Comparison of treatment records and inventory of empty drug containers to quantify antimicrobial usage in dairy herds

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): Diego B. Nobrega, Jeroen De Buck, S. Ali Naqvi, Gang Liu, Sohail Naushad, Vineet Saini, Herman W. Barkema
Assessment of antimicrobial use (AMU) is vital for interpreting the origin of changes in antimicrobial resistance (AMR). The objectives of the present study were to estimate the association between AMU determined using on-farm treatment records (TR) and inventory of empty drug containers (INV). Herds were selected to represent Canadian dairy farms. Producers were asked to record animal health events and treatments on a standard General Health Event form. For inventory data, 40-L receptacles were placed at various locations considered convenient to deposit all empty drug containers. Antimicrobial defined-daily dosages (ADD) were calculated for 51 Canadian herds using the 2 methods. Estimation of AMU was 31,840 ADD using the INV and 14,487 ADD using the TR, indicating that for every TR entry, 2.20 times more treatments were observed using the INV. Mastitis, reproductive conditions, and dry cow therapy were the most frequent reasons for antimicrobial therapy when assessing TR. For all antimicrobials evaluated, mean ADD was higher using the INV versus TR. Regardless, a strong positive correlation (0.80) was observed between the 2 methods, indicating that herds with increased number of ADD recorded using the INV also had increased number of ADD recorded using TR. Furthermore, a positive association was observed for the 6 most commonly used antimicrobials. In comparison to methods used in surveillance programs on AMU in livestock that assume a constant use in all herds (i.e., sales data), INV provided a herd-level specific quantity of AMU positively correlated with AMU recorded at the animal level in general. The INV was easy to implement and provided a measure of total AMU in the herd. Availability of such information would be valuable for interpreting changes in AMR at the herd level and enabling evaluation of interventions for decreasing AMR.



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Acid or erythromycin stress significantly improves transformation efficiency through regulating expression of DNA binding proteins in Lactococcus lactis F44

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): Binbin Wang, Huawei Zhang, Dongmei Liang, Panlong Hao, Yanni Li, Jianjun Qiao
Lactococcus lactis is a gram-positive bacterium used extensively in the dairy industry and food fermentation, and its biological characteristics are usually improved through genetic manipulation. However, poor transformation efficiency was the main restriction factor for the construction of engineered strains. In this study, the transformation efficiency of L. lactis F44 showed a 56.1-fold increase in acid condition (pH 5.0); meanwhile, erythromycin stress (0.04 μg/mL) promoted the transformation efficiency more significantly (76.9-fold). Notably, the transformation efficiency of F44e (L. lactis F44 harboring empty pLEB124) increased up to 149.1-fold under the synergistic stresses of acid and erythromycin. In addition, the gene expression of some DNA binding proteins (DprA, RadA, RadC, RecA, RecQ, and SsbA) changed correspondingly. Especially for radA, 25.1-fold improvement was detected when F44e was exposed to pH 5.0. Overexpression of some DNA binding proteins could improve the transformation efficiency. The results suggested that acid or erythromycin stress could improve the transformation efficiency of L. lactis through regulating gene expression of DNA binding proteins. We have proposed a simple but promising strategy for improving the transformation efficiency of L. lactis and other hard-transformed microorganisms.



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Effects of the level and duration of maternal diets with negative dietary cation-anion differences prepartum on calf growth, immunity, and mineral and energy metabolism

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): C. Collazos, C. Lopera, J.E.P. Santos, J. Laporta
The objectives were to investigate the effects that maternal diets containing negative dietary cation-anion differences (DCAD) fed in the last 42 d of gestation may have on the acid–base status, hematology, mineral and energy metabolism, growth, and health of calves. The experiment was a randomized block design with a 2 × 2 factorial arrangement of 2 levels of negative DCAD (−70 or −180 mEq/kg) and 2 feeding durations (the last 21 d prepartum and the last 42 d prepartum). Bulls and heifers (n = 60) born to these dams were weighted at birth and fed 3.8 L of colostrum for their first feeding, and only heifers (n = 44, 9–12/treatment) were kept thereafter. Heifer body weight was also recorded at 21 d, 42 d, 62 d, 3 mo, and 6 mo of age. Blood was collected at birth, before colostrum feeding, and at 1, 2, 3, 21, and 42 d of age and assayed for minerals, metabolites, and cell counts. Heifers born to dams fed the last 42 d prepartum weighed 2.8 and 4.8 kg less at birth and 62 d, respectively, compared with calves born to dams fed the last 21 d prepartum; however, body weight at 3 and 6 mo of age was similar. Concentrations of ionized calcium did not differ among treatments at birth, but heifers born to −180 DCAD dams had increased blood concentrations at 3 d of age, whereas those born to −70 DCAD dams did not. At birth, heifers born to −180 DCAD dams experienced a subtle and transient metabolic acidosis (pH = 7.33 ± 0.02; pCO2 = 53.0 ± 2.4 mmHg; HCO3⁻ = 27.6 ± 0.7 mmol/L) compared with the more evident metabolic acidosis observed in those born to −70 DCAD cows (pH = 7.28 ± 0.02; pCO2 = 59.3 ± 2.4 mmHg; HCO3⁻ = 27.8 ± 0.7 mmol/L). Heifers born to −180 DCAD dams had reduced concentrations of β-hydroxybutric acid and nonesterified fatty acids compared with those born to −70 DCAD dams. Efficiency of IgG transfer from colostrum into blood and serum concentrations did not differ among treatments. There was no relationship between measures of metabolic acidosis and measures of efficiency of IgG absorption. Percentage of lymphocytes and neutrophils was altered by maternal treatments; however, treatments did not affect calf morbidity. Extending the duration of feeding up to 42 d or reducing the level of negative DCAD to −180 mEq/kg in maternal diets exerted a transient metabolic acidosis in the calves and slightly affected measures of mineral, energy metabolism, and growth.



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A dynamic model to simulate potassium balance in dairy cows

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): M. Berg, J. Plöntzke, S. Leonhard-Marek, K.E. Müller, S. Röblitz
High-performing dairy cows require a particular composition of nutritional ingredients, adapted to their individual requirements and depending on their production status. The optimal dimensioning of minerals in the diet, one being potassium, is indispensable for the prevention of imbalances. Potassium balance in cows is the result of potassium intake, distribution in the organism, and excretion, and it is closely related to glucose and electrolyte metabolism. In this paper, we present a dynamical model for potassium balance in lactating and nonlactating dairy cows based on ordinary differential equations. Parameter values were obtained from clinical trial data and from the literature. To verify the consistency of the model, we present simulation outcomes for 3 different scenarios: potassium balance in (1) nonlactating cows with varying feed intake, (2) nonlactating cows with varying potassium fraction in the diet, and (3) lactating cows with varying milk production levels. The results give insights into the short- and long-term potassium metabolism, providing an important step toward the understanding of the potassium network, the design of prophylactic feed additives, and possible treatment strategies.



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Rheological and sensory performance of a protein-based sweetener (MNEI), sucrose, and aspartame in yogurt

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): Nicoletta A. Miele, Erliza K. Cabisidan, Giuseppe Blaiotta, Serena Leone, Paolo Masi, Rossella Di Monaco, Silvana Cavella
Sweeteners and flavors are generally added to yogurt to make them more palatable. However, the addition of these ingredients may affect the fermentation process of yogurt as well as its physical and sensory characteristics. Consumers prioritize yogurt products that are "natural." A modified single-chain form of the natural sweet protein monellin extracted from the fruit of Dioscoreophyllum cumminsii, called MNEI, could be a useful alternative to artificial sweeteners. The aim of the present work was to evaluate new rapid sensory methods in combination with rheology to assess the viability of using MNEI to develop sweetened yogurts without the calories of sugar. We studied the gelation and cooling kinetics of 4 yogurt samples (unsweetened or sweetened with MNEI, aspartame, or sucrose) by using a rheometer. Furthermore, the 4 yogurts, with and without addition of a flavoring agent, were characterized from a sensory perspective using a combination of 2 rapid sensory methods, ultra flash profile and flash profile. Rheological results showed that, when added at typical usage levels, aspartame, sucrose, and MNEI did not generally affect the yogurt fermentation process or its rheological properties. Sensory results demonstrated that texture attributes of yogurts with aspartame and sucrose were strongly linked to sweetness and flavor perception, but this was not true for MNEI-sweetened yogurts. In contrast to results obtained from samples sweetened with sucrose and aspartame, MNEI protein did not sweeten the yogurt when added before fermentation. This study highlights the enhancing effect of flavor on sweetness perception, supporting previous reports that noted synergistic effects between sucrose or aspartame and flavors. Hence, future studies should be conducted to determine how sweet proteins behave in yogurt when added after fermentation.



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Invited review: Sustainable forage and grain crop production for the US dairy industry

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): N.P. Martin, M.P. Russelle, J.M. Powell, C.J. Sniffen, S.I. Smith, J.M. Tricarico, R.J. Grant
A resilient US dairy industry will be underpinned by forage and crop production systems that are economically, environmentally, and socially sustainable. Land use for production of perennial and annual forages and grains for dairy cattle must evolve in response to multiple food security and environmental sustainability issues. These include increasing global populations; higher incomes and demand for dairy and other animal products; climate change with associated temperature and moisture changes; necessary reductions in carbon and water footprints; maintenance of soil quality and soil nutrient concerns; and competition for land. Likewise, maintaining producer profitability and utilizing practices accepted by consumers and society generally must also be considered. Predicted changes in climate and water availability will likely challenge current feed and dairy production systems and their national spatial distribution, particularly the western migration of dairy production in the late 20th century. To maintain and stabilize profitability while reducing carbon footprint, particularly reductions in methane emission and enhancements in soil carbon sequestration, dairy production will need to capitalize on genetic and management innovations that enhance forage and grain production and nutritive value. Improved regional and on-farm integration of feed production and manure utilization is needed to reduce environmental nitrogen and phosphorus losses and mitigate greenhouse gas emissions. Resilient and flexible feed production strategies are needed to address each of these challenges and opportunities to ensure profitable feeding of dairy cattle and a sustainable dairy industry.



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Relationship between intramammary infection prevalence and somatic cell score in commercial dairy herds

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): G.E. Shook, R.L. Bamber Kirk, F.L. Welcome, Y.H. Schukken, P.L. Ruegg
We examined consistency of the relationship between intramammary infection (IMI) and somatic cell score (SCS) across several classes of cow, herd, and sampling time variables. Microbial cultures of composite milk samples were performed by New York Quality Milk Production Services from 1992 to 2004. SCS was from the most recent Dairy Herd Improvement test before IMI sampling. Records were analyzed from 79,308 cows in 1,124 commercial dairy herds representing a broad range of production systems. Three binary dependent variables were presence or absence of contagious IMI, environmental IMI, and all IMI. Independent variables in the initial models were SCS, SCS², lactation number, days in milk, sample day milk yield, use of coliform mastitis vaccine, participant type (required by regulation or voluntary), production system (type of housing, milking system, and herd size), season of sampling, year of sampling, and herd; also the initial models included interactions of SCS and SCS² with other independent variables, except herd and milk yield. Interaction terms characterize differences in the IMI-SCS relationship across classes of the independent variables. Models were derived using the Glimmix macro in SAS (SAS Institute Inc., Cary, NC) with a logistic link function and employing backward elimination. The final model for each dependent variable included all significant independent variables and interactions. Simplified models omitted SCS² and all interactions with SCS. Interactions of SCS with days in milk, use of coliform mastitis vaccine, participant type, season, and year were not significant in any of the models. Interaction of SCS with production system was significant for the all IMI model, whereas interaction of SCS with lactation number was significant for the environmental and all IMI models. Each 1 point increase in SCS (or doubling of somatic cell count) was associated with a 2.3, 5.5%, and 9.1% increase in prevalence of contagious, environmental, and all IMI, respectively. Empirical receiver operator characteristic curves and areas under the curve were derived for final and simplified models. The areas under the curve for simplified and final models within each type of IMI differed by 0.009 or less. We concluded that the relationship of IMI with SCS was generally stable over time and consistent across seasons, production systems, and cow factors.



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Genetic parameters for health traits using data collected from genomic information nucleus herds

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): M. Abdelsayed, M. Haile-Mariam, J.E. Pryce
As with many other countries, data availability has been a limitation in Australia for developing breeding values for health traits. A genomic information nucleus of approximately 100 herds across the country, selected on the basis of their record keeping, has recently been established in Australia and is known as Ginfo. The objective of this study was to evaluate the feasibility of developing genomic breeding values for health traits using farmer-collected data from Ginfo herds. Having this genotyped population opens up opportunities to develop new genomic breeding values, such as dairy health traits. In these herds, the 4 most recorded groups of health diseases identified were mastitis, reproductive problems, lameness, and metabolic disorders with incidence levels of 16, 9, 2, and 1.5%, respectively. Heritability estimates from pedigree and genomic analysis ranged from 0.01 to 0.03 for mastitis, 0.005 to 0.02 for reproductive disorders, 0 to 0.02 for lameness, and 0.00 to 0.06 for metabolic disorders. However, although heritability is low, there is sufficient genetic variation to make genetic progress feasible (coefficient of variation ranging from 3 to 26.3%). Genetic correlations between health and milk production traits (0.08 to 0.48) and overall type (−0.00 to 0.57) are unfavorable, but favorable with other economical traits, such as fertility (0.10 to 0.51), survival (−0.16 to −0.37), and somatic cell count (0.07 to 0.55). For a genomic reference population of 11,458 cows, the reliability of genomic predictions is comparatively low (<30%), but is promising for health traits, such as mastitis (∼30%) and a broader-based all disease trait (∼28%), when bulls have daughters in the reference population, but not when they only have genomic information (0 to 18%). Further improvement of the reliabilities of health breeding values continues to be an important objective. The study has provided a good foundation for future research to develop breeding values for health traits.



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Short communication: The effect of storage conditions and storage duration on milk ELISA results for pregnancy diagnosis

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): E.M. Wynands, S.J. LeBlanc, D.F. Kelton
The objective of this study was to evaluate the effect of storage temperature and time from sample collection to analysis on test classification of a commercially available ELISA for diagnosis of pregnancy using the measurement of pregnancy-associated glycoproteins (PAG) in milk samples from dairy cows. Few studies have evaluated the effects of sample handling on milk PAG results. Using a repeated-measures study design, we evaluated sample storage at 5 temperatures: 37°C, 22°C, 4°C, −20°C, or −80°C. Sample aliquots from 45 cows (20 with a pregnant test result, 10 open, and 15 recheck) were stored for 4, 7, 14, 28, 60, 90, or 365 d. The measured PAG level was influenced by storage duration and condition. Samples stored for 365 d had a slightly increased PAG level, whereas samples stored for all other durations showed a slight decline in PAG level compared with the initial result. The reason for an increase in PAG level following long-term storage is not known. This will not affect dairy producers using the test but may be important in samples stored for research applications. The changes in PAG level were small and within the expected variation for this test. Fewer than 6% of samples changed in classification and, as expected, they were samples near the test interpretation cut-points.



http://ift.tt/2fM8cSW

Characterization of luteal dynamics in lactating Holstein cows for 32 days after synchronization of ovulation and timed artificial insemination

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): A. Ricci, P.D. Carvalho, M.C. Amundson, P.M. Fricke
Approximately 20 to 30% of cows diagnosed not pregnant 32 d after timed artificial insemination (TAI) lack a corpus luteum (CL), and cows submitted to a resynchronization protocol in the absence of a CL have about 10% fewer pregnancies per AI (P/AI) than cows with a CL. An understanding of luteal dynamics after synchronization of ovulation and TAI may help refine strategies for reinseminating cows failing to conceive. Lactating Holstein cows (n = 141) were synchronized for first TAI using a Double-Ovsynch protocol. Thrice weekly from 4 to 32 d after TAI, blood samples were collected for evaluation of plasma progesterone (P4) concentrations, and CL diameter was measured using transrectal ultrasonography. Pregnancy status was determined using transrectal ultrasonography 32 d after TAI. Nonsynchronized cows (n = 4) were removed from the study. For cows diagnosed pregnant 32 d after TAI (n = 57), P4 increased from 4 to 15 d and then remained constant until 32 d after TAI, whereas CL volume increased from 4 to 11 d and then remained constant until 32 d after TAI. For cows diagnosed not pregnant 32 d after TAI (n = 80), P4 profiles were evaluated using statistical cluster analysis based on the day after TAI that P4 decreased to <1 ng/mL, resulting in 5 clusters: (1) CL regression 15 d after TAI (1.3%), (2) CL regression 18 to 22 d after TAI (55.0%), (3) CL regression 25 to 27 d after TAI (17.5%), (4) CL regression 29 to 32 d after TAI (5.0%), and (5) CL maintained until 32 d after TAI (21.3%). Plasma pregnancy-associated glycoprotein (PAG) levels at 25 and 32 d after TAI differed among clusters and were below the cut-off value of the assay for the classification of cows as not pregnant for cows in clusters 2, 3, and 4, whereas more than half of the cows in cluster 5 had increased plasma PAG levels. We conclude that at least half of the nonpregnant cows that maintained their CL until 32 d after TAI were initially pregnant but underwent early pregnancy loss based on increased plasma PAG levels at 25 and 32 d after TAI.



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Housing and management characteristics of calf automated feeding systems in the Upper Midwest United States

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): M.W. Jorgensen, K. Janni, A. Adams-Progar, H. Chester-Jones, J.A. Salfer, M.I. Endres
Automated milk feeders are used by dairy producers to manage preweaned calves in group housing, but little is known about how these feeding systems are being used in the United States. To better understand how US dairy producers are operating these systems, this study investigated characteristics of barn design, environment, and management practices on 38 farms in the Upper Midwest United States via a questionnaire and on-farm measurements. Farms using automated feeders ranged in size from 7 to 300 calves on site. Natural ventilation was used on 50% of the farms, followed by barns with mechanical ventilation (39.5%), tunnel ventilation (7.9%), or outdoor facilities (sheltered plastic domes; 2.6%). Calves were kept in groups of 17.6 ± 9.8 animals (range: 5.9 to 60.5) with an average space allowance of 4.6 ± 2.0 m²/animal (range: 1.6 to 11.9). Calves on these farms received 3.7 ± 0.75 L (range: 2 to 6) of colostrum, but 22% of the tested calves had serum total protein values lower than 5.0 g/dL. Calves had an initial daily allowance of 5.4 ± 2.1 L (range: 3 to 15 L) of milk or milk replacer, rising to a peak amount of 8.3 ± 2.0 L (range: 5 to 15 L) over 18 ± 11.4 d (range: 0 to 44 d). Milk replacer was fed to calves on 68.4% of the farms compared with whole milk supplemented with nutrient balancer on 23.7% and whole milk alone on 7.9% of the farms. Calves were completely weaned at 56.8 ± 9.0 d of age (range: 40 to 85.5) and 52.1 ± 7.5 d (range: 40 to 79) since introduction into the group pen with the feeder. Notably, bacterial contamination of milk was common; the median coliform count was 10,430 cfu/mL (interquartile range: 233,111; range: 45 to 28,517,000) and standard plate count was 2,566,867 cfu/mL (interquartile range: 15,860,194; range 6,668 to 82,825,000) for samples collected from the feeder tube end (or feeder hose). Some areas of deficiency might be of concern as they might be influencing the success of using automated calf feeding systems. In particular, a better understanding of the dynamics of pathogen load is needed in both the group pen area and in the automated feeder unit itself, as these reservoirs represent significant risk to calf health and welfare.



