bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphology Effect on the Kinetic Parameters and Surface Thermodynamic Properties of Ag3PO4 Micro‐/Nanocrystals
Authors: Huang Zai-Yin , Li Xing-Xing , Liu Zuo-Jiao , He Liang-Ming , Tan Xue-Cai
Published: November 2015

Considerable effort has been exerted using theoretical calculations to determine solid surface energies. Nanomaterials with high surface energy depending on morphology and size exhibit enhanced reactivity. Thus, investigating the effects of morphology, size, and nanostructure on the surface energies and kinetics of nanomaterials is important. This study determined the surface energies of silver phosphate (Ag3PO4) micro‐/nanocrystals and their kinetic parameters when reacting with HNO3 by using microcalorimetry. This study also discussed rationally combined thermochemical cycle, transition state theory, basic theory of chemical thermodynamics with thermokinetic principle, morphology dependence of reaction kinetics, and surface thermodynamic properties. Results show that the molar surface enthalpy, molar surface entropy, molar surface Gibbs free energy, and molar surface energy of cubic Ag3PO4 micro‐/nanocrystals are larger than those of rhombic dodecahedral Ag3PO4 micro‐/nanocrystals. Compared with rhombic dodecahedral Ag3PO4, cubic Ag3PO4 with high surface energy exhibits higher reaction rate and lower activation energy, activation Gibbs free energy, activation enthalpy, and activation entropy. These results indicate that cubic Ag3PO4 micro‐/nanocrystals can overcome small energy barrier faster than rhombic dodecahedral Ag3PO4 micro‐/nanocrystals and thus require lower activation energy.
Molecular Targets in Alzheimer’s Disease: From Pathogenesis to Therapeutics
Authors: Cheng Xuan , Zhang Lu , Lian Ya-Jun
Published: November 2015

Alzheimer’s disease(AD) is characterized by progressive cognitive decline usually beginning with impairment in the ability to form recent memories. Nonavailability of definitive therapeutic strategy urges developing pharmacological targets based on cell signaling pathways. A great revival of interest in nutraceuticals and adjuvant therapy has been put forward. Tea polyphenols for their multiple health benefits have also attracted the attention of researchers. Tea catechins showed enough potentiality to be used in future as therapeutic targets to provide neuroprotection against AD. This review attempts to present a concise map of different receptor signaling pathways associated with AD with an insight into drug designing based on the proposed signaling pathways, molecular mechanistic details of AD pathogenesis, and a scientific rationale for using tea polyphenols as proposed therapeutic agents in AD.
Spiral Enteroscopy Utilizing Capsule Location Index for Achieving High Diagnostic and Therapeutic Yield
Authors: Mandaliya Rohan , Korenblit Jason , O’Hare Brendan , Shnitser Anastasia , Kedika Ramalinga , Matro Rebecca , Halegoua-De Marzio Dina , Infantolino Anthony , Conn Mitchell
Published: November 2015

Background and Aim. Spiral enteroscopy (SE) is a new small bowel endoscopic technique. Our aim is to review the diagnostic and therapeutic yield, safety of SE, and the predictive role of prior capsule endoscopy (CE) at an academic center. Methods. A retrospective review of patients undergoing SE after prior CE between 2008 and 2013 was performed. Capsule location index (CLI) was defined as the fraction of total small bowel transit time when the lesion was seen on CE. Results. A total of 174 SEs were performed: antegrade (147) and retrograde (27). Abnormalities on SE were detected in 65% patients. The procedure was safe in patients with surgically altered bowel anatomy (n=12). The diagnostic yield of antegrade SE decreased with increasing CLI range. The diagnostic yield of retrograde SE decreased on decreasing CLI range. A CLI cutoff of 0.6 was derived that determined the initial route of SE. Vascular ectasias seen on CE were detected in 83% cases on SE; p<0.01. Conclusions. SE is safe with a high diagnostic and therapeutic yield. CLI is predictive of the success of SE and determines the best route of SE. The type of small bowel pathology targeted by SE may affect its utility and yield.
RNA-Based Vaccines in Cancer Immunotherapy
Authors: McNamara Megan A. , Nair Smita K. , Holl Eda K.
Published: November 2015

RNA vaccines traditionally consist of messenger RNA synthesized byin vitrotranscription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.
Evaluation of Loop-Mediated Isothermal Amplification Assay for the Detection of Pneumocystis jirovecii in Immunocompromised Patients
Authors: Singh Preeti , Singh Sundeep , Mirdha Bijay Ranjan , Guleria Randeep , Agarwal Sanjay Kumar , Mohan Anant
Published: November 2015

Pneumocystis pneumonia (PCP) is one of the common opportunistic infection among HIV and non-HIV immunocompromised patients. The lack of a rapid and specific diagnostic test necessitates a more reliable laboratory diagnostic test for PCP. In the present study, the loop-mediated isothermal amplification (LAMP) assay was evaluated for the detection of Pneumocystis jirovecii. 185 clinical respiratory samples, including both BALF and IS, were subjected to GMS staining, nested PCR, and LAMP assay. Of 185 respiratory samples, 12/185 (6.5%), 41/185 (22.2%), and 49/185 (26.5%) samples were positive by GMS staining, nested PCR, and LAMP assay, respectively. As compared to nested PCR, additional 8 samples were positive by LAMP assay and found to be statistically significant (p<0.05) with the detection limit of 1 pg. Thus, the LAMP assay may serve as a better diagnostic tool for the detection of P. jirovecii with high sensitivity and specificity, less turn-around time, operational simplicity, single-step amplification, and immediate visual detection.
Learning Bounds of ERM Principle for Sequences of Time-Dependent Samples
Authors: Yao Mingchen , Zhang Chao , Wu Wei
Published: November 2015

