bluuebunny/crossref_metadata_2025 huggingface dataset:
The two-ball bounce problem
Authors: Berdeni Y. , Champneys A. , Szalai R.
Published: June 2015

A popular classroom demonstration is revisited in which a light ball and a much larger heavier ball are vertically aligned and dropped together onto a hard surface. Careful experimental data obtained using a high-speed camera is compared to a lumped-mass Newtonian restitution model. Good macroscopic agreement is found, provided there is sufficient separation between the two balls as they are dropped. An alternative continuum model based on elastic membrane theory is developed to explain the limit in which the balls are initially touching. The model assumes the lower ball deforms to a truncated sphere upon its impact with the floor, exciting an elastic wave which subsequently launches the upper ball like a particle on a trampoline, before the lower ball leaves the ground. A favourable comparison with experimental data is found for the case of negligible initial separation between the balls.
Neural correlates of individual differences in circadian behaviour
Authors: Evans Jennifer A. , Leise Tanya L. , Castanon-Cervantes Oscar , Davidson Alec J.
Published: June 2015

Daily rhythms in mammals are controlled by the circadian system, which is a collection of biological clocks regulated by a central pacemaker within the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Changes in SCN function have pronounced consequences for behaviour and physiology; however, few studies have examined whether individual differences in circadian behaviour reflect changes in SCN function. Here, PERIOD2::LUCIFERASE mice were exposed to a behavioural assay to characterize individual differences in baseline entrainment, rate of re-entrainment and free-running rhythms. SCN slices were then collected for
ex vivo
bioluminescence imaging to gain insight into how the properties of the SCN clock influence individual differences in behavioural rhythms. First, individual differences in the timing of locomotor activity rhythms were positively correlated with the timing of SCN rhythms. Second, slower adjustment during simulated jetlag was associated with a larger degree of phase heterogeneity among SCN neurons. Collectively, these findings highlight the role of the SCN network in determining individual differences in circadian behaviour. Furthermore, these results reveal novel ways that the network organization of the SCN influences plasticity at the behavioural level, and lend insight into potential interventions designed to modulate the rate of resynchronization during transmeridian travel and shift work.
Mechanical morphogenesis and the development of neocortical organisation
Authors: Foubet Ophélie , Toro Roberto
Published: June 2015

The development and evolution of complex neocortical organisations is thought to result from the interaction of genetic and activity-dependent processes. Here we propose that a third type of process – mechanical morphogenesis – may also play an important role. We review recent theoretical and experimental results in non-linear physics showing how homogeneous growth can produce a rich variety of forms, in particular neocortical folding. The mechanical instabilities that produce these forms also induce heterogeneous patterns of stress at the scale of the organ. We review the evidence showing how these stresses can influence cell proliferation, migration and apoptosis, cell differentiation and shape, migration and axonal guidance, and could thus be able to influence regional neocortical identity and connectivity.
Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells
Authors: Wamaitha Sissy E. , del Valle Ignacio , Cho Lily T.Y. , Wei Yingying , Fogarty Norah M.E. , Blakeley Paul , Sherwood Richard I. , Ji Hongkai , Niakan Kathy K.
Published: June 2015

Transcription factor-mediated reprograming is a powerful method to study cell fate changes. In this study, we demonstrate that the transcription factor Gata6 can initiate reprograming of multiple cell types to induced extraembryonic endoderm stem (iXEN) cells. Intriguingly, Gata6 is sufficient to drive iXEN cells from mouse pluripotent cells and differentiated neural cells. Furthermore, GATA6 induction in human embryonic stem (hES) cells also down-regulates pluripotency gene expression and up-regulates extraembryonic endoderm (ExEn) genes, revealing a conserved function in mediating this cell fate switch. Profiling transcriptional changes following Gata6 induction in mES cells reveals step-wise pluripotency factor disengagement, with initial repression of Nanog and Esrrb, then Sox2, and finally Oct4, alongside step-wise activation of ExEn genes. Chromatin immunoprecipitation and subsequent high-throughput sequencing analysis shows Gata6 enrichment near pluripotency and endoderm genes, suggesting that Gata6 functions as both a direct repressor and activator. Together, this demonstrates that Gata6 is a versatile and potent reprograming factor that can act alone to drive a cell fate switch from diverse cell types.
Histone modifications predispose genome regions to breakage and translocation
Authors: Burman Bharat , Zhang Zhuzhu Z. , Pegoraro Gianluca , Lieb Jason D. , Misteli Tom
Published: June 2015

Chromosome translocations are well-established hallmarks of cancer cells and often occur at nonrandom sites in the genome. The molecular features that define recurrent chromosome breakpoints are largely unknown. Using a combination of bioinformatics, biochemical analysis, and cell-based assays, we identify here specific histone modifications as facilitators of chromosome breakage and translocations. We show enrichment of several histone modifications over clinically relevant translocation-prone genome regions. Experimental modulation of histone marks sensitizes genome regions to breakage by endonuclease challenge or irradiation and promotes formation of chromosome translocations of endogenous gene loci. Our results demonstrate that histone modifications predispose genome regions to chromosome breakage and translocations.
Intestinal apical polarity mediates regulation of TORC1 by glucosylceramide in C. elegans
Authors: Zhu Huanhu , Sewell Aileen K. , Han Min
Published: June 2015