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Hydroxy-selenomethionine: A novel organic selenium source that improves antioxidant status and selenium concentrations in milk and plasma of mid-lactation dairy cows

Publication date: Available online 4 October 2017
Source:Journal of Dairy Science
Author(s): P. Sun, J. Wang, W. Liu, D.P. Bu, S.J. Liu, K.Z. Zhang
This study aimed to evaluate the effect of hydroxy-selenomethionine (HMSeBA), a novel organic selenium (Se) source, on milk performance, antioxidative status, and Se concentrations in the milk and plasma of mid-lactation dairy cows compared with that of sodium selenite (SS). Fifty mid-lactation dairy cows with similar days in milk, milk yield, and parity received the same basal diet containing 0.06 mg of Se/kg of DM. They were assigned to 1 of 5 treatments according to a randomized complete block design: negative control (without Se supplementation), SS supplementation (0.3 mg of Se/kg of DM; SS-0.3) or HMSeBA supplementation (0.1, 0.3, or 0.5 mg of Se/kg of DM: SO-0.1, SO-0.3, and SO-0.5, respectively). The experiment lasted for 10 wk, including a pretrial period of 2 wk. The results indicated that neither Se supplementation nor Se source affected dry matter intake, milk yield, milk composition, or blood biochemical parameters, except for milk fat percentage. Simultaneously, milk fat percentage and milk fat yield increased linearly as the quantity of HMSeBA supplementation was increased. Production of 4% FCM and ECM was elevated linearly as dietary HMSeBA increased. The SO-0.3 group showed higher serum activity of glutathione peroxidase, total antioxidant capacity, and superoxide dismutase than the SS-0.3 group, but malondialdehyde content was not affected by Se source. Furthermore, HMSeBA supplementation linearly increased the activities of serum glutathione peroxidase and superoxide dismutase, but decreased malondialdehyde content. Compared with the SS-0.3 group, the SO-0.3 group showed augmented concentrations of total Se in milk and plasma, and total Se milk-to-plasma concentration ratio. In addition, increasing doses of HMSeBA linearly increased the concentrations of total Se in the milk and plasma. This study demonstrates that HMSeBA improves antioxidant status and increases milk and plasma Se concentrations more effectively than SS, indicating that HMSeBA could replace SS as an effective organic Se source for lactating dairy cows.



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An Interesting Case of Pyoderma Gangrenosum with Immature Hystiocytoid Neutrophils

Abstract

We present a unique case of a 36-year-old male who developed more than twenty Pyoderma gangrenosum ulcers demonstrating on histopathology a dense inflammatory infiltrate composed of histiocytoid mononuclear immature cells with a strong positivity for myeloperoxidase and Leder stain, suggesting a myeloid lineage in the absence of a concomitant myeloproliferative disorder. Histiocytoid Sweet syndrome is now recognized as a histological subtype of Sweet syndrome. Although Pyoderma gangrenosum and Sweet syndrome belong to the spectrum of neutrophilic diseases, to the best of our knowledge, this is the first case of a "Histiocytoid Pyoderma gangrenosum" encompassing immature granulocytes in the absence of leukemia cutis.

http://ift.tt/2fMQXRn

Pleomorphic fibroma of the skin with MDM2 immunoreactivity: a potential diagnostic pitfall

Abstract

Pleomorphic fibroma is a rare benign cutaneous neoplasm characterized by spindle-shaped cells and multinucleated giant cells scattered throughout collagenous stroma. These morphologic features can lead to diagnostic confusion, including atypical lipomatous tumor as one consideration. In contrast to atypical lipomatous tumor, previous studies have found pleomorphic fibroma to be negative for MDM2 immunohistochemical staining and MDM2 gene amplification. Here, we present a case of pleomorphic fibroma of skin with nuclear MDM2 immunoreactivity in the absence of MDM2 gene amplification, underscoring the superiority of fluorescence in situ hybridization as a diagnostic test in this differential diagnosis. The RB1 locus is also explored for differential diagnosis with pleomorphic / spindle cell lipoma and related entities.

http://ift.tt/2y2gekn

Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate to severe melasma

Publication date: Available online 4 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Eunice Del Rosario, Stephanie Florez- Pollack, Lucio Zapata, Katia Hernandez, Andrea Tovar-Garza, Michelle Rodrigues, Linda S. Hynan, Amit G. Pandya
BackgroundMelasma is a common pigmentary disorder that is often difficult to treat. Tranexamic acid (TA) has emerged as a promising treatment for melasma; however, few controlled studies exist.ObjectiveTo determine the efficacy of oral TA in patients with moderate to severe melasmaMethodsPatients with moderate to severe melasma were treated with 250 mg of TA or placebo capsules twice daily for 3 months and sunscreen followed by 3 months of treatment with sunscreen only. The primary outcome measure was the modified Melasma Area and Severity Index (mMASI) score.Results44 patients were enrolled and 39 completed the study. At 3 months, there was a 49% reduction in mMASI score in the TA group vs. 18% in the control group. Patients with severe melasma improved more than those with moderate melasma. Three months after stopping treatment, there was a 26% reduction in mMASI in the TA group compared to the baseline visit versus a 19% reduction in the placebo arm. No serious adverse events were noted in either group.LimitationsSingle center study enrolling predominantly Hispanic womenConclusionsOral TA appears to be an effective treatment for moderate to severe melasma with minimal side effects.



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Risk of Infection in Patients with Atopic Dermatitis Treated with Dupilumab: A Meta-Analysis of Randomized Controlled Trials

Publication date: Available online 4 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Patrick Fleming, Aaron M. Drucker
BackgroundAtopic dermatitis (AD) is characterized by skin barrier defects, Th2 activation, and increased risk for cutaneous and extracutaneous infections. In clinical trials, dupilumab appeared to decrease rates of skin infections in AD.ObjectiveWe aimed to determine the impact of dupilumab on rates of skin and other infections in patients with moderate-to-severe AD.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of dupilumab for AD. We searched the PubMed database for relevant studies. Risk ratios (RR) and 95% confidence intervals (CI) for skin infections, herpesvirus infections and overall infections and infestations were calculated for dupilumab compared with placebo using binary random-effects meta-analysis. For the analysis of eczema herpeticum, Peto odds ratios (OR) were calculated.ResultsEight RCTs in 4 publications with 2,706 participants were included with follow-up time ranging from 4-52 weeks. Meta-analysis including all dosing schedules and follow-up times showed a RR of skin infection of 0.54 (95% CI: 0.42-0.70) and an OR of eczema herpeticum of 0.34 (95% CI: 0.14-0.84) for dupilumab compared with placebo. No significant association was found for dupilumab with overall herpesvirus infections (RR=1.16, 95% CI: 0.78-1.74) and overall infections (RR=0.98, 95% CI: 0.83-1.16).LimitationsOur analysis is limited by short follow-up time in most trials and relatively low number of patients treated with dupilumab to date.ConclusionDupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate-to-severe AD. The mechanism underlying this association is uncertain, but is likely related to improvement in AD severity.



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Nail Braces for Severe Paronychia Induced by Epidermal Growth Factor Receptor Inhibitors: An alternative to nail extraction

Publication date: Available online 4 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Chi-Feng Yen, Yung-Yi Lee




http://ift.tt/2yq44mT

Detection And Characterization Of Igg, Ige And Iga Autoantibodies In Patients With Bullous Pemphigoid Associated With Dipeptidyl Peptidase-Iv Inhibitors

Publication date: Available online 4 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Luca Fania, Adele Salemme, Alessia Provini, Gianluca Pagnanelli, Maria Chiara Collina, Damiano Abeni, Biagio Didona, Giovanni Di Zenzo, Cinzia Mazzanti




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Treatment for facial alopecia areata: A systematic review with evidence-based analysis

Publication date: Available online 4 October 2017
Source:Journal of the American Academy of Dermatology
Author(s): Aizuri Murad, Wilma Bergfeld




http://ift.tt/2fMRaUI

Efficient interplay effect mitigation for proton pencil beam scanning by spot-adapted layered repainting evenly spread out over the full breathing cycle

Publication date: Available online 4 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Per Rugaard Poulsen, John Eley, Ulrich Langner, Charles B. Simone, Katja Langen
PurposeTo develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS).MethodsA new flexible repainting scheme with spot-adapted numbers of repaintings evenly spread out over the whole breathing cycle (here assumed to be 4s) was developed. Twelve fields from five thoracic and upper abdominal PBS plans were delivered three times with the new repainting scheme to an ion chamber array on a motion stage: once static and twice with 4s,3cm peak-to-peak sinusoidal motion with delivery started at maximum inhale and maximum exhale. For comparison, all dose measurements were repeated with no repainting and with 8 repaintings. For each motion experiment, the 3%/3mm gamma pass rate was calculated using the motion-convolved static dose as reference. Simulations were first validated with the experiments and then used to extend the study to 0-5cm motion magnitude, 2-6s motion periods, patient-measured liver tumor motion, and 1-6 fraction treatments. The effect of the proposed method was evaluated for the five clinical cases by 4D dose reconstruction in the planning 4DCT scan. The target homogeneity index, HI=(D2-D98)/Dmean, of a single fraction delivery was reported.ResultsThe gamma pass rates were 59.6±9.7% (no repainting), 76.5±10.8% (8 repaintings), and 92.4±3.8% (new repainting scheme). Simulations reproduced the experimental gamma pass rates with 1.3% root-mean-square error and demonstrated largely improved gamma pass rates with the new repainting scheme for all investigated motion scenarios. One- and two-fraction deliveries with the new repainting scheme had similar gamma pass rates as 3-4 and 6-fraction deliveries with 8 repaintings. The mean HI for the five test cases was 14.2% (no repainting), 13.7% (8 repaintings), 12.0% (new repainting scheme), and 11.6% (4D dose without interplay effects).ConclusionsA novel repainting strategy for efficient interplay effect mitigation was proposed, implemented, and shown to outperform conventional repainting in experiments, simulations and dose reconstructions. This strategy may allow for safe and more optimal clinical delivery of thoracic and abdominal proton PBS and better facilitate hypofractionated and stereotactic treatments.



