Modified CFBG-based approach for chromatic dispersion compensation in high speed DWDM links.

Chromatic dispersion (CD) is a major concern in high speed fiber optics communication systems. This work presents an efficient optical compensation technique with reduced complexity to mitigate CD effects in single mode fiber (SMF) at high data rates. The proposed method includes a post-dispersion mitigation system using a single linear chirped fiber Bragg grating (CFBG) with tanh apodization. Here, various parameters of CFBG, such as grating length, effective refractive index, and apodization function, are optimized to achieve effective CD compensation. Then, the system is extended to a 16-channel WDM link with each channel carrying data at 25 Gbps over 100 km. The simulation results show that the proposed model enhances the system performance while minimizing overall system complexity. The proposed system is also compatible with the prevailing fiber optics networks. The results are consistent with the findings published in recent studies.

Study protocol: families and childhood transitions study (FACTS) - a longitudinal investigation of the role of the family environment in brain development and risk for mental health disorders in community based children.

BACKGROUND: Extant research has demonstrated that parenting behaviour can be a significant contributor to the development of brain structure and mental health during adolescence. Nonetheless, there is limited research examining these relationships during late childhood, and particularly in the critical period of brain development occurring between 8 and 10 years of age. The effects of the family environment on the brain during late childhood may have significant implications for later functioning, and particularly mental health. The Families and Childhood Transitions Study (FACTS) is a multidisciplinary longitudinal cohort study of brain development and mental health, with two waves of data collection currently funded, occurring 18-months apart, when child participants are aged approximately 8- and 10-years old. METHODS/DESIGN: Participants are 163 children (M age [SD] = 8.44 [0.34] years, 76 males) and their mothers (M age [SD] = 40.34 [5.43] years). Of the 163 families who consented to participate, 156 completed a video-recorded and observer-coded dyadic interaction task and 153 completed a child magnetic resonance imaging brain scan at baseline. Families were recruited from lower socioeconomic status (SES) areas to maximise rates of social disadvantage and variation in parenting behaviours. All experimental measures and tasks completed at baseline are repeated at an 18-month follow-up, excluding the observer coded family interaction tasks. The baseline assessment was completed in October 2015, and the 18-month follow up will be completed May 2017. DISCUSSION: This study, by examining the neurobiological and mental health consequences of variations in parenting, has the potential to significantly advance our understanding of child development and risk processes. Recruitment of lower SES families will also allow assessment of resilience factors given the poorer outcomes often associated with this population.

Oxycodone N-oxide.

The title compound, (5R,9R,13S,14S,17R)-14-hydroxy-3-methoxy-17-methyl-4,5-epoxymorphinan-6-one N-oxide, C(18)H(21)NO(5), has been prepared in a diastereomerically pure form by the reaction of oxycodone with 3-chloroperbenzoic acid and subsequent crystallization of the product from chloroform. The crystal packing shows that the molecule exhibits intramolecular O-H···O [D···A = 2.482 (2) Å] hydrogen bonding. In addition, there are weak intermolecular C-H...O interactions which, along with van der Waals forces, stabilize the structure. The new chiral center at the 17-position is demonstrated to be R.

The effect of hydrogen bonding on the conformations of 2-(1H-indol-3-yl)-2-oxoacetamide and 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide.

In the title compounds, C(10)H(8)N(2)O(2), (I), and C(12)H(12)N(2)O(2), (II), the two carbonyl groups are oriented with torsion angles of -149.3 (3) and -88.55 (15)°, respectively. The single-bond distances linking the two carbonyl groups are 1.528 (4) and 1.5298 (17) Å, respectively. In (I), the molecules are linked by an elaborate system of N-H···O hydrogen bonds, which form adjacent R(2)(2)(8) and R(4)(2)(8) ring motifs to generate a ladder-like construct. Adjacent ladders are further linked by N-H···O hydrogen bonds to build a three-dimensional network. The hydrogen bonding in (II) is far simpler, consisting of helical chains of N-H···O-linked molecules that follow the 2(1) screw of the b axis. It is the presence of an elaborate hydrogen-bonding system in the crystal structure of (I) that leads to the different torsion angle for the orientation of the two adjacent carbonyl groups from that in (II).

