Antiphasic 40 Hz Oscillatory Current Stimulation Affects Bistable Motion Perception

When viewing ambiguous stimuli, conscious perception alternates spontaneously between competing interpretations of physically unchanged stimulus information. As one possible neural mechanism underlying the perceptual switches, it has been suggested that neurons dynamically change their pattern of synchronized oscillatory activity in the gamma band (30–80 Hz). In support of this hypothesis, there is correlative evidence from human electroencephalographic (EEG) studies for gamma band modulations during ambiguous perception. To establish a causal role of gamma band oscillations in the current study, we applied transcranial alternating current stimulation (tACS) at 40 Hz over occipital–parietal areas of both hemispheres during the presentation of bistable apparent motion stimuli that can be perceived as moving either horizontally or vertically. In this paradigm, the switch between horizontal and vertical apparent motion is likely to involve a change in interhemispheric functional coupling. We examined gamma tACS effects on the durations of perceived horizontal and vertical motion as well as on interhemispheric EEG coherence and found a decreased proportion of perceived horizontal motion together with an increase of interhemispheric gamma band coherence. In a control experiment using 6 Hz tACS, we did not observe any stimulation effects on behavior or coherence. Furthermore, external stimulation at 40 Hz was only effective when applied with 180° phase difference between hemispheres (anti-phase), as compared to in-phase stimulation with 0° phase difference. These findings suggest that externally desynchronizing gamma oscillations between hemispheres impairs interhemispheric motion integration and in turn biases conscious experience of bistable apparent motion.     

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis

Sepsis is characterized by overlapping phases of excessive inflammation temporally aligned with an immunosuppressed state, defining a complex clinical scenario that explains the lack of successful therapeutic options. Here we tested whether the formyl-peptide receptor 2/3 (Fpr2/3)—ortholog to human FPR2/ALX (receptor for lipoxin A4)—exerted regulatory and organ-protective functions in experimental sepsis. Coecal ligature and puncture was performed to obtain nonlethal polymicrobial sepsis, with animals receiving antibiotics and analgesics. Clinical symptoms, temperature, and heart function were monitored up to 24 h. Peritoneal lavage and plasma samples were analyzed for proinflammatory and proresolving markers of inflammation and organ dysfunction. Compared with wild-type mice, Fpr2/3^−/− animals exhibited exacerbation of disease severity, including hypothermia and cardiac dysfunction. This scenario was paralleled by higher levels of cytokines [CXCL1 (CXC receptor ligand 1), CCL2 (CC receptor ligand 2), and TNFα] as quantified in cell-free biological fluids. Reduced monocyte recruitment in peritoneal lavages of Fpr2/3^−/− animals was reflected by a higher granulocyte/monocyte ratio. Monitoring Fpr2/3^−/− gene promoter activity with a GFP proxy marker revealed an over threefold increase in granulocyte and monocyte signals at 24 h post-coecal ligature and puncture, a response mediated by TNFα. Treatment with a receptor peptido-agonist conferred protection against myocardial dysfunction in wild-type, but not Fpr2/3^−/−, animals. Therefore, coordinated physio-pharmacological analyses indicate nonredundant modulatory functions for Fpr2/3 in experimental sepsis, opening new opportunities to manipulate the host response for therapeutic development.Sepsis is a clinical syndrome expression of the host reaction to pathogen invasion, as a consequence of either direct dissemination into the bloodstream or postsurgical trauma and gut ischemia/reperfusion-mediated pathogen translocation. The complexity of sepsis is due to multiple local and systemic immune responses that involve release of soluble mediators such as cytokines, bioactive lipid mediators, and cell stress markers, leading to multiple organ failure and ultimately death (1). Originally believed to result exclusively from an overzealous inflammatory response (e.g., cytokine storm), the lack of efficacy of anticytokine therapy in several clinical trials demonstrated that the pathogenesis of sepsis is complex. Notwithstanding the difficulty in clinical cases to establish the beginning of the infection (and the temporal recruitment of failing organs), it is now appreciated that the systemic inflammatory response syndrome (SIRS) can overlap with a compensatory anti-inflammatory response syndrome (CARS) (2). Immunosuppression associated with CARS may explain the failure of classical anti-inflammatory strategies in patients (3, 4).The acute inflammatory reaction against pathogens is in many cases successful, leading to healing and recovery of biological function. To achieve this end point, specific mediators and pathways of endogenous protection must be engaged by the host to promote what is now referred to as “resolution of inflammation” (5). Proresolving mediators share a set of properties that are emerging as paradigmatic (6); these include modulation of immune cell recruitment [inhibition of polymorphonuclear (PMN) migration and promotion of monocyte influx], augmentation of phagocytosis (leading to bacteria containment), promotion of apoptosis and efferocytosis, and eventually tissue/organ repair with restoration of physiological function (6, 7). It is perhaps for these organic and multifactorial biological actions that proresolving mediators like the protein annexin A1 (AnxA1) and the bioactive lipids lipoxin A₄ (LXA₄) and resolvin D₂ exert protection in models of experimental sepsis (8–10). Of relevance, the receptor target for AnxA1 and LXA₄ is a G protein-coupled receptor that belongs to the formyl-peptide receptor (FPR) family, termed FPR2/ALX. To establish the validity of FPR2/ALX for the development of innovative therapeutic approaches, proof-of-concept data within loss-of-function settings should be established.In the mouse, the human FPR2/ALX gene corresponds to two genes, termed Fpr2 and Fpr3, which share the first of the two exons (11). LXA₄ and AnxA1 are largely inactive in a transgenic mouse that lacks both murine genes (12) as shown in models of acute inflammation and ischemia-reperfusion injury (12–15). Herein we establish the patho-pharmacology of Fpr2/3 in experimental polymicrobial sepsis as a way to validate the human ortholog as a genuine receptor target for innovative treatments in sepsis.     

