Evaluation of locally-administered controlled-release doxycycline hyclate gel in smokers and non-smokers in the management of periodontitis: An Indian study

Purpose: To assess the clinical and biological effect of locally-administered controlled-release 10 % doxycycline hyclate gel in smokers and non-smokers for the management of periodontitis. Methods: Forty periodontitis patients were enrolled in this study from December 2012 to February 2013 at the Department of Periodontology and Implantology of the Institute of Dental Sciences and Dental Unit of Rohilkhand Medical College, Bareilly, Uttar Pradesh (UP), India. For each patient, probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), gingival index (GI), and sulcular bleeding index (SBI) were recorded. Changes in microbial counts were assessed by measuring colonyforming units (CFU) of three major periodontal pathogens. Clinical and microbial parameters were recorded at baseline and one month after scaling and root planing plus controlled local drug delivery of 10 % doxycycline hyclate gel in smokers and non-smokers. Results: A statistically significant change (p < 0.01) in PPD was observed among smokers between baseline (4.26 ± 0.12mm) and re-evaluation at one month (3.20 ± 0.11) with a change of 24.88 %. A statistically significant difference was found between smokers and non-smokers in PPD at the end of a 1-month re-evaluation (p < 0.05). None of the other parameters showed improvement in smokers following treatment. Conclusion: These results indicate that 10 % doxycycline hyclate gel, when administered locally into the periodontal pocket, shows clinical and microbial improvement, among smokers and non-smokers, in the management of periodontitis. Therefore, 10 % doxycycline gel is potentially an effective therapeutic strategy in the management of periodontitis

Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution

During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

Background Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it

Ispitivanje kompatibilnosti nateglinida s pomoćnim tvarima u razvoju tableta nateglinida za trenutno oslobađanje

Experiments were done to assess the compatibility of nateglinide with selected excipients in the development of immediate release tablets of nateglinide by thermal and isothermal stress testing (IST) techniques. To evaluate the drug-excipient compatibility, different techniques such as differential scanning calorimetric (DSC) study, infra-red (IR) spectrophotometric study and isothermal stress testing were adopted. The results of DSC study showed that magnesium stearate exhibited some interaction with nateglinide. However, the results of IR, and IST studies showed that all the excipients used in the formula were compatible with nateglinide. Optimized formulations developed using the compatible excipients were found to be stable over 3 months of accelerated stability studies (40 ± 2 C and 75 ± 5 % RH). Overall, compatibility of excipients with nateglinide was successfully evaluated using a combination of thermal and IST methods and the formulations developed using the compatible excipients were found to be stable.Koristeći termičke metode kao što su diferencijalna pretražna kalorimetrija (DSC) i infra-crvena spektrofotometrija (IR), te izotermička stres-testiranja (IST) ispitana je kompatibilnost nateglinida s izabranim ekscipiensima u razvoju tableta nateglinida za trenutno oslobađanje. Rezultati DSC ispitivanja pokazala su da magnezijev stearat stupa u određenu interakciju s nateglinidom. Međutim, IR i IST ispitivanja pokazuju da su svi upotrijebljeni ekscipiensi kompatibilni s nateglinidom. Optimirana formulacija bila je stabilna preko 3 mjeseca u testovima ubrzanog starenja (40 ± 2 C i 75 ± 5 % RH). Kompatibilnost ekscipiensa s nateglinidom uspješno je evaluirana koristeći kombinaciju termičke i IST metode, a formulacije razvijene koristeći kompatibilne ekscipiense bile su stabilne

Positive Evolutionary Selection of an HD Motif on Alzheimer Precursor Protein Orthologues Suggests a Functional Role

HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001). The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the “transcription binding site turnover.” CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs

Divergence of the Yeast Transcription Factor FZF1 Affects Sulfite Resistance

Changes in gene expression are commonly observed during evolution. However, the phenotypic consequences of expression divergence are frequently unknown and difficult to measure. Transcriptional regulators provide a mechanism by which phenotypic divergence can occur through multiple, coordinated changes in gene expression during development or in response to environmental changes. Yet, some changes in transcriptional regulators may be constrained by their pleiotropic effects on gene expression. Here, we use a genome-wide screen for promoters that are likely to have diverged in function and identify a yeast transcription factor, FZF1, that has evolved substantial differences in its ability to confer resistance to sulfites. Chimeric alleles from four Saccharomyces species show that divergence in FZF1 activity is due to changes in both its coding and upstream noncoding sequence. Between the two closest species, noncoding changes affect the expression of FZF1, whereas coding changes affect the expression of SSU1, a sulfite efflux pump activated by FZF1. Both coding and noncoding changes also affect the expression of many other genes. Our results show how divergence in the coding and promoter region of a transcription factor alters the response to an environmental stress

The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

Background Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it

Review Article - Changing trends in hair restoration surgery

Androgenetic alopecia is an important and common cause for baldness. Despite recent advances, the drug therapy of this condition remains unsatisfactory. Surgical hair restoration is the only permanent method of treating this condition. Introduction of recent techniques such as follicular unit transplantation have improved the cosmetic results and patient satisfaction. This article discusses the latest trends in hair restoration surgery

A context aware collaborative service provisioning system for mobile-commerce

In the process of service provisioning, providing required service to the user without user intervention, with reduction of the cognitive over loading is a real challenge. In this paper we propose a user centred context aware collaborative service provisioning system, which make use of context along with collaboration to provide the required service to the user dynamically. The system uses a novel approach of query expansion along with interactive and rating matrix based collaboration. Performance of the system is evaluated in Mobile-Commerce environment. The results show that the system is time efficient and perform with better precision and recall in comparison with context aware system