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Consensus Contouring Guidelines for Post-Operative Completely Resected Cavity Stereotactic Radiosurgery (SRS) for Brain Metastases

Publication date: Available online 4 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hany Soliman, Mark Ruschin, Lilyana Angelov, Paul D. Brown, Veronica L.S. Chiang, John P. Kirkpatrick, Simon S. Lo, Anita Mahajan, Kevin S. Oh, Jason P. Sheehan, Scott G. Soltys, Arjun Sahgal
PurposeCavity stereotactic radiosurgery (SRS) is an emerging treatment option after surgical resection of brain metastases. No guidelines for contouring the surgical cavity volume have been reported. The aim of this study was to propose contouring guidelines based on consensus contours generated by 10 international experts.MethodsTen post-operative completely resected cases with varying clinical scenarios and locations within the brain were selected. For each case, 10 experts independently contoured the surgical cavity clinical target volume (CTV). All the contours were analyzed and agreement was calculated using the Simultaneous Truth and Performance Level Estimation (STAPLE) with the kappa statistic. A follow-up survey was also completed by each investigator in order to summarize their contouring rationale based on a number of different clinical scenarios. Both the results from the survey and consensus STAPLE contours were summarized to establish contouring guidelines.ResultsThere was a high level of agreement between the expert CTV contours (mean sensitivity=0.75, mean specificity=0.98), and the mean kappa was 0.65. The agreement was statistically significant at p<0.001 for all cases. Based on these results and analyses of the survey answers, recommendations for CTV include: fusion of the pre-operative MRI to aid in volume delineation, contouring the entire surgical tract regardless of the preoperative location of the tumor, the CTV should be extended 5-10mm along the dura overlying the bone flap to account for microscopic disease extension in cases with preoperative dural contact, and a margin of up to 5mm into the adjacent sinus is sufficient when there is pre-operative venous sinus contact.ConclusionsConsensus contouring guidelines for post-operative completely resected cavity SRS treatment were established based on expert contours and clinical practice. However, in the absence of clinical data supporting the recommendations in this paper, these guidelines serve as a baseline for further study and refinement.



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Low-power laser irradiation inhibits PDGF-BB-induced migration and proliferation via apoptotic cell death in vascular smooth muscle cells

Abstract

Vascular restenosis after injury of blood vessel has been implicated in various responses including apoptosis, migration, and proliferation in vascular smooth muscle cells (VSMCs) stimulated by diverse growth factors underlying platelet-derived growth factor (PDGF). Previous studies evaluated the effects of low-power laser (LPL) irradiation over various wavelength ranges on VSMC events in normal and pathologic states. However, whether VSMC responses are affected by LPL irradiation remains unclear. The purpose of this study is to explore the effects of LPL (green diode laser 532-nm pulsed wave of 300 mW at a spot diameter of 1 mm) irradiation on the responses, apoptosis, migration, and proliferation of VSMCs. The effect of LPL irradiation was tested on VSMCs through cytotoxicity, proliferation, migration, and apoptotic assays. Aortic ring assay was used to assess the effect of LPL irradiation on aortic sprout outgrowth. Protein expression levels were determined by western blotting. LPL irradiation did not affect VSMC viability but slightly attenuated PDGF-BB-induced proliferation in VSMCs. In addition, LPL irradiation inhibited PDGF-BB-evoked migration of VSMCs. Aortic sprout outgrowth in response to PDGF-BB was diminished in cells treated with LPL. In contrast, LPL irradiation evoked apoptosis in VSMCs in the presence of PDGF-BB. Similarly, activation of caspase-3 and Bax, as well as p38 mitogen-activated protein kinase (MAPK), in VSMCs treated with PDGF-BB was enhanced by exposure to LPL. These findings indicate that LPL irradiation induces vascular apoptosis via p38 MAPK activation and simultaneously inhibits VSMC proliferation and migration in response to PDGF-BB.

http://ift.tt/2wzfFv8

The Use of Chewing Gum for Xerostomia and Hyposalivation After Radiotherapy for Oral and Oropharyngeal Tumors

Conditions:   Head and Neck Cancer;   Radiation Therapy Complication;   Xerostomia;   Hyposalivation
Intervention:   Dietary Supplement: Chewing gum
Sponsors:   Odense University Hospital;   Danish Cancer Society;   OPEN - Odense Patient data Explorative Network
Recruiting

http://ift.tt/2xjRXTy

Are optic nerve heads of patients with helicobacter pylori infection more susceptible to glaucomatous damage?

Abstract

Background

To compare retinal nerve fiber layer thicknesses (RNFLT) of patients with or without Helicobacter pylori infection and to reveal the possible RNFLT changes after H. pylori eradication.

Materials and methods

Sixty-five eyes of 65 patients that tested positive for H. pylori (Group 1) and 48 eyes of 48 patients that tested negative for H. pylori (Group 2) were included. RNFLT analyses were performed with spectral-domain (SD) optical coherence tomography (OCT) in a total of five regions: the superior, inferior, nasal, and temporal quadrants and the average. Then, a comparison was made between groups. After H. pylori eradication in 38 patients, RNFLTs were compared with both pre-eradication values and Group 2.

Results

The groups were similar in terms of age and gender. Temporal quadrant RNFLT was thinner in Group 1 than in Group 2 (P=.02). After H. pylori eradication, RNFLTs did not differ from pre-eradication values in Group 1 (P>.05 for all), whereas temporal quadrant RNFLT after H. pylori eradication was thinner compared to Group 2 (P=.03).

Conclusions

H. pylori may cause the localized defects on RNFL that are the early signs of glaucoma.

http://ift.tt/2fTPsEw

Certolizumab pegol and secukinumab for treating active psoriatic arthritis following inadequate response to disease-modifying antirheumatic drugs: a systematic review and economic evaluation.

In active psoriatic arthritis, certolizumab and secukinumab had some incremental cost-effectiveness ratios of £20,000-30,000 per QALY, depending on psoriasis severity and the previous treatments used.

http://ift.tt/2y1aVBI

Understanding Pathways to Successful Aging: Behavioral and Social Factors Related to Alzheimer's Disease: Proceedings of a Workshop–in Brief.

A strong body of research demonstrates associations between the incidence of Alzheimer's disease and individuals' personality characteristics, level of social engagement, and educational attainment. To advance understanding of the causal pathways leading to Alzheimer's, the Board on Behavioral, Cognitive, and Sensory Sciences convened a workshop in June 2017. This workshop was designed to build on a 2015 workshop that focused on the importance of delineating causal relationships underlying associations between behavioral, social, and biological factors and long-term health. This publication briefly summarizes the presentations and discussions from the workshop.

http://ift.tt/2xjHZRN

Portacaval shunting causes differential mitochondrial superoxide production in brain regions

Publication date: December 2017
Source:Free Radical Biology and Medicine, Volume 113
Author(s): Elena A. Kosenko, Lyudmila A. Tikhonova, Gubidat A. Alilova, Carmina Montoliu, George E. Barreto, Gjumrakch Aliev, Yury G. Kaminsky
The portacaval shunting (PCS) prevents portal hypertension and recurrent bleeding of esophageal varices. On the other hand, it can induce chronic hyperammonemia and is considered to be the best model of mild hepatic encephalopathy (HE). Pathogenic mechanisms of HE and dysfunction of the brain in hyperammonemia are not fully elucidated, but it was originally suggested that the pathogenetic defect causes destruction of antioxidant defense which leads to an increase in the production of reactive oxygen species (ROS) and the occurrence of oxidative stress. In order to gain insight into the pathogenic mechanisms of HE in the brain tissue, we investigated the effects of PCS in rats on free radicals production and activity levels of antioxidant and prooxidant enzymes in mitochondria isolated from different brain areas. We found that O2^·− production, activities of Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GT), nitric oxide synthase (NOS), and levels of carbonylated proteins differed between the four brain regions both in the amount and response to PCS. In PCS rats, Mn-SOD activity in the cerebellum was significantly decreased, and remained unchanged in the neocortex, hippocampus and striatum compared with that in sham-operated animals. Among the four brain regions in control rats, the levels of the carbonyl groups in mitochondrial proteins were maximal in the cerebellum. 4 weeks after PCS, the content of carbonylated proteins were higher only in mitochondria of this brain region. Under control conditions, O2^·− production by submitochondrial particles in the cerebellum was significantly higher than in other brain regions, but was significantly increased in each brain region from PCS animals. Indeed, the production of O2^·− by submitochondrial particles correlated with mitochondrial ammonia levels in the four brain regions of control and PCS-animals. These findings are the first to suggest that in vivo levels of ammonia in the brain directly affect the rate of mitochondrial O2^·− production.

Graphical abstract

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Regulatory role of NADPH oxidase 2 in the polarization dynamics and neurotoxicity of microglia/macrophages after traumatic brain injury

Publication date: December 2017
Source:Free Radical Biology and Medicine, Volume 113
Author(s): Jing Wang, Merry W. Ma, Krishnan M. Dhandapani, Darrell W. Brann
Traumatic brain injury (TBI) is a leading cause of death and disability. Secondary injuries that develop after the initial trauma contribute to long-lasting neurophysiological deficits. Polarization of microglia/macrophages toward a pro-inflammatory (M1) phenotype may increase the progression of secondary injury following TBI; however, the regulatory and functional mechanisms underlying these changes remain poorly defined. In the present study, we showed elevated expression of NADPH oxidase 2 (NOX2) and activation of nuclear factor-kappa B (NF-κB) predominantly in microglia/macrophages at 4- and 7-days after controlled cortical impact in mice. Delayed inhibition of NOX2, beginning one day after TBI, reduced reactive oxygen species production of myeloid cells and protected neurons from oxidative damage. Moreover, delayed NOX inhibition or global genetic NOX2 knockout suppressed the M1 "pro-inflammatory" profile of microglia/macrophages and simultaneously increased the M2 "anti-inflammatory" profile in the injured brain. These changes were associated with marked down-regulation of the classical NF-κB pathway in microglia/macrophages and reduced production of pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-1β, after TBI. Finally, we demonstrated that wild-type microglia/macrophages isolated from the ipsilateral cortex at 7 days post-TBI were neurotoxic to co-cultured primary neurons, whereas this neurotoxicity was largely attenuated in microglia/macrophages from NOX2-KO mice. Taken together, our study shows a direct link between NOX2 and the NF-κB pathway in microglia/macrophages after TBI, and it provides a novel mechanism by which NOX2 activation leads to the enhanced inflammatory response and neuronal damage after brain injury. Our data also supports the therapeutic potential of targeting NOX2, which may provide efficacy with an extended therapeutic window after TBI.

Graphical abstract

http://ift.tt/2gesrtc

Synthesis and properties of rotaxane-cross-linked polymers using a double-stranded γ-CD-based inclusion complex as a supramolecular cross-linker

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Keumhee Jang, Keisuke Iijima, Yasuhito Koyama, Satoshi Uchida, Shigeo Asai, Toshikazu Takata
A vinylic supramolecular cross-linker (VSC) was prepared from γ-cyclodextrin (γ-CD) and a macromonomer for the purpose of simple and easy introduction of rotaxane cross-links into polymers via the radical polymerization of vinyl monomers. The synthesis of VSC as a pseudocross-linked cross-linker was performed by the simple mixing of γ-CD and a poly(ethylene glycol)-based terminal-bulky macromonomer in water. The radical polymerization of typical vinyl monomers such as N,N-dimethyl acrylamide in the presence of the VSC afforded the corresponding rotaxane cross-linked polymers (RCPs) under both photoinitiated and redox polymerization conditions. In particular, RCPs exhibited mechanical properties endowed by the rotaxane cross-links that were superior to those of chemically cross-linked polymers, demonstrating the significant usefulness of the VSCs.

Graphical abstract

http://ift.tt/2xjrCoC

Fabrication of lightweight microcellular foams in injection-molded polypropylene using the synergy of long-chain branches and crystal nucleating agents

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Long Wang, Yuta Hikima, Shota Ishihara, Masahiro Ohshima
Herein, we have fabricated microcellular injection-molded foams by combining long-chain branched polypropylene (LCBPP) and 1,3:2,4 bis-O-(4-methylbenzylidene)-D-sorbitol gelling agent (MD) using a core-back foam injection molding (FIM) technique. Microcellular foams of LCBPP/MD blends having an average cell diameter of approximately 2.5 μm and a cell density on the order of 10¹⁰ cells/cm³ were achieved with a void fraction of 50%. Fast scanning chip calorimetry results revealed that the added MD acted as effective nucleating agents and promoted crystallization for the LCBPP. Interestingly, the development of microcellular foams led to notable advances in tensile toughness from 44.1 MJ/m³/(g·cm⁻³) and 111% of neat LCBPP foams to 172.1 MJ/m³/(g·cm⁻³) and 440% of LCBPP/MD blend foams in terms of specific breaking energy and elongation at break, respectively. These results revealed that the lightweight microcellular PP with improved toughness could be developed using FIM, which offers a viable approach to fabricate injection-molded products for large-scale applications.

Graphical abstract

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Molecular dynamics of fully biobased poly(butylene 2,5-furanoate) as revealed by broadband dielectric spectroscopy

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Michelina Soccio, Daniel E. Martínez-Tong, Angel Alegría, Andrea Munari, Nadia Lotti
This work presents the molecular dynamics of both fully amorphous and semicrystalline poly(butylene 2,5-furanoate) (PBF). Broadband dielectric spectroscopy experiments were combined with temperature modulated differential scanning calorimetry measurements. The results showed that the subglass molecular dynamics is characterized by the existence of two dielectric relaxation processes, being the faster one associated to the glycolic subunit, whereas the slower relaxation was assigned to the link in between the ester group and the furan ring. Crystallization affected differently the contribution of these two components. Additionally, crystallization had a stronger effect on the α relaxation process, related to the segmental dynamics of the amorphous phase. In the semicrystalline state, the PBF amorphous phase was described as being composed by different fractions, including a completely rigid one, with distinctly slower mobilities and reduced contributions to the dielectric relaxation, compared to the fully amorphous polymer.

Graphical abstract

http://ift.tt/2xjKKTu

Development of hybrid diblock copolypeptide amphiphile/magnetic metal complexes and their spin crossover with lower-critical-solution-temperature(LCST)-type transition

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Arie Tsubasa, Soichi Otsuka, Takahiro Maekawa, Ryota Takano, Shinichi Sakurai, Timothy J. Deming, Keita Kuroiwa
Diblock copolypeptide amphiphiles have been attracting much interest as motifs for self-assembly in the production of nanostructures such as nanoparticles, nanosheets, and nanofibers. In this study, we first focus on the self-assembly of magnetic metal complexes in water using diblock copolypeptides. In addition, not only were nanocomposites formed, but also observed were the development of lower critical solution temperature (LCST) and LCST-induced spin crossover phenomenon, which are discussed. Three composites composed of the iron complex [Fe^II(ppi)2(NCS)2] (ppi = N-phenyl-2-pyridinalimine) and the diblock copolypeptide amphiphiles 1 and 2 or the polypeptide 3 (containing glutamic acid and leucine) were prepared. Supramolecular structures such as sheets and rectangular morphologies were obtained from composites. A perfectly reversible spin crossover with LCST was successfully generated in the case of composites made with 1. The technique of combining polypeptide molecules and discrete coordination compounds thus makes it possible to design flexible, reversible, and spin-controllable metastable systems.

Graphical abstract

http://ift.tt/2xjHase

Physical gelation of supramolecular hydrogels cross-linked by metal-ligand interactions: Dynamic light scattering and microrheological studies

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Hiroto Ozaki, Tsutomu Indei, Tsuyoshi Koga, Tetsuharu Narita
Microrheology based on diffusing-wave spectroscopy, dynamic light scattering (DLS), and macrorheology were performed on solutions of polyacrylamide-derivative associating polymer containing imidazole groups. By adding Ni ion, the physical gel is formed by metal-ligand bond. The physical gel point, where the percolation of a transient network is supposed to occur, was microrheologically determined. In the DLS measurement showing ergodicity at all the conditions studied, we observed three modes in the autocorrelation functions: fast, intermediate, and slow modes. The fast mode is the collective diffusion (gel mode), while the slow mode is attributed to the diffusion of clusters. For the intermediate mode, with increase in Ni ion concentration, the transition from diffusive mode to relaxation mode was observed near the microrheologically determined physical gel point. In postgel regime, intermediate mode can be attributed to the macroscopic relaxation since the activation energies are comparable with the relaxation energy estimated by macrorheology.

Graphical abstract

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Synthesis of rotaxane cross-linked polymers with supramolecular cross-linkers based on γ-CD and PTHF macromonomers: The effect of the macromonomer structure on the polymer properties

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Keisuke Iijima, Daisuke Aoki, Hideyuki Otsuka, Toshikazu Takata
Vinylic supramolecular cross-linkers (VSCs) consisting of γ-cyclodextrin (γ-CD) and terminal bulky macromonomers (TBMs) based on polytetrahydrofuran (PTHF) were designed, synthesized, and used to introduce rotaxane cross-linkers into vinyl polymers in order to endow the resulting rotaxane-cross-linked polymers (RCPs) with improved mechanical properties. Special attention was focused on the impact of the TBM structure on the properties of RCPs. VSCs, which formed in situ upon mixing γ-CD and the TBMs in water, were added to radical polymerization systems based on N,N-dimethylacrylamide to afford the corresponding RCPs. These RCPs were substantially tougher than covalently cross-linked polymers (CCPs), indicating a strong impact of the VSCs on the mechanical properties of the RCPs. VSCs obtained from macromonomers with longer PTHF chains afforded tougher RCPs compared to RCPs derived from TBMs with shorter PTHF chains, which highlights the importance of the flexible region of the polymer chain at the cross-linking points.

Graphical abstract

http://ift.tt/2xjrBRA

Precise size control of sub-10 nm structures of cholesteryl-containing mesogen-jacketed liquid crystalline polymers

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Zhen-Yu Zhang, Pei-Long Liao, Zhihao Shen, Xing-He Fan
A series of mesogen-jacketed liquid crystalline polymers (MJLCPs) with polynorbornene as the main chain and cholesteryl mesogenic units at the ends of the side chain, PNbnChol (n = 1, 3, 5, which is the number of benzene rings in the rigid side-chain core), were prepared by ring-opening metathesis polymerization. The phase behaviors of the polymers were investigated by differential scanning calorimetry, polarized light microscopy, and one-dimensional/two-dimensional X-ray scattering. The polymer with one benzene as the rigid core in the side chain shows only a smectic phase with interdigitated packing of cholesteryl units at low temperatures and is amorphous at high temperatures. While polymers containing three or five benzenes in the rigid side-chain core provide two different SmA phases at different temperatures, a smectic phase with double-layer-like packing of cholesteryl units at low temperatures and the smectic phase with interdigitated packing of cholesteryl units at high temperatures. The introduction of cholesteryl to MJLCPs can fabricate precisely controlled sub-10 nm scale ordered structures that can be maintained at high temperatures.

Graphical abstract

http://ift.tt/2xjFJtK

Insight into the influence of OA-Fe3O4 nanoparticles on the morphology and scCO2 batch-foaming behavior of cocontinuous LLDPE/PS immiscible blends at semi-solid state

Publication date: 27 October 2017
Source:Polymer, Volume 129
Author(s): Guangchun Zhang, Shaofeng Zhang, Jian Qiu, Zhiwei Jiang, Haiping Xing, Minggang Li, Tao Tang
The influence of oleic acid modified Fe3O4 (OA-Fe3O4) nanoparticles on the morphology and foaming behavior of cocontinuous linear low density polyethylene/polystyrene (LLDPE/PS) immiscible blends (60/40 by weight) was studied. The morphology observation showed that the addition of nanofillers resulted in the increased dispersion degree of both LLDPE and PS components and even the transformation of phase structure from cocontinuous structure to sea-island structure, when enough amounts of nanoparticles were added. Meanwhile the introduction of enough amounts of OA-Fe3O4 nanoparticles effectively enhanced the foaming ability of LLDPE/PS blend at semi-solid state during scCO2 batch foaming. The mechanism analysis for the change of foaming behavior showed that the improved foaming capacity resulted from the change of the phase structure of LLDPE/PS blends and heterogeneous nucleation of OA-Fe3O4 nanofillers. Sorption and desorption measurements showed that the addition of OA-Fe3O4 nanoparticles in the LLDPE/PS blend increased the solubility of CO2, and the presence of enough amount of OA-Fe3O4 decreased the desorption rate of CO2 in the initial period of depressurization process, which are beneficial to cell nucleation and growth. Furthermore, it was found that the melt behavior and crystalline properties of LLDPE/PS blends were not the key factors to improved foaming behavior of the blends in the presence of OA-Fe3O4 nanoparticles.

Graphical abstract

http://ift.tt/2xjW4Pd

Photoresponsive supramolecular copolymers from diarylethene–perylene bisimide hydrogen bonded complexes

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Bimalendu Adhikari, Tomoya Suzuki, Lin Xu, Mitsuaki Yamauchi, Takashi Karatsu, Shiki Yagai
Photoresponsive molecular assembly based on diarylethene (DAE) is an interesting class of supramolecular system as it can allow remarkable morphological transition via small structural changes upon photoisomerization. Herein, we report coassemblies of diarylethene and perylene bisimide through complementary multiple hydrogen-bonding. The open isomer of the diarylethene and the perylene bisimide coassemble to afford photoresponsive helical supramolecular polymer nanofibers. The ring-closure photoreaction of the diarylethene unit enables transformation of helical nanofibers to non-helical fibers. The non-helical fibers can only be obtained through the photoisomerization, and are never achievable by thermal coaggregation of the close isomer and the perylene bisimide. This study illustrates that the proper incorporation of photochromic units into a non-equilibrated molecular assembly system achieved by strong intermolecular interaction enables us to design new self-assembled products in terms of morphology and functions, which are not obtainable through the self-assembly of ground state molecules under either kinetic or thermodynamic control.

Graphical abstract

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Editorial board

Publication date: 16 October 2017
Source:Polymer, Volume 128





http://ift.tt/2xk8uGJ

Supramolecular hydrogels with multi-cylindrical lamellar bilayers: Swelling-induced contraction and anisotropic molecular diffusion

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Kei Mito, Md. Anamul Haque, Tasuku Nakajima, Maki Uchiumi, Takayuki Kurokawa, Takayuki Nonoyama, Jian Ping Gong
Novel, supramolecular, anisotropic hydrogels (called MC-PDGI gels) are presented in this study. These MC-PDGI gels consist of multi-cylindrical lipid bilayers aligned in a uniaxial manner and embedded in a soft hydrogel matrix. The bilayers and the hydrogel interact weakly due to hydrogen bonding. These MC-PDGI gels swell after exposure to water, which causes their volume and diameter to increase while simultaneously causing their length to decrease. This anisotropic swelling-induced contraction behavior is the result of competition between the isotropic elasticity of the hydrogel matrix and the interfacial tension of the lipid bilayers. Moreover, the MC-PDGI gels exhibit unique quasi one-dimensional diffusion behavior owing to the difficulty of molecular penetration through the multi-layered lipid bilayers. These materials would be useful for prolonged drug release or as an actuator.

Graphical abstract

http://ift.tt/2xViKd8

Graphical Contents list & Author index

Publication date: 16 October 2017
Source:Polymer, Volume 128





http://ift.tt/2xU17ud

Mechanical properties of supramolecular elastomers prepared from polymer-grafted polyrotaxane

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Kosuke Minato, Koichi Mayumi, Rina Maeda, Kazuaki Kato, Hideaki Yokoyama, Kohzo Ito
Supramolecular slide-ring (SR) elastomers without solvent were fabricated by cross-linking of polymer-grafted polyrotaxane in which α-cyclodextrins (CDs) with poly-ε-caprolactone (PCL) side chains are threaded on a polyethylene glycol (PEG) axial linear chain. The cross-links in the SR elastomers are capable of sliding along the backbone in response to applied stress. Mechanical properties of the SR elastomers with different cross-linking densities were compared with those of fixed cross-link (FC) elastomers prepared from PCL-grafted hydroxypropyl cellulose (HPC) to understand the influence of the slidable cross-links. The SR elastomers are found to undergo less strain-hardening at large strains and demonstrate higher strains at break than the conventional FC elastomers with the same Young's moduli.

Graphical abstract

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Supramolecular polymers

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Toshikazu Takata




http://ift.tt/2xjNQGT

Supramolecular polymeric assemblies of π-conjugated molecules possessing phenylisoxazoles

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Toshiaki Ikeda, Takeharu Haino
Supramolecular polymeric stacks of flat molecular components provide a highly ordered molecular organization that results in unique functions. The engineering of molecular organization, therefore, has attracted a great deal of attention both in supramolecular chemistry and in material science. The electronic and structural properties of molecular components determine the forthcoming supramolecular organization structure and properties. Non-covalent intermolecular interactions are responsible for directional growth in supramolecular polymerization. We have discovered that a phenylisoxazole ring system drives supramolecular polymerization in a directional way. π-Conjugated molecular components possessing phenylisoxazole moieties constructively assemble to form one-dimensional stacked assemblies via π–π stacking and dipole–dipole interaction. The introduction of a chirality onto the molecular components results in supramolecular helical organizations with unique photophysical functions. Switchable circularly polarized luminescence (CPL) and circular dichroism (CD) are developed in the supramolecular helical organizations. The grown assemblies provide highly entangled fibrillar networks, giving rise to organogels. The photo-responsive organogels and toroidal nanostructures are fabricated with the assistance of a photo-addressable azobenzene group. A light-harvesting system is developed in the organogels.

Graphical abstract

http://ift.tt/2xViECi

Hydrophobically modified polyacrylates (hmPAAs) with long alkyl chains – Self-assembly in aqueous solution

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Sven Riemer, Sylvain Prévost, Michaela Dzionara, Urs Gasser, Michael Gradzielski
Hydrophobically modified polyacrylates (hmPAAs) obtained by Atomic Transfer Radical Copolymerisation (ATRP) of mixtures of different alkyl acrylates and t-butyl acrylate and subsequent hydrolysis of the t-butyl acrylate to polyacrylic acid (PAA), were studied with respect to their aggregation behaviour in aqueous solution. The hydrophobic modifications were long alkyl chains that were varied systematically from dodecyl to stearyl, thereby expecting a strong propensity for hydrophobic aggregation. Their structure in aqueous solution was investigated comprehensively by small-angle neutron scattering (SANS) and complemented by dynamic light scattering (DLS) experiments. In these random copolymers the degree of amphiphilicity and hydrophobicity was varied by the percentage of alkyl chains and pH. Due to the length of the alkyl chain all these copolymers have a tendency for microphase separation, but this tendency and the structure of the formed hydrophobic domains depend in a systematic fashion on the precise molecular composition. The domain size scales with the length of the hydrophobic alkyl modification and, for chains of C16 and longer, there is apparently a tendency for elongation. Another interesting observation is that for 20 mol% hydrophobic modification rather self-contained and isolated hydrophobic micellar domains are formed. In contrast, the copolymers with 10 mol% alkyl modification contain interconnected hydrophobic domains as evidenced from the low-q scattering seen in SANS and confirmed by DLS observations. This tendency is further enhanced when fully charging the copolymers. In summary, the molecular design of such random amphiphilic copolymers allows in a nice way to control the aggregation state in solution.

Graphical abstract

http://ift.tt/2xU11CR

Mechanically linked supramolecular polymer architectures derived from macromolecular [2]rotaxanes: Synthesis and topology transformation

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Daisuke Aoki, Toshikazu Takata
This review article deals with the construction and function of dynamic macromolecular systems having mechanically linked polymer chains which can undertake a topology transformation to induce structure and property changes. Synthesis of a macromolecular [2]rotaxane (M2R) possessing a macromolecular switch function is first described, which is a structure-definite ideal polyrotaxane consisting of one polymer axle and one macrocycle wheel. Its application to the synthesis of rotaxane cross-linked polymers (RCP) and topology-transformable polymers is discussed along with their properties, where the rotaxane-linking of polymer chains plays a crucial role. The M2R-based cross-linker is prepared and applied to the synthesis of RCPs by adding it into radical polymerization systems of vinyl monomers. RCPs have high stretchability and toughness. Rotaxane-linked block copolymers and cyclic polymers synthesized by introducing polymer chains onto the wheel and axle components of M2R are subjected to the topology transformation using the switch function of M2R to cause remarkable structure and property changes.

Graphical abstract

http://ift.tt/2xViCdE

RAFT polymerization, characterization, and post-polymerization modification of a copolymer of vinylbenzyl chloride: Towards thiolate functionalized copolymers

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Farhad Faghihi, Paul Hazendonk
A procedure for the synthesis of well-defined random copolymers bearing multiple thiolate functionalities is presented. Reactive copolymers of vinylbenzyl chloride (VBC, 15 mol%) with methyl methacrylate (MMA, 85 mol%) were synthesized via free radical and RAFT polymerizations. The microstructure of these copolymers was characterized by monitoring the polymerization reaction. Post-polymerization modification of this reactive precursor was conducted by an initial substitution of VBC chloride with thiouronium (TU) followed by conversion of TU into thiolate via reaction with either KOH or NaBH4. The reaction with NaBH4, which was found to yield better result, was further investigated by monitoring the changes of the copolymer functional groups throughout the entire process using NMR. Further mechanistic insight was obtained by studying a model reaction between benzyl thiouronium, which is the small-molecule counterpart of TU-bearing vinylbenzyl repeating units, and NaBH4. Analysis of this model reaction confirmed the formation of thiolate groups and their subsequent transformation into inter or intra-molecular disulfide bonds.

Graphical abstract

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Design and properties of supramolecular elastomers

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Takato Kajita, Atsushi Noro, Yushu Matsushita
Supramolecular elastomers are supramolecular soft polymeric materials with both transient cross-links and (semi)permanent cross-links, where transient cross-links have a finite relaxation time and are typically composed of noncovalent bonds such as hydrogen bonds, metal–ligand coordination bonds, etc., whereas (semi)permanent cross-links such as covalent bonds, crystalline segments and glassy hard domains have an infinite relaxation time. Excellent elastomeric properties were induced by a combination of all the above molecular features. However, if soft polymeric materials have only supramolecular/transient cross-links with a finite relaxation time, the materials eventually flow within a finite time and cannot behave as elastomers; in other words, they are merely supramolecular polymers that have only transient cross-links or bonds. Therefore, the key to preparing higher-performance supramolecular elastomers is their molecular design. Here, we firstly review the fundamental design of supramolecular polymers to make the differences between supramolecular polymers and supramolecular elastomers clear. Second, we discuss the simultaneous incorporation of (semi)permanent cross-links and supramolecular cross-links into polymeric materials to prepare supramolecular elastomers. Finally we summarized their properties and potential applications.

Graphical abstract

http://ift.tt/2xU0Zed

Impact of a subtle structural difference on the kinetic behavior of metastable supramolecular assemblies

Publication date: 16 October 2017
Source:Polymer, Volume 128
Author(s): Tomoya Fukui, Masayuki Takeuchi, Kazunori Sugiyasu
Molecular self-assembly under kinetic control has many opportunities leading to novel phenomena and applications. However, a mechanistic insight into the intricate kinetic behavior is still lacking. Herein, we demonstrate that even a subtle change in the molecular structure affects the kinetic behavior of metastable supramolecular assembles. Interestingly, the kinetic process influenced the size of the final outcomes (in this study, nanosheet structures) in a manner opposite to that predicted by the thermodynamic model. Our findings illustrate the difference between thermodynamically and kinetically controlled molecular self-assemblies. We believe that this study will expand the potential applications of molecular self-assemblies.

Graphical abstract

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Intraoperative Neurophysiological Monitoring (Motor and Somatosensory Evoked Potentials) in Dorsal Root Entry Zone Lesioning for Brachial Plexus Avulsion Pain

Aims: To address the feasibility and importance of intraoperative neurophysiological monitoring (IONM) in dorsal root entry zone (DREZ) lesioning for brachial plexus avulsion pain. Methods: Muscle motor evoked potential (mMEP) and somatosensory evoked potential (SSEP) were applied during DREZ lesioning for brachial plexus avulsion pain. Results: IONM of mMEPs and SSEPs was feasible for monitoring of the spinal cord during DREZ lesioning. With the exception of 3 unrecordable mMEPs in ipsilateral arms, mMEPs were preserved and referenced to look for changes according to lesioning in 6 upper extremities (66.6%) and 8 lower extremities. All 3 patients with >50% reduction in baseline mMEP amplitude after lesioning in either the ipsilateral upper or lower extremities showed postoperative ataxia and weakness of the lower extremities (100%). Only 2 out of 9 patients (22.2%) with brachial plexus avulsion pain had discernible baseline SSEPs in the ipsilateral upper extremities. One of 2 patients with discernible SSEPs in the upper extremities showed significant SSEP events during the DREZ lesioning and experienced postoperative ataxia and weakness in the legs despite the absence of a SSEP event in the lower extremities. Conclusion: Significant events on IONM were common during DREZ lesioning for brachial plexus avulsion pain and were closely related to the occurrence of postoperative neurological deficits.
Stereotact Funct Neurosurg 2017;95:330-340

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The Relationship of Electrophysiologic Subthalamic Nucleus Length as a Predictor of Outcomes in Deep Brain Stimulation for Parkinson Disease

Background: Intraoperative measurement of subthalamic nucleus (STN) width through microelectrode recording (MER) is a common proxy for optimal electrode location during deep brain stimulation (DBS) surgery for Parkinson disease. We assessed whether the MER-determined STN width is a predictor of postoperative Unified Parkinson Disease Rating Scale (UPDRS) improvement. Methods: Records were reviewed for patients who underwent single-sided STN DBS placement for Parkinson disease between 2005 and 2010 at the UAB Medical Center. Reviews of preoperative and 3-month postoperative UPDRS part III, intraoperative MER records, and postoperative MRI scans were conducted. Results: The final cohort consisted of 73 patients (mean age 59 ± 9.7 years, length of disease 13 ± 9.7 years). STN widths were defined as depths associated with increased background activity and motor-driven, spiking action potentials on MER. The mean contralateral UPDRS improvement was 58% (± 24). The mean STN width was 5.1 mm (± 1.6, min = 0.0, max = 8.7). No significant relationship between STN width and UPDRS improvement was found, with and without AC-PC normalization (R²Conclusion: This analysis raises questions about seeking the maximal electrophysiological width of STN as a proxy for optimal outcome in DBS for PD. We suggest this strategy for DBS placement in Parkinson disease be subject to more robust prospective investigation.
Stereotact Funct Neurosurg 2017;95:341-347

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Scholar : These new articles for Pediatric Hematology and Oncology are available online

The online platform for Taylor & Francis Online content New for Pediatric Hematology and Oncology and online now on Taylor & Francis Online: Original Articles Persistent positive metaiodobenzylguanidine scans after autologous peripheral blood stem cell transplantation may indicate maturation of stage 4 neuroblastoma Yasuhiro Okamoto MD, Yuichi Kodama MD, PhD, Takuro Nishikawa MD, PhD, Almitra Rindiarti MD, Takayuki Tanabe MD, Shunsuke Nakagawa MD, Takako Yoshioka MD, PhD, Koji Takumi MD, PhD, Tatsuru Kaji MD, PhD & Yoshifumi Kawano MD, PhD Pages: 1-8 | DOI: 10.1080/08880018.2017.1348414 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

lncRNAs HIF1A-AS2 facilitates the up-regulation of HIF-1α by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia

Publication date: December 2017
Source:Biomedicine & Pharmacotherapy, Volume 96
Author(s): Lingjuan Li, Mingyue Wang, Zhujun Mei, Wenfeng Cao, Yun Yang, Yanmei Wang, An Wen
Angiogenesis serves as an important protective mechanism against ischemic stroke, because angiogenesis promotes the generation of collateral circulation and consequently improves the blood supply to cerebral infraction areas. Long noncoding RNAs (lncRNAs), which can act as a competing endogenous RNA, mediate protein-coding gene expression by sponging miRNA. Based on previous studies, the present study hypothesized that lncRNAs HIF1A-AS2 by sponging to miR-153-3p might regulate expression of HIF-1α and its down-stream targets, thereby influencing angiogenesis in hypoxia. Permanent middle cerebral artery occlusion (pMCAO) model was established in SD rats to explore the association between angiogenesis and expression profiles of miR-153-3p and HIF-1α in infraction areas. The effect of HIF1A-AS2 on angiogenesis was investigated in an in vitro study by using human umbilical vein endothelial cells (HUVECs). Results showed that angiogenesis was induced during pMCAO. pMCAO decreased miR-153-3p RNA level in infraction areas, but increased protein levels of HIF-1α, VEGFA and Notch1. HIF1A-AS2 was up-regulated in HUVECs in hypoxia. Luciferase reporter assay indicated that HIF1A-AS2 serves as a 'sponge' to miR-153-3p, which decreased the post-transcriptional silencing of HIF-1α by miR-153-3p. This function of HIF1A-AS2 facilitated the activation of HIF-1α/VEGFA/Notch1 cascades, by which HUVECs viability, migration ability and tube formation were promoted. These results suggest an enhanced angiogenesis in HUVECs. In short, HIF1A-AS2 facilitates the up-regulation of HIF-1α by sponging to miR-153-3p, whereby promoting angiogenesis in HUVECs in hypoxia. The present study revealed an important mechanism for understanding angiogenesis in hypoxia, thus laid theoretical basis for developing new strategy for the treatment of ischemic stroke.



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MicroRNA-29a inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes by repressing STAT3

Publication date: December 2017
Source:Biomedicine & Pharmacotherapy, Volume 96
Author(s): Jinxiang Liu, Dan Fei, Jie Xing, Juan Du
Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) with aberrant expression of microRNA (miRNA) have been reported to be involved in the initiation, progression, and perpetuation of rheumatoid arthritis (RA). In this study, we explored the biological function and underlying mechanism of microRNA-29a (miR-29a) in cultured RA-FLS from RA patients. The expression of miR-29a in serum, synovial tissues, and FLS from RA patients and health donors was detected by real-time quantitative RT-PCR (qRT-PCR). The effects of miR-29a on cell proliferation, apoptosis, and inflammatory cytokine levels in RA-FLS were also determined using Counting Assay Kit-8 (CCK-8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA) respectively. Luciferase reporter assay was carried out to identify the target genes of miR-29a. We observed that expression of miR-29a was markedly downregulated in serum, synovial tissues and FLS of RA patients. miR-29a overexpression in RA-FLS significantly inhibited proliferation, promoted apoptosis, and suppressed expression of inflammatory cytokines. Signal transducer and activator of transcription 3 (STAT3) was identified to be a direct target of miR-29a in RA-FLS. miR-29a overexpression suppressed the expression of STAT3, as well as phosphorylated STAT3(p-STAT3) and its downstream targets protein (Cyclin D1 and Bcl-2). In addition, the levels of miR-29a were inversely correlated with that of STAT3 in synovial tissues. Rescue experiments showed that overexpression of STAT3 effectively reversed the effect of miR-29a on proliferation and apoptosis in RA-FLS. These data indicate that miR-29a inhibits proliferation and induces apoptosis in RA-FLS by targeting STAT3, suggesting that promoting miR-29a expression may yield therapeutic benefits in the treatment of RA.



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Study of the non-clinical healing activities of the extract and gel of Portulaca pilosa L. in skin wounds in wistar rats: A preliminary study

Publication date: December 2017
Source:Biomedicine & Pharmacotherapy, Volume 96
Author(s): Albenise Santana Alves Barros, Helison Oliveira Carvalho, Igor Victor Ferreira dos Santos, Talisson Taglialegna, Tafnis Ingret dos Santos Sampaio, Jonatas Lobato Duarte, Caio Pinho Fernandes, José Carlos Tavares Carvalho
IntroductionPortulaca pilosa L., belonging to the family Portulacaceae, is a common herbaceous plant in the Americas and in the Amazon, is popularly known as love-grown and is traditionally used as an aid in the treatment of burns, buds, insect bites and wound healing. This study aims to evaluate the non-clinical topical healing activity of the P. pilosa gel (GPP) and the propyleneglycol extract of P. pilosa (EPP) in Wistar rats.MethodsFor the healing activity, wistar rats were divided into the following groups: negative control (GVE – vehicle, 150mg/kg), positive control (Fibrinase^®- FIB, 100U/kg), Portulaca pilosa gel 10%, (GPP, 150mg/kg), and propylenglycollic extract of Portulaca pilosa (EPP, 150 mg/kg), which were submitted to a surgical procedure to obtain the wounds, and were treated topically for 7days. After treatment, the treated area was removed and a histopathological analysis was performed.ResultsThe EPP when analyzed in HPLC was able to identify the presence of gallic acid. EPP significantly modulated the tissue inflammatory response, presenting low number of inflammatory cells in the histopathological study. Treatment with EPP and GPP significantly stimulated angiogenesis and this response was superior to the fibrinase^® group. Treatment with EPP and GPP significantly stimulated the proliferation of fibroblasts. The groups treated with EPP and GPP presented an organization pattern of the epidermis and dermis better than the control group, with a mild inflammatory process, with fibroblast proliferation and increased formation of collagen fibers.ConclusionThus, from the results obtained it can be suggested that the phytochemical marker of the P. pilosa species for healing activity is gallic acid and, together with the macroscopic and microscopic findings triggered by the topical applications of EPP and GPP, it can be concluded that this plant species has topical healing activity, with great potential for use, since this pharmacological action is associated with a possible topical anti-inflammatory activity.