Clinical and radiographic evaluation of Bio-Gen with biocollagen compared with Bio-Gen with connective tissue in the treatment of class II furcation defects: a randomized clinical trial

Objective

Treatment of furcation defects are thought to be challenging. The purpose of this study was to evaluate the clinical and radiographic parameters of Bio-Gen with Biocollagen compared with Bio-Gen with connective tissue in the treatment of Class II furcation defects.

Material and Methods

In this clinical trial, 24 patients with Class II furcation defect on a buccal or lingual mandibular molar were recruited. After oral hygiene instruction, scaling and root planing and achievement of acceptable plaque control, the patients were randomly chosen to receive either connective tissue and Bio-Gen (case group) or Biocollagen and Bio-Gen (control group). The following parameters were recorded before the first and re-entry surgery (six months later): vertical clinical attachment level (VCAL), gingival index (GI), plaque index (PI), horizontal probing depth (HPD), vertical probing depth (VPD), gingival recession (GR), furcation vertical component (FVC), furcation to alveolar crest (FAC), fornix to base of defect (FBD), and furcation horizontal component (FHC) were calculated at the time of first surgery and during re-entry. A digital periapical radiograph was taken in parallel before first surgery and re-entry. The radiographs were then analyzed by digital subtraction. The differences with p value <0.05 were considered significant.

Results

Only the mean changes of FAC, FHC, mean of FHC, FBD in re-entry revealed statistically significant differences between the two groups. HPD, VPD, FBD, FAC, and FHC showed statistically significant differences after 6 months in the case group. However, in the control group, statistically significant differences were found in GR and HPD. We did not observe any significant difference in radiographic changes among the two groups.

Conclusion

The results of this trial indicate that better clinical outcomes can be obtained with connective tissue grafts in combination with bone material compared with a resorbable barrier with bone material. The differences in radiographic changes between the two groups, however, were not statistically significant.     