Massive perinatal left ventricle infarction treated with tissue plasminogen activator: No ECMO - A case report.

Neonatal myocardial infarction due to coronary thrombus is a rare cause of acute heart failure and is associated with high morbidity and mortality. We present a rare case of a full-term newborn who developed coronary artery thrombus treated with intracoronary recombinant tissue plasminogen activator infusion while undergoing therapeutic hypothermia. Also, we describe a unique treatment strategy to support systemic circulation sparing the patient from neonatal extracorporeal membrane oxygenation and its complications. Neonatal myocardial infarction should be suspected and ruled out in sick newborns.

Effect of satapushpa churnam with tila tailam in oligomenorrhea associated with polycystic ovarian syndrome.

BACKGROUND: Current medical intervention of Polycystic Ovarian Syndrome (PCOS) mainly includes hormonal therapies which have long-term health consequences. OBJECTIVE: This study aimed to evaluate the effect of natural drug satapushpa (Anethum sowa Kurz.) powder with tilatailam (sesame oil) as anupanam (vehicle) in oligomenorrhoea associated with PCOS. MATERIALS AND METHODS: A single-group, before and after intervention study in the outpatient department and inpatient department of Government Ayurveda teaching hospital for women and children was done among women aged 18-35 years. Individuals diagnosed with oligomenorrhoea for more than three consecutive menstrual cycles and fulfilling Rotterdam's criteria of PCOS were included. Six grams of powder was given morning and evening along with 12 ml of tilatailam for three months. Effectiveness was assessed at 3rd and 6th months. RESULTS: A total of 30 patients were recruited; the mean (SD) age was 22.6 (3.9) years. Majority were students (86.7%), residing in urban areas (60%), and unmarried (80%). Almost one-third of the participants had kapha-vata prakriti. There was no significant change in menstrual duration and amount of bleeding. However, a significant reduction in the menstrual interval was observed after three months of treatment (p = <0.001). Similarly, the median interquartile range (IQR) volume of the right ovary was reduced from 10 (7.2-14.8) to 5.3 (4.7-7.6) cm3 (p=<0.001), and the median (IQR) volume of the left ovary reduced from 9.1 (6.7-11.9) to 5.1 (4.6-7.1) cm3 (p=<0.001). CONCLUSION: Treating PCOS using satapushpa powder and tilatailam for three months effectively regularizes the menstrual interval and reduces ovarian volume.

Indolyl-quinuclidinols inhibit ENOX activity and endothelial cell morphogenesis while enhancing radiation-mediated control of tumor vasculature.

There is a need for novel strategies that target tumor vasculature, specifically those that synergize with cytotoxic therapy, in order to overcome resistance that can develop with current therapeutics. A chemistry-driven drug discovery screen was employed to identify novel compounds that inhibit endothelial cell tubule formation. Cell-based phenotypic screening revealed that noncytotoxic concentrations of (Z)-(+/-)-2-(1-benzenesulfonylindol-3-ylmethylene)-1-azabicyclo[2. 2.2]octan-3-ol (analog I) and (Z)-(+/-)-2-(1-benzylindol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-ol (analog II) inhibited endothelial cell migration and the ability to form capillary-like structures in Matrigel by > or =70%. The ability to undergo neoangiogenesis, as measured in a window-chamber model, was also inhibited by 70%. Screening of biochemical pathways revealed that analog II inhibited the enzyme ENOX1 (EC(50) = 10 microM). Retroviral-mediated shRNA suppression of endothelial ENOX1 expression inhibited cell migration and tubule formation, recapitulating the effects observed with the small-molecule analogs. Genetic or chemical suppression of ENOX1 significantly increased radiation-mediated Caspase3-activated apoptosis, coincident with suppression of p70S6K1 phosphorylation. Administration of analog II prior to fractionated X-irradiation significantly diminished the number and density of tumor microvessels, as well as delayed syngeneic and xenograft tumor growth compared to results obtained with radiation alone. Analysis of necropsies suggests that the analog was well tolerated. These results suggest that targeting ENOX1 activity represents a novel therapeutic strategy for enhancing the radiation response of tumors.