TORC1 (target of rapamycin complex 1) plays a central role in regulating growth, development, and behavior in response to nutrient cues. We previously showed that leucine-derived monomethyl branched-chain fatty acids (mmBCFAs) and derived glucosylceramide promote intestinal TORC1 activity for post-embryonic development and foraging behavior in Caenorhabditis elegans. Here we show that clathrin/adaptor protein 1 (AP-1)-dependent intestinal apical membrane polarity and polarity-dependent localization of the vacuolar-type H+-ATPase (V-ATPase) mediate the impact of the lipid pathway on intestinal TORC1 activation. Moreover, NPRL-3 represses mmBCFA-dependent intestinal TORC1 activity at least partly by regulating apical membrane polarity. Our results provide new insights into TORC1 regulation by lipids and membrane polarity in a specific tissue.
Structural basis for allosteric, substrate-dependent stimulation of SIRT1 activity by resveratrol
Authors: Cao Duanfang , Wang Mingzhu , Qiu Xiayang , Liu Dongxiang , Jiang Hualiang , Yang Na , Xu Rui-Ming
Published: June 2015

Sirtuins with an extended N-terminal domain (NTD), represented by yeast Sir2 and human SIRT1, harbor intrinsic mechanisms for regulation of their NAD-dependent deacetylase activities. Elucidation of the regulatory mechanisms is crucial for understanding the biological functions of sirtuins and development of potential therapeutics. In particular, SIRT1 has emerged as an attractive therapeutic target, and the search for SIRT1-activating compounds (STACs) has been actively pursued. However, the effectiveness of a class of reported STACs (represented by resveratrol) as direct SIRT1 activators is under debate due to the complication involving the use of fluorogenic substrates in in vitro assays. Future efforts of SIRT1-based therapeutics necessitate the dissection of the molecular mechanism of SIRT1 stimulation. We solved the structure of SIRT1 in complex with resveratrol and a 7-amino-4-methylcoumarin (AMC)-containing peptide. The structure reveals the presence of three resveratrol molecules, two of which mediate the interaction between the AMC peptide and the NTD of SIRT1. The two NTD-bound resveratrol molecules are principally responsible for promoting tighter binding between SIRT1 and the peptide and the stimulation of SIRT1 activity. The structural information provides valuable insights into regulation of SIRT1 activity and should benefit the development of authentic SIRT1 activators.
Using spatial analyses of bearded vulture movements in southern Africa to inform wind turbine placement
Authors: Reid Tim , Krüger Sonja , Whitfield D. Philip , Amar Arjun
Published: June 2015

Concerns over CO2 emissions during energy generation and its effect on climate change have led to increases in the use of renewables, such as wind energy. However, there are also serious environmental concerns over this type of energy production due to its impacts on bats and birds.

In southern Africa, bearded vultures have declined by >30% during recent decades. They are now regionally critically endangered with only around 100 active pairs remaining. This species is considered vulnerable to collision with wind turbines which are planned within their southern African range.

In this study, we develop habitat use models using data obtained from 21 bearded vultures of different ages fitted with GPS tags from 2009 to 2013. We further refined these models by incorporating flying heights at risk of collision to predict important areas of use that may conflict with wind turbines.

Adult and non‐adult bearded vultures mostly used areas with high elevations and steep and rugged topography in the core area; adults tended to use areas in relatively close proximity to their nest sites, whereas non‐adult birds used areas dispersed over the entire species range and were more likely to fly at risk‐height in areas that were less used by adults. Altitudes of fixes of adults and non‐adults showed that they spent 55% and 66% of their time, respectively, at heights that placed them at risk of collision.

Examining the locations of two proposed wind farms in relation to our model of predicted ‘at risk’ usage suggested poor positioning. Indeed, one of these wind farms was located within the 1% of ‘worst’ (most heavily used) sites for non‐adult bearded vultures suggesting that its current location should be reconsidered to reduce the impact on this vulnerable species.

Synthesis and applications. We demonstrate the value of habitat use models for identifying intensively used areas, in order to greatly reduce conflicts with developments such as wind turbines. This tool is operable at the scale of regional and national development plans informed by the habitat use of potentially vulnerable species. Such models should provide important supplementary assessments of site‐specific development proposals.
Comparison of current practice and best practice guidelines for the nutritional management of patients with liver cirrhosis: An Australian survey of dietitians in clinical practice
Authors: Nguyen Trang
Published: June 2015

Aim

Malnutrition is common in patients with chronic liver disease and is recognised as a prognostic factor with evidence suggesting that sufficient nutritional support can improve outcomes. However, malnutrition in this patient population continues to be underdiagnosed and managed in clinical practice. This paper outlines a study aimed to determine current practice among dietitians, compares this with best practice guidelines and identifies barriers to achieving best practice.

Methods

This study aims to involved an anonymous online survey questionnaire targeted at dietitians with at least 12 months of experience working with patients with liver cirrhosis.

Results

A total of 41 completed surveys were received and analysed. Results showed that the majority (85%) of respondents were using the European Society of Clinical Nutrition and Metabolism guidelines. Over 85% of surveyed dietitians reported that they were currently recommending high‐energy and high‐protein diets to their patients. Methods used to calculate dietary requirements varied, with some respondents using actual weight and others using dry weight. There was also variation in nutrition assessment tool used among surveyed respondents. Thirty‐six per cent of respondents reported that nasogastric feeding always or often commenced when recommended. The most commonly reported barrier to achieving best practice was patient compliance.