Isolation and identification of Enterococcus faecalis from necrotic root canals using multiplex PCR

This study was designed to survey the incidence of Enterococcus faecalis infection in symptomatic and asymptomatic root canals of necrotic teeth using PCR and to isolate the bacterium for further screening. Sixty patients categorized according to their clinical symptoms were used for sampling by insertion of paper points into the root canals and absorbing all the fluids present within them. The samples were incubated in 1.0 ml 2xYT (containing 16 g bacto tryptone, 10 g yeast extract and 5.0 g NaCl per liter) for 24 h at 37 degrees C without aeration prior to multiplex PCR analysis. To assist the isolation of E. faecalis, sub-samples were further grown in the same medium supplemented with 6.5% NaCl and back-inoculated into bile esculin. Using multiple cultivation-dependent and PCR analyses, 6 cases (10%) of E. faecalis were identified. Four isolates were obtained from asymptomatic cases of chronic apical periodontitis, and the other two were associated with phoenix abscess and acute apical abscess, respectively. No E. faecalis infection was found in 5 patients with acute apical periodontitis or in 9 with chronic suppurative periodontitis. Our results indicate that there is no significant difference in the incidence of E. faecalis between symptomatic and asymptomatic necrotic dental root canals (P > 0.05).     

Gap Balancing Sacrifices Joint-Line Maintenance to Improve Gap Symmetry: A Randomized Controlled Trial Comparing Gap Balancing and Measured Resection

A total knee arthroplasty can be completed using two techniques; measured resection or gap balancing. A prospective blinded randomized controlled trial was completed with 103 patients randomized to measured resection (n=52) or gap balancing (n=51). Primary outcome measure was femoral component rotation. Secondary outcome measures were joint-line change, gap symmetry and function and quality-of-life outcomes. Gap balancing resulted in a significantly raised joint-line compared to measured resection. Gap symmetry was significantly better using gap balancing. Functional outcomes and quality-of-life were not significantly different at 24 months. Using computer navigation, gap balancing significantly raises the joint-line in order to improve gap symmetry. This does not result in a clinical difference in function or quality of life at 24 months.     

Effects of pinacidil,verapamil, and heart rate on afterdepolarizations in the guinea-pig heart in vivo

Summary Recently, ionic current simulation in the Luo-Rudy model has elucidated putative mechanisms of afterdepolarizations under various experimental conditions. The present study was aimed at gaining insight into the differential mechanism of different types of afterdepolarizations in the guinea-pig heart in vivo. The effects of pharmacological and heart rate perturbations on early (EADs) and delayed (DADs) afterdepolarizations, induced by either digoxin, CsCl, or BayK 8644 were studied, using mid-myocardial left ventricular monophasic action potential (MAP) recordings. Digoxin insignificantly shortened sinus cycle length (SCL) and CsCl and BayK 8644 differentially prolonged SCL and MAP duration. Digoxin induced phase 3-EADs and DADs and CsCl or BayK 8644 induced phase 2- and phase 3-EADs. Pinacidil shortened MAP duration, suppressed almost all the phase 2-EADs and some of the phase 3-EADs, but not the DADs. In a few cases, DADs were manifested following the abolishment of phase 2-EADs by pinacidil, but this phenomenon did not occur in the presence of hexamethonium. Verapamil prolonged SCL, did not significantly affect phase 2-EADs, but suppressed almost all of the DADs, including those which appeared after pinacidil, and all but one of the phase 3-EADs. The effects of pinacidil and verapamil were independent of the mode of afterdepolarization induction. A pacing-induced heart rate increase, which shortened MAP duration, and vagal stimulation, which prolonged MAP duration, attenuated and enhanced phase 2-EADs, respectively. The amplitude of phase 3-EADs was inversely related to the heart rate. These data, taken together, are consistent with those obtained previously by others in a computer model and recent observations on CsCl-induced EADs in the guinea-pig Purkinje fibers in vitro which have indicated that the mechanism of phase 2-EADs is different from that of DADs and that late phase 3-EADs generated under conditions of Ca²⁺ overload and DADs share similar properties.     

Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis

Metabolic Brain Disease - Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary...