Neurexin and Neuroligins Maintain the Balance of Ghost and Satellite Boutons at the Drosophila Neuromuscular Junction.
Neurexins and neuroligins are common synaptic adhesion molecules that are associated with autism and interact with each other in the synaptic cleft. The Drosophila neuromuscular junction (NMJ) bouton is a well-known model system in neuroscience, and ghost and satellite boutons, respectively, indicate the poor development and overgrowth of the NMJ boutons. However, the Drosophila neurexin (DNrx) and Drosophila neuroligins (DNlgs) are mainly observed in type Ib boutons, indicating the ultrastructural and developmental phenotypes of the Drosophila NMJ. Here, we identified the ultrastructural and developmental features of ghost and satellite boutons by utilizing dneurexin (dnrx) and dneuroligins (dnlgs) fly mutants and other associated fly strains. Ghost boutons contain synaptic vesicles with multiple diameters but very rarely contain T-bar structures and swollen or thin subsynaptic reticulum (SSR) membranes. The muscle cell membrane is invaginated at different sites, stretches to the ghost bouton from different directions, forms several layers that enwrap the ghost bouton, and then branches into the complex SSR. Satellite boutons share a common SSR membrane and present either a typical profile in which a main bouton is encircled by small boutons or two atypical profiles in which the small boutons are grouped together or distributed in beads without a main bouton. Electron and confocal microscopy data showed that dnrx, dnlg1, dnlg2, dnlg3, and dnlg4 mutations led to ghost boutons; the overexpression of dnrx, dnlg1, dnlg2, dnlg3, and dnlg4 led to satellite boutons; and the dnlg2;dnlg3 double mutation also led to satellite boutons. These results suggested that DNrx and DNlgs jointly maintain the development and function of NMJ boutons by regulating the balance of ghost and satellite boutons in Drosophila.


Variations in the Bioactive Compounds Composition and Biological Activities of Loofah (Luffa cylindrica) Fruits in Relation to Maturation Stages.
The present work aimed to determine the antioxidant and antiproliferative potential of Luffa cylindrica fruits collected at two different maturation stages and to identify and compare their functional components composition. The MeOH extracts of L. cylindrica fruits harvested at 60 - 65 days after seeding (S1) and 85 - 90 days after seeding (S2) were investigated for their antioxidant activity using various assays. Furthermore, the antiproliferative activity of the extracts against HeLa human cervical cancer cells was explored with xCELLigence real time cell analyzer, while the effect of the samples on the membrane integrity of the same cell line was assessed using LDH cytotoxicity leakage assay. Ultimately, the phytochemicals were analyzed using GC/MS and HPLC/TOF-MS. The S1 sample had higher contents and more diversity in the phenolic compounds composition than S2. Furthermore, the S1 extract showed the highest antioxidant and antiproliferative activity, while the S2 extract had higher cytotoxicity towards HeLa cells. The findings revealed that the time of harvest has a big impact on the phytochemicals content and activity and that harvesting L. cylindrica at an early stage before the beginning of the development of the cellulose fibrous system is recommended for a rich phytochemical composition and efficient antioxidant and antiproliferative activities.


Relative food prices and obesity in US Metropolitan areas: 1976-2001.
This study investigates the impact of food price on obesity, by exploring the co-occurrence of obesity growth with relative food price reduction between 1976 and 2001. Analyses control for female labor participation and metropolitan outlet densities that might affect body weight. Both the first-difference and fixed effects approaches provide consistent evidence suggesting that relative food prices have substantial impacts on obesity and such impacts were more pronounced among the low-educated. These findings imply that relative food price reductions during the time period could plausibly explain about 18% of the increase in obesity among the U.S. adults in metropolitan areas.


A new approach to rheumatoid arthritis: treating inflammation with computerized nerve stimulation.
Doctors currently treat rheumatoid arthritis, a crippling autoimmune disease, with an arsenal of drugs that, while often effective, can have serious side effects. Authors Ulf Andersson and Kevin J. Tracey describe a circuit between the immune system and the nervous system that enabled development of an implanted nerve stimulator to treat the disorder, now being tested by a patient in Bosnia. If further clinical trials show as much promise as this initial case, similar devices may be developed for a broad range of inflammation-related diseases, from diabetes to congestive heart failure.


Relationship among skin tests, bronchial challenge and serology in house dust and Candida albicans allergic asthma.
One hundred and ninety-six asthmatic patients were examined by inhalation challenge using house dust and candida albicans; an early, dual or late bronchial response was induced where IgE, C3 and C4 were elevated. In some of late responses by candida inhalation there was a decrease or almost no increase in IgE and a fall in C3 and C4. There was a considerable correlation between skin tests and bronchial responses. An induced bronchial response, early, dual or late, was identified as Type I, While candida-induced late bronchial responses were Type I and Type III. There is some question whether Type I plus Type III mechanism may be involved in the dual bronchial response provoked with candida.


A peptide targeted contrast agent specific to fibrin-fibronectin complexes for cancer molecular imaging with MRI.
A peptide targeted contrast agent, CLT1-(Gd-DTPA), was synthesized for molecular imaging of fibronectin-fibrin complexes in tumor tissue with magnetic resonance imaging (MRI). The T(1) and T(2) relaxivities of CLT1-(Gd-DTPA) were 4.22 and 4.45 mM(-1) s(-1) at 3 T, respectively. The targeted contrast agent specifically bound to tumor tissue and resulted in significant tumor contrast enhancement at a dose of 0.1 mmol Gd/kg for at least 60 min in mice bearing HT-29 human colon carcinoma xenografts as shown in dynamic MR images. In contrast, a control nontargeted contrast agent, Gd(DTPA-BMA), was cleared rapidly with little tumor enhancement 60 min postinjection. Tumor enhancement with CLT1-(Gd-DTPA) was significantly reduced after coinjection with a 3-fold excess of free CLT1 peptide. The preliminary study has shown that CLT1-(Gd-DTPA) can specifically bind to the fibrin-fibronectin complexes in tumor tissues, resulting in significant tumor enhancement. The targeted contrast agent has a potential for cancer molecular imaging with MRI.


Managing conflict of interest in research: some suggestions for investigators.
Conflict of interest situations threaten to compromise objectivity and tempt researchers to act wrongly. Allowing oneself to drift into such situations without appropriate preparation is negligence which is, itself, a sort of wrongdoing. Since conflict of interest is unlikely to be eliminated or tamed by the professional--and institutional--level safeguards currently under discussion, individual researchers must make their own preparations. We offer individuals ten strategies for managing their own conflicts of interest.


Interface Design of SnO2@PANI Nanotube With Enhanced Sensing Performance for Ammonia Detection at Room Temperature.
Gas sensors with excellent stability and a high response at room temperature has drawn a great deal of attention and demand for them is huge. Surface designs provide inspiration toward making more useful sensor devices. The facile electrospinning process and Ar plasma treatment are used to fabricate rich and stable oxygen vacancies that contain a core-shell structured SnO2 polyaniline (PANI) nanotube. It shows that the induced surface oxygen vacancies would accelerate the PANI shell to generate more protons, which can enhance its sensor responsibility through reacting with the target Ammonia (NH3) gas. It was also found that the obtained oxygen vacancies can be well-protected by the coated PANI shell, which enhance and stabilize the gas response. It shows that the room temperature for the gas response of NH3 can reach up to 35.3 at 100 ppm. Finally, its good stability is demonstrated by the response-recovery performances carried out over 3 months and multiple cycles. This work indicates that this well-designed PANI-coated plasma-treated SnO2 is a potential way to design ammonia gas sensors.


Exploring Autonomic Alterations during Seizures in Temporal Lobe Epilepsy: Insights from a Heart-Rate Variability Analysis.
Epilepsy's impact on cardiovascular function and autonomic regulation, including heart-rate variability, is complex and may contribute to sudden unexpected death in epilepsy (SUDEP). Lateralization of autonomic control in the brain remains the subject of debate; nevertheless, ultra-short-term heart-rate variability (HRV) analysis is a useful tool for understanding the pathophysiology of autonomic dysfunction in epilepsy patients. A retrospective study reviewed medical records of patients with temporal lobe epilepsy who underwent presurgical evaluations. Data from 75 patients were analyzed and HRV indices were extracted from electrocardiogram recordings of preictal, ictal, and postictal intervals. Various HRV indices were calculated, including time domain, frequency domain, and nonlinear indices, to assess autonomic function during different seizure intervals. The study found significant differences in HRV indices based on hemispheric laterality, language dominancy, hippocampal atrophy, amygdala enlargement, sustained theta activity, and seizure frequency. HRV indices such as the root mean square of successive differences between heartbeats, pNN50, normalized low-frequency, normalized high-frequency, and the low-frequency/high-frequency ratio exhibited significant differences during the ictal period. Language dominancy, hippocampal atrophy, amygdala enlargement, and sustained theta activity were also found to affect HRV. Seizure frequency was correlated with HRV indices, suggesting a potential relationship with the risk of SUDEP.