Conclusions

From the study, it appears that most dietitians are consistently recommending high‐energy and protein intake. However, there is significant variation in practice for weights used in calculating nutritional requirements, assessing nutritional status and nasogastric tube use for nutrition support.
Viral activities and life cycles in deep subseafloor sediments
Authors: Engelhardt Tim , Orsi William D. , Jørgensen Bo Barker
Published: June 2015

Viruses are highly abundant in marine subsurface sediments and can even exceed the number of prokaryotes. However, their activity and quantitative impact on microbial populations are still poorly understood. Here, we use gene expression data from published continental margin subseafloor metatranscriptomes to qualitatively assess viral diversity and activity in sediments up to 159 metres below seafloor (mbsf). Mining of the metatranscriptomic data revealed 4651 representative viral homologues (RVHs), representing 2.2% of all metatranscriptome sequence reads, which have close translated homology (average 77%, range 60–97% amino acid identity) to viral proteins. Archaea‐infecting RVHs are exclusively detected in the upper 30 mbsf, whereas RVHs for filamentous inoviruses predominate in the deepest sediment layers. RVHs indicative of lysogenic phage–host interactions and lytic activity, notably cell lysis, are detected at all analysed depths and suggest a dynamic virus–host association in the marine deep biosphere studied here. Ongoing lytic viral activity is further indicated by the expression of clustered, regularly interspaced, short palindromic repeat‐associated cascade genes involved in cellular defence against viral attacks. The data indicate the activity of viruses in subsurface sediment of the Peruvian margin and suggest that viruses indeed cause cell mortality and may play an important role in the turnover of subseafloor microbial biomass.
Micro ribonucleic acid (RNA)‐101 inhibits cell proliferation and invasion of lung cancer by regulating cyclooxygenase‐2
Authors: Lv Peng , Zhang Peng , Li Xin , Chen Yuan
Published: June 2015

Background

Micro ribonucleic acid (miR‐101) can regulate the expression of cyclooxygenase‐2 (COX‐2) and participate in the pathogenesis of malignant tumors. This study investigates the effects of miRNA‐101 and COX‐2 in lung cancer and the impact of miR‐101 on the proliferation and invasion of human lung cancer A549 cell line.

Methods

The expression of miR‐101 in 20 separate lung cancer tissues was detected by real time polymerase chain reaction; COX‐2 expression was also detected. A549 cells were transfected with miR‐101 or negative control oligonucleotide duplex mimic (miR‐NC). In vivo tumorigenesis abilities were detected in localized human lung cancer xeno‐transplant models in BALB/c nude mice.

Results

MiR‐101 expression was significantly lower and the level of COX‐2 significantly higher in lung cancer tissues than in adjacent parenchyma (2.918 ± 1.006 vs. 5.953 ± 1.976, P = 0.001; 0.887 ± 0.260 vs. 0.355 ± 0.156, P = 0.001, respectively). Correlation analysis revealed that miR‐101 negatively correlated with COX‐2 in lung cancer tissues (R = −0.596, P = 0.002). Compared with A549‐miR‐NC cells, the expression of COX‐2 was significantly decreased in A549 cells transfected with miR‐101 (P < 0.001). The proliferation of A549 cells was markedly inhibited after transfection of miR‐101. The in vivo tumor growth of A549 cells transfected with miR‐101 was significantly slower than wide type A549 cells.

Conclusion

MiR‐101 expression is decreased in lung cancer, inducing an increase in COX‐2 level. Enforced expression of miR‐101 can remarkably reduce the cell proliferation and invasion ability of lung cancer cells.
Late Gadolinium Enhancement on Cardiac MRI Correlates with QT Dynamicity Represented by QT/RR Relationship in Patients with Ventricular Arrhythmias
Authors: Sakamoto Naka , Sato Nobuyuki , Talib Ahmed Karim , Sugiyama Eitaro , Minoshima Akiho , Tanabe Yasuko , Fujino Takayuki , Takeuchi Toshiharu , Akasaka Kazumi , Saijo Yasuaki , Kawamura Yuichiro , Hasebe Naoyuki
Published: June 2015

Background

The distribution of late gadolinium enhancement (LGE) on the cardiac MRI (CMR) indicates myocardial fibrosis and provides information of possible reentry substrates. QT dynamicity reflecting repolarization abnormalities has gained attention as a potential prognostic predictive factor.

Objective

To clarify the correlation between the LGE distribution on CMR and QT dynamicity represented by the QT/RR relationship.

Methods

CMR and QT/RR analyses using Holter monitoring were performed in 34 patients (24 males, 60 ± 11 years) with ventricular tachycardia (VT) and/or ventricular fibrillation (VF). The LGE on CMR was scored using a 4‐point score in 17 left ventricular segments. The sum of the LGE scores was calculated for each patient. The QT/RR slope and daytime/nighttime QT/RR ratio (day/night ratio) were calculated. The correlation between the slope or the day/night QT/RR ratio and late enhancement findings was analyzed.

Results

All patients were divided into 23 LGE positive (LGE(+)) and 11 LGE negative (LGE(−)) patients. The slopes of the QTe/RR and QTa /RR were significantly steeper in the LGE(+) than in LGE(−) patients (0.21 ± 0.03 vs 0.13 ± 0.02; P < 0.001, 0.19 ± 0.03 vs 0.13 ± 0.02; P < 0.001, respectively), and both slopes were significantly correlated with the total LGE scores (r = 0.83, P < 0.001; r = 0.71, P < 0.001, respectively). In the LGE(+) patients, the QTe day/night (1.37 ± 0.38 vs 0.91 ± 0.33; P = 0.002) and QTa day/night ratios (1.33 ± 0.26 vs 1.06 ± 0.30; P = 0.011) were significantly greater than those in the LGE(−) patients.

Conclusion

The LGE distribution was closely related to the QT dynamicity, suggesting that a combination of these markers can be a powerful tool for understanding the background pathophysiology.
Coexistence of Andersen–Tawil Syndrome with Polymorphisms in hERG1 Gene (K897T) and SCN5A Gene (H558R) in One Family
Authors: Jagodzińska Michalina , Szperl Małgorzata , Ponińska Joanna , Kosiec Agnieszka , Gajda Robert , Kukla Piotr , Biernacka Elżbieta Katarzyna
Published: June 2015

Background

Andersen–Tawil Syndrome (ATS) is a channelopathy caused by mutations in KCNJ2 gene. It is characterized by symptoms of ventricular arrhythmias, periodic paralysis or muscle weakness, and dysmorphic features. ATS can present with the triad of symptoms, any combination or none of them. Risk factors for dangerous arrhythmias are unknown. The study assessed the impact of K897T polymorphism in hERG1 gene and H558R polymorphism in SCN5A gene coexisting with R218Q mutation in KCNJ2 in one family on clinical manifestation.

Methods

Family members underwent clinical assessment, ECG and genotyping. Holter monitoring was performed in mutation carriers and additionally in one family member with no mutation, but with K897T polymorphism.

Results

Proband with ATS mutation, K897T and H558R polymorphisms and proband's sister with ATS mutation and K897T polymorphism presented following symptoms: loss of consciousness, bidirectional and polymorphic ventricular tachycardia and about 5000 ventricular extrasystoles. Symptoms presented by the member with only the ATS mutation and by member with ATS mutation and H558R polymorphism were not as severe. U wave appeared in all examined family members regardless of the mutation presence. Studied individuals with ATS mutation had the T‐peak–U‐peak interval longer than 200 ms. In all ATS mutation carriers it was longer than in family members with no mutation. T‐peak–T‐end interval was the longest (>120 ms) in members with coexisting mutation and K897T polymorphism.

Conclusion

ATS severity possibly depends on other genes’ polymorphisms. In the presented family, it could depend on the presence of K897T polymorphism in hERG1.
The Effect of Diuresis on the Paced QRS Complexes in Pacing‐Dependent Patients with Heart Failure
Authors: Sheng Fuqiang , Chen Bin , He Maorong , Zhang Meilin , Shen Guoying , Zhao Xiaowei
Published: June 2015

Background

Augmentation of the amplitude of QRS complexes with diuretic therapy for patients with congestive heart failure has been well documented. However, the effect of diuresis on the paced QRS complexes in pacing‐dependent patients with heart failure is scarce.

Objective

To investigate the effect of diuresis on the paced QRS complexes in pacing‐dependent patients with heart failure.

Method

Thrity‐two consecutive pacing‐dependent patients with heart failure were enrolled in this study. Before and after diuresis, the sums of paced QRS amplitude of leads I+II (ΣpQRSI+II), six limb leads (ΣpQRS6L), leads V1–V3 (ΣpQRSV1‐V3), leads V4–V6 (ΣpQRSV4‐V6), leads V1–V6 (ΣpQRSV1‐V6), and lead aVR (pQRSaVR), paced QRS duration (pQRSd), paced QT intervals (pQT) and the body weight of each patient were measured, then the % changes (Δ%) in paced electrocardiogram (ECG) variables and the Δ% in body weight were evaluated.

Results

Compared with before diuresis, paced ECG variables significantly increased and body weight significantly decreased after diuresis, Δ% in paced QRS amplitude(s) in all ECG variables (ΣpQRSI+II, ΣpQRS6L, ΣpQRSV1‐V3, ΣpQRSV4‐V6, ΣpQRSV1‐V6, and pQRSaVR) correlated well with Δ% in body weight (r = 0.416, r = 0.849, r = 0.901, r = 0.371, r = 0.837, r = 0.619, and P = 0.018, P < 0.001, P < 0.001, P = 0.037, P < 0.001, P < 0.001), while there was no correlation between Δ% in pQRSd and pQT and Δ% in body weight.

Conclusions

The changes in amplitude of paced QRS complexes may be useful for the monitoring of therapy of pacing‐dependent patients with heart failure.
Anti‐VEGF treatment in branch retinal vein occlusion: a real‐world experience over 4 years
Authors: Rezar Sandra , Eibenberger Katharina , Bühl Wolf , Georgopoulos Michael , Schmidt‐Erfurth Ursula , Sacu Stefan ,   Macula Study Group Vienna
Published: June 2015

Purpose

To determine long‐term outcome of intraocular antagonism of vascular endothelial growth factor (VEGF) in macular oedema (ME) secondary to branch retinal vein occlusion (BRVO).

Methods

A total of 28 consecutive patients were treated with either intravitreal bevacizumab (IVB) or intravitreal ranibizumab (IVR) in the first series and were evaluated after a mean follow‐up of 5 years for their functional and anatomical outcome.

