bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural vitamin C intake and the risk of head and neck cancer: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium
Authors: Edefonti Valeria , Hashibe Mia , Parpinel Maria , Turati Federica , Serraino Diego , Matsuo Keitaro , Olshan Andrew F. , Zevallos Jose P. , Winn Deborah M. , Moysich Kirsten , Zhang Zuo‐Feng , Morgenstern Hal , Levi Fabio , Kelsey Karl , McClean Michael , Bosetti Cristina , Galeone Carlotta , Schantz Stimson , Yu Guo‐Pei , Boffetta Paolo , Amy Lee Yuan‐Chin , Chuang Shu‐Chun , La Vecchia Carlo , Decarli Adriano
Published: December 2014

Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual‐level pooled data from ten case‐control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study‐specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non‐alcohol energy‐adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR = 0.54, 95% CI: 0.45–0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR = 0.52, 95% CI: 0.40–0.68, p for trend = 0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations.
Netrin-1 Is a Critical Autocrine/Paracrine Factor for Osteoclast Differentiation
Authors: Mediero Aránzazu , Ramkhelawon Bhama , Perez-Aso Miguel , Moore Kathryn J. , Cronstein Bruce N.
Published: December 2014

Bone metabolism is a vital process that involves resorption by osteoclasts and formation by osteoblasts, which is closely regulated by immune cells. The neuronal guidance protein Netrin-1 regulates immune cell migration and inflammatory reactions, but its role in bone metabolism is unknown. During osteoclast differentiation, osteoclast precursors increase expression of Netrin-1 and its receptor Unc5b. Netrin-1 binds, in an autocrine and paracrine manner, to Unc5b to promote osteoclast differentiation in vitro, and absence of Netrin-1 or antibody-mediated blockade of Netrin-1 or Unc5b prevents osteoclast differentiation of both murine and human precursors. We confirmed the functional relationship of Netrin-1 in osteoclast differentiation in vivo using Netrin-1-deficient (Ntn1-/-) or wild-type (WT) bone marrow transplanted mice. Notably, Ntn1-/- chimeras have markedly diminished osteoclasts, as well as increased cortical and trabecular bone density and volume compared with WT mice. Mechanistic studies revealed that Netrin-1 regulates osteoclast differentiation by altering cytoskeletal assembly. Netrin-1 increases regulator of Rho-GEF subfamily (LARG) and repulsive guidance molecule (RGMa) association with Unc5b, which increases expression and activation of cytoskeletal regulators RhoA and focal adhesion kinase (FAK). Netrin-1 and its receptor Unc5b likely play a role in fusion of osteoclast precursors because Netrin-1 and DC-STAMP are tightly linked. These results identify Netrin-1 as a key regulator of osteoclast differentiation that may be a new target for bone therapies. © 2015 American Society for Bone and Mineral Research.
Thymol and Carvacrol Prevent Cisplatin‐Induced Nephrotoxicity by Abrogation of Oxidative Stress, Inflammation, and Apoptosis in Rats
Authors: EM El‐Sayed , AR Abd‐Allah , AM Mansour , AA EL‐Arabey
Published: December 2014

The aim of the present study is to assess the possible protective effects of thymol and carvacrol against cisplatin (CP)‐induced nephrotoxicity. A single dose of CP {6 mg/kg, intraperitoneally (i.p.)} injected to male rats revealed significant increases in serum urea, creatinine, and tumor necrosis factor alpha levels. It also increased kidney contents of malondialdehyde and caspase‐3 activity with significant reduction in serum albumin, kidney content of reduced glutathione as well as catalase, and superoxide dismutase activity as compared to that of the control group. In contrast, administration of thymol {20 mg/kg, orally (p.o.)} and/or carvacrol (15 mg/kg, p.o.) for 14 days before CP injection and for 7 days after CP administration restored the kidney function and examined oxidative stress parameters. In conclusion, thymol was more effective nephroprotective than carvacrol. Moreover, a combination of thymol and carvacrol had a synergistic nephroprotective effect that might be attributed to antioxidant, anti‐inflammatory, and antiapoptotic activities.
HDAC4 Degradation Mediates HDAC Inhibition‐Induced Protective Effects Against Hypoxia/Reoxygenation Injury
Authors: Du Jianfeng , Zhang Ling , Zhuang Shougang , Qin Gang Jian , Zhao Ting cun
Published: December 2014

Histone deacetylases (HDACs) play a crucial role in the regulation of gene expression through remodeling of chromatin structures. However, the molecular mechanisms involved in this event remain unknown. In this study, we sought to examine whether HDAC inhibition‐mediated protective effects involved HDAC4 sumoylation, degradation, and the proteasome pathway. Isolated neonatal mouse ventricular myocytes (NMVM) and H9c2 cardiomyoblasts were subjected to 48 h of hypoxia (H) (1% O2) and 2 h of reoxygenation (R). Treatment of cardiomyocytes with trichostatin A (TSA) attenuated H/R‐elicited injury, as indicated by a reduction of lactate dehydrogenase (LDH) leakage, an increase in cell viability, and decrease in apoptotic positive cardiomyocytes. MG132, a potent proteasome pathway inhibitor, abrogated TSA‐induced protective effects, which was associated with the accumulation of ubiquitinated HDAC4. NMVM transduced with adenoviral HDAC4 led to an exaggeration of H/R‐induced injury. TSA treatment resulted in a decrease in HDAC4 in cardiomyocytes infected with adenoviral HDAC4, and HDAC4‐induced injury was attenuated by TSA. HDAC inhibition resulted in a significant reduction in reactive oxygen species (ROS) in cardiomyoblasts exposed to H/R, which was attenuated by blockade of the proteasome pathway. Cardiomyoblasts carrying wild type and sumoylation mutation (K559R) were established to examine effects of HDAC4 sumoylation and ubiquitination on H/R injury. Disruption of HDAC4 sumoylation brought about HDAC4 accumulation and impairment of HDAC4 ubiquitination in association with enhanced susceptibility of cardiomyoblasts to H/R. Taken together, these results demonstrated that HDAC inhibition stimulates proteasome dependent degradation of HDAC4, which is associated with HDAC4 sumoylation to induce these protective effects. J. Cell. Physiol. 230: 1321–1331, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Semaglutide, a once‐weekly human GLP‐1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel
Authors: Kapitza Christoph , Nosek Leszek , Jensen Lene , Hartvig Helle , Jensen Christine B. , Flint Anne
Published: December 2014