Maternal late pregnancy anxiety and stress is associated with children's health: a longitudinal study.
Maternal prenatal anxiety and stress (PNS) have been positively associated to physical health prob lems in offspring in the first year of life. Whether these associations are transient, persistent, or even progressive over time, is as yet unknown. The goal of this study is to investigate associations between late pregnancy PNS and child health from 18 months to age 6. Mothers were recruited in late pregnancy, and had uncomplicated, singleton pregnancies without physical health problems. Around week 37 of pregnancy, mothers reported on their PNS by means of questionnaires, and provided saliva for determination of circadian cortisol concentrations. Children's illnesses in the preceding year were assessed using maternal reports at 30, 48, 60, and 72 months. Antibiotic use was obtained from medical records between one and six years. Multilevel models (N¼174) showed a positive relation between maternal prenatal general and pregnancy-specific anxiety during late pregnancy and offspring respiratory illnesses and symptoms. Interaction effects with time indicated that more PNS was related to more respiratory illnesses until toddlerhood, but not later in life. Furthermore, maternal prenatal cortisol concentrations were related to child digestive illnesses. A steeper maternal cortisol decline over the day was related to more child digestive illnesses, until around three years of age. Finally, children of mothers who suffered more from daily hassles during pregnancy received more antibiotics between one and six years of age. PNS was not related to general and skin illnesses. Summarizing, this study showed that late pregnancy anxiety and cortisol was associated with children's respiratory and digestive illnesses till the age of 3.0-3.5 years. Additionally, more daily hassles were related to more prescribed antibiotics between one and six years. These findings point in the direction of possible effects of PNS persisting beyond the first year of life and into toddlerhood, but disappearing at older ages.


The first line of offense.
The front line of offense Community health workers extend the hospital's reach beyond its own four walls, an imperative under the new quality and payment measures. How should you manage this new staff?


S-glutathionylation of Hsp90 enhances its degradation and correlates with favorable prognosis of breast cancer.
Heat shock protein 90 (Hsp90) is a ubiquitous chaperone to interact with numerous proteins to regulate multiple cellular processes, especially during cell proliferation and cell cycle progression. Hsp90 exists in a high level in tumor cells and tissues, and thus serves as a prognostic biomarker or therapeutic target in cancers. We herein report that Hsp90 is subjected to S-glutathionylation, a redox-dependent modification to form a disulfide bond between the tripeptide glutathione and cysteine residues of proteins, primarily at C366 and C412 in the presence of reactive oxygen species. The modification led to the loss of the ATPase activity. The level of Hsp90 was obviously reduced by S-glutathionylation, owing to C-terminus of Hsc70-interacting protein (CHIP)-mediated ubiquitin proteasome system. S-glutathionylation of Hsp90 was found to crosstalk with its C-terminal phosphorylation of Hsp90 that impedes the binding of Hsp90 with CHIP, demonstrating the importance of chaperone code in modulating Hsp90 function. Further biophysical analyses indicated that S-glutathionylation caused structural change of Hsp90, underlying the aforementioned functional regulation. Moreover, in accordance with the analysis of 64 samples collected from patients of breast cancer, the expression level of Hsp90 inversely correlated with the glutathionylated status of Hsp90. The ratio of total expression to glutathionylated status of Hsp90 was coherent to expression of biomarkers in breast cancer sample, potentiating the prognostic value in the cancer treatment.


[Immunotherapeutic principles in the treatment of tumors].
Numerous clinical and experimental immunological studies have shown that the activity of the immune system plays a decisive role in the course of tumor-macro-organism interaction. The aim of the present paper was to characterize the basic principles which should be taken into consideration in the complex strategy of cancer management. The best therapeutic effect can be achieved when the immune system is changed from the state of tumor-protective activity into tumor-destructive activity. This can be achieved by the combined effect of three synergistic procedures: (1) elimination of the suppressive influence of tumor cells on the immune system; (2) elimination of the suppressive activity of the immune system; (3) stimulation of anti-tumor effector cell populations of the immune system. (Ref. 53.)


Chronic airspace disease: Review of the causes and key computed tomography findings.
Chronic airspace diseases are commonly encountered by chest, body or general radiologists in everyday practice. Even though there is significant overlap in the imaging findings of different causes of chronic airspace disease, some key clinical, laboratory and imaging findings can be used to guide the radiologist to the correct diagnosis. The goal of this article is to review and compare these features.


Insulin, glucagon and somatostatin localization in the pancreas of metamorphosed Xenopus laevis.
The current study was designed to determine if insulin, glucagon and somatostatin-containing cells are present in the pancreas of adult Xenopus laevis. Localization methods utilized included cytochemical aldehyde fuchsin (AF) staining as well as the immunochemical peroxidase antiperoxidase (PAP) procedure for light microscopy. The results show numerous large clusters of AF-positive cells within a network of highly vascularized acinar tissue. PAP immunochemical localization with insulin antibody on adjacent sections demonstrates positive immunoreactivity to AF-positive cell groups and also the presence of immunoreactive insulin (IRI). Cells exhibiting this immunoreactivity are located in the central region of the islet-like structures. Serial sections not only show PAP immunoreactivity for IRI, but also for immunoreactive glucagon (IRG) and immunoreactive somatostatin (IRS) in the same islet-like structure. IRG and IRS-containing cells are situated around the periphery of the islet-like structures, surrounding the central core of IRI-containing cells. Antibody specificity was confirmed by homologous and heterologous antigen immuno-absorbance assays, as well as incubation of adjacent sections in preimmune sera. Based on this data we conclude that: the distribution of cells of the endocrine pancreas of metamorphosed Xenopus laevis is similar to that of many mammals and certain urodeles. Given the apparent specificity of the antigen-antibody reactions, it appears that Xenopus insulin, glucagon and somatostatin are structurally conserved.


Structural convergence of maize and wheat straw during two-year decomposition under different climate conditions.
Straw decomposition plays an important role in soil carbon sequestration. Litter quality and climate condition are considered to be key factors that regulate straw decomposition. This study investigated the decomposition characteristics of wheat and maize straw under cold temperate, warm temperate, and midsubtropic climate conditions, and examined whether the chemical structures of straw residues became similar during decomposition under different climate conditions. Straws were put in 0.074-mm-mesh size litter bags to exclude soil fauna and buried in black soil plots at three experimental stations located in the aforementioned climate regions to rule out the impact of soil type. The decomposition rate constants of wheat straw and maize straw increased linearly with temperature, and the former was more sensitive to temperature. Climate conditions and straw quality had marked effects on the residual material structure in the first half year of decomposition, but then decreased. Wheat and maize straw showed common decomposition characteristics with a decrease of O/N-alkyl carbons and di-O-alkyls, and a simultaneous increase of alkyl carbons, aromatic carbons, aromatic C-O groups, and COO/N-C ═ O groups. Overall, the results indicated that the chemical compositions of the two types of straw became similar after 2-year decomposition under different climate conditions.


Variable-temperature structural studies on valence tautomerism in cobalt bis(dioxolene) molecular complexes.
A variable-temperature single-crystal structural study of five valence tautomeric cobalt molecular complexes, CoII(3,5-DBSQ)2(DBPy)2 (1), CoII(3,5-DBSQ)2(DBPy)2·1.33C7H8 (1S), CoII(3,5-DBSQ)2(DCPy)2·C7H8 (2S), CoII(3,5-DBSQ)2(TBPy)2 (3) and CoII(3,5-DBSQ)2(TCPy)2 (4) (S = toluene, 3,5-DBSQ = 3,5-di-tert-butylsemiquinonate, DBPy = 3,5-dibromopyridine, DCPy = 3,5-dichloropyridine, TBPy = 3,4,5-tribromopyridine and TCPy = 3,4,5-trichloropyridine) is reported. The re-crystallization of (1S) in toluene at 277 K resulted in a concomitant formation of a solvent-free polymorph, CoII(3,5-DBSQ)2(DBPy)2 (1). Thermally induced valence tautomerism (VT) is observed only in (1S), (1) and (2S) [hs-CoII(3,5-DBSQ)2L2 ↔ ls-CoIII(3,5-DBSQ)(3,5-DBCat)L2 (hs = high spin, ls = low spin, 3,5-DBCat = 3,5-di-tert-butylcatecholate)], whereas (3) and (4) remain locked in the hs-CoII(3,5-DBSQ)2 state during cooling of the sample. Multi-temperature single-crystal studies demonstrate the change in cobalt coordination environment during the VT conversion. The non-solvated compound (1) shows a sharp VT transition (T1/2 ∼ 245 K with ΔT ∼ 10 K) from hs-CoII(3,5-DBSQ)2(DBPy)2 to ls-CoIII(3,5-DBSQ)(3,5-DBCat)(DBPy)2 oxidation state, whereas the other polymorph with lattice solvent (1S) results in a broad transition (T1/2 ∼ 150 K with ΔT ∼ 100 K). This increase in the VT transition temperature for (1) relative to (1S) illustrates the effect of lattice solvent on the VT transition mechanism. Additionally, the influence of halogen substitutions on the pyridine ring is discussed with respect to observed VT behaviour in the studied compounds.


Management of narcolepsy during pregnancy.
The management of pregnancy in patients with narcolepsy poses many questions regarding therapy, including the risk to the mother and fetus related to the disease, potential risks at the time of conception, the risk to both the mother and the fetus of the medications used to treat narcolepsy, and the risk to the infant from medications that might be secreted in breast milk. There are no detailed practice parameters on the treatment of narcolepsy patients during pregnancy. We surveyed narcolepsy specialists from around the world to determine their clinical approach to the management of patients with narcolepsy at the time of conception, during pregnancy and while breastfeeding. Survey invitations were sent via e-mail to 75 clinicians worldwide between 2/2011 and 3/2011 with 34 responses (USA, n=10; Brazil, n=3; Czech Republic, n=2; France, n=2; Italy; n=2; Netherlands, n=2; Canada, n=1; Denmark, n=1; Finland, n=1; Germany, n=1; Japan, n=1; Spain, n=1; unknown n=7). Responders who completed the survey had 20 years (median range, 5-35) of experience in sleep medicine practice with a median number of five narcolepsy patients seen per week. The number of pregnant narcoleptic patients followed per physician was five (median range 1-40). The survey results indicated that the management of patients with narcolepsy varies greatly from clinician to clinician and from country to country. The majority of the clinicians stopped the narcolepsy medications at the time of conception, during pregnancy, and during breastfeeding some reduced the dose and others did not change the dosage, depending on the particular medication. The findings from our survey and literature review suggest that the perceived risks of narcolepsy medication during pregnancy to the mother and the fetus usually are overestimated, as the risk for teratogenic effects from narcolepsy medications in therapeutic doses is essentially nonexistent. However, the potential for rare complications during pregnancy and congenital abnormalities cannot be excluded. Most narcolepsy patients have vaginal delivery without complications. In rare cases patients had cataplexy that interfered with delivery, but if caesarian is required there appears to be no increased anaesthetic or surgical risks. Further prospective information for the appropriate treatment of narcolepsy patients during pregnancy is needed.


Idiopathic subglottic stenosis: a familial predisposition.
Idiopathic subglottic stenosis is a narrowing of the trachea at the level of the cricoid cartilage of unknown etiology. It is a rare condition for which the real incidence has never been established owing to the difficulty of making the diagnosis. Although there is a female preponderance, no familial cases have been reported in the literature. We describe two pairs of sisters as well as a mother and daughter presenting with idiopathic subglottic stenosis. All known causes of tracheal stenosis were excluded, including prolonged intubation, surgery, autoimmune and inflammatory disorders, infection and gastroesophageal reflux disease. These are the first cases reported in the literature that suggest a genetic predisposition for idiopathic subglottic stenosis.


[Ketanserin as antioxidant].
Free radicals have been related to the pathogenesis of some cardiovascular diseases. Several drugs used to treat these diseases were shown to have antioxidant properties. Our purpose was to evaluate if ketanserin, a selective S2 receptor antagonist with proven antihypertensive efficacy and which beneficially affects hemorheology, also is able to inhibit lipid peroxidation. Lipid peroxidation was induced in different biological systems in vitro and evaluated by the formation of thiobarbituric acid-reactive products. Ketanserin 50 microM inhibited copper-dependent lipid peroxidation in human red-cell suspensions by 40.8% and the subsequent hemolysis by 57,3%. It was less efficient in inhibiting hydrogen peroxide-dependent lipid peroxidation and hemolysis in the same system. Ketanserin 100 microM inhibited lipid peroxidation induced by a mixture of copper(II) and hydrogen peroxide in hepatic microsomal suspensions and in brain total homogenates by 86.2% and 56.7%, respectively. These results proved an antioxidant effect for ketanserin which was unknown, although its therapeutic relevance remains undetermined.


Genetic aspects of the blood transfusion effect.
The genetic requirements for the induction of the blood transfusion effect have been investigated in a genetically well-defined model. The survival of fully vascularized, heterotopic murine cardiac allografts was measured after a single preoperative transfusion of blood from mice selected to share MHC and/or minor histocompatibility (miH) antigens with the organ donor. The effect of a transfusion from a donor unrelated to the heart donor (third-party transfusion) on allograft survival was also determined. Five strain combinations were used for these experiments. The results obtained illustrate a number of important aspects of the blood transfusion effect in this model: (1) Donor-specific blood transfusion, where MHC and miH were shared by the blood donor and the organ donor, always induced prolonged graft survival. (2) The sharing of the whole MHC (H-2) by the blood donor and organ donor was found to be sufficient to prolong allograft survival in the five fully allogeneic strain combinations tested. (3) The sharing of miH antigens only was not sufficient to induce prolonged cardiac allograft survival. Special cases were identified showing that several factors could interact to potentiate the action of miH antigens in the induction of the blood transfusion effect. (4) Transfusion with blood from a third-party donor was effective in some strain combinations. In one recipient, blood from several third-party strains of mice, sharing neither MHC nor miH antigens with the organ donor, induced prolonged graft survival. We suggest that the mechanism by which third-party blood has a beneficial effect on graft survival is through crossreaction(s) between the blood donor and the organ donor. The results obtained in this study fit very well with one model for the cellular mechanism by which the transfusion effect may be mediated. This may be the means by which blood from randomly selected donors has a beneficial effect on graft survival in clinical transplantation.


Increased biosynthesis of complement components by cultured monocytes, synovial fluid macrophages and skynovial membrane cells from patients with rheumatoid arthritis.
Monocytes, synovial fluid (SF) and synovial membrane (SM) macrophages from patients with rheumatoid arthritis (RA) were maintained in short-term tissue culture for up to 10 days, and the synthesis of C4, C2, C3, C5, factor B(B), D, properdin (P), C3b inactivator (C3bINA) and beta 1H globulin studied. Functionally active C2, B, D, P, C3bINA and beta 1H were synthesized by the cells in each type of culture. C4, C3 and C5 could be detected, but were functionally inactive. RA monocytes synthesized more C2 than monocytes from patients with degenerative joint disease (DJD) (P < 0.001). Similar studies revealed that SF macrophages synthesized more C3 than SM macrophages (P < 0.001) which in turn produced more C2 than monocytes (P < 0.001). Other experiments showed that SF macrophages synthesized more of each component than the other cell types. SM macrophages made more C2 than B than RA and DJD monocytes, but synthesized only small quantities of P, D and beta 1H. RA monocytes synthesized more of each component than DJD monocytes. The results of these studies show that (1) in RA, complement components can be synthesized locally in the inflamed joints, and (2) local factors in the joints probably stimulate complement synthesis.


Selecting embryos with the highest implantation potential using data mining and decision tree based on classical embryo morphology and morphokinetics.
The objective of this work was to determine which embryonic morphokinetic parameters up to D3 of in vitro development have predictive value for implantation for the selection of embryos for transfer in clinical practice based upon information generated from embryo transfers with known implantation data (KID). A total of 800 KID embryos (100% implantation rate (IR) per transfer and 0% IR per transfer) cultured in an incubator with Time-Lapse system were retrospectively analysed. Of them, 140 embryos implanted, whereas 660 did not. The analysis of morphokinetic parameters, together with the embryo morphology assessment on D3, enabled us to develop a hierarchical model that places the classical morphological score, the t4 and t8 morphokinetic values, as the variables with the best prognosis of implantation. In our decision tree, the classical morphological score is the most predictive parameter. Among embryos with better morphological scores, morphokinetics permits deselection of embryos with the lowest implantation potential.


Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10).
Green tea catechins (GT-catechins) have been reported to have an antioxidative effect. We investigated the effect of long-term GT-catechin intake on aging and oxidative damage using aged mice with accelerated senescence (SAMP10), a model of brain senescence with cerebral atrophy and cognitive dysfunction. Major atrophy was observed in the rhinencephalon, hippocampus and striatum of 12-month-old untreated SAMP10 mice. Similarly, levels of 8-oxodeoxyguanosine (8-oxodG), a marker of oxidative DNA damage, were higher in these parts of the cerebrum than in the cerebral cortex and liver. GT-catechin intake effectively suppressed such atrophy in 12-month-old SAMP10 mice. A preventive effect of GT-catechin intake on oxidative DNA damage was also observed in the rhinencephalon (an area particularly susceptible to atrophy) at 6 months of age, i.e. during the early stages of atrophy. A suppressive effect of GT-catechin intake on cognitive dysfunction, as determined by the learning time needed to acquire an avoidance response and assessments of working memory in a Y-maze, was also found in 12-month-old mice. These results suggest that GT-catechin intake partially improves the morphologic and functional alterations that occur naturally in the brains of aged SAMP10 mice.


Characterization of mouse tissue kallikrein 5.
Mouse tissue kallikreins (Klks) are members of a large, multigene family consisting of 37 genes, 26 of which can code for functional proteins. Mouse tissue kallikrein 5 (Klk5) has long been thought to be one of these functional genes, but the gene product, mK5, has not been isolated and characterized. In the present study, we prepared active recombinant mK5 using an Escherichia coli expression system, followed by column chromatography. We then determined the biochemical and enzymatic properties of purified mK5. mK5 had trypsin-like activity for Arg at the P1 position, and its activity was inhibited by typical serine protease inhibitors. mK5 degraded gelatin, fibronectin, collagen type IV, high-molecular-weight kininogen, and insulin-like growth factor binding protein-3. Our data suggest that mK5 may be implicated in the process of extracellular matrix remodeling.


Autologous cultured adipose derived mesenchymal stem cells combined with hyaluronic acid hydrogel in the treatment of discogenic low back pain: a study protocol for a phase II randomised controlled trial.
Discogenic low back pain (DLBP) is a common disease, and its occurrence is closely related to intervertebral disc (IVD) degeneration. At present, none of the traditional treatment methods can repair the degenerated IVD. The emergence of stem cell therapy makes it possible to repair and regenerate IVD tissue, among which adipose derived mesenchymal stem cells (ADMSCs) transplantation therapy has become a hot spot of current research. Therefore, this trial aimed to investigate the safety and efficacy of using autologous cultured ADMSCs combined with hyaluronic acid (HA) hydrogel in the treatment of DLBP. This study is a randomised, dose-escalation, placebo-controlled, double-blind, single-centre, phase II clinical trial to evaluate the efficacy and safety of autologous cultured ADMSCs combined with HA hydrogel in the treatment of patients with DLBP. The 100 eligible patients will be randomly divided into three experimental groups with different doses and one placebo control group in a ratio of 1:1:1:1. All patients will undergo liposuction to obtain ADMSCs, followed by autologous cultured ADMSC mixtures or placebo transplantation after 3 weeks. The patients will be followed up to 24 months after the transplant. The primary end point of this trial is the Visual Analogue Scale. Secondary end points include the Oswestry Disability Index, Japanese Orthopaedic Association Scores, the Mos 36-item short form, the Modic classification, Pfirrmann grade, height and segment range of motion of the IVD, vital signs (temperature, pulse, respiration, blood pressure), blood routine, liver and kidney function, immunological examination, urinalysis and treatment emergent adverse events. The study protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University and registered in the Chinese Clinical Trial Registry. Dissemination of the results will be presented at a conference and in peer-reviewed publications. ChiCTR2200058291.


Chinese family management of chronic childhood conditions: a cluster analysis.
This study compared the management of chronic childhood conditions in Chinese families and identified predictors of management style. A survey was conducted in 2008-2009 on a convenience sample of 387 caregivers of children with chronic conditions. Six family management styles (FMSs) were identified: accomplished, uncertain managing, joint managing, managing with difficulty, struggling, and competent managing. The FMSs were related to the functioning of the family and the child. Changes in parents' employment, geographic location, and diagnosis predicted family placement in a cluster. Understanding Chinese FMSs will further aid in providing culturally appropriate family-centered care. Awareness of the predictors of FMSs can assist nurses in detecting which families need more help.


Development of a versatile resource for post-genomic research through consolidating and characterizing 1500 diverse wild and cultivated soybean genomes.
With advances in next-generation sequencing technologies, an unprecedented amount of soybean accessions has been sequenced by many individual studies and made available as raw sequencing reads for post-genomic research. To develop a consolidated and user-friendly genomic resource for post-genomic research, we consolidated the raw resequencing data of 1465 soybean genomes available in the public and 91 highly diverse wild soybean genomes newly sequenced. These altogether provided a collection of 1556 sequenced genomes of 1501 diverse accessions (1.5 K). The collection comprises of wild, landraces and elite cultivars of soybean that were grown in East Asia or major soybean cultivating areas around the world. Our extensive sequence analysis discovered 32 million single nucleotide polymorphisms (32mSNPs) and revealed a SNP density of 30 SNPs/kb and 12 non-synonymous SNPs/gene reflecting a high structural and functional genomic diversity of the new collection. Each SNP was annotated with 30 categories of structural and/or functional information. We further identified paired accessions between the 1.5 K and 20,087 (20 K) accessions in US collection as genomic "equivalent" accessions sharing the highest genomic identity for minimizing the barriers in soybean germplasm exchange between countries. We also exemplified the utility of 32mSNPs in enhancing post-genomics research through in-silico genotyping, high-resolution GWAS, discovering and/or characterizing genes and alleles/mutations, identifying germplasms containing beneficial alleles that are potentially experiencing artificial selection. The comprehensive analysis of publicly available large-scale genome sequencing data of diverse cultivated accessions and the newly in-house sequenced wild accessions greatly increased the soybean genome-wide variation resolution. This could facilitate a variety of genetic and molecular-level analyses in soybean. The 32mSNPs and 1.5 K accessions with their comprehensive annotation have been made available at the SoyBase and Ag Data Commons. The dataset could further serve as a versatile and expandable core resource for exploring the exponentially increasing genome sequencing data for a variety of post-genomic research.


Professional skills and frame of work organization in managing borderline personality disorder. Shared philosophy or ambivalence--a qualitative study from the view of caregivers.
Caregivers' experiences and beliefs of working with borderline personality disorder (BPD) in a psychiatric organization were investigated using a qualitative analysis of 29 in-depth interviews. The analysis identified eight characteristics, which were organized in two core concepts. The first of these core concepts, professional skills of mental health work, comprised the categories of empathy for persons with BPD, interest in treating the disorder, feelings of professional frustration and need for a common outlook. The second core concept, frame of work organization, that is categories common to the organization, included ambivalence between the professions of the caregivers, the need for structure in organizing the work, forms of emotional support to the caregivers and the need for a shared philosophy of care. A tentative model was proposed to illustrate the effects of these factors on the type and outcome of work that interact with the care of the patient. It is concluded that ambivalence in the division of labour may be a critical hindrance to the development of cooperation in the care of BPD patients. It is suggested that a shared common philosophy will support corresponding ethical standards by individual practitioners for the benefit of patient outcome.