Many generalization results in learning theory are established under the assumption that samples are independent and identically distributed (i.i.d.). However, numerous learning tasks in practical applications involve the time-dependent data. In this paper, we propose a theoretical framework to analyze the generalization performance of the empirical risk minimization (ERM) principle for sequences of time-dependent samples (TDS). In particular, we first present the generalization bound of ERM principle for TDS. By introducing some auxiliary quantities, we also give a further analysis of the generalization properties and the asymptotical behaviors of ERM principle for TDS.
Immunomodulatory Effects of Cinobufagin on Murine Lymphocytes and Macrophages
Authors: Yu Yang , Wang Hui , Meng Xianhua , Hao Lu , Fu Yue , Fang Linlin , Shen Dan , Yu Xiaomeng , Li Jingshung
Published: November 2015

Cinobufagin (CBG), a major bioactive component of the traditional Chinese medicine ChanSu, has been reported to have potent pharmacological activity. In this study, we aimed to elucidate the effects of CBG on the activity of immune cells in mice. Peritoneal macrophages and splenocytes from mice were prepared and cultured in RPMI1640 supplemented with 10% fetal bovine serum. Concanavalin (ConA), lipopolysaccharide (LPS), and CBG (0.0125, 0.05, 0.15, or 0.25 μg/mL) were added to the culture medium, and the phagocytic activity of macrophages was detected by MTT assays. Additionally, lymphocyte secretion of interleukin- (IL-)2 and IL-10 was detected by enzyme-linked immunosorbent assay, and the cell cycle distribution and cell surface markers were detected by flow cytometry. Our results demonstrated that CBG promoted lymphocyte proliferation; this effect was suppressed by combined treatment with ConA or LPS. Moreover, CBG also significantly improved the CD4+/CD8+ratio in spleen lymphocytes and increased the percentage of spleen lymphocytes in the S phase. Finally, we found that CBG enhanced the secretion of IL-2 and IL-10 and increased the phagocytosis ability of macrophages. In summary, CBG could enhance activity of immune cells.
Food and Feeding Dynamics ofStolephorus commersonnii(Lacepede, 1803) (Family: Engraulidae) from South Andaman
Authors: Arun Kumar M. , Padmavati G. , Venu S.
Published: November 2015

The feeding dynamics ofStolephorus commersonniialong the coastal waters of South Andaman during October, 2011, to September, 2012, were examined by employing “point’s method.” The results of the present study has shown thatS. commersonniimainly is a planktonivorous carnivore chiefly feeding in the pelagic realm on planktonic crustaceans, bivalves, gastropods, and miscellaneous food items. The copepods formed the main prey item, contributing their maximum during November 2011 (47.55%) and lowest in December (24.21%) which was confirmed by various food preference indices. There was no significant seasonal variation in the feeding preference. Lower length classes fed mainly on planktonic copepods and amphipods whereas the higher length classes fed mainly on postlarval shrimps and planktonic crustaceans likeLucifersp. andAcetessp. Feeding intensity was seasonal, but independent of the length of fish. Gastrosomatic index was highest during monsoon, indicating active feeding. During the period when a maximum percentage of fully mature individuals were present, the feeding intensity was found to be low. The trophic level of this species was found to be2.96±0.11.
Pharmacokinetic Comparability of a Biosimilar Trastuzumab Anticipated from Its Physicochemical and Biological Characterization
Authors: Miranda-Hernández Mariana P. , López-Morales Carlos A. , Piña-Lara Nelly , Perdomo-Abúndez Francisco C. , Pérez Néstor O. , Revilla-Beltri Jorge , Molina-Pérez Aarón , Estrada-Marín Larisa , Flores-Ortiz Luis F. , Ruiz-Argüelles Alejandro , Medina-Rivero Emilio
Published: November 2015

Comparability between a biosimilar and its reference product requires the evaluation of critical quality attributes that may impact on its pharmacological response. Herein we present a physicochemical characterization of a biosimilar trastuzumab focused on the attributes related to the pharmacokinetic response. Capillary isoelectrofocusing (cIEF) and cation exchange chromatography (CEX) were used to evaluate charge heterogeneity; glycosylation profiles were assessed through hydrophilic interaction liquid chromatography (HILIC); aggregates content was evaluated through size exclusion chromatography (SEC) while binding affinity to FcRn was evaluated using isothermal titration calorimetry (ITC). The biosimilar trastuzumab and its reference product exhibited a high degree of similarity for the evaluated attributes. In regard to the pharmacokinetic parameters, randomized, double blind, and two-arm parallel and prospective study was employed after the administration of a single intravenous dose in healthy volunteers. No significant differences were found between the pharmacokinetic profiles of both products. Our results confirm that similarity of the critical quality attributes between a biosimilar product, obtained from a different manufacturing process, and the reference product resulted in comparable pharmacokinetic profiles, diminishing the uncertainty related to the biosimilar’s safety and efficacy.
Observations on the Biology and Anatomy of Myerslopiidae (Hemiptera, Membracoidea)
Authors: Rakitov Roman
Published: November 2015