The effect of semaglutide, a once‐weekly human glucagon‐like peptide‐1 (GLP‐1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. Postmenopausal women with T2D (n = 43) on diet/exercise ± metformin received ethinylestradiol (0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before (semaglutide‐free) and during (steady‐state 1.0 mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0.5 mg 4 weeks; 1.0 mg 5 weeks). Bioequivalence of oral contraceptives was established if 90%CI for the ratio of pharmacokinetic parameters during semaglutide steady‐state and semaglutide‐free periods was within prespecified limits (0.80–1.25). The bioequivalence criterion was met for ethinylestradiol area under the curve (AUC0–24 h) for semaglutide steady‐state/semaglutide‐free; 1.11 (1.06–1.15). AUC0–24 h was 20% higher for levonorgestrel at semaglutide steady‐state vs. semaglutide‐free (1.20 [1.15–1.26]). Cmax was within bioequivalence criterion for both contraceptives. Reductions (mean ± SD) in HbA1c (–1.1 ± 0.6%) and weight (–4.3 ± 3.1 kg) were observed. Semaglutide pharmacokinetics were compatible with once‐weekly dosing; the semaglutide dose and dose‐escalation regimen were well tolerated. Adverse events, mainly gastrointestinal, were mild to moderate in severity. Asymptomatic increases in mean amylase and lipase were observed. Three subjects had elevated alanine aminotransferase levels ≥3x the upper limit of normal during semaglutide/oral contraceptive coadministration, which were reported as adverse events, but resolved during follow‐up. Semaglutide did not reduce the bioavailability of ethinylestradiol and levonorgestrel.
Dynamics of testis‐ova in a wild population of Japanese pond frogs, Rana nigromaculata
Authors: Kobayashi Tohru , Kumakura Masahiko , Yoshie Sumio , Sugishima Tomomi , Horie Yoshifumi
Published: December 2014

Although many studies have reported the occurrence of testis‐ova in wild frog populations, the origin and trigger of testis‐ova differentiation/development remain unclear. A high frequency of testis‐ova has been previously reported for wild populations of the Japanese pond frog, Rana nigromaculata (cf. Iwasawa and Asai, '59). In the present study, we aimed to clarify the dynamics of testis‐ova in this frog species, including the origin and artificial induction of testis‐ova. Testis‐ova were observed in both mature frogs and puberty‐stage frogs (i.e., 0‐ and 1‐year‐old frogs). However, the early stages of testis‐ova (∼pachytene stage) were mostly observed in puberty‐stage male frogs at the onset of spermatogenesis. The early stages of testis‐ova were observed in the cysts of early secondary spermatogonia and the single cysts of the primary spermatogonium. This finding indicates that testis‐ova differentiation occurs during spermatogonial proliferation and that it is correlated with the initiation of spermatogenesis. We also examined whether estrogen exposure induced testis‐ova differentiation and how it is correlated with the progression of spermatogenesis. When 1‐year‐old frogs were exposed to estradiol‐17β during spring (i.e., when spermatogenesis was initiated), testis‐ova differentiation was induced in a dose‐dependent manner. However, this phenomenon did not occur in 1‐year‐old frogs during summer, (i.e., when the transition from spermatogonia to spermatocytes mainly occurs). These results present the first evidence that testis‐ova of the Japanese pond frog are derived from primary and early secondary spermatogonia, and that estrogen exposure induces testis‐ova differentiation accompanied by the initiation of spermatogenesis. J. Exp. Zool. 323A: 74–79, 2015. © 2014 Wiley Periodicals, Inc.
Vertex Cuts
Authors: Dunwoody M. J. , Krön B.
Published: December 2014

Given a connected graph, in many cases it is possible to construct a structure tree that provides information about the ends of the graph or its connectivity. For example Stallings' theorem on the structure of groups with more than one end can be proved by analyzing the action of the group on a structure tree and Tutte used a structure tree to investigate finite 2‐connected graphs, that are not 3‐connected. Most of these structure tree theories have been based on edge cuts, which are components of the graph obtained by removing finitely many edges. A new axiomatic theory is described here using vertex cuts, components of the graph obtained by removing finitely many vertices. This generalizes Tutte's decomposition of 2‐connected graphs to k‐connected graphs for any k, in finite and infinite graphs. The theory can be applied to nonlocally finite graphs with more than one vertex end, i.e. ends that can be separated by removing a finite number of vertices. This gives a decomposition for a group acting on such a graph, generalizing Stallings' theorem. Further applications include the classification of distance transitive graphs and k‐CS‐transitive graphs.
Rapid synthesis of [18F]fluoroestradiol: remarkable advantage of microwaving over conventional heating
Authors: Shi Jianfeng , Afari George , Bhattacharyya Sibaprasad
Published: December 2014

16α‐[18F]fluoroestradiol ([18F]FES) is known as a clinically important tracer in nuclear medicine as an estrogen receptor ligand for investigating primary and metastatic breast cancers. Synthesizing [18F]FES is a two‐step process associated with [18F]fluoride incorporation to the precursor (3‐methoxymethyl 16β,17β‐epiestriol‐O‐cyclic sulfone) and subsequent hydrolysis of the [18F]fluorinated intermediate with 2 N HCl. The impact of microwave (MW) heating on both fluorination and hydrolysis reactions was investigated. The duration and temperatures of the fluorination reaction were varied for both MW heating and conventional heating (CH) methods. Chemical and radiochemical purity and radiochemical yields were investigated for CH and compared with MW‐assisted radiosyntheses. Quality control tests of MW‐assisted [18F]FES were performed following US Pharmacopeia procedures for clinical‐grade positron emission tomography pharmaceuticals. The results demonstrate that microwaving not only improves the 18F‐fluoride incorporation (~55% improvement at 110°C for 4 min) but also significantly reduces hydrolysis time (approximately sevenfold reduction at 120°C) in comparison with CH under similar conditions. The overall isolated radiochemical yield of purified [18F]FES was significantly higher (~90% improvement) with MW, and side products were notably fewer. Quality control test results demonstrated that [18F]FES produced by microwaving was suitable for human injection.
Differentiation and growth of bone ornamentation in vertebrates: A comparative histological study among the Crocodylomorpha
Authors: de Buffrénil V. , Clarac F. , Fau M. , Martin S. , Martin B. , Pellé E. , Laurin M.
Published: December 2014

Bone ornamentation, that is, hollow (pits and grooves) or protruding (ridges) repetitive reliefs on the surface of dermal bones, is a frequent, though poorly studied and understood, feature in vertebrates. One of the most typical examples of this characteristic is given by the Crurotarsi, a taxon formed by the crocodilians and their closest allies, which generally display deep ornamentation on skull roof and osteoderms. However, the ontogenetic process responsible for the differentiation and development of this character remains controversial. This study was conducted to settle the question on histological and microanatomical evidence in several crurotarsan taxa. Observational and experimental data in extant and extinct crocodyliforms show that bone ornamentation is initially created, and later maintained during somatic growth (that is indefinite in crocodilians), by a complex process of bone remodeling comprising local resorption of superficial bone cortices, followed by partial reconstruction. The superficial reliefs of crocodilian dermal bones are thus permanently modified through pit enlargement, drift, stretching, shrinking, or complete filling. Ridges are also remodeled in corresponding ways. These processes allow accommodation of unitary ornamental motifs to the overall dimensions of the bones during growth. A parsimony optimization based on the results of this study, but integrating also published data on bone histology in non‐crocodyliform crurotarsans and some non‐crurotarsan taxa, suggests that the peculiar mechanism described above for creating and maintaining bone ornamentation is a general feature of the Crurotarsi and is quite distinct from that attributed by previous authors to other vertebrates. J. Morphol. 276:425–445, 2015. © 2014 Wiley Periodicals, Inc.
Prevalence of human papillomavirus and its genotype among 1336 invasive cervical cancer patients in Hunan province, central south China
Authors: Wang Linqian , Wu Baiping , Li Junjun , Chen Liyu
Published: December 2014

Existing data on the genotype distribution of human papillomavirus (HPV) are limited in Hunan province, central south China. To evaluate the prevalence of HPV infection and its genotype among women with invasive cervical cancer in Hunan, a total of 1,336 patients were included in this study between July 2012 and June 2013. Eighteen high‐risk and eight low‐risk genotypes of HPV were detected by Luminex xMAP technology. The results show that HPV prevalence in invasive cervical cancer in Hunan was 75.7%. A single HPV infection was found in 82.3% of the HPV‐positive samples, and 91.8% of the cases had high‐risk HPV infection. The most common HPV type was HPV 16 (50.6%), followed by HPV 58 (12.4%), HPV 52 (10.9%), HPV 18 (7.3%), HPV 33 (5.5%), HPV 59 (4.2%), HPV 39 (4.0%), HPV 61 (3.4%), HPV 31 (3.3%), and HPV 56 (3.2%). A single infection with HPV 16 was detected in 42.5% of the samples, which was significantly more frequent than any other HPV type in this population. Dual‐infection with HPV 16 and HPV 52 were relatively common. The available vaccines for HPV 16 and 18 are therefore expected to have a substantial impact on reducing the burden of cervical cancer in China, even though HPV 18 showed a lower frequency. In addition to HPV 16 and 18, other HPV types including 58, 52, and 33, should be targeted in the next generation HPV vaccines. J. Med. Virol. 87:516–521, 2015. © 2014 Wiley Periodicals, Inc.
Optimal design of fatigue life for RCP with PoP package by using the Taguchi method
Authors: Cheng Hsin‐En , Chen Rong‐Sheng
Published: December 2014