[Ureterosigmoidostomy with the formation of low pressure reservoir: history or operation of choice? 15 years of experience].
To examine the long-term outcomes of Mainz Pouch II ureterosigmoidostomy with the formation of a submucosal and extramural by Hassan (Hassan Abol-Enein) tunnels. Mainz Pouch II ureterosigmoidostomies with the formation a submucosal tunnel (open-end technique) comprised group 1 (n=17) and with the formation of extramural ureteral implantation by Hassan - group 2 (n=15). The mean age of patients was 58+/-6.0 years, ranging from 16 to 76 years; among them there were 22 (68.8%) men and 10 (31.2%) women. Average follow-up was 14.7+/-6.0 years. All patients were continent during the daytime and at nighttime. Reservoir-ureteral reflux was detected in 2.4% (5 RU) observations and the obstruction only 1.4% (2 RU). Chronic pyelonephritis in the postoperative period was observed in 3 (9.75%) patients, whereas before surgery in 20 (62.5%) patients. The both modifications of the operation did not impair renal secretory function postoperatively in the majority of patients; in 2 of them its improvement was noted. Two patients experienced a decrease in the renal secretory function due to inadequate formation of extramural anastomosis. Mainz Pouch II and Hassan operations enable maintaining normal urination, optimize antireflux protection and are technically simple, provided the indications are carefully observed. The low incidence of complications of ureterosigmoidostomy, both in the immediate and in the long term implies that these operations may be the method of choice for continent bladder replacement in selected patients.


Spontaneous regression of primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) colliding with invasive ductal carcinoma of the breast: a case report.
Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer.


Triple-Function Au-Ag-Stuffed Nanopancakes for SERS Detection, Discrimination, and Inactivation of Multiple Bacteria.
New strategies combining sensitive pathogenic bacterial detection and high antimicrobial efficacy are urgently desirable. Here, we report smart triple-functional Au-Ag-stuffed nanopancakes (AAS-NPs) exhibiting (1) controllably oxidative Ag-etching thickness for simultaneously obtaining the best surface-enhanced Raman scattering (SERS) enhancement and high Ag-loading antibacterial drug delivery, (2) expressive Ag+-accelerated releasing capability under neutral phosphate-buffered saline (PBS) (pH ∼ 7.4) stimulus and robust antibacterial effectiveness involving sustainable Ag+ release, and (3) three-in-one features combining specific discrimination, sensitive detection, and inactivation of different pathogenic bacteria. Originally, AAS-NPs were synthesized by particle growth of the selective Ag-etched Au@Ag nanoparticles with K3[Fe(CN)6], followed by the formation of an unstable Prussian blue analogue for specifically binding with bacteria through the cyano group. Using specific bacterial "fingerprints" resulting from the introduction of dual-function 4-mercaptophenylboronic acid (4-MPBA, serving as both the SERS tag and internal standard) and a SERS sandwich nanostructure that was made of bacteria/SERS tags/AAS-NPs, three bacteria (E. coli, S. aureus, and P. aeruginosa) were highly sensitively discriminated and detected, with a limit of detection of 7 CFU mL-1. Meanwhile, AAS-NPs killed 99% of 1 × 105 CFU mL-1 bacteria within 60 min under PBS (pH ∼ 7.4) pretreatment. Antibacterial activities of PBS-stimulated AAS-NPs against S. aureus, E. coli, and P. aeruginosa were extraordinarily increased by 64-fold, 72-fold, and 72-fold versus PBS-untreated AAS-NPs, respectively. The multiple functions of PBS-stimulated AAS-NPs were validated by bacterial sensing, inactivation in human blood samples, and bacterial biofilm disruption. Our work exhibits an effective strategy for simultaneous bacterial sensing and inactivation.


Healthy mothers with normal cardiotocograms at term. Is maternal age a true determinant of perinatal outcome?
to study the true determinants of adverse perinatal outcome (APO) in term healthy mothers with normal cardiotocograph (CTG), evaluating the real influence of maternal age. In a retrospective study, we assessed a group of 529 term healthy mothers with normal CTGs that regardless of maternal age, evolved spontaneously up to 41 ± 2 weeks. The result of the conservative management was evaluated by means of univariable and multivariable logistic regression analysis, determining the association of maternal age and other clinical and ultrasonographical parameters with APO. In contrast with low CPR MoM (OR = 0.155, p = .014), induction of labor (OR = 2.273, p = .023) and low parity (OR = 0.494, p = .026), maternal age and birth weight centile did not prove to be true determinants of perinatal outcome. The multivariable model for prediction of APO using clinical parameters presented a sensitivity of 35% and 27% for a false positive rate of 10% and 5%, AUC 0.736 (95% CI 0.655-0.818), p < .0001). in healthy old mothers with normal CTGs at term, APO is determined by low CPR, the existence of labor induction and low parity, while no real influence was observed for maternal age, fetal smallness, and interval examination-delivery. These results do not support the current consensus on induction at earlier weeks to prevent adverse outcomes in all cases of advanced maternal age, advocating for a more individualized, customized, and less interventional management based on fetal hemodynamics.


Extracting decision-making features from the unstructured eye movements of clinicians on glaucoma OCT reports and developing AI models to classify expertise.
This study aimed to investigate the eye movement patterns of ophthalmologists with varying expertise levels during the assessment of optical coherence tomography (OCT) reports for glaucoma detection. Objectives included evaluating eye gaze metrics and patterns as a function of ophthalmic education, deriving novel features from eye-tracking, and developing binary classification models for disease detection and expertise differentiation. Thirteen ophthalmology residents, fellows, and clinicians specializing in glaucoma participated in the study. Junior residents had less than 1 year of experience, while senior residents had 2-3 years of experience. The expert group consisted of fellows and faculty with over 3 to 30+ years of experience. Each participant was presented with a set of 20 Topcon OCT reports (10 healthy and 10 glaucomatous) and was asked to determine the presence or absence of glaucoma and rate their confidence of diagnosis. The eye movements of each participant were recorded as they diagnosed the reports using a Pupil Labs Core eye tracker. Expert ophthalmologists exhibited more refined and focused eye fixations, particularly on specific regions of the OCT reports, such as the retinal nerve fiber layer (RNFL) probability map and circumpapillary RNFL b-scan. The binary classification models developed using the derived features demonstrated high accuracy up to 94.0% in differentiating between expert and novice clinicians. The derived features and trained binary classification models hold promise for improving the accuracy of glaucoma detection and distinguishing between expert and novice ophthalmologists. These findings have implications for enhancing ophthalmic education and for the development of effective diagnostic tools.


Scaling properties of critical bubble of homogeneous nucleation in stretched fluid of square-gradient density-functional model with triple-parabolic free energy.
The square-gradient density-functional model with triple-parabolic free energy is used to study the homogeneous bubble nucleation in a stretched liquid to check the scaling rule for the work of formation of the critical bubble as a function of scaled undersaturation Delta mu/Delta mu(spin), the difference in chemical potential Deltamu between the bulk undersaturated and saturated liquid divided by Delta mu(spin) between the liquid spinodal and saturated liquid. In contrast to our study, a similar density-functional study for a Lennard-Jones liquid by Shen and Debenedetti [J. Chem. Phys. 114, 4149 (2001)] found that not only the work of formation but also other various quantities related to the critical bubble show the scaling rule; however, we found virtually no scaling relationships in our model near the coexistence. Although some quantities show almost perfect scaling relations near the spinodal, the work of formation divided by the value deduced from the classical nucleation theory shows no scaling in this model even though it correctly vanishes at the spinodal. Furthermore, the critical bubble does not show any anomaly near the spinodal as predicted many years ago. In particular, our model does not show diverging interfacial width at the spinodal, which is due to the fact that compressibility remains finite until the spinodal is reached in our parabolic models.


Glycosylation variant analysis of recombinant human tissue plasminogen activator produced in urea-cycle-enzyme-expressing Chinese hamster ovary (CHO) cell line.
Tissue plasminogen activator (tPA) was produced in ornithine transcarbamoylase (OTC) cells by introducing the tPA gene into OTC cells. OTC cells were originally derived from Chinese hamster ovary (CHO) cells and express the first two enzymes of the urea cycle, carbamoyl phosphate synthetase I (CPS I) and OTC. To investigate glycosylation variants, tPA variants produced in serum-supplemented culture medium of OTC-tPA cells were separated by lysine-Sepharose 4B chromatography. Unlike in previous studies that used lysine-Sepharose chromatography, two peaks were identified to correspond to eluted glycosylation variants type I and II and type II and the percentages of the type I and type II variants were found to be 23% and 77%, respectively. The biological activities of the type I and II and type II variants were twofold that of the Third International tPA Standard (98/714) produced in the CHO cell line, and the activity of type II variant was 12.6% higher than that of the type I and II variants. These results demonstrate that tPA produced in urea-cycle-enzyme-producing OTC cells have a very high biological activity and the percentage of type II variant which is very valuable for the biopharmaceutical industry is higher than that of any report using CHO cells.