Adults and nymphs ofMapuchea chilensis(Nielson), from the poorly known family Myerslopiidae, were collected from the litter horizon of temperate forests and shrub bogs in southern Chile. The species apparently feeds on roots and creeping stems of angiosperms. Salivary sheaths of captive specimens terminated in vascular bundles. Indirect evidence suggests feeding on phloem sap. Both nymphs and adults are strong jumpers and both actively disperse, as evidenced by their capture in pan traps. The Malpighian tubules of this species produce no brochosomes and, unlike in most previously studied Membracoidea, comprise no specialized secretory segment. Each tubule comprises secretory cells scattered among excretory ones, a condition not previously known among Hemiptera.
Nicotine and Toxicant Exposure among U.S. Smokeless Tobacco Users: Results from 1999 to 2012 National Health and Nutrition Examination Survey Data
Authors: Rostron Brian L. , Chang Cindy M. , van Bemmel Dana M. , Xia Yang , Blount Benjamin C.
Published: November 2015

Background: It has been suggested that smokeless tobacco users have high nicotine and toxicant exposure, but studies with nationally representative data have been limited.

Methods: We analyzed biomarkers of tobacco exposure for 23,684 adult participants from the National Health and Nutrition Examination Survey from 1999 to 2012. The biomarkers analyzed were serum cotinine, urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), blood lead, blood cadmium, blood mercury, urinary arsenic, and urinary N-acetyl-S-(2-cyanoethyl)-L-cysteine. We calculated geometric mean concentrations for each biomarker by tobacco use category and geometric mean ratios adjusting for demographic factors.

Results: Exclusive smokeless tobacco users had higher geometric mean concentrations of serum cotinine [178.9 ng/mL, 95% confidence interval (CI), 145.5–220.0] and NNAL (583.0 pg/mg creatinine, 95% CI, 445.2–763.5) than exclusive cigarette smokers (130.6 ng/mL, 95% CI, 122.3–139.6 and 217.6 pg/mg creatinine, 95% CI, 193.0–245.2, respectively). Smokeless tobacco users also had higher concentrations of blood lead compared with nontobacco users (adjusted geometric mean ratio = 1.30, 95% CI, 1.21–1.38). Based on limited sample sizes, NNAL concentrations for smokeless tobacco users appear to have declined from 2007 to 2008 (geometric mean = 1013.7 pg/mg creatinine, 95% CI, 738.9–1390.8) to 2011 to 2012 (geometric mean = 325.7 pg/mg creatinine, 95% CI, 159.6–664.9).

Conclusions: Exclusive smokeless tobacco users have higher observed levels of exposure to nicotine and carcinogenic tobacco-specific nitrosamines, as measured by cotinine and NNAL biomarker concentrations, than exclusive cigarette smokers. These patterns in NNAL levels for smokeless tobacco users may be changing over time.

Impact: High exposure to harmful constituents among smokeless tobacco users is a continuing health issue. Cancer Epidemiol Biomarkers Prev; 24(12); 1829–37. ©2015 AACR.
Are Doses and Schedules of Small-Molecule Targeted Anticancer Drugs Recommended by Phase I Studies Realistic?
Authors: Roda Desamparados , Jimenez Begoña , Banerji Udai
Published: November 2015

Tolerability of molecularly targeted agents (MTA) used in cancer therapeutics is determined in phase I trials. We reviewed the reported incidence of toxicity in phase III trials at doses and schedules recommended by phase I trials to evaluate whether these recommendations are realistic when drugs are used in larger populations of patients. We systematically reviewed a safety profile of small molecule (SM-MTA) and mAb MTA (MA-MTA) approved by the FDA in the last 12 years. There was a significantly increased percentage of grade 3 or 4 adverse events reported with SM-MTA compared with MA-MTA [40% vs. 27%; RR 1.5; 95% confidence interval (CI), 1.10–2.25, P = 0.038] in phase III studies. Importantly, a substantial proportion of patients (45%) treated with SM-MTA required dose modifications due to drug-related toxicity in phase III trials. However, this toxicity was associated to a definitive study drug discontinuation in only 9%. Overall, 25% of SM-MTA declared recommended phase II doses below MTD based on pharmacokinetic–pharmacodynamic data and these trials were associated with a significantly reduced number of dose modifications in registration trials (32% vs. 50%; RR 0.64; 95% CI, 0.43–0.88, P = 0.01). Tolerability is going to come into further focus due to the need for combinations of SM-MTA and other anticancer agents. There was a higher incidence of grade 3–4 toxicity in phase III trials in combinations versus single-agent SM-MTAs (64% vs. 37%; RR 1.73; 95% CI, 1.3–2.3, P = 0.001). These results indicate that phase I studies underestimate toxicity while recommending doses of SM-MTA. Clin Cancer Res; 22(9); 2127–32. ©2015 AACR.
Short versus Standard Mifepristone and Misoprostol Regimen for Second- and Third-Trimester Termination of Pregnancy for Fetal Anomaly
Authors: Sharp Andrew , Navaratnam Kate , Abreu Patricia , Alfirevic Zarko
Published: November 2015

Background: Termination of pregnancy requires a 48-hour ‘window' between mifepristone and misoprostol. Shorter durations have been used in first-trimester termination, but there are few data available in later termination for fetal anomaly. Material and Methods: We reviewed all terminations for fetal anomaly at ≥13 weeks from May 2013 to May 2014. Cases were managed using a short (≤12 h) or standard (≥36 h) mifepristone-to-misoprostol interval. Results: Two hundred and twenty women underwent a termination of pregnancy for fetal anomaly during the study period, of which 119 were included for analysis. Sixty-six (55%) women were managed according to the short regimen and 53 (45%) women with the standard regimen. The short regimen resulted in a shorter mifepristone-to-delivery interval but was less likely to result in delivery within 12 h of misoprostol. Delivery rates at 24 h were equivocal. There was no difference in blood loss, vaginal delivery rates, complications or bed nights. The short regimen did require more doses of misoprostol. Feticide or previous uterine scar had no effect on outcomes. Discussion: There was no significant difference in clinical outcome for women managed with a short (≤12 h) or a standard (≥36 h) regimen for medical termination of pregnancy for fetal anomaly, suggesting that either regimen could be offered.
Leukotriene B4 Inhibits L-Type Calcium Channels via p38 Signaling Pathway in Vascular Smooth Muscle Cells
Authors: Liu Xiaoyu , Yang Tingting , Miao Langxi , Mei Yan-Ai , Hu Changlong
Published: November 2015

Background/Aims: Arachidonic acid (AA) and its metabolites are important endogenous lipid messengers. In this study, we test the effect of Leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of AA, on L-type calcium channels in A7r5 rat aortic vascular smooth muscle cells. Methods: L-type calcium channel currents were recorded by a patch-clamp technique. The mRNA expression of CaV1.2 was determined by Real-time RT-PCR. The protein expression of CaV1.2 and p38 activity was determined by Western blot analysis. Results: LTB4 inhibits L-type channel currents in A7r5 cells in a dose-and time- dependent manner. LTB4 reduced the mRNA/protein expression of CaV1.2 channels in A7r5 cells. BLT1 receptor antagonist LY29311 abrogated the inhibitory effect of LTB4, while BLT2 receptor antagonist LY255283 had no effect. 5Z-7-oxozeaenol and SB203580, which block TAK1 and p38 kinase respectively, abrogated the LTB4 inhibitory effect on L-type calcium channels. LTB4 increased p38 activity in A7r5 cells. Blockage of Src, PI3K, JNK and NF-κB kinase had no effects on LTB4 inhibition of L-type calcium channel currents in A7r5 cells. Conclusion: We conclude that LTB4 inhibits L-type calcium channels through BLT1-TAk1-p38 signaling pathway. The LTB4 inhibitory effect on L-type calcium channels may be involved in its pathological processes such as atherosclerosis.
Saquinavir Induced Suicidal Death of Human Erythrocytes
Authors: Waibel Sabrina , Bissinger Rosi , Bouguerra Ghada , Abbès Salem , Lang Florian
Published: November 2015

Background/Aims: The antiretroviral protease inhibitor saquinavir is used for the treatment of HIV infections. Effects of saquinavir include induction of apoptosis, the suicidal death of nucleated cells. Saquinavir treatment may further lead to anemia. In theory, anemia could result from accelerated erythrocyte loss by enhanced suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress with increase of reactive oxygen species (ROS) and ceramide. The present study explored, whether and how saquinavir induces eryptosis. Methods: To this end, flow cytometry was employed to estimate erythrocyte volume from forward scatter, phosphatidylserine exposure at the cell surface from annexin-V-binding, [Ca2+]i from Fluo3-fluorescence, ROS abundance from DCFDA fluorescence and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to saquinavir significantly decreased forward scatter (≥ 5 µg/ml), significantly increased the percentage of annexin-V-binding cells (≥ 10 µg/ml), significantly increased Fluo3-fluorescence (15 µg/ml), significantly increased DCFDA fluorescence (15 µg/ml), but did not significantly modify ceramide abundance. The effect of saquinavir on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusions: Saquinavir triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of ROS formation and Ca2+ entry.
Decreased Osteopontin Expression as a Reliable Prognostic Indicator of Improvement in Pulmonary Tuberculosis: Impact of the Level of Interferon-γ-Inducible Protein 10
Authors: Zhu Yunan , Jia Hongyu , Chen Jianing , Cui Guangying , Gao Hainv , Wei Yingfeng , Lu Chong , Wang Lin , Uede Toshimitsu , Diao Hongyan
Published: November 2015

Background/Aims: Osteopontin (OPN) expression is increased during the course of various chronic inflammatory diseases, including tuberculosis (TB). However, its prognostic value in TB management remains unclear. This study aimed to determine whether OPN could associate with other cytokines serving as a reliable biomarker for evaluating the effectiveness of early anti-TB treatments. Methods: Smear-positive pulmonary TB patients (n = 20) were recruited, and the plasma levels of OPN, IP-10, TNF-α, and IL-12 were measured by ELISA before initiation of anti-TB therapy and after sputum smear conversion. The C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were also tracked during anti-TB treatment. Results: OPN expression was significantly elevated in patients with smear-positive pulmonary TB, and was closely related with disease severity. Monitoring during the treatment course revealed that its expression, along with that of IFN-γ-induced protein 10 (IP-10), decreased significantly only after sputum smear conversion. Moreover, OPN levels positively correlated with CRP levels before and after anti-TB treatment. Furthermore, OPN markedly promoted IP-10 expression in peripheral blood mononuclear cells. Conclusion: Association between OPN and IP-10 may serve as a reliable prognostic indicator for improvement during the early treatment of pulmonary TB, and may help clinicians in tailoring an effective TB treatment regimen.
New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity
Authors: Fadaeinasab Mehran , Basiri Alireza , Kia Yalda , Karimian Hamed , Ali Hapipah Mohd , Murugaiyah Vikneswaran
Published: November 2015

Background/Aims: Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1) and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2), along with five known, macusine B (3), vinorine (4), undulifoline (5), isoresrpiline (6) and rescinnamine (7) were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Conclusion: Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations.
Extracellular Adenosine Diphosphate Ribose Mobilizes Intracellular Ca2+ via Purinergic-Dependent Ca2+ Pathways in Rat Pulmonary Artery Smooth Muscle Cells
Authors: Huang Chun , Hu Jinxing , Subedi Krishna P. , Lin Amanda H.Y. , Paudel Omkar , Ran Pixin , Sham James S.K.
Published: November 2015

Background/Aims: Adenosine diphosphate ribose (ADPR), a product of β-NAD+ metabolism generated by the multifunctional enzyme CD38, is recognized as a novel signaling molecule. The catalytic site of CD38 orients extracellularly or intracellularly, capable of generating ADPR outside and inside the cells. CD38-dependent pathways have been characterized in pulmonary artery smooth muscle cells (PASMCs); however the physiological function of extracellular ADPR is unclear. Methods: Ca2+ mobilizing and proliferative effects of extracellular ADPR were characterized and compared with the ATP-induced responses in rat PASMCs; and the expression of purinergic receptor (P2X and P2Y) subtypes were examined in pulmonary arteries. Results: ADPR elicited concentration-dependent increase in [Ca2+]i with a fast transient and a sustained phase in PASMCs. The sustained phase was abolished by Ca2+ removal and inhibited by the non-selective cation channel blocker SKF-96365, but was unaffected by TRPM2 antagonists or nifedipine. The purinergic receptor (P2X) antagonist pyridoxal-phosphate-6-azophenyl-2', 4'-disulfonate inhibited partially the transient and the sustained Ca2+ response, while the P2(XY) inhibitor suramin and the phospholipase C inhibitor U73122 abolished the sustained Ca2+ influx. The P2Y1 antagonist MRS2179 had no effect on the response. By contrast, ATP and ADP activated Ca2+ response exhibited a high and a low affinity component, and the pharmacological profile of ATP-induced Ca2+ response was distinctive from that of ADPR. BrdU incorporation assay showed that ADPR caused significant inhibition whereas ATP caused slight stimulation of PASMC proliferation. RT-PCR analysis found that almost all P2X and P2Y subtypes are expressed in PAs. Conclusion: ADPR and ATP activate Ca2+ responses through different combinations of multiple purinergic receptor subtypes; and extracellular ADPR may exert an autocrine/paracrine action via purinergic receptors on PASMCs.
Licochalcone A Induced Suicidal Death of Human Erythrocytes
Authors: Egler Jasmin , Lang Florian
Published: November 2015

Background: The anti-inflammatory, immunomodulatory, and antimicrobial Glycyrrhiza inflata extract component licochalcone A triggers apoptosis of tumor cells and is thus considered for the treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in the triggering of eryptosis includes Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), and ceramide. The present study explored, whether and how licochalcone A induces eryptosis. Methods: Human erythrocytes drawn from healthy individuals were exposed for 24 hours to 1-10 µg/ml licochalcone A. Flow cytometry was subsequently employed to estimate phosphatidylserine exposure at the cell surface from annexin V binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and ceramide utilizing specific antibodies. In addition, hemolysis was quantified from hemoglobin release. Results: Licochalcone A significantly increased the percentage of annexin-V-binding cells (≥ 5 µg/ml), significantly decreased forward scatter (2.5 - 5 µg/ml), significantly increased Fluo3-fluorescence (≥ 7.5 µg/ml), and significantly increased ceramide abundance (10 µg/ml). The effect of licochalcone on annexin-V-binding was not significantly modified, but hemolysis significantly enhanced by removal of extracellular Ca2+. Conclusions: Licochalcone triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect independent from Ca2+ entry and presumably in part due to ceramide.
Is It Possible to Perform Less Radical Surgery for Invasive Uterine Cervical Cancer?
Authors: Togami Shinichi , Kamio Masaki , Kobayashi Hiroaki , Douchi Tsutomu
Published: November 2015

