Statistical Significance of Precisely Repeated Intracellular Synaptic Patterns

Can neuronal networks produce patterns of activity with millisecond accuracy? It may seem unlikely, considering the probabilistic nature of synaptic transmission. However, some theories of brain function predict that such precision is feasible and can emerge from the non-linearity of the action potential generation in circuits of connected neurons. Several studies have presented evidence for and against this hypothesis. Our earlier work supported the precision hypothesis, based on results demonstrating that precise patterns of synaptic inputs could be found in intracellular recordings from neurons in brain slices and in vivo. To test this hypothesis, we devised a method for finding precise repeats of activity and compared repeats found in the data to those found in surrogate datasets made by shuffling the original data. Because more repeats were found in the original data than in the surrogate data sets, we argued that repeats were not due to chance occurrence. Mokeichev et al. (2007) challenged these conclusions, arguing that the generation of surrogate data was insufficiently rigorous. We have now reanalyzed our previous data with the methods introduced from Mokeichev et al. (2007). Our reanalysis reveals that repeats are statistically significant, thus supporting our earlier conclusions, while also supporting many conclusions that Mokeichev et al. (2007) drew from their recent in vivo recordings. Moreover, we also show that the conditions under which the membrane potential is recorded contributes significantly to the ability to detect repeats and may explain conflicting results. In conclusion, our reevaluation resolves the methodological contradictions between Ikegaya et al. (2004) and Mokeichev et al. (2007), but demonstrates the validity of our previous conclusion that spontaneous network activity is non-randomly organized.     

Sonographically guided core needle biopsy of soft tissue neoplasms

PURPOSE: This study was conducted to evaluate the usefulness of sonography (US)-guided needle biopsy in the diagnosis of soft tissue masses. PATIENTS AND METHODS: Thirty-seven patients with a mean age of 49 years were enrolled in the study. The size of the biopsy needle was selected according to the kind of tumor suspected (ie, primary or metastatic). In patients with suspected metastases, smaller biopsy needles were used; in patients with suspected primary tumors, larger needles were used so that larger specimens could be obtained. Prebiopsy color Doppler sonography (CDUS) was routinely used to guide the cutting needle to areas of the lesion showing sufficient vascularity. From 3 to 6 cores were obtained, depending on their quality. We compared the diagnoses yielded by the core biopsy and the final histopathologic analysis of the resected tumor by classifying the results as "concordant" or "discordant." RESULTS: A total of 37 tumors were examined. Final diagnoses were 24 malignant tumors (6 metastases and 18 primary tumors) and 13 benign tumors. The lesions were diagnosed correctly as either benign or malignant in 35 of the 36 cases for which needle biopsy specimens were adequate, with only 1 misdiagnosis. The diagnoses were concordant in 33 cases (17 primary malignant tumors, 6 metastatic tumors, and 10 benign tumors) and were discordant diagnosis in the other 4 cases (1 primary malignant tumor and 3 benign tumors). No complications were attributable to the needle biopsy. CONCLUSIONS: US-guided percutaneous core needle biopsy of soft tissue neoplasms is an easy, safe, and useful procedure. It can be considered a first-line procedure for the acquisition of tissue specimens adequate for histopathologic diagnosis.     

Calcified plaque resorptive status as determined by high-resolution ultrasound is predictive of successful conservative management of calcific tendinosis

Objective

In patients with calcific tendinosis, the morphology of calcified plaques is associated with response to conservative management. We aimed to determine changes in pain and morphology of plaques in patients with calcific tendinosis and non-arc-shaped plaques identified by high-resolution ultrasonography who received only conservative treatment.

Methods

A total of 33 patients with a mean age of 63.3 ± 10.3 years were included. Pain scores at the time of first and follow-up ultrasound were recorded, and the degree of plaque resolution was calculated.