Increased Arginase1 expression in tumor microenvironment promotes mammary carcinogenesis via multiple mechanisms.
Arginine metabolism plays a significant role in regulating cell function, affecting tumor growth and metastatization. To study the effect of the arginine-catabolizing enzyme Arginase1 (ARG1) on tumor microenvironment, we generated a mouse model of mammary carcinogenesis by crossbreeding a transgenic mouse line overexpressing ARG1 in macrophages (FVBArg+/+) with the MMTV-Neu mouse line (FVBNeu+/+). This double transgenic line (FVBArg+/-;Neu+/+) showed a significant shortening in mammary tumor latency, and an increase in the number of mammary nodules. Transfer of tumor cells from FVBNeu+/+ into either FVB wild type or FVBArg+/+ mice resulted in increase regulatory T cells in the tumor infiltrate, suggestive of an impaired antitumor immune response. However, we also found increased frequency of tumor stem cells in tumors from FVBArg+/-;Neu+/+ transgenic compared with FVBNeu+/+ mice, suggesting that increased arginine metabolism in mammary tumor microenvironment may supports the cancer stem cells niche. We provide in vivo evidence of a novel, yet unexploited, mechanism through which ARG1 may contribute to tumor development.


Disclosure and informed-consent: does it matter how we tell it?
Traditionally, informed consent has been handled by the physician in a one-to-one interchange with the patient. As standards for adequate disclosure become more rigid and demands on physician time increase, however, the physician-patient model may cease to be practical. This study evaluated four alterative disclosure models: a formal discussion, a videotape, a pamphlet, and an informal discussion, each designed and executed by a team of health educators. Study results suggest that the informed consent process is little affected by disclosure medium and that it may be possible to strive for cost-efficiency in disclosure without compromising the quality of the consent obtained. Based on these results, a two-part disclosure process is proposed which allocates certain aspects of the disclosure to the treating physician, others to health education.


Assessment of brain shift related to deep brain stimulation surgery.
Deep brain stimulation (DBS) surgery can significantly improve the quality of life for patients suffering from movement disorders, but the success of the procedure depends on the implantation accuracy of the DBS electrode array. Pre-operative surgical planning and navigation are based on the assumption that the brain tissue is rigid between the time of the acquisition of the pre-operative image set and the time of surgery. A shift of deep brain structures by only a few millimeters can potentially increase the number of required microelectrode and/or macroelectrode tracks and decrease implantation accuracy. We studied 25 subjects that underwent DBS surgery and analyzed brain shift between pre-operative and post-operative 3D MRI scans. Brain shift of up to 4 mm was observed in deep brain structures. On average, the recorded shift was in the direction of gravity, with deeper structures experiencing smaller shift than more superficial structures. The main conclusion of the study is that the brain shift is comparable to the size of the targets in deep brain stimulation surgery and should not be ignored. Techniques that minimize the amount of brain shift may therefore lead to increased accuracy of DBS lead implantation.


A 13-week research-based biochemistry laboratory curriculum.
Here, we present a 13-week research-based biochemistry laboratory curriculum designed to provide the students with the experience of engaging in original research while introducing foundational biochemistry laboratory techniques. The laboratory experience has been developed around the directed evolution of an enzyme chosen by the instructor, with mutations designed by the students. Ideal enzymes for this curriculum are able to be structurally modeled, solubly expressed, and monitored for activity by UV/Vis spectroscopy, and an example curriculum for haloalkane dehalogenase is given. Unique to this curriculum is a successful implementation of saturation mutagenesis and high-throughput screening of enzyme function, along with bioinformatics analysis, homology modeling, structural analysis, protein expression and purification, polyacrylamide gel electrophoresis, UV/Vis spectroscopy, and enzyme kinetics. Each of these techniques is carried out using a novel student-designed mutant library or enzyme variant unique to the lab team and, importantly, not described previously in the literature. Use of a well-established set of protocols promotes student data quality. Publication may result from the original student-generated hypotheses and data, either from the class as a whole or individual students that continue their independent projects upon course completion. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):437-448, 2017.


INTRAOCULAR APPLICATION OF FIBRIN GLUE AS AN ADJUNCT TO PARS PLANA VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT.
To evaluate the efficacy of intraocular application of fibrin glue to seal the retinal breaks during standard pars plana vitrectomy for primary rhegmatogenous retinal detachment. Twenty-six eyes of 26 rhegmatogenous retinal detachment patients were included in the study. Fibrin glue was used to seal the retinal breaks during standard pars plana vitrectomy in all 26 eyes. Each eye was completely filled with a balanced saline solution at the end of the surgery. The success rate of the reattachment surgery, change in best-corrected visual acuity, intraocular pressure, and occurrence of intraoperative and postoperative complications were recorded and analyzed. All eyes, with a mean age of 45.1 ± 18.3 years, were treated with pars plana vitrectomy surgery. During pars plana vitrectomy surgery, the fibrin glue showed excellent adherence and compliance to the retina. The glue was no longer visible through ultrasound scan 14.85 ± 4.56 days after surgery. The retinal breaks were sealed completely, and retina attached in all 26 eyes with no occurrence of rhegmatogenous retinal detachment during the follow-up period. The best-corrected visual acuity at 6 months after operation was significantly improved from preoperation best-corrected visual acuity. After operation, two eyes (2/26) developed an epiretinal membrane. Although three eyes (3/26) had a transient increased intraocular pressure during the 1st week after surgery, the intraocular pressure lowered to the normal range after the application of timolol. One eye (1/26) required daily topical antiglaucoma drops to lower the intraocular pressure. No adverse effects of fibrin glue were observed. The fibrin glue provided a superior adhesive effect for sealing retinal breaks, while showing no additional adverse effects. It is a worthy alternative to gas tamponade for rhegmatogenous retinal detachment vitrectomy surgery.


Magnitude of Deformity Correction May Influence Recovery of Quadriceps Strength After Total Knee Arthroplasty.
Malalignment of the lower extremity is commonly seen in patients with severe osteoarthritis undergoing total knee arthroplasty (TKA) and is believed to play a role in quadriceps strength loss. Deformity correction is typically achieved through surgical techniques to provide appropriate ligamentous balancing. Therefore, this study examined the influence of change in lower extremity alignment on quadriceps strength outcomes after TKA. Seventy-three participants (36 male; mean age, 62 years; and mean body mass index, 29.7 kg/m2) undergoing primary unilateral TKA were used in this investigation. Before surgery and at 1 and 6 months after surgery, measures of isometric knee extensor strength, quadriceps activation, and long-standing plain films were collected. Using the films, measures of mechanical axis, distal femoral angle (DFA), proximal tibial angle, and patellofemoral angle were performed. Hierarchical linear regression was used to evaluate how change in alignment from baseline to 1 and 6 months influenced the change in quadriceps strength. DFA was found to significantly contribute to changes in quadriceps strength at 1 and 6 months after TKA above those contributed by associated covariates. None of the other measures of lower extremity alignment were found to contribute to quadriceps strength in this sample. Reductions in quadriceps strength experienced after TKA are likely to be influenced by changes in lower extremity alignment. Specifically, measures of DFA were found to significantly contribute to these changes. Future work is needed to prospectively examine measures of lower extremity alignment change and recovery after TKA.


[Impact of sequential targeted therapy on progression-free survival in metastatic renal cell carcinoma].
To evaluate the impact of sequential targeted therapy including vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) and everolimus on progression-free survival (PFS) in metastatic renal carcinoma. A total of 17 patients of metastatic renal cell carcinoma from Department of Kidney Cancer and Melanoma, Peking University Cancer Hospital since January 2008 until April 2014 were enrolled into this retrospective study. They took at least 2 lines of VEGFR-TKIs and everolimus. The data of total PFS and PFS of each therapy were extracted and analyzed. The sequential targeted therapies affected total PFS (18.0 vs 46.0 months, Kaplan-Meier survival analysis, P = 0.015) with a statistical dislike of VEGFR-TKI/VEGFR-TKI/mTOR inhibitor (TTM) over VEGFR-TKI/mTOR inhibitor/VEGFR-TKI (TMT) , HR = 5.44 (Cox regression analysis, 95% CI 1.18-25.06). TMT may prolong the total PFS of metastatic renal cell carcinoma.