Height and dental caries among 13-year-old adolescents in India: A sociobehavioral life course approach.

BACKGROUND: The aim of the study was to assess the relationship between height and dental caries among 13-year-old adolescents in schools of Bangalore, India. MATERIALS AND METHODS: A cross-sectional study was undertaken on 1900 schoolchildren aged 13 years from both government and private schools of Bangalore using stratified random sampling. Demographic data; family-related factors; and general and oral health-related factors such as frequency of sugar consumption, dietary habits, oral hygiene practices, and dental attendance were interviewed using both open-ended and close-ended questions. Anthropometric measurements for height and weight were performed. Clinical examination was done and caries was recorded using the decayed, missing, and filled teeth (DMFT) index (WHO criteria, 1997). Data were analyzed using SPSS version 21.0, and descriptive statistics including percentages, mean, and frequencies were performed. Student's t-test and ANOVA were applied to find the significant differences between mean DMFT among groups. Categorical data were analyzed by Chi-square test for differences between groups. Pearson correlation coefficient was used to find the correlation among dental caries and height and body mass index (BMI).P value was set at a statistical significance level of 0.05. RESULTS: The prevalence of dental caries among the study population was 36.3% which was higher among girls as compared to boys. Dental caries was found to be significantly associated with socioeconomic status, family structure, birth order, use of oral hygiene aids, mouthrinsing, last dental visit, weight, and BMI. Height and BMI showed a strong negative correlation with dental caries. CONCLUSION: The present study showed a significant negative correlation between height and dental caries. However, since both caries and height are a dynamic phenomenon, hence a longitudinal study exploring the possible relationship should be considered.

Synthesis and antitubercular activity of a series of hydrazone and nitrovinyl analogs derived from heterocyclic aldehydes.

A series of hydrazone and 3-nitrovinyl analogs of indole-3-carboxaldehydes and related compounds were synthesized and screened for antitubercular activity against Mycobacterium tuberculosis H37R(V) in BACTEC 12B medium using the Microplate Alamar Blue Assay (MABA). Several compounds showed inhibitory activity against M. tuberculosis in primary screening assays at a concentration of 6.25 microg/mL; subsequent dose-response studies indicated that the most active compounds, 3d, 3e & 8b, had IC(50) values of 5.96, 5.4 & 1.6 microg/mL, respectively. These compounds represent potential leads for the further development of novel antitubercular agents.

Novel chemical enhancers of heat shock increase thermal radiosensitization through a mitotic catastrophe pathway.

Radiation therapy combined with adjuvant hyperthermia has the potential to provide outstanding local-regional control for refractory disease. However, achieving therapeutic thermal dose can be problematic. In the current investigation, we used a chemistry-driven approach with the goal of designing and synthesizing novel small molecules that could function as thermal radiosensitizers. (Z)-(+/-)-2-(1-Benzenesulfonylindol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-ol was identified as a compound that could lower the threshold for Hsf1 activation and thermal sensitivity. Enhanced thermal sensitivity was associated with significant thermal radiosensitization. We established the structural requirements for activity: the presence of an N-benzenesulfonylindole or N-benzylindole moiety linked at the indolic 3-position to a 2-(1-azabicyclo[2.2.2]octan-3-ol) or 2-(1-azabicyclo[2.2.2]octan-3-one) moiety. These small molecules functioned by exploiting the underlying biophysical events responsible for thermal sensitization. Thermal radiosensitization was characterized biochemically and found to include loss of mitochondrial membrane potential, followed by mitotic catastrophe. These studies identified a novel series of small molecules that represent a promising tool for the treatment of recurrent tumors by ionizing radiation.

A pharmacokinetic study on Z-(+/-)-2-(1-benzylindole-3-yl-methylene)azabicyclo[2.2.2]octane-3-ol; a novel radio-sensitization agent.

PURPOSE: The purpose of this research was to characterize the pharmacokinetic parameters and to evaluate the absolute bioavailability of the targeted compound: Z-(+/-)-2-(1-benzylindole-3-yl-methylene)azabicyclo[2.2.2]octane-3-ol (BMABO), a novel radio-sensitization agent, after oral delivery. METHODS: Sprague-Dawley rats received a single oral dose of 20 mg/kg and this was compared with intravenous administration of the compound (1 mg/kg). Blood samples were collected at different time points, and plasma BMABO concentrations were determined using a new sensitive and specific LC/MS analytical method, which utilized electrospray ionization. RESULTS: The bioavailability of orally administered BMABO was determined by comparing plasma concentrations after oral gavage delivery with intravenous delivery. Following delivery of the oral dose, the average C (max) was 1,710 +/- 503 ng/ml, and the AUC-value was found to be 3,561 +/- 670 ng min kg/ml mg. Relative to the intravenous dose (100% bioavailability), the bioavailability was 6.2% after oral administration. CONCLUSION: As the current studies demonstrate the novel radio-sensitization agent BMABO may have potential therapeutic valuable in cancer treatment. Further evaluation of the efficacy and toxicity of BMABO will determine the feasibility of the oral route for future clinical studies.

Novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(+/-)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents.

Use of ionizing radiation is essential for the management of many human cancers, and therapeutic hyperthermia has been identified as a potent radiosensitizer. Radiation therapy combined with adjuvant hyperthermia represents a potential tool to provide outstanding local-regional control for refractory disease. (Z)-(+/-)-2-(N-Benzylindol-3-ylmethylene)quinuclidin-3-ol (2) and (Z)-(+/-)-2-(N-benzenesulfonylindol-3-ylmethylene)quinuclidin-3-ol (4) were initially identified as potent thermal sensitizers that could lower the threshold needed for thermal sensitivity to radiation treatment. To define the structural requirements of the molecule that are essential for thermal sensitization, we have synthesized and evaluated a series of (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one (9), and (Z)-(+/-)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol (10) analogs that incorporate a variety of substituents in both the indole and N-benzyl moieties. These systematic structure-activity relationship (SAR) studies were designed to further the development and optimization of potential clinically useful thermal sensitizing agents. The most potent analog was compound 10 (R(1)=H, R(2)=4-Cl), which potently inhibited (93% inhibition at 50 microM) the growth of HT-29 cells after a 41 degrees C/2h exposure.

(Z)-3-(Benzo[b]thiophen-2-yl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile and (E)-3-(benzo[b]thiophen-2-yl)-2-(3,4-dimethoxyphenyl)acrylonitrile. [corrected].

The title compounds, C20H17NO3S, (I), and C19H15NO2S, (II), were prepared by the reaction of benzo[b]thiophene-2-carbaldehyde with (3,4,5-trimethoxyphenyl)acetonitrile and (3,4-dimethoxyphenyl)acetonitrile, respectively, in the presence of methanolic potassium hydroxide. In (I), the C=C bond linking the benzo[b]thiophene and the 3,4,5-trimethoxyphenyl units has E geometry, with dihedral angles between the plane of the bridging unit and the planes of the two adjacent ring systems of 5.2 (3) and 13.1 (2) degrees, respectively. However, in (II), the C=C bond has Z geometry, with dihedral angles between the plane of the bridging unit and the planes of the adjacent benzo[b]thiophene and 3,4-dimethoxyphenyl units of 4.84 (17) and 76.09 (7) degrees, respectively. There are no significant intermolecular hydrogen-bonding interactions in the packing of (I) and (II). The packing is essentially stabilized via van der Waals forces.

3-Ethyl-2-methyl-5-methyl-ene-6,7-di-hydroindol-4(5H)-one.

The title compound, C(12)H(15)NO, a degradation product of molindone hydro-chloride, was prepared by the reaction of molindone with methyl iodide and subsequent reaction of the resulting quaternary ammonium salt with 2N aqueous sodium hydroxide. The newly formed double bond is exocyclic in nature and the carbonyl group is conjugated with the π-electrons of the pyrrole ring. The six-membered ring is in the half-chair conformation. The H atom attached to the N atom is involved in an inter-molecular hydrogen bond with the O atom of a screw-related mol-ecule, thus forming a continuous chain.

Probing mucin interaction behavior of magnetic nanoparticles.

In this study, we developed iron oxide based magnetic nanoparticles (MNPs) by precipitation of iron salts in the presence of ammonia and created four different formulations: without functionality (plain MNPs, no coating), with ß-cyclodextrin (MNPs+ß-CD) or pluronic 127 polymer (MNPs+F-127), and both ß-cyclodextrin and pluronic 127 polymer (MNPs+ß-CD-F-127) functionality for its efficient use in mucosal delivery. We studied the interaction and/or binding behavior of these MNPs formulations with porcine stomach mucin using steady-state fluorescence spectroscopy, and then quantified the bound mucin from absorption studies. Toxicity of these MNPs against cervical cancer cells and red blood cells was evaluated. Ex-vivo studies were performed using freshly collected gastrointestinal, ovarian, pancreas and colon organ tissues of pig to evaluate binding and uptake phenomenon of MNPs. Transport studies of these MNPs in mucin was evaluated using Boyden's chamber assay. All these studies together suggest that the MNPs+ß-CD-F-127 formulation was strongly interacted with mucin and interestingly transported through mucin compared to other MNPs formulations. Hence, MNPs+ß-CD-F-127 formulation could be a good candidate for the mucoadhesive biopharmaceuticals and drug delivery system.

NADPH oxidase activity is essential for Keap1/Nrf2-mediated induction of GCLC in response to 2-indol-3-yl-methylenequinuclidin-3-ols.

Glutamate cysteine ligase, the rate-limiting enzyme for the synthesis of glutathione, represents an important component of chemoprevention paradigms. GCLC and GCLM, the genes encoding glutamate cysteine ligase subunits, are induced by indoles, such as indomethacin. Novel functionalized indole analogues and other structurally related compounds were synthesized and used for a comparative structure analysis of GCLC induction. Use of mouse embryo fibroblasts null for Nrf2 (nuclear factor-erythroid 2p45-related transcription factor) and HepG2 cells overexpressing Keap1 demonstrated that indole analogue-mediated GCLC expression was regulated by Nrf2-Keap1 interactions. Indole analogues capable of inducing GCLC were found to increase NADPH oxidase activity. Indole analogues unable to induce GCLC did not increase oxidase activity. HepG2 cells transfected with FLAG/Keap1 were exposed to indomethacin, and the redox state of Keap1 cysteine residues was assessed. The data indicated that Keap1 exhibited several oxidation states that were sensitive to indomethacin treatment. These indomethacin-mediated changes in thiol oxidation states were suppressed by diphenyleneiodonium, a NADPH oxidase inhibitor. Diphenyleneiodonium also suppressed indole analogue-mediated increases in GCLC mRNA. In summary, the use of the indole analogues identified NADPH oxidase activity as a novel upstream activity regulating Nrf2/Keap1 signaling of GCLC, provided data supporting the hypothesis that Keap1 is a downstream effector for oxidase activity, and afforded in vivo data to support the hypothesis that Keap1 thiols can act as molecular sensors of reactive oxygen species. Finally, the comparative structure analysis suggests that 2-indol-3-yl-methylenequinuclidin-3-ols may represent a prototype for the development of novel chemopreventative agents able to activate Keap1/Nrf2 signaling.

Autism spectrum disorders: Integration of the genome, transcriptome and the environment.

Autism spectrum disorders denote a series of lifelong neurodevelopmental conditions characterized by an impaired social communication profile and often repetitive, stereotyped behavior. Recent years have seen the complex genetic architecture of the disease being progressively unraveled with advancements in gene finding technology and next generation sequencing methods. However, a complete elucidation of the molecular mechanisms behind autism is necessary for potential diagnostic and therapeutic applications. A multidisciplinary approach should be adopted where the focus is not only on the 'genetics' of autism but also on the combinational roles of epigenetics, transcriptomics, immune system disruption and environmental factors that could all influence the etiopathogenesis of the disease. ASD is a clinically heterogeneous disorder with great genetic complexity; only through an integrated multidimensional effort can modern autism research progress further.

Cerebral Ischemic Preconditioning: the Road So Far .

Cerebral preconditioning constitutes the brain's adaptation to lethal ischemia when first exposed to mild doses of a subtoxic stressor. The phenomenon of preconditioning has been largely studied in the heart, and data from in vivo and in vitro models from past 2-3 decades have provided sufficient evidence that similar machinery exists in the brain as well. Since preconditioning results in a transient protective phenotype labeled as ischemic tolerance, it can open many doors in the medical warfare against stroke, a debilitating cerebrovascular disorder that kills or cripples thousands of people worldwide every year. Preconditioning can be induced by a variety of stimuli from hypoxia to pharmacological anesthetics, and each, in turn, induces tolerance by activating a multitude of proteins, enzymes, receptors, transcription factors, and other biomolecules eventually leading to genomic reprogramming. The intracellular signaling pathways and molecular cascades behind preconditioning are extensively being investigated, and several first-rate papers have come out in the last few years centered on the topic of cerebral ischemic tolerance. However, translating the experimental knowledge into the clinical scaffold still evades practicality and faces several challenges. Of the various preconditioning strategies, remote ischemic preconditioning and pharmacological preconditioning appears to be more clinically relevant for the management of ischemic stroke. In this review, we discuss current developments in the field of cerebral preconditioning and then examine the potential of various preconditioning agents to confer neuroprotection in the brain.

Trajectories of adolescent conduct problems in relation to cortical thickness development: a longitudinal MRI study.

Multiple cross-sectional imaging studies have identified structural abnormalities in prefrontal, temporal and limbic regions related to conduct problems (CPs). However, the relationship between development of such neurobiological deficits and developmental pathways of CPs has remained unclear. The current study investigated distinct trajectories of CP and related trajectories of cortical thickness within a community-based sample of adolescents (n=239), age range 12-19, to address this gap. Three trajectory classes were revealed using latent class growth analyses (LCGAs), comprising a 'desisting' CP group, an 'intermediate' CP group and a 'stable low' CP group. Structural magnetic resonance imaging (MRI) scans were collected with a subgroup of 171 adolescents at three waves throughout adolescence (ages 12, 16 and 19). Generalized estimating equation (GEE) analysis-comparing longitudinal changes in cortical thickness and subcortical volume between CP groups for several regions of interest (ROIs)-showed that these CP groups had differential trajectories of cortical thickness in the dorsolateral prefrontal cortex (dl-PFC), and the anterior cingulate cortex (ACC), and volume of the hippocampus. Adolescents in the desisting CP group showed an attenuation of the typical pattern of cortical thinning as present in the intermediate and stable low CP groups, in addition to an exaggeration of the typical pattern of hippocampal volume increase. These findings suggest that a deviant cortical thickness trajectory was related to a desisting CP pathway across adolescence. Such deviant neurodevelopmental growth trajectories may act as an underlying mechanism for developmental CP pathways, and possibly distinguish desisting antisocial adolescents.

Tobacco use among high school children in Bangalore, India: A study of knowledge, attitude and practice.

INTRODUCTION: Tobacco use among school children is becoming a serious problem in developing countries. The early age of initiation underscores the urgent need to intervene and protect this vulnerable group from becoming victims of this addiction. AIM: To assess the knowledge, attitudes, and practices about tobacco use among 13-15 year old school children of Bangalore City. MATERIALS AND METHODS: A cross-sectional study was designed and data on tobacco usage was collected from 1288 students aged 13-15 years studying in six government and private schools of Bangalore using a self-administered closed ended questionnaire. Data was analyzed using SPSS 15.0 and descriptive statistics was applied. Chi-square tests were used to determine the significant differences in the variables of interest. RESULTS: Out of 1288 children, 1281 (99.5%) children had heard about tobacco and 1162 (90.2%) students knew the harmful effects of tobacco. Only 28 (2.2%) had used tobacco products. Peer pressure was the main reason for tobacco use among children and age was not a barrier in buying tobacco products. Television (58%) was the main source of information for tobacco products followed by newspapers (26%) and movies (16%). CONCLUSION: It is encouraging to find that majority of the 13-15 year old children surveyed in the present study did not use tobacco and were aware of the health risks associated with tobacco use. This calls for the school authorities to be included in stricter implementation and monitoring of the implementation of legislation. Regular and systematic education programs catering to teachers, children, and also their parents should be undertaken.