Results

Time between onset of macular oedema and initial treatment was 5.2 ± 0.4/0.1 ± 0.1 (IVB/IVR) months. A mean of 4 intravitreal injections were given per patients in the first 6 months. In months 7–12 intravitreal injections decreased to 2 and further decreased in the second year (months 13–18: 1.14; months 19–24: 0.5) and third year (months 25–30: 0.4; months 31–36: 0.2). After the fourth year, only two of the 28 patients received further treatment. Average visual acuity (VA) increased by 16 letters after 1 year (p < 0.01) and although not statistically significantly, by a mean of 5 letters (p = 0.3) at long‐term evaluation (IVB‐group). However, after mean of 5 years, central retinal sensitivity (CRS) improved by 3.6 dB (p = 0.01) and central retinal thickness (CRT) decreased by 161 μm (p = 0.02). In the IVR‐group, VA and CRS increased significantly (31 letters and respectively 4.4 dB, p < 0.001) and CRT decreased by 229 μm (p < 0.001) after long‐term follow‐up. Final functional results were significantly better in patients with treatment initiation <3 months (79 versus 55 letters, p = 0.01). Microvascular abnormalities were detected in 88% (21 of 24 patients), hyperfluorescence in 42% (10 of 24 patients) on wide‐field fluorescein angiography in both groups.

Conclusions

Inhibition of VEGF provides substantial long‐term benefits for patients with ME secondary to BRVO. Early treatment with anti‐VEGF agents and extended therapeutic surveillance was associated with improved visual recovery.
Virus ecology of fluvial systems: a blank spot on the map?
Authors: Peduzzi Peter
Published: June 2015

The ecology of viruses has been studied only in a limited number of rivers and streams. In light of a recent re‐appraisal of the global fluvial surface area, issues such as abundance and production, host mortality and the influence of suspended particles and biofilms are addressed. Viral life cycles, potential impacts of viruses on water biochemistry and carbon flow, and viral diversity are considered. Variability in trophic levels along with the heterogeneous nature and hydrological dynamics of fluvial environments suggest a prevailingly physical control of virus‐related processes under lotic conditions and more biological control under lentic conditions. Viral lysis likely contributes to a pool of rapidly cycling carbon in environments typically characterized by high proportions of recalcitrant terrestrial carbon. On average, 33.6% (equalling 0.605 Pg C year−1) of the globally respired carbon from fluvial systems may pass through a viral loop. Virus distribution and the proportion of organic material in horizontal transport versus processes in retention zones remain to be determined in detail. The need for up‐scaling the contribution of virus‐related processes in fluvial systems is of global relevance. Further, the role of climate change and the effect of anthropogenic alterations of fluvial systems on viruses require attention. The identification of these considerable knowledge gaps should foster future research efforts.
Site‐specific Substitutions Eliminate Aggregation Properties of Hemopressin
Authors: Song Benben , Kibler Patrick D. , Endsley Aaron N. , Nayak Surendra K. , Galande Amit K. , Jambunathan Kalyani
Published: June 2015

Hemopressin is a naturally occurring and therapeutically relevant peptide with applications in hypertension, pain, addiction, and obesity. We had previously demonstrated that hemopressin converts into amyloid‐like fibrils under aqueous conditions. However, the amino acid residues that modulate the aggregation propensity of hemopressin were not identified. In this study, we designed and synthesized 25 different analogs of hemopressin and analyzed their aggregation properties using the principle of dynamic light scattering. As a result, we were able to identify four conservative changes in the peptide sequence (Val2→DVal2, Asn3→Gln3, Leu7→Npg7, and C‐OH→C‐NH2) that minimize aggregation propensity of hemopressin. The results indicate that hemopressin aggregation is cooperative in nature and involves contribution from multiple amino acids within the peptide chain. The analogs and the corresponding aggregation propensity data reported in this study would be useful for researchers investigating therapeutic properties of hemopressin, which have been hampered due to the tendency of hemopressin to aggregate in aqueous solutions.
Synthesis, Characterization, and Anticancer Activity of Novel Lipophilic Emodin Cationic Derivatives
Authors: Yang Xiang , Zhao Wenna , Hu Xiufang , Hao Xianxiao , Hong Fang , Wang Jianlong , Xiang Liping , Zhu Yunhui , Yuan Yaofeng , Ho Rodney J.Y. , Wang Wenfeng , Shao Jingwei
Published: June 2015

Seventeen novel emodin derivatives were synthesized, and the structures were confirmed by IR, H NMR, MS, and elemental analysis. The cytotoxic activity of the derivatives was evaluated against A375, BGC‐823, HepG2, and HELF cells by MTT assay. Compound 9a with highest potency and low toxicity was selected to further investigate its detailed molecular mechanism. The lead compound 9a induced a loss of the mitochondrial transmembrane potential (▵Ψm), an increase in reactive oxygen species (ROS), release of cytochrome c and activation of caspase‐3 and caspase‐9. In addition, the confocal study showed that emodin derivative 9a (containing asymmetric hydrocarbon tails) was mainly localized in mitochondria, demonstrating a key role of the mitochondria‐mediated apoptosis pathway in cancer cells. Taken together, the results demonstrate that embodin derivative 9a preferentially regulates the ROS‐mediated apoptosis in A375 cells through the induction of cytochrome c expression and activation of caspase‐3 and caspase‐9 proteins.
Combined Treatment Effects Using Bioactive‐Coated Implants and Ceramic Granulate in a Rabbit Femoral Condyle Model
Authors: Preethanath Reghunathan S. , Rajesh Palangadan , Varma Harikrishna , Anil Sukumaran , Jansen John A. , van den Beucken Jeroen J.J.P.
Published: June 2015

Background

Resolution of peri‐implant defects resulting from implant placement in the freshly extracted site demands for a bone graft substitute that stimulates bone regeneration and hence facilitates implant integration. In view of this, the addition of silica to hydroxyapatite (HASi) could enhance the bioactive behavior of ceramic materials and implant surfaces coated with bioactive ceramics might benefit the interaction between bone and implant.