In recent years, the electronic industries tend to offer products with smaller scales, lower cost, larger storage space and integration of various functions. The development of redistributed chip package (RCP) technology is facilitated to reduce package size for three‐dimensional integration and to enhance packaging capability for miniature requirements. Meanwhile, the logic unit is required to be combined with the memory unit to achieve miniaturization and system integration.The RCP with package on package (PoP) is constructed by stacking the RCP for the very fine pitch ball grid array at topside and the stack package ball grid array (SPBGA) at bottom side. The finite element software ANSYS is adopted in this study using the Global/Local modeling approach. The reliability of the RCP with PoP is subjected to a thermal cycle test of ‐40‐125 °C based on JEDEC specification. The Coffin‐Manson strain‐based model and the Morrow energy‐based model are employed for prediction of package fatigue life, in which the SAC387 (95.5Sn3.8Ag0.7Cu) solder joints are treated as viscoplastic behavior according to the Anand constitutive model. The other materials are modeled as elastic behavior.To investigate the solder joint reliability for the stacked package design, a numerical experiment by means of the single factor analysis is first conducted for investigation. The material factors such as Young's Modulus and coefficient of thermal expansion, the geometric factors such as component thickness are evaluated. Accordingly, the significant factors are filtered and analyzed by the Taguchi method to obtain the optimal combination. As a result, the optimal design increases package fatigue life, which contributes a significant improvement by up to 86.5% when comparing with the original model.Copyright © 2014 John Wiley & Sons, Ltd.
An appraisal of eighteen commonly consumed edible plants as functional food based on their antioxidant and starch hydrolase inhibitory activities
Authors: Lee Yian Hoon , Choo Candy , Watawana Mindani I , Jayawardena Nilakshi , Waisundara Viduranga Y
Published: December 2014

BACKGROUND

Eighteen edible plants were assessed for their antioxidant potential based on oxygen radical absorbance capacity (ORAC), 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity, total phenolics, vitamin C content and various lipophilic antioxidants. The inhibitory activities of the plant extracts against the enzymatic activities of α‐amylase and α‐glucosidase were also evaluated.

RESULTS

The antioxidant and starch hydrolase activities of the plants varied widely across a single batch of analysis. The ORAC and DPPH radical scavenging EC50 values varied between 298 and 1984 Trolox equivalents g−1 fresh weight and between 91 and 533 mg kg−1 fresh weight, respectively. The total phenolics and vitamin C contents varied between 32 and 125 mg gallic acid equivalents g−1 fresh weight and between 96 and 285 µg g−1 fresh weight, respectively. All the plants contained neoxanthin, violaxanthin, and α‐ and β‐ carotene in varying amounts. Coccinia grandis, Asparagus racemosus, Costus speciosus, Amaranthus viridis and Annona muricata displayed the highest inhibitory activities against starch hydrolases. They were the most efficient against the breakdown of seven starches exposed to the two enzymes as well.

CONCLUSIONS

Overall, the edible plants were observed to display a high antioxidant potential with starch hydrolase inhibitory properties, which were beneficial in their being recognized as functional food. © 2014 Society of Chemical Industry
Physicochemical properties of caper species seed oils collected from two different harvest years
Authors: Duman Erman , Özcan Mehmet Musa
Published: December 2014

BACKGROUND

In this study the physicochemical properties, fatty acid composition and sterol and tocopheol contents of caper species seed oils were determined.

RESULTS

Brightness (L*) values of oils obtained from caper seeds ranged between 36.76 and 53.48. Viscosity values of oils of Capparis spinosa species were between 41.1 and 48.6 mPa. While oleic acid levels were high in C. spinosa species oils, linoleic acid levels were high in Capparis ovata species oils. Sterol contents of crude oils were between 3140 and 3272 mg kg−1 (mean 3220 mg kg−1) for C. spinosa species and between 3275 and 3312 mg kg−1 (mean 3298 mg kg−1) for C. ovata species. α‐Tocopherol contents of C. spinosa and C. ovata oils averaged 3.87 and 2.63 mg per 100 g respectively. Radical‐scavenging activities of crude oils averaged 29.78% (C. spinosa species) and 26.09% (C. ovata species). Total phenolic concentrations in crude oils averaged 0.642 mg g−1 for C. ovata species (P < 0.01).

CONCLUSION

Caper seeds are a natural source of vegetable oils that are beneficial in terms of health, oil stability and resistance to oxidation. © 2014 Society of Chemical Industry
Qualitative mammographic findings and outcomes of surveillance mammography after partial breast reconstruction with an autologous flap
Authors: Tan V.K. , Cornford E.J. , McCulley S.J. , Macmillan R.D.
Published: December 2014

Background

This study describes the qualitative mammographic features after partial breast reconstruction with an autologous flap, and evaluates the diagnostic accuracy and recall rates of surveillance mammography after volume replacement in breast conserving surgery.

Methods

Patients who had autologous partial breast reconstruction (N = 102) after breast‐conserving surgery using either the myocutaneous latissimus dorsi mini‐flap (N = 39) or fasciocutaneous chest wall perforator flap (N = 63) were reviewed. Mammograms done at one‐year post surgery were analysed for characteristic qualitative features. All surveillance mammograms, diagnostic imaging and medical records were retrospectively reviewed.

Results

Mammograms of partially reconstructed breasts had distinctive features that correlated well with the surgical procedures. Median follow‐up was 3 years, range 0–11 years. Of 295 surveillance mammograms, six (2%) resulted in a recall for further imaging and 3 (1%) proceeded to needle biopsy. Diagnostic imaging was performed for 13 (13/102, 12.7%) patients with symptoms, and only one (1/102, 1%) required a diagnostic biopsy.

