A position anchor sinks the double-drift illusion

When the internal texture of a Gabor patch moves orthogonally to its envelope''s motion, the perceived path, viewed in the periphery, shifts dramatically in position, and direction relative to the true path (the double-drift illusion). Here, we examine positional uncertainty as a critical factor underlying this illusory shift. We presented participants with an anchoring line at different distances from the drifting Gabor''s physical path. Our results indicate that placing an anchor (a fixed line) close to the Gabor''s path halved the magnitude of the illusion. This suppression was symmetrical for anchors placed on either side of the Gabor. In a second experiment, we used crowding to degrade the anchoring line''s position information by embedding it in a set of parallel lines. In this case, despite the presence of the same lines that reduced the illusion when presented in isolation, the illusory shift was now largely restored. We suggest that the adjacent lines crowded each other, reducing their positional certainty, and thus their ability to anchor the location of the moving Gabor. These findings indicate that the positional uncertainty of the equiluminant Gabor patch is critical for the illusory position offset.     

Systematic review of mouse kidney transplantation

A mouse model of kidney transplantation was first described in 1973 by Skoskiewicz et al. Although the mouse model is technically difficult, it is attractive for several reasons: the mouse genome has been characterized and in many aspects is similar to man and there is a greater diversity of experimental reagents and techniques available for mouse studies than other experimental models. We reviewed the literature on all studies of mouse kidney transplantation to report the donor and recipient strain combinations that have been investigated and the resultant survival and histological outcomes. Some models of kidney transplantation have used the transplanted kidney as a life‐supporting organ, however, in many studies the recipient mouse's native kidney has been left in situ. Several different combinations of inbred mouse strains have been reported, with varying degrees of injury, survival or tolerance because of haplotype differences. This model has been exceptionally useful as an investigational tool to understand multiple aspects of transplantation including acute rejection, cellular and humoral rejection mechanisms and their treatment. Furthermore, this model has been used to investigate disease mechanisms beyond transplant rejection including intrinsic renal disease and infection‐associated pathology.     

Effects of ticagrelor pretreatment on electrophysiological properties of stellate ganglion neurons following myocardial infarction

Higher sympathetic activity predisposes to malignant ventricular arrhythmias in the context of myocardial infarction (MI). This is, in part, mediated by the electrical activity of the stellate ganglion (SG). The aim of this study is to examine the effects of ticagrelor pretreatment on the electrophysiological properties of SG neurons following MI in rabbits. MI was induced by isoproterenol (ISO) of 150 mg kg^-1 d^-1 (twice at an interval of 24 hours). Ticagrelor pretreatment was administered at low- (10 mg kg^-1 d^-1) or high-dose (20 mg kg^-1 d^-1). Protein and RNA expression were determined by immunohistochemical analysis and real-time PCR, respectively. The activity of sodium channel current (I_Na), delayed rectifier potassium current (I_KDR), M-type potassium current (I_KM) as well as action potentials (APs) from SG neurons were measured by whole-cell patch-clamp. Intracellular calcium concentrations were measured by confocal microscopy. Compared with the control group, the MI group exhibited a greater amplitude of I_Na, I_KDR and I_KM, significantly altered activation and inactivation characteristics of I_Na, no significant alterations in protein or mRNA expression of sodium and M-type potassium channels, along with higher AP amplitude and frequency and intracellular calcium concentrations. Most of these abnormalities were prevented by pretreatment with low- or high-dose ticagrelor. Our data suggest that ticagrelor exerts cardioprotective effects, potentially through modulating the activity of different ion channels in SG neurons.     

An enzymatic approach to configurationally rare trans‐androsteronyl‐α‐glucoside and Its potential anticancer application

Enzymatic glycosylation of sterols/steroids with glycosyltransferase HP0421 shows protein plasticity on generation of configurationally rare steryl‐α‐glucosides. Investigation of trans‐androsteronyl‐α‐glucoside on tamoxifen‐treated MCF‐7 breast cancer cells shows dose‐dependent depression of cell viability and enhanced drug effectiveness, illustrating a new avenue for the production of novel steryl‐α‐glucosides with useful biological activities.     

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized,Double-Blind Primary Endpoint

ObjectivePublished reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease.Materials and MethodsParticipants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life.ResultsThe study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period.ConclusionDirectional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.     

