Modeling the diverse effects of divisive normalization on noise correlations.

Divisive normalization, a prominent descriptive model of neural activity, is employed by theories of neural coding across many different brain areas. Yet, the relationship between normalization and the statistics of neural responses beyond single neurons remains largely unexplored. Here we focus on noise correlations, a widely studied pairwise statistic, because its stimulus and state dependence plays a central role in neural coding. Existing models of covariability typically ignore normalization despite empirical evidence suggesting it affects correlation structure in neural populations. We therefore propose a pairwise stochastic divisive normalization model that accounts for the effects of normalization and other factors on covariability. We first show that normalization modulates noise correlations in qualitatively different ways depending on whether normalization is shared between neurons, and we discuss how to infer when normalization signals are shared. We then apply our model to calcium imaging data from mouse primary visual cortex (V1), and find that it accurately fits the data, often outperforming a popular alternative model of correlations. Our analysis indicates that normalization signals are often shared between V1 neurons in this dataset. Our model will enable quantifying the relation between normalization and covariability in a broad range of neural systems, which could provide new constraints on circuit mechanisms of normalization and their role in information transmission and representation.

Developments in the management of Chagas cardiomyopathy.

Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising.

Treatment of intrabony defects using guided tissue regeneration and autogenous spongiosa alone or combined with hydroxyapatite/beta-tricalcium phosphate bone substitute or bovine-derived xenograft.

BACKGROUND: The aim of this case-control study was to investigate the clinical regeneration of deep intrabony defects using guided tissue regeneration (GTR) with autogenous spongiosa (ASB) alone or using GTR with a mixture of ASB with a bovine-derived xenograft (BDX) or a synthetic composite bone substitute (hydroxyapatite/beta-tricalcium phosphate [HA/beta-TCP]). METHODS: Sixty-four patients with a total of 93 intrabony defects of 2- or 3-wall morphology and an intrabony component (IC)>or=4 mm participated in this study. Defects were treated with a bioabsorbable membrane and ASB alone or ASB mixed with HA/beta-TCP or BDX. Clinical parameters measured at baseline and 12 months after surgery included IC, bleeding on probing (BOP), and plaque accumulation (PLI). Vertical bone gain (VBG) and percentage relative bone gain (RBG) were used as indicators of treatment efficacy. A stringent plaque control regimen was enforced in all patients during the 12-month observation period. RESULTS: At baseline, no statistically significant differences in any of the clinical parameters were observed between the groups. At 12 months, HA/beta-TCP and BDX treatments produced similar improvements in intrabony tissue regeneration as shown by VBG (P=0.616) and RBG (P=0.826) with significantly better outcomes than ASB alone (P<0.0001). Changes in BOP and PLI did not differ significantly between the groups. CONCLUSION: The combined use of ASB with BDX or HA/beta-TCP led to significantly greater gain of clinical attachment and hard tissue formation compared to the use of ASB alone.

Treatment of Intrabony Defects Using Guided Tissue Regeneration and Autogenous Spongiosa Alone or Combined With Hydroxyapatite/ß-Tricalcium Phosphate Bone Substitute or Bovine-Derived Xenograft.

BACKGROUND: The aim of this case-control study was to investigate the clinical regeneration of deep intrabony defects using guided tissue regeneration (GTR) with autogenous spongiosa (ASB) alone or using GTR with a mixture of ASB with a bovine-derived xenograft (BDX) or a synthetic composite bone substitute (hydroxyapatite/ß-tricalcium phosphate [HA/ß-TCP]). METHODS: Sixty-four patients with a total of 93 intrabony defects of 2- or 3-wall morphology and an intrabony component (IC) ≥4 mm participated in this study. Defects were treated with a bioabsorbable membrane and ASB alone or ASB mixed with HA/ß-TCP or BDX. Clinical parameters measured at baseline and 12 months after surgery included IC, bleeding on probing (BOP), and plaque accumulation (PLI). Vertical bone gain (VBG) and percentage relative bone gain (RBG) were used as indicators of treatment efficacy. A stringent plaque control regimen was enforced in all patients during the 12-month observation period. RESULTS: At baseline, no statistically significant differences in any of the clinical parameters were observed between the groups. At 12 months, HA/ß-TCP and BDX treatments produced similar improvements in intrabony tissue regeneration as shown by VBG (P = 0.616) and RBG (P = 0.826) with significantly better outcomes than ASB alone (P <0.0001). Changes in BOP and PLI did not differ significantly between the groups. CONCLUSION: The combined use of ASB with BDX or HA/ß-TCP led to significantly greater gain of clinical attachment and hard tissue formation compared to the use of ASB alone.

Use of DNA probes in the diagnosis and treatment of periodontitis --a case series.

Aggressive periodontitis is characterized by rapid attachment and bone loss with no underlying systemic disease and is associated with specific bacteria like Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg). In this case series 25 patients were diagnosed with aggressive periodontitis by the aid of DNA probes for Aa and Pg and other periodontal pathogens. The use of DNA probes for the detection of periodontal pathogens may aid in the diagnosis and treatment of aggressive periodontitis. Clinical experience suggests that lowering periodontal pathogens to undetectable levels could improve the long-term stability of periodontal health.

Effect of the interleukin-1 genotype on outcomes of regenerative periodontal therapy with bone replacement grafts.

BACKGROUND: Previous studies have shown an association between a specific genotype for the inflammatory cytokine interleukin (IL)-1 and the severity of periodontal disease. The purpose of this study was to evaluate the effect of the IL-1 genotype on the outcomes of periodontal surgical regenerative treatment with bone replacement grafts. METHODS: Forty-four patients with interproximal intrabony defects were treated with bone replacement grafts. Probing depths (PD) and clinical attachment levels (CAL) were measured before treatment and at least 9 months post-treatment. Whole-mouth plaque index (WMPI) and bleeding index (WMBI) were recorded as well. All patients were tested for the IL-1 genotype. RESULTS: Thirteen (29.55%) of the patients were IL-1 genotype positive. There was no statistically significant difference between the genotype-positive and genotype-negative groups regarding age, smoking status, gender, WMPI, and WMBI. There was no significant difference in PD or CAL between the genotype-positive and genotype-negative groups at baseline. Genotype-positive patients had a smaller reduction in probing depth (1.86 mm versus 2.13 mm) and a greater gain of clinical attachment (1.20 mm versus 0.65 mm). These differences were not statistically significant (P = 0.70, P = 0.40). Multivariate regression analysis showed that presurgical PD significantly influenced post-surgical PD and CAL, and only WMPI significantly influenced CAL. CONCLUSION: In this study, there was no evidence that the IL-1 genotype influences the clinical treatment outcomes of regenerative periodontal therapy with bone replacement grafts.