Conclusions

A conserved breast with an autologous flap within has characteristic mammographic features that differ from those after standard breast conserving surgery. Surveillance mammography after partial breast reconstruction is accurate, and recall/biopsy rates are low. Diagnostic breast ultrasound examination is effective evaluation for the symptomatic patient. J. Surg. Oncol. 2015 111:377–381. © 2014 Wiley Periodicals, Inc.
Adsorption of the anionic surfactant sodium dodecyl sulfate on a C18 column under micellar and high submicellar conditions in reversed‐phase liquid chromatography
Authors: Ortiz‐Bolsico C. , Ruiz‐Angel M. J. , García‐Alvarez‐Coque M. C.
Published: December 2014

Micellar liquid chromatography makes use of aqueous solutions or aqueous‐organic solutions containing a surfactant, at a concentration above its critical micelle concentration. In the mobile phase, the surfactant monomers aggregate to form micelles, whereas on the surface of the nonpolar alkyl‐bonded stationary phases they are significantly adsorbed. If the mobile phase contains a high concentration of organic solvent, micelles break down, and the amount of surfactant adsorbed on the stationary phase is reduced, giving rise to another chromatographic mode named high submicellar liquid chromatography. The presence of a thinner coating of surfactant enhances the selectivity and peak shape, especially for basic compounds. However, the risk of full desorption of surfactant is the main limitation in the high submicellar mode. This study examines the adsorption of the anionic surfactant sodium dodecyl sulfate under micellar and high submicellar conditions on a C18 column, applying two methods. One of them uses a refractive index detector to obtain direct measurements of the adsorbed amount of sodium dodecyl sulfate, whereas the second method is based on the retention and peak shape for a set of cationic basic compounds that indirectly reveal the presence of adsorbed monomers of surfactant on the stationary phase.
Soil Property Changes After Conversion from FOrest to Pasture in Mount Sacinka, Artvin, Turkey
Authors: Ozalp Mehmet , Erdogan Yuksel Esin , Yuksek Turan
Published: December 2014

Turkey's forests have been continuously facing conversion into both agriculture and pasturelands, causing not only degradation and fragmentation of forested lands but also negative changes in soil properties that have not been thoroughly investigated. In order to determine possible changes in some physical and hydrophysical soil parameters along with the dispersion ratio between natural coppice forests and the neighbouring forest‐to‐grassland converted areas, a foothill of Mount Sacinka in Artvin was chosen as a research area. Besides land use, possible effects of elevation change on soil properties due to the mountainous and moderately steep landscape of the region were also taken into consideration. The soil samples were analysed for soil texture, permeability, field capacity, bulk density, organic matter, pH and dispersion ratio. The results indicated that whereas permeability (43·05 mm h−1 in forest and 18·82 mm h−1 in pasture), field capacity (43·45% in forest and 38·08% in pasture) and organic matter (6·36% in forest and 5·34% in pasture) values turned out to be higher in forest soils, bulk density (0·91 g cm−3 in forest and 1·06 g cm−3 in pasture) and pH (5·89 in forest and 6·55 in pasture) values were low in grassland soils, meaning that conversion has negative effects on soil properties. Additionally, the mean dispersion ratios of 27·55% and 33·58% for forest and pastureland soils, respectively, indicated soil erosion problems in both land uses. In addition, as for elevation effect, forest soils especially showed better characteristics at higher elevations with high permeability, field capacity and organic matter and low pH and dispersion ratio. Copyright © 2015 John Wiley & Sons, Ltd.
Liver transplantation in transthyretin amyloidosis: Issues and challenges
Authors: Carvalho Andreia , Rocha Ana , Lobato Luísa
Published: December 2014

Hereditary transthyretin amyloidosis (ATTR) is a rare worldwide autosomal dominant disease caused by the systemic deposition of an amyloidogenic variant of transthyretin (TTR), which is usually derived from a single amino acid substitution in the TTR gene. More than 100 mutations have been described, with V30M being the most prevalent. Each variant has a different involvement, although peripheral neuropathy and cardiomyopathy are the most common. Orthotopic liver transplantation (OLT) was implemented as the inaugural disease‐modifying therapy because the liver produces the circulating unstable TTR. In this review, we focus on the results and long‐term outcomes of OLT for ATTR after more than 2063 procedures and 23 years of experience. After successful OLT, neuropathy and organ impairment are not usually reversed, and in some cases, the disease progresses. The overall 5‐year survival rate is approximately 100% for V30M patients and 59% for non‐ATTR V30M patients. Cardiac‐related death and septicemia are the main causes of mortality. Lower survival is related to malnutrition, a longer duration of disease, cardiomyopathy, and a later onset (particularly for males). Deposits, which are composed of a mixture of truncated and full‐length TTR (type A) fibrils, have been associated with posttransplant myocardial dysfunction. A higher incidence of early hepatic artery thrombosis of the graft has also been documented for these patients. Liver‐kidney/heart transplantation is an alternative for patients with advanced renal disease or heart failure. The sequential procedure, in which ATTR livers are reused in patients with liver disease, reveals that neuropathy in the recipient may appear as soon as 6 years after OLT, and ATTR deposits may appear even earlier. Long‐term results of trials with amyloid protein stabilizers or disrupters, silencing RNA, and antisense oligonucleotides will highlight the value and limitations of liver transplantation. Liver Transpl 21:282–292, 2015. © 2015 AASLD.
CD47 blockade reduces ischemia/reperfusion injury and improves survival in a rat liver transplantation model
Authors: Xiao Zhen‐Yu , Banan Babak , Jia Jianluo , Manning Pamela T. , Hiebsch Ronald R. , Gunasekaran Muthukumar , Upadhya Gundumi A. , Frazier William A. , Mohanakumar Thalachallour , Lin Yiing , Chapman William C.
Published: December 2014