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Scholar : These new articles for Canadian Society of Forensic Science Journal are available online

The online platform for Taylor & Francis Online content New for Canadian Society of Forensic Science Journal and online now on Taylor & Francis Online: Case Report Forensic ballistics analysis of an unusual/unrifled/homemade firearm in the absence of the action Gautam N. Ghadage & Ravindra K. Jagtap Pages: 1-6 | DOI: 10.1080/00085030.2017.1379704 Original Articles Practical use of commercially available compressed (dry gas) alcohol standards Micheal Rosland, Jacqueline Montpetit & Verna Mendes Pages: 1-11 | DOI: 10.1080/00085030.2017.1379245 Review Article Les paramètres clés de l'interprétation des fibres textiles en sciences criminelles. Partie I: Occurrence et bruit de fond Michael Schnegg , Ray Palmer & Genevieve Massonnet Pages: 1-25 | DOI: 10.1080/00085030.2017.1379683 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

MECHANISMS IN ENDOCRINOLOGY: Maternal thyroid dysfunction during pregnancy and behavioural and psychiatric disorders of children: a systematic review

Background

Maternal thyroid dysfunction during pregnancy may lead to persistent neurodevelopmental disorders in the offspring appearing in later life. This study aimed to review the available evidence concerning the relationship between maternal thyroid status during pregnancy and offspring behavioural and psychiatric disorders.

Methods

Systematic electronic database searches were conducted using PubMed, Embase, PsycNET, Scopus, Google Scholar and Cochrane library. Studies including gestational thyroid dysfunction as the exposure and offspring behavioural and psychiatric disorders as the outcome were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed and, after thorough screening by two independent reviewers, 13 articles remained eligible for inclusion in this study.

Results

Indicators of maternal thyroid dysfunction, including low and high thyroid hormone level and autoimmune thyroiditis, during early pregnancy, were found to be associated with several offspring behavioural and psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), autism, pervasive developmental problems, externalising behaviour, in addition to epilepsy and seizure. The majority of associations were found with low maternal thyroid hormone level.

Conclusion

Maternal thyroid function during pregnancy, particularly hypothyroidism, is associated with behavioural and psychiatric disorders in children. Further studies are needed with a capacity to adjust for a fuller range of confounding factors.

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MANAGEMENT OF ENDOCRINE DISEASE: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects

The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce the endogenous hormonal production and the monitoring of AI treatment may be a challenge for the lack of reliable clinical and biochemical markers. Consequently, several AI patients are frequently exposed to relative glucocorticoid excess potentially leading to develop chronic complications, such as diabetes mellitus, dyslipidemia, hypertension and fragility fractures with consequent impaired QoL and increased mortality risk. This review deals with the pathophysiological and clinical aspects concerning the over-replacement therapy of primary and secondary AI.

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Adrenal Cushings syndrome during pregnancy

Cushing syndrome (CS) during pregnancy is a rare condition with only a few cases reported in the literature. Misdiagnosis of CS is common because of overlapping features like fatigue, weight gain, striae and emotional changes that can occur during normal pregnancy. Changes in maternal hormones and their binding proteins complicate assessment of glucocorticoid hormone levels during gestation. CS during pregnancy is most frequently due to an adrenal adenoma and to a lesser degree to adrenocorticotropic hormone (ACTH) hypersecretion by a pituitary adenoma. Furthermore, aberrant expression of luteinizing hormone (LH) receptors in the adrenal cortex has been suggested to be involved in the pathogenesis of adrenal CS during pregnancy. We report three pregnant women with ACTH-independent Cushing's syndrome and an adrenal tumor. After uncomplicated delivery, patient 1 underwent in vivo testing for aberrant hormone receptor expression by the adenoma. Cortisol responses were found after administration of luteinizing hormone-releasing hormone (LHRH), human chorionic gonadotropin (hCG), glucagon, vasopressin and a standard mixed meal. All patients were treated with laparoscopic adrenalectomy. Adrenal tumor tissue of two patients showed positive immunohistochemical staining of LH receptors. Considering the cortisol responses to LHRH and hCG, and the development of CS during pregnancy in these patients, it is likely that ACTH-independent hypercortisolism was induced by the pregnancy-associated rise in hCG levels that activated aberrantly expressed LH receptors in the adrenal adenoma. Remarkably, adrenal adenomas may simultaneously express multiple aberrant receptors and individual ligands may play a role in the regulation of cortisol production in CS during pregnancy.

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MANAGEMENT OF ENDOCRINE DISEASE: Flushing: current concepts

Objective

Flushing can be defined as a sensation of warmth accompanied by erythema that most commonly is seen on the face and which occurs in episodic attacks. Such a problem can be clinically problematic, since many conditions and drugs can be related to flushing, and while often there appears to be no underlying organic disease, it is important to exclude disorders since they may be life-threatening conditions.

Design and methods

We performed a search in MEDLINE using the terms 'flushing' in combination with 'carcinoid syndrome', 'pheochromocytoma', 'mastocytosis', 'menopausal hot flush' and 'treatment'. European and American guidelines relating to neuroendocrine tumours, mastocytosis and menopause were reviewed.

Results

In this review, we discuss the main causes of flushing and propose an algorithm based on pathogenesis, which can be used to guide the clinical evaluation process. We also review recent significant developments in the assessment and treatment of the carcinoid syndrome and menopausal hot flushes, which should guide the clinical practice regarding this common but sometimes confusing condition.

Conclusions

When evaluating flushing, a precise systematic approach is needed to exclude potentially serious underlying causes, although despite this, the cause of the disorder is not always found. If symptoms are not progressive, the patient should be advised about its apparently benign nature in order to avoid unnecessary studies or initiating treatments of minimal benefit.

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A syndromic extreme insulin resistance caused by biallelic POC1A mutations in exon 10

POC1A encodes a protein with a role in centriole assembly and stability, and in ciliogenesis. Biallelic loss-of-function mutations affecting POC1A cause SOFT syndrome, an ultra-rare condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis. Using exome sequencing, we identified a homozygous frameshift mutation (c.1047_1048dupC; p.G337Rfs*25) in a patient presenting with short stature, facial hirsutism, alopecia, dyslipidemia and extreme insulin resistance. The truncating variant affected exon 10, which is retained in only two of the three POC1A-mature RNAs, due to alternative processing of the transcript. Clinical discrepancies with SOFT syndrome support the hypothesis that POC1A mutations affecting exon 10 are associated with a distinct condition, corroborating a previous hypothesis based on a similar case. Furthermore, this report provides an additional example of a genetic condition presenting with clinical heterogeneity due to alternative transcript processing. In conclusion, POC1A mutations in exon 10 should be taken into account in patients with extreme insulin resistance and short stature.

http://ift.tt/2kpeYTH

Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted?

When newborn screening (NBS) for congenital hypothyroidism (CH) using thyroid-stimulating hormone (TSH) as a primary screening test was introduced, typical TSH screening cutoffs were 20–50 U/L of whole blood. Over the years, lowering of TSH cutoffs has contributed to an increased prevalence of detected CH. However, a consensus on the benefit deriving from lowering TSH cutoffs at screening is lacking. The present paper outlines arguments both for and against the lowering of TSH cutoffs at NBS. It includes a review of recently published evidence from Australia, Belgium and Italy. A section focused on economic implications of lowering TSH cutoffs is also provided. One issue that bears further examination is the extent to which mild iodine deficiency at the population level might affect the association of neonatal TSH values with cognitive and developmental outcomes. A debate on TSH cutoffs provides the opportunity to reflect on how to make NBS for CH more effective and to guarantee optimum neurocognitive development and a good quality of life to babies with mild as well as with severe CH. All authors of this debate article agree on the need to establish optimal TSH cutoffs for screening programs in various settings and to ensure the benefits of screening and access to care for newborns worldwide.

http://ift.tt/2yJA0i1

MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility

Male infertility is most commonly caused by spermatogenetic failure, clinically noted as oligo- or a-zoospermia. Today, in approximately 20% of azoospermic patients, a causal genetic defect can be identified. The most frequent genetic causes of azoospermia (or severe oligozoospermia) are Klinefelter syndrome (47,XXY), structural chromosomal abnormalities and Y-chromosomal microdeletions. Consistent with Ohno's law, the human X chromosome is the most stable of all the chromosomes, but contrary to Ohno's law, the X chromosome is loaded with regions of acquired, rapidly evolving genes, which are of special interest because they are predominantly expressed in the testis. Therefore, it is not surprising that the X chromosome, considered as the female counterpart of the male-associated Y chromosome, may actually play an essential role in male infertility and sperm production. This is supported by the recent description of a significantly increased copy number variation (CNV) burden on both sex chromosomes in infertile men and point mutations in X-chromosomal genes responsible for male infertility. Thus, the X chromosome seems to be frequently affected in infertile male patients. Four principal X-chromosomal aberrations have been identified so far: (1) aneuploidy of the X chromosome as found in Klinefelter syndrome (47,XXY or mosaicism for additional X chromosomes). (2) Translocations involving the X chromosome, e.g. nonsyndromic 46,XX testicular disorders of sex development (XX-male syndrome) or X-autosome translocations. (3) CNVs affecting the X chromosome. (4) Point mutations disrupting X-chromosomal genes. All these are reviewed herein and assessed concerning their importance for the clinical routine diagnostic workup of the infertile male as well as their potential to shape research on spermatogenic failure in the next years.

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