulting from both genetic predisposition and environmental factors including the gut microbiota (GM), but deciphering the influence of genetic variants, environmental variables, and interactions with the GM is exceedingly difficult. We previously observed significant differences in intestinal adenoma multiplicity between C57BL/6 J-ApcMin (B6-Min/J) from The Jackson Laboratory (JAX), and original founder strain C57BL/6JD-ApcMin (B6-Min/D) from the University of Wisconsin.
METHODS: To resolve genetic and environmental interactions and determine their contributions we utilized two genetically inbred, independently isolated ApcMin mouse colonies that have been separated for over 20 generations. Whole genome sequencing was used to identify genetic variants unique to the two substrains. To determine the influence of genetic variants and the impact of differences in the GM on phenotypic variability, we used complex microbiota targeted rederivation to generate two Apc mutant mouse colonies harboring complex GMs from two different sources (GMJAX originally from JAX or GMHSD originally from Envigo), creating four ApcMin groups. Untargeted metabolomics were used to characterize shifts in the fecal metabolite profile based on genetic variation and differences in the GM.
RESULTS: WGS revealed several thousand high quality variants unique to the two substrains. No homozygous variants were present in coding regions, with the vast majority of variants residing in noncoding regions. Host genetic divergence between Min/J and Min/D and the complex GM additively determined differential adenoma susceptibility. Untargeted metabolomics revealed that both genetic lineage and the GM collectively determined the fecal metabolite profile, and that each differentially regulates bile acid (BA) metabolism. Metabolomics pathway analysis facilitated identification of a functionally relevant private noncoding variant associated with the bile acid transporter Fatty acid binding protein 6 (Fabp6). Expression studies demonstrated differential expression of Fabp6 between Min/J and Min/D, and the variant correlates with adenoma multiplicity in backcrossed mice.
CONCLUSIONS: We found that both genetic variation and differences in microbiota influences the quantitiative adenoma phenotype in ApcMin mice. These findings demonstrate how the use of metabolomics datasets can aid as a functional genomic tool, and furthermore illustrate the power of a multi-omics approach to dissect complex disease susceptibility of noncoding variants.

DNA replication, segregation and cell division are vital processes and require an interplay of multiple proteins. These processes are highly conserved across bacteria yet similar or dissimilar progeny are produced after cell division. This review describes the bacterial cell division in considerable detail. This includes studies on model microorganisms which produce similar progeny such as Escherichia coli and Vibrio cholerae, and dissimilar progeny such as sporulating Bacillus subtilis, Actinobacteria, Caulobacter crescentus etc. The mechanism of symmetric and asymmetric cell division and its regulation has also been discussed.

The consumption of dietary fibers has been implicated with a lowered risk of human colorectal cancer. Proposed mechanisms involve alterations in the stool consistency, transit time, and formation of short-chain fatty acid by dietary fiber fermentation, and the reorganization of gut microbiota. Here we show that Fibersol-2, a digest-resistant maltodextrin, not only inhibits proliferation of colorectal SW480 cancer cell lines by increasing reactive oxygen species (ROS), but decreases the numbers of the adenoma count in Multiple Intestinal Neoplasia (MIN) mice carrying a mutation in the Adenomatous Polyposis Coli gene by 84 d of age. These observations provide direct evidence that Fibersol-2 intrinsically contains anti-cancer activity, independent of the intestinal metabolism and any potential interactions with the microbiota.

Chronic inflammatory diseases of the intestinal tract have been known to increase risk of developing a form of colorectal cancer known as inflammation-associated cancer. The roles of inflammation in tumor formation and development in Apc(Min/+) mice have been broadly corroborated. The Apc(Min/+) mouse model contains a point mutation in the adenomatous polyposis coli (Apc) gene and only develops intestinal precancerous lesions, the benign adenomas. Thus, it provides an excellent in vivo system to investigate the molecular events involved in the inflammatory process which may contribute to multistep tumorigenesis and carcinogenesis. Recent investigations that employ this model studied the effects of gene alterations, intestinal microorganisms, drugs, diet, exercise and sleep on the inflammatory process and tumor development, and revealed the mechanisms involved in the formation, promotion and carcinogenesis of adenomas with the background of inflammation. Herein, we focus our review on the application of the Apc(Min/+) mouse model for studying inflammation-associated intestinal tumor and find that anti-inflammation is a possible strategy in combating intestinal tumor, but sometimes anti-inflammation cannot help reduce tumor burden. Moreover, various inflammation-related genes are involved in different mechanistic stages of tumor in Apc(Min/+) mice and intricate regulatory effects of inflammation exist in the whole progression of intestinal tumor.