Orthotopic liver transplantation (OLT) remains the standard treatment option for nonresponsive liver failure. Because ischemia/reperfusion injury (IRI) is an important impediment to the success of OLT, new therapeutic strategies are needed to reduce IRI. We investigated whether blocking the CD47/thrombospondin‐1 inhibitory action on nitric oxide signaling with a monoclonal antibody specific to CD47 (CD47mAb400) would reduce IRI in liver grafts. Syngeneic OLT was performed with Lewis rats. Control immunoglobulin G or CD47mAb400 was administered to the donor organ at procurement or to both the organ and the recipient at the time of transplant. Serum transaminases, histological changes of the liver, and animal survival were assessed. Oxidative stress, inflammatory responses, and hepatocellular damage were also quantified. A significant survival benefit was not achieved when CD47mAb400 was administered to the donor alone. However, CD47mAb400 administration to both the donor and the recipient increased animal survival afterward. The CD47mAb400‐treated group showed lower serum transaminases, bilirubin, oxidative stress, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick‐end labeling staining, caspase‐3 activity, and proinflammatory cytokine expression of tumor necrosis factor α, interleukin‐1β, and interleukin‐6. Thus, CD47 blockade with CD47mAb400 administered both to the donor and the recipient reduced liver graft IRI in a rat liver transplantation model. This may translate to decreased liver dysfunction and increased survival of liver transplant recipients. Liver Transpl 21:468–477, 2015. © 2015 AASLD.
LEADERSHIP BY THE MANY THE POWER OF LATINO INCLUSION
Authors: Bordas Juana
Published: December 2014

Bordas contends that leaders everywhere have much to learn from Latino leadership, as we shift from I to We, and become more collaborative and inclusive. She quotes from a number of prominent Latino leaders, including Arturo Vargas, president of the National Association of Latino Elected and Appointed Officials, and Sylvia Puente of Chicago's Latino Policy Forum. Bordas notes the power of national Latino coalition organizations, such as the National Council of La Raza. “Creating a community of leaders is essential.” she writes, “when a group's advancement depends on people power, collective resources, and a critical mass of skilled and motivated people.”
Tailor‐Made Antimicrobial/Antiviral Star Polymer via ATRP of Cyclodextrin and Guanidine‐Based Macromonomer
Authors: Pan Yuanfeng , Xue Yan , Snow Jamie , Xiao Huining
Published: December 2014

Novel star‐like polymers are prepared via atom transfer radical polymerization (ATRP) of polyhexamethylene guanidine hydrochloride (PHMG) macromonomer and acrylamide (AM) using β‐cyclodextrin (CD) with 8‐active and 5‐active sites as a macroinitiator. The resulting star‐like polymers are characterized by gel permeation chromatography (GPC) and 1H NMR and are used for deactivating bacteria and viruses. It is found that star polymers with comparable amounts of PHMG possess excellent antimicrobial activity, which, however, strongly depends on the topological structure (i.e., the arm number and the monomer ratio) of the composing copolymers. The in vitro antibacterial activities of the synthesized polymers are investigated against Escherichia coli in terms of the minimum inhibitory concentration (MIC), whereas the antiviral activity of star copolymers is assessed via a plaque assay against non‐enveloped adenovirus (ADV). The results show that the highest antimicrobial activity is achieved by the star‐like copolymer with the monomer ratio of 20:3 (AM:PHGM, mol/mol), while the number of functional arms is fixed at 8. The incorporation of PHMG also renders the star copolymer highly antiviral, thus permitting it to be used as an effective antibacterial/antiviral agent for various applications.

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Induction of the proapoptotic tumor suppressor gene Cell Adhesion Molecule 1 by chemotherapeutic agents is repressed in therapy resistant acute myeloid leukemia
Authors: Fisser Muriel C. , Rommer Anna , Steinleitner Katarina , Heller Gerwin , Herbst Friederike , Wiese Meike , Glimm Hanno , Sill Heinz , Wieser Rotraud
Published: December 2014

Even though a large proportion of patients with acute myeloid leukemia (AML) achieve a complete remission upon initial therapy, the majority of them eventually relapse with resistant disease. Overexpression of the gene coding for the transcription factor Ecotropic Virus Integration site 1 (EVI1) is associated with rapid disease recurrence and shortened survival. We therefore sought to identify EVI1 target genes that may play a role in chemotherapy resistance using a previously established in vitro model system for EVI1 positive myeloid malignancies. Gene expression microarray analyses uncovered the Cell Adhesion Molecule 1 (CADM1) gene as a candidate whose deregulation by EVI1 may contribute to drug refractoriness. CADM1 is an apoptosis inducing tumor suppressor gene that is inactivated by methylation in a variety of tumor types. In the present study we provide evidence that it may play a role in chemotherapy induced cell death in AML: CADM1 was induced by drugs used in the treatment of AML in a human myeloid cell line and in primary diagnostic AML samples, and its experimental expression in a cell line model increased the proportion of apoptotic cells. CADM1 up‐regulation was abolished by ectopic expression of EVI1, and EVI1 expression correlated with increased CADM1 promoter methylation both in a cell line model and in primary AML cells. Finally, CADM1 induction was repressed in primary samples from AML patients at relapse. In summary, these data suggest that failure to up‐regulate CADM1 in response to chemotherapeutic drugs may contribute to therapy resistance in AML. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.
Droxidopa for the Short‐Term Treatment of Symptomatic Neurogenic Orthostatic Hypotension in Parkinson's Disease (nOH306B)
Authors: Hauser Robert A. , Isaacson Stuart , Lisk Jerome P. , Hewitt L. Arthur , Rowse Gerry
Published: December 2014

