Correction: Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study

This is a correction of an earlier published article

Adaptation of cortical activity to sustained pressure stimulation on the fingertip

Background Tactile adaptation is a phenomenon of the sensory system that results in temporal desensitization after an exposure to sustained or repetitive tactile stimuli. Previous studies reported psychophysical and physiological adaptation where perceived intensity and mechanoreceptive afferent signals exponentially decreased during tactile adaptation. Along with these studies, we hypothesized that somatosensory cortical activity in the human brain also exponentially decreased during tactile adaptation. The present neuroimaging study specifically investigated temporal changes in the human cortical responses to sustained pressure stimuli mediated by slow-adapting type I afferents. Methods We applied pressure stimulation for up to 15 s to the right index fingertip in 21 healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. We analyzed cortical responses in terms of the degrees of cortical activation and inter-regional connectivity during sustained pressure stimulation. Results Our results revealed that the degrees of activation in the contralateral primary and secondary somatosensory cortices exponentially decreased over time and that intra- and inter-hemispheric inter-regional functional connectivity over the regions associated with tactile perception also linearly decreased or increased over time, during pressure stimulation. Conclusion These results indicate that cortical activity dynamically adapts to sustained pressure stimulation mediated by SA-I afferents, involving changes in the degrees of activation on the cortical regions for tactile perception as well as in inter-regional functional connectivity among them. We speculate that these adaptive cortical activity may represent an efficient cortical processing of tactile information.open

Persistent Helicobacter pylori Specific Th17 Responses in Patients with Past H. pylori Infection Are Associated with Elevated Gastric Mucosal IL-1β

10.1371/journal.pone.0039199PLoS ONE76

ATTAIN: Phase III study of etirinotecan pegol versus treatment of physician's choice in patients with metastatic breast cancer and brain metastases

The increasing incidence of breast cancer brain metastases is a major clinical problem with its associated poor prognosis and limited treatment options. The long-acting topoisomerase-1 inhibitor, etirinotecan pegol, was designed to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Motivated by improved survival findings from subgroup analyses from the Phase III BEACON trial, this ongoing randomized, Phase III trial compares etirinotecan pegol to drugs commonly used for advanced breast cancer in patients with stable, treated breast cancer brain metastases who have been previously treated with an anthracycline, taxane and capecitabine. The primary end point is overall survival. Secondary end points include objective response rate, progression-free survival and time to CNS disease progression or recurrence in patients with/without CNS lesions present at study entry. Trial registration number: NCT02915744

MicroRNA-335 acts as a metastasis suppressor in gastric cancer by targeting Bcl-w and specificity protein 1

Aberrant expression of miR-335 has been frequently reported in cancer studies, suggesting that there is a close correlation between miR-335 and cancer during its development, progression, metastasis and prognosis. The expression of miR-335 in gastric cancer and its effects are not known. Relative expression of miR-335 in 4 gastric cancer cell lines and in 70 gastric cancer tissues was confirmed by real-time quantitative reverse transcriptase-PCR compared with controls. Transwell cell migration and Matrigel invasion assay in vitro and metastasis formation assay in vivo were used to examine the effects of miR-335 expression on gastric cancer cell invasion and metastasis. The effect of miR-335 expression on gastric cancer cell proliferation was estimated by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Luciferase reporter assay and western blot were used to examine the potential target genes and related pathways. Gene silencing with small-interfering RNA was used to examine the effects of target genes on gastric cancer cell invasion. miR-335 was dramatically downregulated in gastric cancer cell lines than in the normal gastric cell line GES-1. Low expression of miR-335 was significantly associated with lymph-node metastasis, poor pT stage, poor pN stage and invasion of lymphatic vessels. Overexpression of miR-335 suppressed gastric cancer cell invasion and metastasis in vitro and in vivo, but has no significant effects on cell proliferation. Furthermore, miR-335 might suppress gastric cancer invasion and metastasis by targeting Bcl-w and specificity protein 1 (SP1). Taken together, our results provide evidence that miR-335 might function as a metastasis suppressor in gastric cancer by targeting SP1 directly and indirectly through the Bcl-w-induced phosphoinositide 3-kinase-Akt-Sp1 pathway. miR-335 showing altered expression at different stages of gastric cancer could be a target for gastric cancer therapies and could be further developed as a potential prognostic factor

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone