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Foot and Mouth Disease (FMD) is endemic in Nepal and causes substantial economic losses in the livestock industry. The goal of this study was to perform an epidemiological analysis of FMD outbreaks reported to the Veterinary Epidemiology Center, Tripureshwor, Nepal during 2010-2015, in order to strengthen the National FMD Control Program. These current data were considered in the context of historical data on FMD virus (FMDV) serotypes detected in the country between 1965 and 2015. During 2010-2015, a total of 1333 livestock holdings reported FMD outbreaks in Nepal. On average, 71.2 animals were affected in each outbreak, with a case fatality rate of 3.6%. FMD was reported throughout the country, and the proportion of affected holdings was not significantly among eco-zones, regions, or species. The Hill eco-zone had the highest number of holdings affected (782), followed by Mountain (304), and Terai (247). When analysed by the developmental region, the Western (381) and Central (368) Developmental Regions had the highest numbers of holdings affected. Cattle were the most frequently affected species (39%), followed by buffalo (33%), and goats (19%). FMD occurred throughout the year, with peaks in winter (December/January) and in the pre-monsoon period (April/May). Between 1965 and 2015 FMDV serotype O had the highest prevalence (81%), followed by Asia-1 (11%), A (6%), and C (2%). Serotype C was not detected after 1996, and only serotype O was reported after 2011. These descriptive analyses provide critical landmarks to establish baselines, and document early progress of the ongoing Progressive Control Pathway of FMD (PCP-FMD) which could be useful in Nepal and other South Asian nations., (© 2018 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Correction to: J. Biosci. 40(5), December 2015, 863-871 https://doi.org/10.1007/s12038-015-9570-0 The image of anti-Myc blot of figure 2C (third panel; Malin-Myc [C26S]) was inadvertently used once again for the c-tubulin loading control of figure 2B. The revised figure 2B with the correct image of the c-tubulin loading control is given below. The interpretation and conclusion provided in the article do not change because of the correction.

Considering alarming projections in the prevalence of periodontitis, following study was undertaken to develop chitosan-vanillin crosslinked microspheres loaded in-situ gel (MLIG) implants containing ornidazole and doxycycline hyclate for the treatment of pocket infections. Firstly, microspheres were formulated and optimized using response surface methodology for particle size <50 μm, entrapment efficiency >80%, in-vitro drug release (T 80% ) >7 days and acceptable mucoadhesion. Further, MLIG were optimized for gelation temperature of 34-37 °C and viscosity <1000 cps respectively. FTIR, DSC and XRD graphs disclosed compatibility and alterations in crystallinity of drugs. In-vitro dissolution study demonstrated non-Fickian type of drug release mechanism for twelve days. Stability studies ascertained MLIG implants were sterilizable and stable for about 11.29 months on refrigeration. The formulations exhibited significant (p < 0.001) antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis, and were found biocompatible and biodegradable during preclinical studies. Ligature-induced periodontal rat model, corroborated significant growth (p < 0.05) of gingival tissue after two weeks. Clinical trials revealed, intra-pocket administration of MLIG along with SRP provided significant reduction in clinical parameters as compared to SRP alone. Conclusively, antimicrobials incorporated thermosensitive, biodegradable, mucoadhesive and syringeable MLIG implants appeared as better option for the treatment of periodontitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Corneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme., Methods and Analysis: The Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm., Ethics and Dissemination: The University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication., Trial Registration Number: NCT01969786; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The research aims the development and optimization of capecitabine loaded interpenetrating polymeric network by ionotropic gelation method using polymers locust bean gum and sodium alginate by QbD approach. FMEA was performed to recognize the risks influencing CQAs. BBD was applied to study the effect of factors (polymer ratio, amount of cross-linker and curing time) on responses (particle size, % drug entrapment and % drug release). Polynomial equations and 3-D graphs were plotted to relate between factors and responses. The results of the optimized batch viz. particle size (457.92 ± 1.6 μm), % drug entrapment (74.11 ± 3.1%) and % drug release (90.23 ± 2.1%) were close to the predicted values generated by Minitab® 17. Characterization techniques SEM, EDX, FTIR, DSC and XRD were also performed for the optimized batch. To study the water transport inside IPN microbeads, swelling study was done. In vitro drug release of optimized batch showed controlled drug release for 12 h. Pharmacokinetic study carried out following oral administration in Albino Wistar rats exhibited that optimized microbeads had better PK parameters than free drug. In vitro cytotoxicity against HT-29 cells revealed significant reduction of the cell growth when treated with optimized formulation indicating IPN microbeads as effective dosage form for treating colon cancer., (Copyright © 2018. Published by Elsevier B.V.)

A proper understanding of the force system created by various orthodontic appliances can make treatment of patients efficient and predictable. Reducing the complicated multi-bracket appliances to a simple two-bracket system for the purpose of force system evaluation will be the first step in this direction. However, much of the orthodontic biomechanics in this regard is confined to 2D experimental studies, computer modeling/analysis or theoretical extrapolation of existing models. The objective of this protocol is to design, construct and validate an in vitro 3D model capable of measuring the forces and moments generated by an archwire with a V-bend placed between two brackets. Additional objectives are to compare the force system generated by different types of archwires among themselves and to previous models. For this purpose, a 2 x 4 appliance representing a molar and an incisor has been simulated. An orthodontic wire tester (OWT) is constructed consisting of two multi-axis force transducers or load cells (nanosensors) to which the orthodontic brackets are attached. The load cells are capable of measuring the force system in all the three planes of space. Two types of archwires, stainless-steel and beta-titanium of three different sizes (0.016 x 0.022 inch, 0.017 x 0.025 inch and 0.019 x 0.025 inch), are tested. Each wire receives a single vertical V-bend systematically placed at a specific position with a predefined angle. Similar V-bends are replicated on different archwires at 11 different locations between the molar and incisor attachments. This is the first time an attempt has been made in vitro to simulate an orthodontic appliance utilizing V-bends on different archwires.

Background: Self-care activities are the cornerstone of diabetes care that ensures patients participation to achieve optimal glycemic control and to prevent complications., Objective: The aim of this study is to find the level of self-care activities among diabetics aged ≥20 years residing in a resettlement colony in East Delhi and its association with sociodemographic factors, disease, and treatment profile., Methods: Using cross-sectional survey, 168 known diabetic patients were selected from Nand Nagri, a resettlement colony in East Delhi. Data were collected using Hindi translation of revised version-Summary of Diabetic Self Care Activities along with a pretested semi-open-ended questionnaire. Self-care was assessed on six parameters as follows: (a) general diet, (b) specific diet, (c) exercise, (d) blood sugar testing, (e) foot-care, and (f) smoking. The study period was from November 2014 to April 2016., Results: Nearly 35.1% of respondents belonged to 60-69 years age group. About 52.4% of respondents were female. Fifty-two diabetics (31%) reported having practised diet control on all 7 days in the past 1 week. Nearly 39.3% of patients did not perform any physical activity. The blood test was not practised by 92.3% of respondents. Foot-care was practised by only 19% of patients. There was a significant association between general diet among diabetics with family support (P = 0.020), place of diagnosis (P = 0.033), and treatment funds (P = 0.017). The exercise score among diabetics who were below the poverty line was higher than those above poverty line (P = 0.029). Younger age (P = 0.005) and treatment with insulin (P = 0.008) were positively associated with blood glucose testing. The foot-care practice was better in patients aware of complications and foot-care practices (P < 0.001)., Conclusion: Self-care activities among diabetic patients were very poor. Self-management educational programs at hospitals along with information, education, and communication activities at the community level and one-to-one counseling are recommended., Competing Interests: There are no conflicts of interest

This research was motivated due to substantial requirement of improved treatment for breast cancer which accounts for over 0.52 million deaths annually worldwide. Utilizing nanoparticles carrying active medicaments as targeted delivery carrier is emerging as a promising approach. For a drug to be clinically effective, it needs to be suitably protected in the biological fluid till it is delivered to the targeted site. Keeping above in mind, we prepared and optimized polymeric nanoparticles by polyhydroxybutyrate-co-hydroxyvalerate (PHBV) a biodegradable polymer utilizing modified emulsification solvent evaporation method. The optimized formulation had particle size of 349±3.51nm with entrapment efficiency of 69±1.28%. Nanoparticle formation and its surface morphology were confirmed by various electron microscopes. The in vitro and pharmacokinetic studies demonstrated a sustained release of drug in a non-biological system and into rat's bloodstream respectively. Also, the in vitro cytotoxicity and in vivo toxicological evaluation at the therapeutic dose demonstrated the safety and antitumor efficacy of the formulation. Due to formulation characteristic properties, it was found to be effective in enveloping and chaperoning the drug to the suitable site of action. The PHBV-TPGS combination causes the drug to be released in controlled and sustained modes, thereby reducing drug dose and toxicity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs)., Methods: Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP., Results: The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39 ± 1.82 nm, apparent drug content (ADC) of 72.06 ± 0.86%, and zeta potential (ZP) of -13.91 ± 1.21 mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48 h and followed Korsmeyer-Peppas release kinetic model., Conclusions: A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.

Objective: The objective of the study was to develop interpenetrating polymeric network (IPN) of capecitabine (CAP) using natural polymers locust bean gum (LBG) and sodium alginate (NaAlg)., Significance: The IPN microbeads were optimized by Box-Behnken Design (BBD) to provide anticipated particle size with good drug entrapment efficiency. The comparative dissolution profile of IPN microbeads of CAP with the marketed preparation proved an excellent sustained drug delivery vehicle., Methods: Ionotropic gelation method utilizing metal ion calcium (Ca 2+ ) as a cross-linker was used to prepare IPN microbeads. The optimization study was done by response surface methodology based Box-Behnken Design. The effect of the factors on the responses of optimized batch was exhibited through response surface and contour plots. The optimized batch was analyzed for particle size, % drug entrapment, pharmacokinetic study, in vitro drug release study and further characterized by FTIR, XRD, and SEM. To study the water uptake capacity and hydrodynamic activity of the polymers, swelling studies and viscosity measurement were performed, respectively., Results: The particle size and % drug entrapment of the optimized batch was 494.37 ± 1.4 µm and 81.39 ± 2.9%, respectively, closer to the value predicted by Minitab 17 software. The in vitro drug release study showed sustained release of 92% for 12 h and followed anomalous drug release pattern. The derived pharmacokinetic parameters of optimized batch showed improved results than pure CAP., Conclusion: Thus, the formed IPN microbeads of CAP proved to be an effective extended drug delivery vehicle for the water soluble antineoplastic drug.

Introduction: Clear aligners and to a lesser extent self-ligated brackets are considered to facilitate better oral hygiene than traditional fixed orthodontic appliances. This 3-arm parallel-group prospective randomized clinical trial compared the long-term and short-term effects of clear aligners, self-ligated brackets, and conventional (elastomeric-ligated) brackets on patients' oral hygiene during active orthodontic treatment., Methods: Seventy-one participants (41 boys, 30 girls; mean age, 15.6 years) undergoing orthodontic treatment were randomly allocated through a computer-generated randomization schedule to one of the groups based on the choice of intervention: Clear Aligners (CLA) (Align Technology, San Jose, Calif) (n = 27), preadjusted edgewise fixed appliance with self-ligated brackets (SLB) (Carriere, Carlsbad, Calif (n = 22), or preadjusted edgewise fixed appliance with elastomeric ligated brackets (ELB) (Ortho Organizers Inc., Carlsbad, CA) (n = 22). For each participant, the primary outcome, plaque index (PI), and secondary outcomes, gingival Index (GI) and periodontal bleeding index (PBI), were measured at baseline (T0), after 9 months of treatment (T1), and after 18 months of treatment (T2). Blinding of the clinicians and the patients to the intervention was impossible. It was only done for outcome assessment and for the statistician. Ten participants did not receive the allocated intervention for various reasons., Results: The means and standard deviations of PI at T0 (CLA, 0.50 ± 0.51; SLB, 0.65 ± 0.49; ELB, 0.70 ± 0.73), T1 (CLA, 0.83 ± 0.48; SLB, 1.38 ± 0.72; ELB, 1.32 ± 0.67), and T2 (CLA, 0.92 ± 0.58; SLB, 1.07 ± 0.59; ELB, 1.32 ± 0.67) were similar. The odds ratio (OR) for plaque index (0 or ≥1) comparing SLB or CLA to ELB was not significant. OR for SLB vs ELB = 1.54 at T0 (95% CI, 0.39-6.27), 0.88 at T1 (95% CI, 0.03-24.69), and 0.83 at T2 (95% CI, 0.02-27.70); OR for CLA vs ELB = 1.07 at T0 (95% CI, 0.30-3.88), 0.24 at T1 (95% CI, 0.01-1.98), and 0.17 at T2 (95% CI, 0.01-1.71). However, the odds ratios comparing CLA with ELB for GI (OR = 0.14; P = 0.015) and PBI (OR = 0.10; P = 0.012) were statistically significant at T1., Conclusions: In this prospective randomized clinical trial, we found no evidence of differences in oral hygiene levels among clear aligners, self-ligated brackets, and conventional elastomeric ligated brackets after 18 months of active orthodontic treatment., Registration: The trial is registered at ClinicalTrials.gov (NCT02745626)., Protocol: The protocol was not published before trial commencement., (Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Germline stem cell (GSC) self-renewal and differentiation into gametes is regulated by both intrinsic factors in the germ line as well as extrinsic factors from the surrounding somatic niche. dWnt4, in the escort cells of the adult somatic niche promotes GSC differentiation using the canonical β-catenin-dependent transcriptional pathway to regulate escort cell survival, adhesion to the germ line and downregulation of self-renewal signaling. Here, we show that in addition to the β-catenin-dependent canonical pathway, dWnt4 also uses downstream components of the Wnt non-canonical pathway to promote escort cell function earlier in development. We find that the downstream non-canonical components, RhoA, Rac1 and cdc42, are expressed at high levels and are active in escort cell precursors of the female larval gonad compared to the adult somatic niche. Consistent with this expression pattern, we find that the non-canonical pathway components function in the larval stages but not in adults to regulate GSC differentiation. In the larval gonad, dWnt4, RhoA, Rac1 and cdc42 are required to promote intermingling of escort cell precursors, a function that then promotes proper escort cell function in the adults. We find that dWnt4 acts by modulating the activity of RhoA, Rac1 and cdc42, but not their protein levels. Together, our results indicate that at different points of development, dWnt4 switches from using the non-canonical pathway components to using a β-catenin-dependent canonical pathway in the escort cells to facilitate the proper differentiation of GSCs.

This corrects the article DOI: 10.1038/hdy.2016.79.

Long-circulating nanoparticles (NPs) are promising drug delivery vehicles which target solid tumors via enhanced permeation and retention effect. Plackett-Burman (PBD) and Box-Behnken (BBD) designs were adopted to study the effects of factors viz. polymer concentration, surfactant concentration, homogenizer speed, homogenization time and ultrasonication time on responses. A graphical and numerical optimization technique was used to obtain predicted value of the response. The drug entrapment efficiency was approximately 39±0.85%. The particle size of the nanoparticles was found to be 260±2.85nm, while the zeta potential was -18±2.12mV, indicating more stable particles. SEM, TEM, and AFM were used for characterization of surface morphology and the physicochemical characters of NPs. A pharmacokinetic evaluation carried out intravenous administration in healthy Charles Foster rats displayed enhanced systemic bioavailability and plasma drug concentration. The in vivo-in silico assessment by GastroPlus™ showed good prediction accuracy and presented best-fit model. Nanoparticles were also studied for stability testing and were found to be stable concerning their drug content and physical characters. In vitro cytotoxicity was assessed using MCF-7 for percentage inhibition of human breast cancer cell line. Anticancer studies of optimized NPs showed a significant increase in efficacy as observed by relative tumor volume up to 30 days., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Copy number variation (CNV), which is characterized by large-scale losses or gains of DNA fragments, contributes significantly to genetic and phenotypic variation. Assessing CNV across different European cattle populations might reveal genetic changes responsible for phenotypic differences, which have accumulated throughout the domestication history of cattle as consequences of evolutionary forces that act upon them. To explore pattern of CNVs across European cattle, we genotyped 149 individuals, that represent different European regions, using the Illumina Bovine HD Genotyping array. A total of 9,944 autosomal CNVs were identified in 149 samples using a Hidden Markov Model (HMM) as employed in PennCNV. Animals originating from several breeds of British Isles, and Balkan and Italian regions, on average, displayed higher abundance of CNV counts than Dutch or Alpine animals. A total of 923 CNV regions (CNVRs) were identified by aggregating CNVs overlapping in at least two animals. The hierarchical clustering of CNVRs indicated low differentiation and sharing of high-frequency CNVRs between European cattle populations. Various CNVRs identified in the present study overlapped with olfactory receptor genes and genes related to immune system. In addition, we also detected a CNV overlapping the Kit gene in English longhorn cattle which has previously been associated with color-sidedness. To conclude, we provide a comprehensive overview of CNV distribution in genome of European cattle. Our results indicate an important role of purifying selection and genomic drift in shaping CNV diversity that exists between different European cattle populations.

Purpose: The purpose of the study was to assess and compare the occlusal contacts in dentate and edentulous patients wearing complete denture with varying head posture., Materials and Methods: Ad hoc sampling of 30 subjects (15 dentate and 15 edentulous) based on inclusion and exclusion criteria was done. Subjects were divided into two groups: dentate and edentulous. Each group was further divided into two subgroups based on two head postures-upright 90° and ventroflexed 30°. For recording of every posture, a new sensor was used, and the subject was asked to clench on the sensor in maximum intercuspation position at the two head postures., Results: Data were summarized as mean ± standard error and compared by Student's t -test using SPSS software (windows version 17.0 IBM corporation, New York, USA). A statistically significant correlation between head posture and contact area was found in dentate and denture wearers, i.e., tooth contact area varies with head posture., Conclusion: It was concluded that the occlusal contacts vary at different head posture in dentate as well as in denture wearers. With ventroflexion, the number of tooth contact decreased as compared to upright-erect position in both groups. Clinical implication - since the number of tooth contacts varies with varying head postures, it is recommended that the balancing of the contacts should be done at varying head postures., Competing Interests: There are no conflicts of interest.

The constitution of Nepal provides appointing a council of ministers both at federal and provincial levels without defining portfolios. There is a political agreement that MOH will be retained at the federal level. This article draws evidences around the world to meet health needs of Nepalese, the role of provincial ministry of health and coordinating structure at district/local level. The constitution emphasises on health and pronounced in 46 articles which provides guidance for the creation of federalized governance levels at federal, provincial and local levels. Retaining ministry of health at federal level without creating devolved structure at province and local levels in health sector will create difficulty in translating the spirit of the constitution and may not be effective in addressing health issues nationally and meeting global achievements like SDGs. It is suggested to establish an elaborate health system accordingly in Nepal to ensure constitutional mandate of health as a basic human right.

Background: Cervical cancer is one of the most common malignancies among women in India. There is a high mortality as patients usually present at an advanced stage because of lack of awareness and nonexistent screening programs., Aim: This study was planned to find out awareness about cervical cancer among women and their willingness to utilize screening services in an urban resettlement colony of Delhi, India., Settings and Design: A community-based, cross-sectional study was carried out in a resettlement colony of North-West Delhi., Materials and Methods: Semi-structured interview schedule was used to collect information regarding different aspects of cervical cancer. Analysis was done using SPSS package (SPSS version 16 (UCMS and GTBH, Delhi, India))., Results: A total of 373 women were included in the study. Mean age of study participants was 39.14 years. Two-third of the study population were illiterate. Half of the study population was aware of cervical cancer, and only one-fourth of population were willing to participate in a screening test. Willingness was higher among educated, ever user of family planning method and having knowledge about at least one risk factor, signs or symptoms, or possibility of early diagnosis of cancer cervix., Conclusions: The country's national program advocates for opportunistic and targeted screening of women. An understanding of the factors that influences womens' willingness to participate in screening program is essential for the success of such programs. Hence, this study emphasizes the need for dissemination of knowledge about various aspects of cancer cervix which is critical for uptake of any screening program in a developing country.

Background: Our previous understanding of V-bend mechanics is primarily from two-dimensional (2D) analysis of archwire bracket interactions in the second order. These analyses do not take into consideration the three-dimensional (3D) nature of orthodontic appliances involving the third order., Objective: To quantify the force system generated in a 3D two bracket set up involving the molar and incisors with vertical V-bends., Materials and Methods: Maxillary molar and incisor brackets were arranged in a dental arch form and attached to load cells capable of measuring forces and moments in all three planes (x, y, and z) of space. Symmetrical V-bends (right and left sides) were placed at 11 different locations along rectangular beta-titanium archwires of various sizes at an angle of 150degrees. Each wire was evaluated for the 11 bend positions. Specifically, the vertical forces (Fz) and anterio-posterior moments (Mx) were analysed. Descriptive statistics were used to interpret the results., Results: With increasing archwire size, Fz and Mx increased at the two brackets (P < 0.05). The vertical forces were linear and symmetric in nature, increasing in magnitude as the bends moved closer to either bracket. The Mx curves were asymmetric and non-linear displaying higher magnitudes for molar bracket. As the bends were moved closer to either bracket a distinct flattening of the incisor Mx curve was noted, implying no change in its magnitude., Conclusions: This article provides critical information on V-bend mechanics involving second order and third order archwire-bracket interactions. A model for determining this force system is described that might allow for easier translation to actual clinical practice., (© The Author 2016. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Lafora disease (LD) is an autosomal recessive form of a fatal disorder characterized by the myoclonus epilepsy, ataxia, psychosis, dementia, and dysarthria. A hallmark of LD is the presence of abnormal glycogen inclusions called Lafora bodies in the affected tissues including the neurons. LD can be caused by defects either in the laforin phosphatase coded by the EPM2A gene or in the malin E3 ubiquitin ligase coded by the NHLRC1 gene. The mouse models of LD, created by the targeted disruption of the LD genes, display several neurodegenerative changes. Prominent among them are the autophagic defects, abnormally large lysosomes, neurofibrillary tangles, amyloid beta deposits, and abnormal mitochondria. However, whether or not such neurodegenerative changes are a direct effect of the loss of laforin/malin was not unequivocally established. Here, we show that laforin- or malin-deficient neurons and fibroblasts display a significantly higher number of fragmented mitochondria. Loss of laforin or malin resulted in increased levels of the mitochondrial fission GTPase Drp1, its enhanced mitochondrial targeting, and increased intracellular calcium levels. Intriguingly, laforin and malin display opposite effects on the cellular level of parkin, an ubiquitin ligase of Drp1; loss of laforin led to reduced levels of parkin while the loss of malin resulted in increased parkin levels. Laforin and malin, however, interact with and positively regulate the activity of parkin, thus explaining the molecular basis of increased Drp1 levels in LD tissues. Our results suggest that laforin and malin are novel regulators of mitochondrial quality control pathway and that the mitochondrial dysfunction resulting from the increased Drp1 levels could underlie neuropathology in LD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The stress and strain relationship in the gauge region of six cruciform geometries is studied: the ISO standard geometry with slits in arms, two geometries with thinned gauge areas, two geometries with thinned gauge areas and slits in arms, and one modified ISO standard geometry with slits in arms and a thinned gauge area. For all the geometries, finite element simulations are performed under uniaxial loading to compare the plastic strain, the von Mises stress distribution and the in-plane stress evolution. Results show that less plastic strain can be achieved in the gauge of the two ISO standard geometries. For the remaining cruciform geometries, a strong non-linear coupling between applied forces in arms and gauge stresses is generated. The evolution of this non-linear coupling depends on the geometry type, applied biaxial load ratio and the elastic-plastic properties of the material. Geometry selection criteria are proposed to reduce this non-linear coupling.

During Drosophila oogenesis, germline stem cells (GSCs) self-renew and differentiate to give rise to a mature egg. Self-renewal and differentiation of GSCs are regulated by both intrinsic mechanisms such as regulation of gene expression in the germ line and extrinsic signaling pathways from the surrounding somatic niche. Epigenetic mechanisms, including histone-modifying proteins, nucleosome remodeling complexes, and histone variants, play a critical role in regulating intrinsic gene expression and extrinsic signaling cues from the somatic niche. In the GSCs, intrinsic epigenetic modifiers are required to maintain a stem cell fate by promoting expression of self-renewal factors and repressing the differentiation program. Subsequently, in the GSC daughters, epigenetic regulators activate the differentiation program to promote GSC differentiation. During differentiation, the GSC daughter undergoes meiosis to give rise to the developing egg, containing a compacted chromatin architecture called the karyosome. Epigenetic modifiers control the attachment of chromosomes to the nuclear lamina to aid in meiotic recombination and the release from the lamina for karyosome formation. The germ line is in close contact with the soma for the entirety of this developmental process. This proximity facilitates signaling from the somatic niche to the developing germ line. Epigenetic modifiers play a critical role in the somatic niche, modulating signaling pathways in order to coordinate the transition of GSC to an egg. Together, intrinsic and extrinsic epigenetic mechanisms modulate this exquisitely balanced program.

Predicting the macroscopic and microscopic mechanical response of metals and alloys subjected to complex loading conditions necessarily requires a synergistic combination of multiscale material models and characterization techniques. This article focuses on the use of a multiscale approach to study the difference between intergranular lattice strain evolution for various grain families measured during in situ neutron diffraction on dog bone and cruciform 316L samples. At the macroscale, finite element simulations capture the complex coupling between applied forces and gauge stresses in cruciform geometries. The predicted gauge stresses are used as macroscopic boundary conditions to drive a mesoscale full-field elasto-viscoplastic fast Fourier transform crystal plasticity model. The results highlight the role of grain neighborhood on the intergranular strain evolution under uniaxial and equibiaxial loading., (© The Author(s) 2017.)

Protraction of mandibular posterior teeth requiring absolute anchorage has always been a challenge, especially when the space is located in the anterior region, since more teeth must be protracted. Traditionally, skeletal anchorage devices have been used for anchorage reinforcement during protraction. However, drawbacks such as requirement of a surgical step, inability to tolerate heavy forces, and patient willingness to undergo such surgical procedures can be limiting factors. Additionally, the mechanics involved can sometimes create undesirable side effects, thereby limiting their application in such situations. This report describes the use of a fixed functional appliance as an anchorage-reinforcement device for en-masse protraction of mandibular posterior teeth into a missing lateral incisor space., (Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Community based education trains health professional students to deal with the community health problems. The attitude and skills they gain as planners for health care provision are applicable in both hospital and community settings. BP Koirala Institute of Health Sciences has implemented a model of Community based education which encompasses the health institutions, organisations and the communities of the sixteen districts in eastern Nepal and refers to this concept as the 'Teaching District" concept of B P Koirala Institute of Health Sciences. This paper seeks to describe the concept and its implementation. Almost 20 years have passed since first initiated; and pending a comprehensive evaluation, this concept has gathered a great deal of experience to serve as a model for partnership between academic health sciences institutions with the district health system of Nepal.

Bacterial infections continue to be a major cause of deaths globally, particularly in resource-poor settings. In the absence of rapid and affordable diagnostic solutions, patients are mostly administered broad spectrum antibiotics leading to antibiotics resistance and poor recovery. Culture diagnosis continues to be a gold standard for diagnosis of bacterial infection, despite its long turnaround time of 24 to 48 h. We have developed a portable immunomagnetic cell capture (iMC(2)) system that allows rapid culture diagnosis of bacterial pathogens. Our approach involves the culture growth of the blood samples in broth media for 6 to 8 h, followed by immunomagnetic enrichment of the target cells using the iMC(2) device. The device comprises a disposable capture chip that has two chambers of 5 ml and 50 μl volume connected through a channel with a manual valve. Bacterial cells bound to antibody coated magnetic nanoparticles are swept from the 5 ml sample chamber into the 50 μl recovery chamber by moving an external magnetic field with respect to the capture chip using a linear positioner. This enables specific isolation and up to 100× enrichment of the target cells. The presence of bacteria in the recovered sample is confirmed visually using a lateral flow immunoassay. The system is demonstrated in buffer and blood samples spiked with S. typhi. The method has high sensitivity (10 CFU ml(-1)), specificity and a rapid turnaround time of less than 7 h, a significant improvement over conventional methods.

The homeodomain-interacting protein kinase-2 (HIPK2) is a highly conserved serine/threonine kinase and is involved in transcriptional regulation. HIPK2 is a highly unstable protein, and is kept at a low level under normal physiological conditions. However, exposure of cells to physiological stress - such as hypoxia, oxidative stress, or UV damage - is known to stabilize HIPK2, leading to the HIPK2-dependent activation of p53 and the cell death pathway. Therefore HIPK2 is also known as a stress kinase and as a stress-activated pro-apoptotic factor. We demonstrate here that exposure of cells to heat shock results in the stabilization of HIPK2 and the stabilization is mediated via K63-linked ubiquitination. Intriguingly, a sub-lethal heat shock (42 °C, 1 h) results in the cytoplasmic localization of HIPK2, while a lethal heat shock (45 °C, 1 h) results in its nuclear localization. Cells exposed to the lethal heat shock showed significantly higher levels of the p53 activity than those exposed to the sub-lethal thermal stress, suggesting that both the level and the nuclear localization are essential for the pro-apoptotic activity of HIPK2 and that the lethal heat shock could retain the HIPK2 in the nucleus to promote the cell death. Taken together our study underscores the importance of HIPK2 in stress mediated cell death, and that the HIPK2 is a generic stress kinase that gets activated by diverse set of physiological stressors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Germline stem cell (GSC) self-renewal and differentiation are required for the sustained production of gametes. GSC differentiation in Drosophila oogenesis requires expression of the histone methyltransferase dSETDB1 by the somatic niche, however its function in this process is unknown. Here, we show that dSETDB1 is required for the expression of a Wnt ligand, Drosophila Wingless type mouse mammary virus integration site number 4 (dWnt4) in the somatic niche. dWnt4 signaling acts on the somatic niche cells to facilitate their encapsulation of the GSC daughter, which serves as a differentiation cue. dSETDB1 is known to repress transposable elements (TEs) to maintain genome integrity. Unexpectedly, we found that independent upregulation of TEs also downregulated dWnt4, leading to GSC differentiation defects. This suggests that dWnt4 expression is sensitive to the presence of TEs. Together our results reveal a chromatin-transposon-Wnt signaling axis that regulates stem cell fate.

Objective: To quantify the effects of tip-back mechanics on the maxillary first molars and incisors., Materials and Methods: Sixteen subjects with Class II end-on malocclusion were treated with an intrusion arch to achieve distalization of the maxillary molar through tip-back mechanics. Lateral cephalograms were taken prior to molar tip-back (T1), after molar tip-back (T2), and after molar root uprighting (T3). Data were analyzed using the Friedman's and Wilcoxon signed rank tests to evaluate differences in time points (P ≤ .016)., Results: The maxillary first molar distalized 1.53 mm (P = .001) with 6.65° (P = .001) of distal tipping and 0.86 mm (P = .001) of extrusion at T2. Minor relapse of the first molar (mesial direction) was seen at T3. The maxillary incisors flared labially 0.4 mm, and the incisor root apex moved palatally 1.19 mm (P = .005) at T2. At T3, the incisor root apex moved palatally 1.5 mm (P = .003) from T1. An angular change from T1 of 3.31° (P = .008) and 3.53° (P = .014) was seen at T2 and T3, respectively, as a result of palatal root movement of the maxillary incisors., Conclusions: A significant amount of distalization of maxillary molars was attained at the crown level with tip-back mechanics. Palatal root angulation change was significant in the incisors with minimal anteroposterior movement of the incisal edge.

Lafora disease (LD), an autosomal recessive and fatal form of neurodegenerative disorder, is characterized by the presence of polyglucosan inclusions in the affected tissues including the brain. LD can be caused by defects either in the EPM2A gene coding for the laforin protein phosphatase or the NHLRC1 gene coding for the malin ubiquitin ligase. Since the clinical symptoms of LD patients representing the two genetic groups are very similar and since malin is known to interact with laforin, we were curious to examine the possibility that the two proteins regulate each other's function. Using cell biological assays we demonstrate here that (i) malin promotes its own degradation via autoubiquitination, (ii) laforin prevents the auto-degradation of malin by presenting itself as a substrate and (iii) malin preferentially degrades the phosphatase-inactive laforin monomer. Our results that laforin and malin regulate each other's stability and activity offers a novel and attractive model to explain the molecular basis of locus heterogeneity observed in LD.

Objectives: To investigate the effects of surface roughness on the removal torque and bone-to-implant contact of four different orthodontic mini-implants., Materials and Methods: Mini-implants and circular discs were made from alloy Ti6Al4V grade 5. On the basis of surface treatment, the study was divided into four groups-group 1: machined (n = 32), no surface treatment; group 2: acid etched (n = 32), with hydrochloric acid; group 3 (n = 32), grit blasted with alumina; and group 4, grit blasted + acid etched (n = 32). Mean surface roughness (Ra) and quadratic average roughness (Rq) from each group were measured two dimensionally in non-contact mode by the optical profilometer. Contact angle measurement of discs from each group was done with a contact angle goniometer. Contact angle of liquids with different hydrophobicity and hydrophilicity was measured: 1. highly hydrophilic liquid sodium chloride (NaCl), 2. lightly hydrophobic liquid dimethylsulfoxide, 3. distilled water, and 4. human blood. One hundred and twenty-eight miniscrews, differing in surface treatment, were placed into the tibias and femurs of adult male New Zealand white rabbits. Rabbits were euthanized after 8 weeks and removal torque and bone-to-implant contact were measured., Results: Surface roughness of group 3 was significantly greater than other groups (P < 0.05). Group 4 had significantly lower contact angle measurements, both for blood and sodium chloride (NaCl; 40.26 degrees, 27.20 degrees) when compared to other three groups (P ≤ 0.01). Group 4 had significantly higher torque and bone-to-implant contact than group 3 (P = 0.007), group 2 (P = 0.003), and group 1 (P = 0.0002)., Conclusion: Surface roughness and wettability of mini-implants influence their biological response., (© The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The purpose of this study was to evaluate the alveolar bone dimensions and arch perimeter discrepancy in unilateral palatally impacted canines., Methods: This retrospective split-mouth study reviewed 207 cone-beam computed tomography (CBCT) scans of patients with unilateral or bilateral impacted canines referred for orthodontic treatment. Out of 207 CBCT scans, only 39 scans in which canines were unilaterally palatally impacted were approved for the study based on our inclusion and exclusion criteria. Two fiducial lines were used to orient the examiners and standardize the measurements. Arch perimeter, buccopalatal (BP) width, and alveolar height were measured both on the impacted and non-impacted side. Two different examiners measured all the parameters. A one-sample Kolmogorov-Smirnov test was used to examine normality of distribution of outcomes. Wilcoxon Signed Rank tests were used for comparing arch width and alveolar bone height between the impacted and non-impacted sides. For arch perimeter, the paired-sample t-test was used., Results: The arch perimeter, BP width, and alveolar bone height was significantly decreased on the impacted side (P < 0.05). The mean arch perimeter on the impacted side was 41.7 ± 2.5mm compared to 43.5 ± 2.37 on the non-impacted side. Similarly, BP width and alveolar bone height on the impacted side was 6.87 ± 1.08 mm and 18.12 ± 2.28 mm, respectively, whereas on the non-impacted side was 8.70 ± 1.13 mm and 19.49 ± 2.09 mm, respectively., Conclusion: There was a significant decrease in the arch perimeter and alveolar bone dimensions (BP width and alveolar bone height) on the impacted side., (© The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Papillomaviruses and polyomaviruses are small ds-DNA viruses infecting a wide-range of vertebrate hosts. Evidence supporting co-evolution of the virus with the host does not fully explain the evolutionary path of papillomaviruses and polyomaviruses. Studies analyzing CpG dinucleotide frequencies in virus genomes have provided interesting insights on virus evolution. CpG dinucleotide depletion has not been extensively studied among papillomaviruses and polyomaviruses. We sought to analyze the relative abundance of dinucleotides and the relative roles of evolutionary pressures in papillomaviruses and polyomaviruses., Methods: We studied 127 full-length sequences from papillomaviruses and 56 full-length sequences from polyomaviruses. We analyzed the relative abundance of dinucleotides, effective codon number (ENC), differences in synonymous codon usage. We examined the association, if any, between the extent of CpG dinucleotide depletion and the evolutionary lineage of the infected host. We also investigated the contribution of mutational pressure and translational selection to the evolution of papillomaviruses and polyomaviruses., Results: All papillomaviruses and polyomaviruses are CpG depleted. Interestingly, the evolutionary lineage of the infected host determines the extent of CpG depletion among papillomaviruses and polyomaviruses. CpG dinucleotide depletion was more pronounced among papillomaviruses and polyomaviruses infecting human and other mammals as compared to those infecting birds. Our findings demonstrate that CpG depletion among papillomaviruses is linked to mutational pressure; while CpG depletion among polyomaviruses is linked to translational selection. We also present evidence that suggests methylation of CpG dinucleotides may explain, at least in part, the depletion of CpG dinucleotides among papillomaviruses but not polyomaviruses., Conclusions: The extent of CpG depletion among papillomaviruses and polyomaviruses is linked to the evolutionary lineage of the infected host. Our results highlight the existence of divergent evolutionary pressures leading to CpG dinucleotide depletion among small ds-DNA viruses infecting vertebrate hosts.

Lafora disease (LD) is an autosomal recessive, progressive, and fatal form of a neurodegenerative disorder characterized by the presence of Lafora polyglucosan bodies. LD is caused by defects in either the laforin protein phosphatase or the malin E3 ubiquitin ligase. Laforin and malin were shown play key roles in proteolytic processes, unfolded stress response, and glycogen metabolism. Therefore, the LD proteins laforin and malin are thought to function as pro-survival factors and their loss thus could result in neurodegeneration. To understand the molecular pathway leading to the cell death in LD, in the present study, we investigated the possible role of LD proteins in the p53-mediated cell death pathway. We show that loss of laforin or malin results in the increased level and activity of p53, both in cellular and animal models of LD, and that this is primarily due to the increased levels of Hipk2, a proapoptotic activator of p53. Overexpression of laforin or malin confers protection against Hipk2-mediated cell death by targeting the Hipk2 to the cytoplasmic compartment. Taken together, our study strengthens the notion that laforin and malin are pro-survival factors, and that the activation of Hipk2-p53 cell death pathway might underlie neurodegeneration in LD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Hantaviruses are important emerging zoonotic pathogens. The current understanding of hantavirus evolution is complicated by the lack of consensus on co-divergence of hantaviruses with their animal hosts. In addition, hantaviruses have long-term associations with their reservoir hosts. Analyzing the relative abundance of dinucleotides may shed new light on hantavirus evolution. We studied the relative abundance of dinucleotides and the evolutionary pressures shaping different hantavirus segments., Methods: A total of 118 sequences were analyzed; this includes 51 sequences of the S segment, 43 sequences of the M segment and 23 sequences of the L segment. The relative abundance of dinucleotides, effective codon number (ENC), codon usage biases were analyzed. Standard methods were used to investigate the relative roles of mutational pressure and translational selection on the three hantavirus segments., Results: All three segments of hantaviruses are CpG depleted. Mutational pressure is the predominant evolutionary force leading to CpG depletion among hantaviruses. Interestingly, the S segment of hantaviruses is GpU depleted and in contrast to CpG depletion, the depletion of GpU dinucleotides from the S segment is driven by translational selection. Our findings also suggest that mutational pressure is the primary evolutionary pressure acting on the S and the M segments of hantaviruses. While translational selection plays a key role in shaping the evolution of the L segment. Our findings highlight how different evolutionary pressures may contribute disproportionally to the evolution of the three hantavirus segments. These findings provide new insights on the current understanding of hantavirus evolution., Conclusions: There is a dichotomy among evolutionary pressures shaping a) the relative abundance of different dinucleotides in hantavirus genomes b) the evolution of the three hantavirus segments.

Protraction of posterior teeth into edentulous spaces is a challenge. This report describes the treatment of a 19-year-old woman with missing mandibular first molars owing to caries. A fixed functional appliance was used for anchorage reinforcement during mandibular second molar protraction. Eight millimeters of bilateral protraction was done with bodily mesial movement of the molars and no lingual tipping of the incisors., (Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Rationale: We showed that the metabolite peaks of (15)N(3) -citrulline ((15)N(3) -CIT) and (15)N(3) -arginine ((15)N(3) -ARG) could be detected when (15) N(4) -ARG was metabolized by nitric oxide synthase (NOS) in endothelial cells. The usefulness of these metabolites as potential surrogate indices of nitric oxide (NO) generation is evaluated., Methods: A hydrophilic-interaction liquid chromatography/electrospray tandem mass spectrometric assay (LC/MS/MS) was utilized for the simultaneous analysis of (15)N(4) -ARG, ARG, CIT, (15)N(3) -CIT and (15)N(3) -ARG. (15)N(3) -CIT and (15)N(3) -ARG from impurities of (15)N(4) -ARG were determined and corrected for the calculation of their concentration. (15)N(4) -ARG-derived NO, i.e., (15)NO formation was determined by analyzing (15)N-nitrite accumulation by another LC/MS/MS assay., Results: After EA.hy926 human endothelial cells were challenged with (15)N(4) -ARG for 2 hours, the peak intensities of (15)N(3) -CIT and (15)N(3) -ARG significantly increased with (15)N(4) -ARG concentration and positively correlated with (15)N-nitrite production. The estimated Km values were independent of the metabolite (i.e., (15)N(3) -CIT, (15)N(3) -CIT+(15)N(3) -ARG or (15) N-nitrite) used for calculation. However, after correction for its presence as a chemical contaminant of (15)N(4) -ARG, (15)N(3) -ARG was only a marginal contributor for the estimation of NOS activity., Conclusions: These data suggest that the formation of (15)N(3) -CIT can be used as an indicator of NOS activity when (15)N(4) -ARG is used as a substrate. This approach may be superior to the radioactive (14)C-CIT method which can be contaminated by (14)C-urea, and to the (14)N-nitrite method which lacks sensitivity., (Copyright © 2015 John Wiley & Sons, Ltd.)

Introduction: The temporomandibular joint (TMJ) is a complex joint that often develops degenerative joint disease. Clinical examination alone cannot usually diagnose this accurately, and a radiographic examination complements and aids in diagnosis and treatment. The osseous components of the TMJ complex are best imaged using computed tomography. The evolution of cone-beam computed tomography (CBCT) offers a low radiation dose and a high spatial resolution alternative and is becoming the imaging modality of choice for the TMJ. To further reduce the dose and yet not compromise the diagnostic task at hand, some alternative rotation acquisition protocols are available but have not been adequately evaluated. The aim of this study was to evaluate the diagnostic efficacy of 2 CBCT acquisition protocols to detect degenerative changes associated with the TMJ complex., Methods: Thirty-four TMJs, from 17 dry human skulls, were obtained from the anatomy department at the School of Dental Medicine of the University of Connecticut. The sample consisted of complete dentate and partially dentate skulls with no identifiable markers such as age, sex, or ethnicity. Small and large lesions simulating early and established arthritic changes were created on the mandibular condyle. Each defect was randomly created on the medial pole, articulating surface, or lateral pole. After simulating the articular disc with rubber dam material, the condyle and the glenoid fossa were articulated and positioned in place by a rubber band. The skulls were scanned by using an Accuitomo CBCT scanner (J. Morita Corp, Kyoto, Japan) with 180° and 360° rotation protocols. Two operators scored the lesions and compared the results to the gold standard, which was the master list of where the lesions were made on the condyles., Results: On the 102 randomly selected sites, 39 large and 33 small lesions were made, and the rest of the sites had no lesions. The detection rates for areas with large lesions and areas with no lesions were 100% between the examiners. However, of the 33 small lesions, each examiner was able to identify 32 of them with the 360° scans: a 97.4% detection rate when compared with the gold standard. With the 180° scan, 94.9% of the small lesions were detected when compared with the gold standard, and 96.9% were detected with the 360° scan. The overall interexaminer reliability was over 90% for both imaging protocols (Cronbach's alpha, 92.4% for 180° and 97% for 360°)., Conclusions: Based on the results of this study, the 180° CBCT acquisition protocol can detect small and large arthritic lesions with high reliability and is comparable with the 360° spin acquisition., (Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Folate molecules self-assemble in the form of stacks to form liquid-crystalline solutions. Nanocarriers from self-assembled folates are composed of highly ordered structures, which offer high encapsulation of drug (95-98%), controlled drug release rates, active cellular uptake and biocompatibility. Recently, we have shown that the release rates of methotrexate can be controlled by varying the size of nanoparticles, cross-linking cation and cross-linking concentration. The present study reports the in vitro cytotoxic behavior of methotrexate loaded liquid-crystalline folate nanoparticles on cultured HeLa cells. Changing drug release rates can influence cytotoxicity of cancer cells. Therefore, to study the correlation of release rate and cytotoxic behavior, the effect of release controlling parameters on HeLa cells was studied through MTT assay. It is reported that by controlling the methotrexate release, the survival rates of HeLa cells can be controlled. Released methotrexate kills HeLa cells as effectively as free methotrexate solution. The co-culture based in vitro cellular uptake study through fluorescence microscopy on folate receptor positive and negative cancer cells shows that the present nanocarrier has the potential to distinguish cancer cells from normal cells. Overall, the present study reports the in vitro performance of self-assembled liquid-crystalline folate nanoparticles, which will be a platform for further in vivo studies and clinical trials., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The purpose of this twin case comparison was to assess the short- and long-term effects of nonsurgical treatment vs orthognathic surgical treatment for Class II correction. Two identical twins (age 13 years 3 months) were treated for Class II correction where one patient was treated nonsurgically using a fixed functional appliance, while the other was treated using orthognathic mandibular advancement surgery. The patients were recalled and evaluated 5 years in retention. Comparing changes in the short and long term, surgical treatment led to superior skeletal results compared to the nonsurgical twin. However, the soft tissue profile was remarkably similar for both patients suggesting that soft tissue profile changes may not necessarily follow similar changes in the bony skeletal structures.

Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts.

Immunological memory comprising of antigen-specific B and T cells contributes to the acquisition of long-term resistance to pathogens. Interactions between CD40 on B cells and CD40L on T cells are responsible for several aspects of acquired immune responses including generation of memory B cells. In order to gain insights into events leading to memory B cell formation, we analyzed the genome-wide expression profile of murine naive B cells stimulated in the presence of anti-CD40. We have identified over 8,000 genes whose expression is altered minimally 1.5-fold at least at one time point over a 3-day time course. The array analysis indicates that changes in expression level of maximum number of these genes occur within 24 h of anti-CD40 treatment. In parallel, we have studied the events following CD40 ligation by examining the expression of known regulators of naive B cell to plasma cell transition, including Pax5 and BLIMP1. The expression profile of these regulatory genes indicates firstly, that CD40 signaling activates naïve B cells to a phenotype that is intermediate between the naive and plasma cell stages of the B cell differentiation. Secondly, the major known regulator of plasma cell differentiation, BLIMP1, gets irreversibly downregulated upon anti-CD40 treatment. Additionally, our data reveal that CD40 signaling mediated BLIMP1 downregulation occurs by non-Pax5/non-Bcl6 dependent mechanisms, indicating novel mechanisms at work that add to the complexity of understanding of B cell master regulatory molecules like BLIMP1 and Pax5., (© 2014 Wiley Periodicals, Inc.)

Mini-implants have been successfully incorporated into orthodontic practice all over the world. One of the most popular applications of mini-implant anchorage is to facilitate retraction of the anterior teeth. This article reviews the mechanics involved in anterior tooth retraction with mini-implant supported anchorage. An attempt has been made to synthesize information available in the literature and present it in a manner that is easily understandable from a clinical perspective. We discuss the fundamental differences mini-implant based incisor retraction has when compared to conventional techniques, mechanical factors affecting this process and provide a step-by-step analysis of incisor retraction. In addition, various models of space closure are discussed that have evolved through careful evaluation of in vitro and in vivo experiments., (© 2014 British Orthodontic Society.)

Treatment of an impacted maxillary central incisor poses a unique challenge to the orthodontist because of its position within the esthetic zone, requiring careful management of the soft tissues and an effective biomechanical setup for alignment. This article describes a novel method of extending an extrusion wire from cross tubes attached on the base archwire for forced eruption of impacted central incisors. The effectiveness and versatility of this method are demonstrated with 2 patients., (Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

Introduction: Median sternotomy is the preferred approach for open heart surgeries. The sternotomy incision is predominantly closed with either steel wire or polyester suture. The type of material used is primarily based on the surgeon's choice, and both materials achieve a good result. No prospective clinical study has been undertaken to evaluate differences in the incidence of wound infection and the degree of pain associated with both techniques., Patients and Methods: Our randomized controlled double-blind study included 200 adults undergoing single-valve replacement. The technique of surgery, apart from the material used for sternal closure, was the same in both groups. Postoperatively, patients were analyzed for wound infection and wound pain based on the ASEPSIS score and Numeric Pain Rating Score, respectively., Results: The polyester suture group had a significantly higher mean ASEPSIS score, indicating a higher incidence of wound infection, and more late wound complications. The polyester suture group also had a significantly higher mean pain score. The steel wire group had significantly higher mediastinal drain output in the first 48 h after surgery., Conclusion: The use of polyester suture for sternal closure in adult patients results in increased wound infection, wound pain, and late wound complications, but lower mediastinal drain output.

Understanding and improving the durability of long-lasting insecticidal nets (LLINs) in the field is critical for the success of malaria prevention using mosquito nets, as well as contributing to procurement decisions based on the number of years of protection, rather than the current practice of unit cost. Using the recently published guidelines from the World Health Organization (WHO) some progress has been made in the monitoring and assessment of performance of nets in the field. This paper describes the protocol of an ongoing retrospective study of the attrition rate, physical integrity and bioefficacy of three polyester LLIN products that were distributed during 2010 to 2013 in Nepal. It is hoped that robust and auditable data on net survival (physical integrity and bioefficacy) of these three brands in different environments will assist the Nepal National Malaria Control Programme in planning future LLIN-replacement strategies, including behaviour-change communication about LLIN care and maintenance. The advantages and disadvantages of prospective and retrospective cross-sectional approaches are discussed, including appropriate strategies to validate the timing for mass distribution of nets. Similar studies should be done in other countries to (i) track LLIN durability to support management of resupply, and (ii) inform procurement decisions at the global level. New, more predictive, textile laboratory testing is also urgently needed.

The potential pharmacokinetic (PK) interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY) and Achyranthes bidentata radix (AB) extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW), OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg) was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS. The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed. Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42-4.10 hr, and mostly excreted into urine. The PK of baclofen was not affected by AB extract pretreatment. However, significantly lower maximum plasma concentration (C max) and longer time to reach C max (T max) were observed in OY pretreated rats without changes in the area under the curve (AUC) and the fraction excreted into urine (F urine). The absorption rate (K a ) of baclofen was significantly decreased in OY pretreated rats. These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.