Results

At follow-up, 90.9% (30 of 33) of patients reported improvement in pain, and 84.8% (28 of 33) patient had more than 50% elimination of plaques. Most of increased vascularity observed in color Doppler ultrasonography during 1st visit disappeared at follow-up.

Conclusions

In patients with calcific tendinosis, non-arc-shaped plaques determined by high-resolution ultrasonography are likely to resolve and conservative management is warranted.     

The role of high-resolution ultrasonography in management of calcific tendonitis of the rotator cuff

This article predicts the possibility of resorption of the calcific plaques in the shoulder using high-resolution ultrasonography (HRUS) and color Doppler ultrasound (CDUS), and evaluates the therapeutic effect of US-guided fine-needle multiple punctures of the calcific plaque. A total of 100 patients with calcific tendenosis were divided into 3 groups: In group 1, patients having chronic shoulder pain received conservative treatment; in group 2, patients having acute exacerbation of shoulder pain also received conservative treatment; and group 3 patients received US-guided fine-needle multiple punctures or aspiration. In CDUS, all images were classified as grade 0 (no color flow signals), grade 1 (weak spotty color flow signal), grade 2 (few rod-like color flow signals), grade 3 (many rod-like or linear color flow signals). In the follow-up study, marked improvement of patients' clinical condition with more than 50% size reduction of calcific plaque was defined as an effective treatment. There was no significant difference between group 1 and group 3 (p = 0.558) in CDUS, but there was a significant difference between group 1 and group 2 (p = 0.000), and group 2 and group 3 (p = 0.000) on the basis of classification of grade < 1 and grade > or = 1. There was also significant difference in the follow-up result of effective management between group 1 and group 3 (p = 0.000), and group 1 and group 2 (p = 0.000). In conclusion, HRUS with CDUS proved to be a good modality in evaluating the possibility of resorption of shoulder calcification and, if CDUS > or = grade 1 in calcific tendonitis, we highly recommend conservative treatment with regular follow-up. On the other hand, if CDUS < grade 1, fine-needle repeated puncture could be considered as an effective alternative treatment.     

Anticardiolipin antibodies and vascular access thrombosis in Taiwanese haemodialysis patients with chronic hepatitis C: a retrospective study

Hepatitis C virus causes various extrahepatic immunologic abnormalities. Vascular access thrombosis (VAT) is a major cause of morbidity in chronic haemodialysis (HD) patients. Immunoglobulin-G anticardiolipin antibody (IgG-ACA) is strongly associated with venous and arterial thrombosis in patients with normal renal function. Previous investigations have reported the association of raised IgG-ACA titre recurrent with VAT in HD patient, and also few equivalent studies were reported the same in Taiwan. This study attempted to determine whether raised IgG-ACA titres are associated with increased risk of recurrent VAT in HD patients with chronic hepatitis C. This study enrolled 98 chronic hepatitis C patients undergoing HD. IgG-ACA titre and hepatitis C marker were measured for all subjects. Raised IgG-ACA titres were present in 29.6% (29/98) of patients. In both groups (raised and normal IgG-ACA), the type of shunt did not differ (p = 0.416). There was strong association between raised IgG-ACA titre and recurrent VAT (p = 0.0004). In predicting for more or one episodes of VAT using multiple logistic regression, synthetic graft (p < 0.0001), raised IgG-ACA titre (p = 0.039), presence of hepatitis B (p = 0.004) and haemodialysis duration (p = 0.039) were significant factors. The prevalence of raised IgG-ACA titres was 39.6% among chronic hepatitis C with HD patients. There was strong association between raised IgG-ACA titre and recurrent VAT, and this finding may be the consequence of pathogenetic role of raised IgG-ACA titres on the development of VAT status in HD patients with chronic hepatitis C.     

Endothelin binding to cultured calf adrenal zona glomerulosa cells and stimulation of aldosterone secretion.