Purpose

To evaluate the bone response to implants coated with hydroxyapatite‐silica (HASi) or hydroxyapatite (HA) and either or not combined with HASi and HA ceramic bone substitute particles, respectively, on bone‐to‐implant contact (BIC) and bone formation using a rabbit femoral condyle implant model with a gap design.

Material and Methods

A total of 32 custom‐made, titanium implants (Ti: diameter 5 mm, length 8 mm) with two‐sided gaps were fabricated and coated with either HASi or HA using pulsed laser deposition (PLD). The implants were installed bilaterally in the femoral condyles of 16 New Zealand white rabbits. According to a randomization protocol, one gap of HASi‐coated and HA‐coated implants was filled with HASi particles and HA particles, respectively, and the other gap was left empty. After an implantation period of 8 weeks, the retrieved specimens were analyzed via histology and histomorphometry (i.e., bone to implant contact [BIC] and bone volume [BV]).

Results

The BIC and BV around the implants were analysed for HASi‐ and HA‐coated implants with and without the use of HASi and HA bone substitute material. Comparison of HASi‐ and HA‐coated implants showed similar BIC for HASi‐ (55.7 + 11.0) and HA‐coated implants (50.3 + 19.7). When coated implants were combined with bone substitute materials, HASi‐coated and particle‐filled implants showed higher BIC (64.3 ± 6.8%) compared with HA‐coated and HA‐filled implants (54.5 ± 10.9%). Similarly, the BV within the region of interest showed significantly higher values for the HASi‐coated and HASi‐filled implants (21.1 ± 1.7%) compared with HA‐coated and HA‐filled implants (12.8 ± 4.9%).

Conclusions and Clinical Implications

Within the limitations of this study, it can be concluded that silicon substitution in HA favors bone regeneration compared with HA, especially when used as bone substitute material. Further studies using different healing periods will elucidate the resorption pattern of HASi granules in comparison with HA.
Chromium allergy and dermatitis: prevalence and main findings
Authors: Bregnbak David , Johansen Jeanne D. , Jellesen Morten S. , Zachariae Claus , Menné Torkil , Thyssen Jacob P.
Published: June 2015

The history of chromium as an allergen goes back more than a century, and includes an interventional success with national legislation that led to significant changes in the epidemiology of chromium allergy in construction workers. The 2015 EU Leather Regulation once again put a focus on chromium allergy, emphasizing that the investigation of chromium allergy is still far from complete. Our review article on chromium focuses on the allergen's chemical properties, its potential exposure sources, and the allergen's interaction with the skin, and also provides an overview of the regulations, and analyses the epidemiological pattern between nations and across continents. We provide an update on the allergen from a dermatological point of view, and conclude that much still remains to be discovered about the allergen, and that continued surveillance of exposure sources and prevalence rates is necessary.
SPECIAL‐INTEREST SPILLOVERS AND TOBACCO TAXATION
Authors: Hoffer Adam J.
Published: June 2015

This study explores the effects tobacco special interest has had on cigarette tax rates. Using a spatial econometric model to control for tax competition and the endogeneity present in state tax rates, this study finds that tobacco special interest has played a significant role in influencing state cigarette tax rates. Pounds of tobacco grown in a state and tobacco industry campaign contributions are associated with lower cigarette tax rates. The empirical results show that the magnitude of the special‐interest effect can be two to five times as large when the spatial spillover effects are included. (JEL C23, H71, H73)
The significance of extracellular mucin in breast fine needle aspiration specimens
Authors: Shield P. W. , Ribu D. L. , Cominos D.
Published: June 2015

Objective

To determine if all breast fine needle aspiration (FNA) specimens with abundant extracellular mucin require excisional biopsy.

Methods

Fifty cases of breast FNA containing extracellular mucin, reported with a recommendation for biopsy and with histological follow‐up were reviewed. Cellular features were noted, and the cases reclassified ignoring the presence of mucin and then correlated with histological outcome.

Results

Subsequent histology showed benign changes in 20% (10/50), two cases (4%) of atypical ductal hyperplasia (ADH) and 76% (38/50) to be malignant lesions, including three cases of ductal carcinoma in situ (DCIS). When the FNA cases were reviewed disregarding the presence of mucin, 11 cases were reclassified as benign and one case that contained mucin‐like material but no epithelial cells reviewed as non‐diagnostic. All cases of invasive mixed and mucinous carcinoma (MC) would have been reported with a recommendation for histological examination. In addition, the three cases each of fibroadenoma (FA) and a benign mucocoele‐like lesion (MLL) were correctly identified as benign. However, two cases each of DCIS and ADH would have been reported benign with no recommendation for further histology.