Background/Aims: A retrospective analysis was performed to evaluate the possibility of less radical surgery for early-stage invasive uterine cervical cancer without compromising the oncological outcome. Methods: The analysis was performed on 175 patients with invasive uterine cervical cancer in FIGO stage IA2-IIB, all of whom underwent primary radical hysterectomy. Relationship of tumor size with the incidence of pathologic parametrial involvement and the pelvic lymph node metastasis were investigated. Results: Fifty-one patients had tumor size ≤2 cm and 124 had tumor size >2 cm. Patients with tumor size ≤2 cm had a significantly lower incidence of parametrial invasion (p < 0.0001), lymph node metastasis (p < 0.0001), lymph vascular space involvement (p < 0.0001) and recurrence (p = 0.0002) than patients with tumor size >2 cm. Five-year relapse-free survival rate was 98 and 73%, respectively (p = 0.0004). Conclusion: It is suggested that less radical surgery may be appropriate for some cases with tumor size <2 cm.
Lipomatous Change in Uveal Melanoma: Histopathological, Immunohistochemical and Cytogenetic Analysis
Authors: Yavuzyigitoglu Serdar , Kilic Emine , Vaarwater Jolanda , de Klein Annelies , Paridaens Dion , Verdijk Robert M. ,   On behalf of the Rotterdam Ocular Melanoma Study Group (ROMS)
Published: November 2015

Purpose: The aim of this study was to describe a case of lipomatous change in uveal melanoma. Procedures: The patient presented with a 2-year history of blurry vision. A full examination of the right eye revealed a dome-shaped pigmented subretinal mass in the choroid with a thickness of 9 mm and a diameter of 15 mm. The eye was enucleated and prepared for histopathologic, genetic and molecular investigation. Results: Histopathology revealed a small circumscribed area consisting of mature adipocytic appearing cells with abundant clear cytoplasm and small peripheral flattened nuclei within a spindle-cell melanoma of the uvea. The cytoplasm of the adipocytic cells stained negative for periodic acid-Schiff and Alcian blue and positive for Melan-A, HMB-45 and tyrosinase, confirming melanocytic lineage. Fluorescence in situ hybridization analysis confirmed trisomy of chromosome 6p22 and disomy of chromosome 3p13 in the nuclei of both the tumor spindle type B cells and in the nuclei of lipomatous tumor cells. Conclusions: Lipomatous change can be added to the many histopathologic faces of uveal melanoma. To our knowledge, this is the first report of lipomatous change in uveal melanoma performed with cytogenetic investigations.
Metabolic Mechanisms in Obesity and Type 2 Diabetes: Insights from Bariatric/Metabolic Surgery
Authors: Cătoi Adriana Florinela , Pârvu Alina , Mureşan Adriana , Busetto Luca
Published: November 2015

Obesity and the related diabetes epidemics represent a real concern worldwide. Bariatric/metabolic surgery emerged in last years as a valuable therapeutic option for obesity and related diseases, including type 2 diabetes mellitus (T2DM). The complicated network of mechanisms involved in obesity and T2DM have not completely defined yet. There is still a debate on which would be the first metabolic defect leading to metabolic deterioration: insulin resistance or hyperinsulinemia? Insight into the metabolic effects of bariatric/metabolic surgery has revealed that, beyond weight loss and food restriction, other mechanisms can be activated by the rearrangements of the gastrointestinal tract, such as the incretinic/anti-incretinic system, changes in bile acid composition and flow, and modifications of gut microbiota; all of them possibly involved in the remission of T2DM. The complete elucidation of these mechanisms will lead to a better understanding of the pathogenesis of this disease. Our aim was to review some of the metabolic mechanisms involved in the development of T2DM in obese patients as well as in the remission of this condition in patients submitted to bariatric/metabolic surgery.
Prenatal Evaluation of the Fetal Conus Medullaris on a Routine Scan
Authors: Rodríguez M. Angeles , Prats Pilar , Rodríguez Ignacio , Comas Carmina
Published: November 2015

Objective: To assess the ability to identify the conus medullaris (CM) and measure the conus-sacrum distance (CS distance) on a routine scan and the relationship with maternal and fetal factors. Methods: This was a prospective study. The assessment of the CM and the CS distance and the influence of the body mass index (BMI), gestational age (GA) and fetal position were analyzed. The correlation between the femur length (FL) and the GA with the CS distance was evaluated. Results: A total of 696 fetuses were analyzed. The CM could be visualized in 82.3% of the cases, and the CS distance could be analyzed in 81.2% of the cases. The CM assessment was statistically associated with BMI and fetal position but not with GA. The CS distance assessment was statistically associated with BMI and GA but not with fetal position. We determined a significant association between the FL/CS distance and between the GA/CS distance. Conclusions: Assessment of the CM is possible on most routine scans. The CS distance could be introduced to routine scans for the assessment of prenatal skin-covered spinal dysraphism. High BMI, advanced GA and breech presentation could be potential factors limiting the feasibility of evaluating the CM.
Cryosurgery during Imiquimod (Immunocryosurgery) for Periocular Basal Cell Carcinomas: An Efficacious Minimally Invasive Treatment Alternative
Authors: Gaitanis Georgios , Kalogeropoulos Chris D. , Bassukas Ioannis D.
Published: November 2015