Endothelin-1 expression correlates with atypical histological features in mammary phyllodes tumours

BACKGROUND AND AIMS: Endothelin-1 expression is increased in infiltrating duct carcinoma and is associated with larger tumour size, higher histological grade and lymphovascular permeation. This has not been evaluated in phyllodes tumours, which are uncommon fibroepithelial lesions with potential for local recurrences or distant metastasis. While the grading of phyllodes tumours depends on a combination of histological parameters, prediction of their behaviour remains difficult. METHOD: A large series of 461 phyllodes tumours (291 benign, 115 borderline malignant and 55 frankly malignant) were evaluated for endothelin-1 expression in both the epithelial cells and stromal cells by immunohistochemistry; results were correlated with the tumour grade. RESULTS: For benign phyllodes tumours, the epithelial staining of endothelin was negative, weak, moderate and strong in 6%, 26%, 15% and 53% of cases respectively; results were 4%, 18%, 19% and 59% respectively for borderline and 6%, 18%, 6% and 70% respectively for frankly malignant tumours. For the stromal staining, the negative, weak, moderate and strong staining was 32%, 19%, 18% and 31% respectively for benign phyllodes, 24%, 13%, 10% and 53% respectively for borderline and 8%, 16%, 17% and 59% respectively for frankly malignant tumours. There was correlation between epithelial and stromal staining, and the stromal staining correlated with histological features of stromal cellularity, stromal cell nuclear pleomorphism, margin status and stromal overgrowth. CONCLUSION: These observations suggest a close relationship between the epithelial and stromal elements in phyllodes tumours; endothelin may play a significant role in the malignant progression of phyllodes tumours.     

Identification of a basal-like subtype of breast ductal carcinoma in situ

Microarray profiling of invasive breast carcinomas has identified subtypes including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor-prognosis, basal-like tumors have been immunohistochemically characterized as estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study was to determine the prevalence of basal-like ductal carcinoma in situ in a population-based series of cases using immunohistochemical surrogates. A total of 245 pure ductal carcinoma in situ cases from a population-based, case-control study were evaluated for histologic characteristics and immunostained for ER, HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were unclassified (negative for all 4 defining markers). The basal-like subtype was associated with unfavorable prognostic variables including high-grade nuclei (P < .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001). These studies demonstrate the presence of a basal-like in situ carcinoma, a potential precursor lesion to invasive basal-like carcinoma.     

Prenatal immune activation potentiates endocannabinoid-related plasticity of inhibitory synapses in the hippocampus of adolescent rat offspring

There is strong evidence that immune activation from prenatal infection increases the risk for offspring to develop schizophrenia. The endocannabinoid (eCB) system has been implicated in the pathophysiology of schizophrenia while models of cortical dysfunction postulate an imbalance between neuronal excitation and inhibition in the disorder. The current study examined the impact of prenatal immune activation on eCB-mediated inhibitory mechanisms. We compared two forms of eCB-related plasticity of evoked inhibitory postsynaptic currents, namely depolarization-induced suppression of inhibition (DSI) and metabotropic glutamate receptor-induced long term depression (mGluR-iLTD), in both the dorsal and ventral hippocampus between adolescent offspring from rat dams that received either saline or bacterial lipopolysaccharide (LPS) during pregnancy. Compared to prenatal saline offspring, prenatal LPS offspring displayed prolonged DSI and stronger mGluR-iLTD in the dorsal and ventral hippocampus, respectively. The sensitivity of mGluR-iLTD to the CB1 receptor antagonist AM251 was also lower in the dorsal hippocampus of prenatal LPS compared to prenatal saline offspring. Testing whether changes in eCB receptor signaling or levels could contribute to these changes in inhibitory transmission, we found region specific increases in 2-arachidonoylglycerol-stimulated signaling and in basal and mGluR-induced levels of anandamide in prenatal LPS offspring when compared to prenatal saline offspring. Our findings indicate that prenatal immune activation can lead to long-term changes in eCB-related plasticity of hippocampal inhibitory synaptic transmission in adolescent rat offspring. Perturbation of the eCB system resulting from prenatal immune activation could represent a mechanism linking early life immune events to the development of psychopathology in adolescence.     

Frailty and Clinical Outcomes in Advanced Heart Failure Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review and Meta-analysis

Background

Frailty has been identified as a risk factor for adverse clinical outcomes after cardiac intervention or surgery. However, whether it increases the risk of adverse outcomes in patients undergoing left ventricular assist device (LVAD) therapy has been controversial. Therefore, we conducted a systematic review and meta-analysis of the frailty measures and clinical outcomes of length of stay and mortality in this setting.