Do pit-building predators prefer or avoid barriers? Wormlions' preference for walls depends on light conditions.
Ambush site selection by sit-and-wait predators is a complex process, involving biotic and abiotic considerations, which greatly affect hunting success and costs. Wormlions are fly larvae that dig pit-traps in loose soil and hunt the arthropod prey falling into their pits. They are abundant in urban environments, found below buildings that provide cover, and many of their pits are dug adjacent to walls. We examined here under what conditions wormlions prefer to dig their pits next to walls. We analysed our dataset in two ways: frequency comparisons among the different treatment combinations and a simulation null model assuming random movement. While the frequency comparisons suggested that wormlions avoided the walls under some cases, the simulation null model suggested that a combination of shallow sand and strong light in the centre led to an attraction towards the walls, independent of the wormlions' initial location. We suggest that wall attraction results from the certain amount of shade the walls provide. We also demonstrate that shallow sand and strong illumination are unfavourable microhabitats, either leading to more frequent movement or the digging of smaller pits. We locate our results within the broader context of sit-and-wait predators and of animals' attraction to barriers.


Effects of metformin and ganirelix on subcutaneous endometriosis in a mouse model of autophagy-related cell death.
This study aimed to investigate the efficacy of metformin and ganirelix on subcutaneous endometriotic tissues created in an experimental mouse model. Five groups were formed with eight animals in each group. One of the groups was set as the control group. Endometriotic lesions were created by transplanting 40 mouse autologous endomyometrial tissues into the mouse subcutaneous tissue to a highly vascular surface. Gene expression analyzes of tissues were performed as HIF-1α, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7α, and WNT10α gene analyzes. Drug effects were examined by histological examination. HIF1a and WNT2 protein expressions were examined immunohistochemically. Gene expression coefficients of control, metformin day 1 (Met1g), metformin day 7 (Met7g), ganirelix day 1 (Gnx1g), and ganirelix day 7 (Gnx7g) groups are shown in tables. Data are presented as mean and standard error. Beclin2 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and general 7th day groups were found to have significantly decreased compared with the control group coefficient. Beclin1 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and genirelix 7th day groups were found to have significantly decreased compared with the control group coefficient. LC3BII gene expression coefficients of metformin 1st day and metformin 7th day groups were found to have significantly decreased compared with LC3BII gene expression coefficients of control, genirelix 1st day, and genirelix 7th day groups. These findings were supported by histological and immunohistochemical staining. These genes are actively involved in the autophagy pathway, and we think that the use of metformin in endometriosis might create an autophagy-based suppression mechanism.


Nanocarriers for vascular delivery of anti-inflammatory agents.
There is a need for improved treatment of acute vascular inflammation in conditions such as ischemia-reperfusion injury, acute lung injury, sepsis, and stroke. The vascular endothelium represents an important therapeutic target in these conditions. Furthermore, some anti-inflammatory agents (AIAs) (e.g., biotherapeutics) require precise delivery into subcellular compartments. In theory, optimized delivery to the desired site of action may improve the effects and enable new mechanisms of action of these AIAs. Diverse nanocarriers (NCs) and strategies for targeting them to endothelial cells have been designed and explored for this purpose. Studies in animal models suggest that delivery of AIAs using NCs may provide potent and specific molecular interventions in inflammatory pathways. However, the industrial development and clinical translation of complex NC-AIA formulations are challenging. Rigorous analysis of therapeutic/side effect and benefit/cost ratios is necessary to identify and optimize the approaches that may find clinical utility in the management of acute inflammation.


Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA.
Herein, DNA duplex was constructed through the hybridization of adenosine triphosphate (ATP)-responsive aptamer and its cDNA in which GC-rich motif could be used to load doxorubicin (DOX), and then, cationic polymer PEI25K was used as a carrier to simultaneously condense DOX-Duplex and Bcl-2 siRNA to prepare the ternary nanocomplex polyethylenimine (PEI)/DOX-Duplex/siRNA. The ATP concentration gradient between the cytosol and extracellular environment could achieve the stable loading of DOX in duplex and the rapid drug release in an ATP-responsive manner. Using human prostate tumor cell line PC-3 as a model, an obvious induction of cell proliferation could be detected with a cell viability of 53.3%, which was stronger than single cargo delivery, indicating the synergistic effect between these two components. The enhanced anti-proliferative effect of ternary nanocomplex could be attributed to the improved induction of cell apoptosis in a mitochondria-mediated pathway and cell-cycle arrest at the G2 phase. Overall, the ATP-responsive nanocarrier for co-delivering DOX and Bcl-2 siRNA has been demonstrated to be a smart delivery system with favorable anti-proliferative effect, especially for solving the multidrug resistance of tumors.


PLCE1 rs2274223 polymorphism and susceptibility to esophageal cancer: a meta-analysis.
To investigate and study the relationship between the PLCE1 rs2274223 gene polymorphism and susceptibility to esophageal cancer by meta-analysis. The literature was searched in Wanfang, CNKI, PubMed, CBM, Web of Science, MEDLINE, EMBASE, Springer, Elsevier and Cochrane databases from the date of January 1st 2004 to April 1st 2014 to collect case-control studies on the PLCE1 polymorphism and susceptibility to esophageal cancer. For the population genotype distributions of both esophagus cancer and control groups, their odds ratios (ORs) and 95% confidence intervals (CIs) were taken as effect indexes. Disqualified studies were excluded. Odds ratios of PLCE1 rs2274223 genotype distributions in the group of patients with esophageal cancer and the group of healthy control were calculated. The meta- analysis software, RevMan5.0, was applied for heterogeneity test, pooled OR and 95% confidence intervals. Sensitivity analysis and publication bias were also explored. A total of twelve case-control studies were included, covering a total of 9, 912 esophageal cancer cases and 13, 023 controls were included. The pooled odds ratio of PLCE1 rs2274223 genotype GA vs AA was 1.29 (95%CI=1.17~1.43), p<0.01, GG vs AA was 1.65 (95%CI=1.32~2.05), p<0.01, GG/GA vs AA was 1.30 (95%CI=1.16~1.46), p<0.01 and GG vs GA/AA was 1.48 (95%CI=1.22~1.80), p<0.01. The PLCE1 rs2274223 polymorphism was thus associated with risk of esophageal cancer in all genetic models. In the stratified analysis by ethnicity, and source of controls, no significantly increased risk was observed for white persons. There was no obvious publication bias detected. This meta-analysis showed there was a significantly association between PLCE1 rs2274223 polymorphism and esophageal cancer in yellow race populations. Due to some minor limitations, our findings should be confirmed in further studies.


Genomic regions associated with ventro-cranial chronic pleuritis in pig.
Ventro-cranial chronic pleuritis can be a result of pleuropneumonia and enzootic pneumonia. These diseases cause severe losses in intensive pig production worldwide, but host resistance is difficult to breed for. It could be beneficial to use marker-assisted selection, and a step towards this is to identify genomic regions associated with the trait. For this purpose, 7304 pigs from 11 boar families were analysed for associations between single nucleotide polymorphisms and ventro-cranial chronic pleuritis. The pigs were genotyped by the use of the iSelect Custom 7 K porcine SNP Chip. Quantitative trait loci (QTL), significant at the chromosome-wide level, were identified on Sus scrofa chromosomes (SSC) 2, 4, 11, 12 and 13 in four different boar families. The QTL on SSC 4 in family G was also significant at the genome-wide threshold according to Bonferroni correction. We have identified a number of candidate genes, but the causative mutations still need to be identified. Markers closely associated with the resistance traits have a strong potential for use in breeding towards animals with improved characteristics concerning ventro-cranial chronic pleuritis.


Waveguide Absorption Spectroscopy of Bovine Serum Albumin in the Mid-Infrared Fingerprint Region.
Protein sensing in biological fluids provides important information to diagnose many clinically relevant diseases. Mid-infrared (MIR) absorption spectroscopy of bovine serum albumin (BSA) is experimentally demonstrated on a germanium on silicon (GOS) waveguide in the 1900-1000 cm-1 (5.3-10.0 μm) region of the MIR. GOS waveguides were shown to guide light up to a wavelength of 12.9 μm. The waveguide absorption spectrum of water, showing molecular bending vibrations, was obtained experimentally and compared with a theoretical model showing good agreement. Measurement of a concentration series of BSA protein in phosphate buffered saline (PBS) from 0.1 mg/mL to 100 mg/mL was performed on the waveguide using filter paper as a flow strip, and the amide I, II, and III peaks were observed and quantified.