BACKGROUND: The role of the Wells score for patients who develop signs and symptoms of pulmonary embolism (PE) during hospitalization has not been sufficiently validated. The aim of this study is to evaluate the performance of the Wells score for inpatients with suspected PE and to evaluate the prevalence of pulmonary embolism.
METHODS: We conducted a cross sectional study nested in the prospective Institutional Registry of Thromboembolic Disease at Hospital Italiano de Buenos Aires from June 2006 to March 2011. We included patients who developed symptoms of pulmonary embolism during hospitalization. Patients were stratified based on the Wells score as PE likely (>4 points) or PE unlikely (≤4 points). The presence of pulmonary embolism was defined by pre-specified criteria.
RESULTS: Six hundred and thirteen patients met the inclusion criteria, with an overall prevalence of PE of 36%. Two hundred and nineteen (34%) were classified as PE likely and 394 (66%) as PE unlikely with a prevalence of PE of 66% and 20%, respectively. The Wells score showed a sensitivity of 65 (95% CI 59-72), specificity 81 (95% CI 77-85), positive predictive value 66 (95% CI 60-72) and negative predictive value 80 (95% CI 77-84).
CONCLUSIONS: The Wells Score is accurate to predict the probability of PE in hospitalized patients and this population had a higher prevalence of PE than other cohorts. However, the score is not sufficiently predictive to rule out a potentially fatal disorder.

A preliminary linkage map was constructed by applying backcross and testcross strategy using microsatellite (SSR) markers developed for Xiphophorus and Poecilia reticulata in ornamental fish, molly Poecilia sp. The linkage map having 18 SSR loci consisted of four linkage groups that spanned a map size of 516.1cM. Association between genotypes and phenotypes was tested in a random fashion and QTL for dorsal fin length was found to be linked to locus Msb069 on linkage group 2. Coincidentally, locus Msb069 was also reported as putative homologue primer pairs containing SSRs repeat motif which encoded hSMP-1, a sex determining locus. Dorsal fin length particularly in males of Poecilia latipinna is an important feature during courtship display. Therefore, we speculate that both dorsal fin length and putative hSMP-1 gene formed a close proximity to male sexual characteristics.

Cannabis, or marijuana, the most commonly used illicit drug in the world, has been shown to be responsible for suppressing the production and secretion of androgens, particularly testosterone. However, despite such findings in animals, the chronic effects of marijuana use on human endocrine systems have proved to be inconsistent. Here, we investigated the reference ranges of urinary levels of testosterone (T) and epitestosterone (E) as well as their metabolic ratio of T/E in a Korean male population (n=337), which would enable an evaluation of abnormal changes in steroid metabolism induced by habitually administered cannabis. The T/E ratio was significantly decreased in the marijuana group (n=18), while the urinary testosterone concentrations were also tended to decrease. This study is the first to provide data for the reference values of two urinary androgens and T/E values among control Korean males, and, furthermore, suggests that the T/E ratio, though not testosterone levels, might be used to understand the suppression of human male gonadal function affected by smoking marijuana.

Hexokinase family includes hexokinases I, II, III and IV, that catalyze the phosphorylation of glucose to produce glucose 6-phosphate. Hexokinase IV, also known as glucokinase, is only half size of the other types of hexokinases that contain two hexokinase domains. Despite the enormous progress in the study of hexokinases, the evolutionary relationship between glucokinase and other hexokinases is still uncertain, and the molecular processes leading to the emergence of hexokinases in vertebrates remain controversial. Here we clearly demonstrated the presence of a single hexokinase-like gene in the amphioxus Branchiostoma japonicum, Bjhk, which shows a tissue-specific expression pattern, with the most abundant expression in the hepatic caecum, testis and ovary. The phylogenetic and synteny analyses both reveal that BjHK is the archetype of vertebrate hexokinases IV, i.e. glucokinases. We also found for the first time that recombinant BjHK showed functional enzyme activity resembling vertebrate hexokinases I, II, III and IV. In addition, a native glucokinase activity was detected in the hepatic caecum. Finally, glucokinase activity in the hepatic caecum was markedly reduced by fasting, whereas it was considerably increased by feeding. Altogether, these suggest that Bjhk represents the archetype of glucokinases, from which vertebrate hexokinase gene family was evolved by gene duplication, and that the hepatic caecum plays a role in the control of glucose homeostasis in amphioxus, in favor of the notion that the hepatic caecum is a tissue homologous to liver.