Background/Aim: Periocular basal cell carcinomas (pBCC) remain a treatment challenge. Our aim was to retrospectively evaluate the feasibility and efficacy of immunocryosurgery for the treatment of pBCC. Methods: Immunocryosurgery is given in 5-week cycles of daily imiquimod, with cryosurgery on day 14. Patients treated between 1/1/2008 and 31/12/2014 were included in this study. Results: Immunocryosurgery was offered to 19 patients. Of these, 16 (i.e. 6 males and 10 females, average age 74.9 years, median tumor diameter 15 mm, range 5-60 mm), with 1 tumor each, were treated. Six tumors (37.5%) were relapses after surgery and 2 were of metatypical histology. All BCC were high risk for recurrence after treatment; 10 tumors had 2 risk factors for relapse, 5 had 3, and 1 had 4. The follow-up period ranged between 3 and 60 months (average 25.6 months). Of the 16 tumors treated, 14 (all with a diameter <40 mm) cleared with immunocryosurgery (total efficacy 87.5%); 7 out of 16 tumors (44%; all with a diameter ≤20 mm) cleared with 1 conventional 5-week immunocryosurgery treatment cycle. Seven additional tumors (including 2 with a diameter >20 mm) required intensified treatment schemes (of up to 10 weeks) for clearance. The 2 tumors that did not clear responded partially and were also the 2 largest ones (diameter 40 and 60 mm). Of the 14 cleared tumors, 2 relapsed during follow-up; 1 cleared with immunocryosurgery. At the last examination during follow-up, 13 out of 16 (81%) patients were in sustained clinical remission. Conclusions: For most pBCC, immunocryosurgery is a feasible and efficacious alternative to surgical excision.
The Impact of Feet Callosities, Arm Posture, and Usage of Electrolyte Wipes on Body Composition by Bioelectrical Impedance Analysis in Morbidly Obese Adults
Authors: Roekenes Jessica , Strømmen Magnus , Kulseng Bård , Martins Catia
Published: November 2015

Objective: This study evaluated the impact of feet callosities, arm posture, and use of electrolyte wipes on body composition measurements by bioelectrical impedance analysis (BIA) in morbidly obese adults. Methods: 36 morbidly obese patients (13 males, aged 28-70 years, BMI 41.6 ± 4.3 kg/m2) with moderate/severe feet callosities participated in this study. Body composition (percent body fat (%BF)) was measured while fasting using multi-frequency BIA (InBody 720®), before and after removal of callosities, with and without InBody® electrolyte wipes and custom-built auxiliary pads (to assess arm posture impact). Results from BIA were compared to air displacement plethysmography (ADP, BodPod®). Results: Median %BF was significantly higher with auxiliary pads than without (50.1 (interquartile range 8.2) vs. 49.3 (interquartile range 9.1); p < 0.001), while no differences were found with callosity removal (49.3 (interquartile range 9.1) vs. 50.0 (interquartile range 7.9); NS) or use of wipes (49.6 (interquartile range 8.5) vs. 49.3 (interquartile range 9.1); NS). No differences in %BF were found between BIA and ADP (49.1 (IQR: 8.9) vs. 49.3 (IQR: 9.1); NS). Conclusion: Arm posture has a significant impact on %BF assessed by BIA, contrary to the presence of feet callosities and use of electrolyte wipes. Arm posture standardization during BIA for body composition assessment is, therefore, recommended.
Health Services for Management of Chronic Non-Cancer Pain in Kuwait: A Case Study Review
Authors: Lakha S. Fatima , Pennefather Peter , Badr Hanan E. , Mailis-Gagnon Angela
Published: November 2015

The experience of chronic pain is universal, yet pain management services delivered by health professionals vary substantially, depending on the context and patient. This review is a part of a series that has examined the issue of chronic non-cancer pain services and management in different global cities. The review is structured as a case study of the availability of management services for people living with chronic non-cancer pain within the context of the Kuwaiti health systems, and the cases are built from evidence in the published literature identified through a comprehensive review process. The evolution of the organizational structure of the public and private health systems in Kuwait is described. These are discussed in terms of their impact on the delivery of comprehensive chronic pain management service by health professionals in Kuwait. This review also includes a description of chronic pain patient personas to highlight expected barriers as well as compliance issues with services likely to be encountered in Kuwait. The case study analysis and persona descriptions illustrate a need to move beyond pain symptom management towards considering the entire person and his/her individual experience of pain such that health care success is judged by enhancement of patient well-being rather than access to services. A road map for improving integrative chronic pain management in Kuwait is discussed.
A checklist of birds of Kerala, India
Authors: J Praveen
Published: November 2015

A checklist of birds of Kerala State is presented in this paper.  Accepted English names, scientific binomen, prevalent vernacular names in Malayalam, IUCN conservation status, endemism, Wildlife (Protection) Act schedules, and the appendices in the CITES, pertaining to the birds of Kerala are also given.  The State of Kerala has 500 species of birds, 17 of which are endemic to Western Ghats, and 24 species fall under the various threatened categories of IUCN.

 
A checklist of fishes of Kerala, India
Authors: Bijukumar A. , Raghavan Rajeev
Published: November 2015

A checklist of the fishes of Kerala State is presented, along with their scientific and common names (English and Malayalam), endemism, IUCN Red List status, listing under different Schedules of the Indian Wildlife (Protection) Act and in the Appendices of Convention on International Trade in Endangered Species of Wild Flora and Fauna (CITES). Nine Hundred and five species of fishes are recorded from the inland and marine waters of Kerala comprising of 41 orders and 172 families. Close to 30% of the freshwater fish species found in Kerala are endemic to the State. Only 8% of the total fishes of Kerala are listed as threatened in the IUCN Red List, of which the majority are freshwater species. Several hundred fish species occurring in the marine waters of Kerala have not yet been assessed for their conservation status by IUCN. 