Conclusions

Breast FNA specimens with mucinous material may arise from sampling of a range of benign and malignant processes; however, a biopsy should be recommended, even in cases of low cellularity, owing to sampling problems and the frequent co‐occurrence of significant lesions. FNA is highly accurate at predicting carcinoma with mucinous differentiation although it is not possible to reliably predict if the lesion represents pure MC or a mixed carcinoma.
Differentiation syndrome in acute myeloid leukemia after treatment with azacitidine
Authors: Laufer Christin B. , Roberts Owen
Published: June 2015

We report a case report of hyperleukocytosis, fever, hypotension, pulmonary and pericardial effusions, and acute kidney injury during initial treatment with azacitidine in a patient with AML‐MRC. Collectively, the symptomatology resembled differentiation syndrome. Azacitidine has been previously associated with fever, peripheral edema, and hyperleukocytosis, but its side effect profile has never been described as similar to differentiation syndrome. The patient's deteriorating course quickly turned around after treatment with dexamethasone. This potential reaction, and potential treatment, is important for clinicians to be aware of.
Modelling soil salinity across a gilgai landscape by inversion of EM38 and EM31 data
Authors: Huang J. , Mokhtari A. R. , Cohen D. R. , Monteiro Santos F. A. , Triantafilis J.
Published: June 2015

The soil in arid and semi‐arid areas is often markedly saline, which can severely limit agricultural productivity. Increasingly, geophysical methods are being implemented to map the levels and areal extent of soil salinity. One of the most effective methods is electromagnetic (EM) induction with instruments designed to measure apparent soil electrical conductivity (ECa). This study describes the generation of electromagnetic conductivity images (EMCIs) by inverting ECa data obtained with the EM38 and EM31 devices along two closely‐spaced transects by the EM inversion approach in the EM4Soil package. The EM38 ECa data are shown to be a more effective predictor of soil ECe. Calibration equations based on calculated true electrical conductivity (σ) and measured electrical conductivity of a saturated soil‐paste extract (ECe) provide reliable estimates of ECa. The patterns of σ in a test of the method in soil developed over thick alluvium on a clay plain in central New South Wales, Australia, compare favourably with existing pedological mapping; the mounds and depressions of gilgai were strongly differentiated from the more sandy alluvial sediments that characterize prior stream channels. The overall approach is potentially useful for generating a single calibration equation that can be used to predict ECe at various depths in the soil. Improvements in EMCI modelling can also be sought by joint inversion of EM with other geophysical datasets.
Health‐related quality of life in patients with idiopathic normal pressure hydrocephalus
Authors: Junkkari A. , Sintonen H. , Nerg O. , Koivisto A. M. , Roine R. P. , Viinamäki H. , Soininen H. , Jääskeläinen J. E. , Leinonen V.
Published: June 2015

Background and purpose

Factors affecting health‐related quality of life (HRQoL) were explored in patients with idiopathic normal pressure hydrocephalus (iNPH).

Methods

Using the 15D instrument HRQoL was evaluated in 132 patients diagnosed with iNPH by clinical and neuroradiological examinations. The severity of iNPH symptoms was measured with the iNPH grading scale (iNPHGS), depressive symptoms with the Beck Depression Inventory (BDI‐21) and cognitive impairment with the Mini‐Mental State Examination.

Results

The mean (SD) 15D score (on a 0–1 scale) of patients with iNPH was significantly lower than that of an age‐ and gender‐matched sample of the general population [0.718 (0.103) vs. 0.870 (0.106); P < 0.001]. The mean 15D score was lower in iNPH patients with moderate or severe depressive symptoms than in patients without depressive symptoms (P = 0.003). According to stepwise multiple linear regression analysis, a higher total iNPHGS score (b = −0.62, P < 0.001) and a higher BDI‐21 total score (β = −0.201, P = 0.025) predicted a lower 15D score; in combination, these explained 51% of the variance in the 15D score (R2 = 0.506, P < 0.001).

Conclusions

Idiopathic normal pressure hydrocephalus impairs patients’ HRQoL on multiple dimensions, similarly to other chronic diseases. Potentially treatable depressive symptoms contribute greatly to the HRQoL impairment of iNPH patients, but only if they are moderate or severe. The 15D portrayed HRQoL dimensions affected by iNPH in a similar way to broader assessment batteries and thus is a potentially useful tool for treatment evaluation and cost−utility analysis.
The use of radiography for diagnosis of apical infection of equine cheek teeth
Authors: Isgren C. M. , Townsend N. B.
Published: June 2015

Despite recent developments in advanced imaging, radiography remains the most commonly employed imaging modality for investigating apical infection of cheek teeth in horses. Radiographic technique, knowledge of the normal anatomy and horse compliance are paramount for acquiring good quality dental radiographs. Interpretation of subtle pathology can be difficult for even the most experienced radiologist; however, in more chronic cases, identification of dental abnormalities is easier.
Remaining questions in the case for balanced harvesting
Authors: Burgess Matthew G , Diekert Florian K , Jacobsen Nis S , Andersen Ken H , Gaines Steven D
Published: June 2015

Balanced harvesting – harvesting all species and sizes in an ecosystem in proportion to their productivity – is a fisheries management strategy that has been suggested recently to increase yields, while reducing overall ecosystem impact. However, some aspects of balanced harvesting are controversial, including its call for extensive harvesting of juveniles and forage fish. Balanced harvesting also calls for targeting species and size‐classes that are not currently marketable, possibly at a significant economic cost. Some have argued that this cost is outweighed by the ecological benefits of maintaining the ecosystem size and trophic structures and by the benefits of extra yield for food security. There is broad consensus that balanced harvesting would require major changes to fishery management institutions and consumer behaviour, and it is unclear to what extent it is physically possible with current technologies. For this reason, we argue that steps to implement balanced harvesting are difficult to justify until the case for it is more clearly resolved. We outline some of the pivotal questions that must be answered to make a convincing case for or against balanced harvesting, many of which can be answered empirically. In identifying these questions, we hope to offer a constructive path forward in resolving some of the key issues in the balanced harvesting debate.
Does class attendance matter? Results from a second‐year medical school dermatology cohort study
Authors: Eisen Daniel B. , Schupp Clayton W. , Isseroff Rivkah R. , Ibrahimi Omar A. , Ledo Lynda , Armstrong April W.
Published: June 2015

Background

Little is known about the impacts of class attendance and learning preferences on academic performance in dermatology.