Endothelins are a group of potent vasoconstrictors whose structure was deduced from genomic DNA. ET-1 was first isolated from culture supernatants from porcine endothelial cells and ET-3 was identified from a rat DNA library. We report on the binding of 125I-ET-1 to zona glomerulosa cells in culture and on its ability to stimulate aldosterone secretion. Cultured calf adrenal zona glomerulosa cells have saturable, high affinity [Kd = 1.00 +/- 0.17 X 10(-10) M (SEM)] receptors which bind ET-1 in a temperature and time dependent manner. Binding was specific and angiotensin II, vasopressin, ANP, BNP, apamin, calcium channel agonists or antagonists did not interact with the receptor. ET-3 displaced 125I-ET-1 from the receptor with a relative potency of 0.39 +/- 0.1% (SEM) that of ET-1. ET-1 incubated with cultured glomerulosa cells stimulated aldosterone secretion in a dose dependent manner but it was less potent than angiotensin II. ET-3 had less than 1% the relative potency of ET-1 stimulating aldosterone secretion. This data suggest that ET-1 is an independent stimulator of aldosterone secretion and we are speculating that it might be important in those situations, like in malignant hypertension, where endothelial damage might result in increased ET-1 production.     

Characteristics of Taiwanese patients of PNH in the international PNH registry

Background

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and acquired hematopoietic stem cell disease, with florid clinical presentations. Although this disease has been characterized in the western countries, its clinical and laboratory features in Taiwan have not yet been reported.

Results

As a part of an international prospective, non-interventional, observational registration trial of PNH, we have analyzed 63 patients recruited between 2009 and 2015 in Taiwan, with comparison to the 3857 patients in the rest of the world (ROW). The median age of diagnosis of our patients is 46 (range 9–84), without sex preponderance. While most of the clinical and laboratory presentations of our patients are similar to the ROW, ours have higher lactate dehydrogenase levels, lower hemoglobin, and higher frequencies of symptoms including shortness of breath and erectile dysfunction at the time of diagnosis. The incidence of thromboembolism was not statistically different between ours and the ROW (6.7 % vs 13.5 %, P = 0.178). The patients in Taiwan were treated more frequently with corticosteroid (53.2 % vs 32 %, P < 0.001), but less frequently with cyclosporine/anti-thymocyte globulin and heparin/warfarin, both P < 0.001).

Conclusions

This is the first systematic review on the Taiwanese PNH patients. Our analysis would provide key information about our PNH patients and would help understanding the basic characteristics of this rare disease in Taiwan.

Trial registration

This trial has been registered to ClinicalTrails.gov NCT01374360.

     

Mutation within the herpes simplex virus DNA polymerase gene conferring resistance to (R)-9-(3,4-dihydroxybutyl)guanine.

Five herpes simplex virus mutants known or presumed to contain mutations in their DNA polymerase genes conferring resistance to acyclovir and arabinosyladenine also proved to exhibit some degree of resistance to (R)-9-(3,4-dihydroxybutyl)guanine (buciclovir). For one mutant, a buciclovir resistance mutation was mapped to a region of the viral DNA polymerase gene proposed to encode the deoxynucleoside 5'-triphosphate binding domain. These data implicate the viral polymerase as a target of buciclovir action that contributes to its antiviral selectivity.     

Food as ego-protective remedy for people experiencing shame. Experimental evidence for a new perspective on weight-related shame

The well-explored association between shame and bulimia is based on research with clinical samples, which limits its generalizability. Moreover, these correlational studies are unable to draw clear conclusions about causality. To fill this gap, we conducted two experimental studies to examine whether shame elicits a desire for food in nonclinical participants. Compared with controls, participants experiencing shame found a buffet meal more desirable and were more likely to binge eat (Experiment 1); they also ate more than controls in a comparative taste test (Experiment 2). Our findings suggest that shame elicits the desire to obtain food to protect the devalued self but may lead to overeating and the risk of losing control over one's weight. We provide the first experimental evidence showing the link between shame and desire for food and offer a new perspective on the causal relationship between shame and binge eating.