Neurogenic orthostatic hypotension (nOH) results from failure of norepinephrine responses to postural change to maintain standing systolic blood pressure (s‐SBP). Droxidopa is an oral prodrug of norepinephrine. Study nOH306 enrolled patients with Parkinson's disease (PD) and symptomatic nOH. Subjects underwent up to 2 weeks of double‐blind titration of droxidopa or placebo, followed by 8 weeks of double‐blind maintenance treatment (100‐600 mg thrice‐daily). For the initial 51 subjects (study nOH306A, previously reported), the primary efficacy measure, Orthostatic Hypotension Questionnaire (OHQ) composite score, did not demonstrate significant change versus placebo at maintenance week 8. For the subsequent 171 subjects (study nOH306B, reported here), the primary efficacy measure was change versus placebo on item 1 (“dizziness, lightheadedness, feeling faint, or feeling like you might black out”) of the Orthostatic Hypotension Symptom Assessment (OHSA) subsection of the OHQ at maintenance week 1. At week 1, mean (standard deviation) improvement on OHSA item 1 was 2.3 (2.95) for droxidopa versus 1.3 (3.16) for placebo (P = 0.018). In addition, mean increase in s‐SBP at week 1 was 6.4 (18.85) for droxidopa versus 0.7 (20.18) mmHg for placebo (nominal P value: 0.032). Differences in change in OHSA item 1 scores from baseline to maintenance weeks 2, 4, and 8 were not statistically significant. Adverse‐event (AE) incidence was similar across groups, but 12.4% of droxidopa and 6.1% of placebo subjects withdrew because of AEs. The most common AEs on droxidopa (vs. placebo) were headache (13.5% vs. 7.3%) and dizziness (10.1% vs. 4.9%). Study nOH306B demonstrated subjective (OHSA item 1) and objective (s‐SBP) evidence of short‐term droxidopa efficacy (vs. placebo) for symptomatic nOH in PD. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Seasonality effects on dengue: basic reproduction number, sensitivity analysis and optimal control
Authors: Rodrigues Helena Sofia , Monteiro M. Teresa T. , Torres Delfim F. M.
Published: December 2014

Dengue is a vector‐borne disease transmitted from an infected human to an Aedes mosquito, during a blood meal. Dengue is still a major public health problem. A model for the disease transmission is presented, composed by human and mosquitoes compartments. The aim is to simulate the effects of seasonality, on the vectorial capacity and, consequently, on the disease development. Using entomological information about the mosquito behavior under different temperatures and rainfall, simulations are carried out, and the repercussions analyzed. The basic reproduction number of the model is given, as well as a sensitivity analysis of model's parameters. Finally, an optimal control problem is proposed and solved, illustrating the difficulty of making a trade‐off between reduction of infected individuals and costs with insecticide. Copyright © 2014 John Wiley & Sons, Ltd.
Measurement of activity and concentration of paraoxonase 1 (PON‐1) in seminal plasma and identification of PON‐2 in the sperm of boar ejaculates
Authors: Barranco Isabel , Roca Jordi , Tvarijonaviciute Asta , Rubér Marie , Vicente‐Carrillo Alejandro , Atikuzzaman Mohammad , Ceron Jose J. , Martinez Emilio A. , Rodriguez‐Martinez Heriberto
Published: December 2014

This study revealed and characterised the presence of the antioxidant enzymes paraoxonase (PON) type 1 (PON‐1, extracellular) and type 2 (PON‐2, intracellular) in boar semen. To evaluate PON‐1, an entire ejaculate from each of ten boars was collected and the seminal plasma was harvested after double centrifugation (1,500g for 10 min). Seminal plasma was analysed for concentration as well as enzymatic activity of PON‐1 and total cholesterol levels. Seminal‐plasma PON‐1 concentration ranged from 0.961 to 1.670 ng/ml while its enzymatic activity ranged from 0.056 to 0.400 IU/ml, which represent individual variance. Seminal‐plasma PON‐1 concentration and enzymatic activity were negatively correlated (r = −0.763; P < 0.01). The activity of seminal‐plasma PON‐1 negatively correlated with ejaculate volume (r = −0.726, P < 0.05), but positively correlated with sperm concentration (r = 0.654, P < 0.05). Total seminal‐plasma cholesterol concentration positively correlated with PON‐1 activity (r = 0.773; P < 0.01), but negatively correlated with PON‐1 concentration (r = −0.709; P < 0.05). The presence of intracellular PON‐2 was determined via immunocytochemistry in spermatozoa derived from artificial insemination. PON‐2 localised to the post‐acrosomal area of the sperm head and principal piece of the tail in membrane‐intact spermatozoa. In summary, PON is present in boar semen, with PON‐1 at low levels in seminal plasma and PON‐2 within the spermatozoa. Further studies are needed to characterise the relationship between antioxidant PONs with sperm and other seminal‐plasma parameters. Mol. Reprod. Dev. 82: 58–65, 2015. © 2014 Wiley Periodicals, Inc.
Markovian Approach to Free‐Radical Polymerization with Simultaneous Long‐Chain Branching and Scission: Effect of Branching and Scission Kinetics
Authors: Tobita Hidetaka
Published: December 2014