Objectives

This study was designed to examine the effects of medical student class attendance and learning preferences on students' academic performance in an introductory dermatology course.

Methods

A total of 101 second‐year medical students enrolled in a required introductory dermatology course were surveyed regarding their learning preferences. Records of class attendance and scores on the final examination were reviewed.

Results

The most frequently cited reason for attending classes was social expectation (96%), whereas the least cited was learning well in a classroom‐type setting (65%). The top reasons cited by students for not attending classes were availability of lectures online (35%), preference for individual study outside the classroom setting (26%), and the inconvenience of traveling to class (24%). Multivariate analysis found no statistically significant relationship between class attendance and performance on the final examination (estimate −0.074, standard error 0.12; P = 0.54) after adjusting for sex, age, Medical College Admission Test (MCAT) score, having children at home, and reason for attending class. Those who prefer to learn by watching online videos scored significantly higher on the final examination (prefer online videos: 87 ± 5.5; neutral: 86 ± 5.9; do not prefer online videos: 82 ± 2.6 [P = 0.049]).

Conclusions

Class attendance was not associated with improved academic performance in a dermatology course. Those who preferred to learn by watching online videos demonstrated a higher level of performance than those who did not prefer to learn this way.
Serum levels of thymus and activation‐regulated chemokine can be used in the clinical evaluation of atopic dermatitis
Authors: Gu Chao‐Ying , Gu Lei , Dou Xia
Published: June 2015

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2‐type cells in lesional skin. Thymus and activation‐regulated chemokine (TARC) is overproduced in AD patients, and its serum levels are significantly higher in individuals with AD than in those with other inflammatory skin diseases.

Objectives

The purpose of this study was to examine whether serum levels of TARC can assess the severity of AD and be used in the clinical evaluation of AD.

Methods

A total of 73 AD patients, 11 patients with generalized atopic eczema (AE), and 30 healthy control subjects were enrolled. SCORAD (SCORing of Atopic Dermatitis) indices were calculated according to skin symptom scores. The Th2 chemokines TARC kit was then used to obtain serum TARC values in each group. Finally, statistical analysis was used to identify any correlations between serum TARC level and SCORAD index in AD and AE patients.

Results

Mean serum TARC values were 159.95 in healthy controls, 146.46 in the mild AD group, 202.71 in the moderate AD group, 1216.61 in the severe AD group and 1554.50 in the severe AE group. The serum TARC level was significantly correlated with SCORAD score in AD patients (P < 0.01). However, there was no significant correlation between SCORAD score and TARC in AE patients (P = 0.610).

Conclusions

The serum TARC level can be used to assess the severity of AD and as a reference index for the fast clinical evaluation of AD.
Ureteral relaxation through calcitonin gene‐related peptide release from sensory nerve terminals by hypotonic solution
Authors: Materazzi Serena , Minocci Daiana , De Siena Gaetano , Benemei Silvia , Nassini Romina
Published: June 2015

Objectives

To evaluate the influence of hypotonic solutions on ureteral relaxation mediated by the release of calcitonin gene‐related peptide from intramural sensory nerve endings.

Methods

Urine osmolarity of Sprague–Dawley rats drinking water low in salt content (Fiuggi water) or a reference water for 7 days was measured. Release of calcitonin gene‐related peptide‐like immunoreactivity from slices of rat ureter and urinary bladder by hypotonic solutions was assessed by an immunometric assay. The mechanism through which hypotonic solutions inhibit neurokinin A‐induced phasic contractions of isolated rat ureters was evaluated by organ bath studies.

Results

A 7‐day consumption of Fiuggi water in rats reduced urine osmolarity by ~40%. Exposure to hypotonic solutions released calcitonin gene‐related peptide‐like immunoreactivity from slices of rat ureter. This response was abated in a calcium‐free medium, after capsaicin desensitization, and in the presence of the unselective transient receptor potential channel antagonist, ruthenium red. Exposure of isolated rat ureteral preparations to a hypotonic solution inhibited neurokinin A‐evoked phasic contraction. This response was attenuated by capsaicin desensitization and in the presence of the calcitonin gene‐related peptide receptor antagonist, calcitonin gene‐related peptide8‐37. Transient receptor potential vanilloid 1 or transient receptor potential vanilloid 4 antagonists did not affect the neurogenic and calcitonin gene‐related peptide‐dependent relaxation.

Conclusion

Present data show that hypotonic solution evokes calcitonin gene‐related peptide release from capsaicin‐sensitive intramural sensory nerves, thus inhibiting ureteral contractility, through a transient receptor potential‐dependent mechanism. However, this mechanism does not involve transient receptor potential vanilloid 1 or transient receptor potential vanilloid  4. Future studies with appropriate in vivo models should investigate the hypothesis that hypostenuric urine diffusing into the ureteral tissue might favor ureteral relaxation through this novel mechanism.