 
Genetic Susceptibility to Lipid Levels and Lipid Change Over Time and Risk of Incident Hyperlipidemia in Chinese Populations
Authors: Lu Xiangfeng , Huang Jianfeng , Mo Zengnan , He Jiang , Wang Laiyuan , Yang Xueli , Tan Aihua , Chen Shufeng , Chen Jing , Gu C. Charles , Chen Jichun , Li Ying , Zhao Liancheng , Li Hongfan , Hao Yongchen , Li Jianxin , Hixson James E. , Li Yunzhi , Cheng Min , Liu Xiaoli , Cao Jie , Liu Fangcao , Huang Chen , Shen Chong , Shen Jinjin , Yu Ling , Xu Lihua , Mu Jianjun , Wu Xianping , Ji Xu , Guo Dongshuang , Zhou Zhengyuan , Yang Zili , Wang Renping , Yang Jun , Yan Weili , Peng Xiaozhong , Gu Dongfeng
Published: November 2015

Background—

Multiple genetic loci associated with lipid levels have been identified predominantly in Europeans, and the issue of to what extent these genetic loci can predict blood lipid levels increases over time and the incidence of future hyperlipidemia remains largely unknown.

Methods and Results—

We conducted a meta-analysis of genome-wide association studies of lipid levels in 8344 subjects followed by replication studies including 14 739 additional individuals. We replicated 17 previously reported loci. We also newly identified 3 Chinese-specific variants in previous regions (
HLA-C
,
LIPG
, and
LDLR
) with genome-wide significance. Almost all the variants contributed to lipid levels change and incident hyperlipidemia >8.1-year follow-up among 6428 individuals of a prospective cohort study. The strongest associations for lipid levels change were detected at
LPL
,
TRIB1
,
APOA1-C3-A4-A5
,
LIPC
,
CETP
, and
LDLR
(
P
range from 4.84×10
−4
to 4.62×10
−18
), whereas
LPL
,
TRIB1
,
ABCA1
,
APOA1-C3-A4-A5
,
CETP
, and
APOE
displayed significant strongest associations for incident hyperlipidemia (
P
range from 1.20×10
−3
to 4.67×10
−16
). The 4 lipids genetic risk scores were independently associated with linear increases in their corresponding lipid levels and risk of incident hyperlipidemia. A
C
-statistics analysis showed significant improvement in the prediction of incident hyperlipidemia on top of traditional risk factors including the baseline lipid levels.

Conclusions—

These findings identified some evidence for allelic heterogeneity in Chinese when compared with Europeans in relation to lipid associations. The individual variants and those cumulative effects were independent risk factors for lipids increase and incident hyperlipidemia.
Constitutionalism, Religion, and Education
Authors: Brown Nathan J. , Kissane Bill , Madeley John
Published: November 2015

This article compares the constitutional protection of religious education in Egypt, Ireland, and Norway. It shows that such protection has, in each case, path-dependent qualities that suggest religious education is relatively immune to constitutional attack. This immunity has been marked both at the point of independence and in the more secularizing periods that followed. It cannot be explained by different historical trajectories or by differences in confessional culture. Although the stakes are high in this area (for states, religious bodies, and parents), contrary to what separationist understandings of the modern state would expect, each state has maintained an openly accommodationist relationship with religious bodies in this field more than any other. The conclusion explores some reasons for why these accommodationist practices, which span three centuries, have continued.
Depression, Anxiety, and Severity of Obesity in Adolescents
Authors: Fox Claudia K. , Gross Amy C. , Rudser Kyle D. , Foy Allison M. H. , Kelly Aaron S.
Published: November 2015

The purposes of this study were to characterize the impact of depression and anxiety on the severity of obesity among youth seeking weight management treatment and to determine the extent to which emotional eating mediates the relationship between depression and/or anxiety and degree of obesity. This cross-sectional, retrospective chart review of 102 adolescent patients from a weight management clinic analyzed demographics, body mass index, depression (Patient Health Questionnaire-9), and anxiety (Generalized Anxiety Disorder Scale-7) screens and the Child Eating Behavior Questionnaire, Emotional Over-Eating subscale. After adjusting for demographics and emotional eating, the odds of having severe obesity versus obesity were 3.5 times higher for patients with depression compared with those without (odds ratio [OR] = 3.5; 95% CI = 1.1, 11.3; P = .038) and nearly 5 times higher for those with anxiety (OR = 4.9; CI = 1.2, 20.9; P = .030). Emotional eating, however, was not a mediator between depression/anxiety and degree of adiposity.
Lactobacillus acidophilus Mixture in Treatment of Children Hospitalized With Acute Diarrhea
Authors: Pinto Jamie M. , Petrova Anna
Published: November 2015

Despite unproven effectiveness, Lactobacillus acidophilus is a widely used probiotic in the treatment of pediatric diarrhea. In this report, we evaluated the association between length of stay (LOS) for 290 young children hospitalized with acute diarrhea and adjuvant therapy with a probiotic mixture containing 80% L acidophilus that was included in treatment for 22.4% of them. Overall, no association between LOS and use of L acidophilus was recorded after controlling for age, length of diarrhea symptoms, duration of intravenous fluids, and prior exposure to antibiotic. However, LOS was directly associated with use of L acidophilus in children with negative stool studies, and no such association was recorded in children with positive stool for rotavirus or other infections. We concluded that adjuvant therapy with L acidophilus mixture is not beneficial for young children hospitalized with acute diarrhea.