The effect of branching and scission kinetics on the branched structure formation is investigated by using the analytic solution for the weight‐average chain length in a matrix formula, and the Monte Carlo simulation method, both based on the Markov chain statistics. The illustrative calculations, envisaged for the production of low‐density polyethylene, showed that the effect of different kinetics employed for the present study could be negligible when the final monomer conversion is smaller than about 25%, normally used for the commercial production processes. On the other hand, if the polymerization is continued up to higher conversion range, the functional forms for branching and scission kinetics start to show significant effects on the formed branched structure.
Lattice models applied to cyclic behavior description of quasi‐brittle materials: advantages of implicit integration
Authors: Vassaux M. , Richard B. , Ragueneau F. , Millard A. , Delaplace A.
Published: December 2014

Comprehension and quantification of quasi‐brittle materials behavior require complex experiments when focusing on cyclic or multi‐axial loadings. As an alternative, virtual testing, which can be computed using lattice discrete elements models (LDEM), is particularly interesting. LDEM already provide a physical description of the quasi‐brittle materials behavior, but further attention has to be paid to numerical integration. LDEM are explicitly integrated, such integration has been proven in the literature to be accurate when cracking is involved, by means of efficient schemes such as the ‘Saw‐tooth’ algorithm. In order to extend the range of application of the LDEM to more complex loading paths, such as compressive or cyclic loadings, involving contact and friction mechanisms, qualitativeness as well as quantitativeness of explicit integration has to be assessed anew. We hereby propose an implicit quasi‐static integration scheme for LDEM based on specific non‐linearities encountered in quasi‐brittle materials, namely contact and fracture, to circumvent expected stability and accuracy issues. Efficiency of both schemes is investigated by means of simulations of a uniaxial cyclic test and a compression test. Copyright © 2014 John Wiley & Sons, Ltd.
Phase‐contrast helium‐3 MRI of aerosol deposition in human airways
Authors: Sarracanie Mathieu , Grebenkov Denis , Sandeau Julien , Coulibaly Soulé , Martin Andrew R. , Hill Kyle , Pérez Sánchez José Manuel , Fodil Redouane , Martin Lionel , Durand Emmanuel , Caillibotte Georges , Isabey Daniel , Darrasse Luc , Bittoun Jacques , Maître Xavier
Published: December 2014

One of the key challenges in the study of health‐related aerosols is predicting and monitoring sites of particle deposition in the respiratory tract. The potential health risks of ambient exposure to environmental or workplace aerosols and the beneficial effects of medical aerosols are strongly influenced by the site of aerosol deposition along the respiratory tract. Nuclear medicine is the only current modality that combines quantification and regional localization of aerosol deposition, and this technique remains limited by its spatial and temporal resolutions and by patient exposure to radiation. Recent work in MRI has shed light on techniques to quantify micro‐sized magnetic particles in living bodies by the measurement of associated static magnetic field variations. With regard to lung MRI, hyperpolarized helium‐3 may be used as a tracer gas to compensate for the lack of MR signal in the airways, so as to allow assessment of pulmonary function and morphology. The extrathoracic region of the human respiratory system plays a critical role in determining aerosol deposition patterns, as it acts as a filter upstream from the lungs. In the present work, aerosol deposition in a mouth–throat phantom was measured using helium‐3 MRI and compared with single‐photon emission computed tomography. By providing high sensitivity with high spatial and temporal resolutions, phase‐contrast helium‐3 MRI offers new insights for the study of particle transport and deposition. Copyright © 2014 John Wiley & Sons, Ltd.
Imaging of amide proton transfer and nuclear Overhauser enhancement in ischemic stroke with corrections for competing effects
Authors: Li Hua , Zu Zhongliang , Zaiss Moritz , Khan Imad S. , Singer Robert J. , Gochberg Daniel F. , Bachert Peter , Gore John C. , Xu Junzhong
Published: December 2014

Chemical exchange saturation transfer (CEST) potentially provides the ability to detect small solute pools through indirect measurements of attenuated water signals. However, CEST effects may be diluted by various competing effects, such as non‐specific magnetization transfer (MT) and asymmetric MT effects, water longitudinal relaxation (T1) and direct water saturation (radiofrequency spillover). In the current study, CEST images were acquired in rats following ischemic stroke and analyzed by comparing the reciprocals of the CEST signals at three different saturation offsets. This combined approach corrects the above competing effects and provides a more robust signal metric sensitive specifically to the proton exchange rate constant. The corrected amide proton transfer (APT) data show greater differences between the ischemic and contralateral (non‐ischemic) hemispheres. By contrast, corrected nuclear Overhauser enhancements (NOEs) around −3.5 ppm from water change over time in both hemispheres, indicating whole‐brain changes that have not been reported previously. This study may help us to better understand the contrast mechanisms of APT and NOE imaging in ischemic stroke, and may also establish a framework for future stroke measurements using CEST imaging with spillover, MT and T1 corrections. Copyright © 2014 John Wiley & Sons, Ltd.