Local Progression Kinetics of Geographic Atrophy in Age-Related Macular Degeneration Are Associated With Atrophy Border Morphology.
To assess the impact of distinct atrophy border characteristics based on spectral-domain optical coherence tomography (SD-OCT) imaging on local atrophy progression. Patients with geographic atrophy (GA) secondary to AMD were recruited in the context of the Longitudinal Fundus Autofluorescence in Age-related Macular Degeneration and Directional Spread in Geographic Atrophy studies (NCT00393692, NCT02051998). Horizontal and vertical SD-OCT scans were acquired at sequential visits using a device allowing for anatomically accurate registration of follow-up to baseline scans. For quantification of local atrophy progression, the lateral spread of GA (LSGA) was measured. Further, border types were independently graded. Comparison of LSGA between the different border types was performed using linear mixed-effects models. Seventy-two eyes of 49 patients (27 female) aged 74.0 years (Inter quartile range [IQR], 68.1-79.0) were included into this analysis. A total of 258 border sections were analyzed longitudinally over a median period of 1.2 years (IQR, 0.9-1.6). At baseline, 17.1% borders were classified as 'regular', 47.7% as 'irregular', and 35.3% as 'splitting'. Sixty-two percent of the eyes exhibited more than one border type. LSGA was slowest in 'regular' borders (62.85 ± 25.29 μm/y), followed by 'irregular' borders (91.15 ± 15.05 μm/y) and fastest in 'splitting' borders (183.15 ± 18.17 μm/y). Differences between the 'splitting' and each other border type were statistically significant (P < 0.001). The results indicate that SD-OCT-based assessment of local GA border morphology can serve as a predictor for local atrophy progression. These observations help to better understand the natural history and potential pathogenetic factors of GA development and progression.


Tolerance to and Postoperative Outcomes With Early Oral Feeding Following Elective Bowel Surgery: A Systematic Review.
Although practice guidelines recommend resuming oral feeding immediately after gastrointestinal surgery, many practitioners remain reluctant to order early oral feeding (EOF). Therefore, this review aimed to clarify the tolerance to and postoperative outcomes with EOF among patients undergoing bowel surgery. A systematic review of the literature published between January 1990 and July 2022 with the time of oral intake (early or delayed until resolution of ileus) as the exposure variable was conducted using PubMed and Scopus databases. Outcomes of interest included tolerance to EOF and postoperative adverse effects or complications. After screening 1,667 research articles, 18 randomized control trials, six prospective case series, and four cohort studies met our inclusion criteria, collectively representing data from 2,647 patients in eleven countries. These studies indicate that while most patients tolerate EOF, 5-25% may not tolerate EOF until the fourth postoperative day (POD). Moreover, EOF, at best, has no advantage over delayed feeding in terms of vomiting, nausea, nasogastric tube requirement, or other postoperative complications. In addition, early return of bowel function, lower risk of diarrhea, and lower pain score with EOF are inconsistently reported, and shorter hospitalization with EOF may be limited to those who tolerate oral feeding on POD 0 or 1. Nevertheless, shorter hospitalization with EOF could reduce the cost of hospitalization. A substantial number of patients may not be able to tolerate oral feeding after bowel surgery until POD 4, and in patients who tolerate EOF, the only clear benefit is a shorter length of hospitalization.


Topical trans-resveratrol ameliorates steroid-induced anterior and posterior segment changes in rats.
Steroid-induced hypertension and glaucoma is associated with increased extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous studies have shown that single drop application of trans-resveratrol lowers IOP in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is attributed to activation of adenosine A1 receptors, which may lead to increased matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of repeated topical application of trans-resveratrol for 21 days in SIOH animals on IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal morphology and retinal redox status. We observed that treatment with trans-resveratrol results in significant and sustained IOP reduction in SIOH rats. This IOP reduction is associated with significantly higher aqueous humor total MMP-2 level; significantly reduced TM thickness and increased number of TM cells. Treatment with trans-resveratrol also significantly increased ganglion cell layer (GCL) thickness, the linear cell density in the GCL and inner retina thickness; and significantly reduced retinal oxidative stress compared to the SIOH vehicle-treated group. In conclusion, repeated dose topical application of trans-resveratrol produces sustained IOP lowering effect, which is associated with increased level of aqueous humor MMP-2, normalization of TM and retinal morphology and restoration of retinal redox status.


[The overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis. Clinical and therapeutic analysis of 5 cases].
Autoimmune hepatitis and primary biliary cirrhosis are two different liver diseases. The aim of this study is to relate the clinical, serologic and histologic features of patients presenting the overlap syndrome, and to evaluate their response to therapy. This is a retrospective study concerning patients presenting overlap syndrome diagnosed between january 1998 and December 2001. Five patients fulfilled the diagnosis criteria of overlap syndrome. The optimal type of treatment of the overlap syndrome was not known. Treatment with UDCA or immunosuppressor alone are not efficient. Combination of these drugs should be evaluated in further studies.


Dramatic response to topical dorzolamide in X-linked retinoschisis.
Macular involvement is commonly seen in cases with X-linked retinoschisis (XLRS) which includes foveal schisis and cystic maculopathy. Although no definitive treatment has been described, the use of topical 2% dorzolamide hydrochloride in such cases has shown varied response. We herein report a case of XLRS with foveal schisis showing good response to topical dorzolamide. This case highlights the importance of topical dorzolamide in a patient with XLRS.


Interaction of insulin-like growth factor I with porcine thyroid cells cultured in monolayer.
The interaction of insulin-like growth factor I (IGF-I) with porcine thyroid cells cultured in monolayer was studied. Specific binding of [125I]iodo-IGF-I to thyroid cells was a reversible process dependent on the time and temperature of incubation. A steady state was achieved in 18 h at 4 C and averaged 14.2 +/- 2% (mean +/- SD)/10(6) cells. Binding of [125I]iodo-IGF-I was inhibited by unlabeled IGF-I; half-maximal inhibition occurred at concentrations of 2-5 ng/ml. Multiplication-stimulating activity (rat IGF-II) and pork insulin had relative potencies of 1:20 and 1:300 compared with IGF-I. Scatchard analysis of binding data revealed a single class of IGF-I receptors with a Ka of 4.3 X 10(10) M-1, 49,000 binding sites were estimated per cell. Affinity cross-linking and autoradiography demonstrated the presence of type I IGF receptors. Thyroid cells also had specific receptors for insulin, but specific binding of [125I]iodoinsulin (2.03 +/- 0.03%/10(6) cells) was much lower than that of [125I]iodo-IGF-I. Preincubation of thyroid cells with IGF-I or insulin caused a concentration-dependent decrease in [125I]iodo-IGF-I binding due to an apparent loss of receptors. Preincubation with epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, or TSH did not alter subsequent binding of [125I]iodo-IGF-I. Low concentrations of IGF-I stimulated DNA synthesis and proliferation of thyroid cells and acted synergistically with epidermal growth factor. Multiplication-stimulating activity and insulin had relative potencies in stimulating DNA synthesis comparable to their abilities to inhibit the binding of [125I]iodo-IGF-I to thyroid cells, suggesting that their effects are mediated primarily by IGF-I receptors. Preincubation with IGF-I did not alter cAMP responsiveness to TSH. We, thus, demonstrated the presence of functional and regulated IGF-I receptors on porcine thyroid cells.


Longitudinal study of the pubertal growth spurt in children born small for gestational age without postnatal catch-up growth.
Most children born small for gestational age (SGA) experience extensive catch-up growth during the first months of life (87%) and by the age of 2 years only 13% are below -2 SDS for height. The long-term outcome, including pubertal growth spurt, of the subset of children born SGA without postnatal catch-up (SGAWPC) has been evaluated in very few surveys, and in none of them was the landmarks of puberty well described. Thus, a longitudinal study was conducted in these children throughout puberty since this is the only reliable way to accurately evaluate the pubertal growth spurt. In an observational, retrospective and multicenter collaborative study, from an initial group of 553 SGA children, a subset of 15 boys (BW = 2,070 +/- 379.6 g) and 16 girls (BW = 2,244 +/- 331.1 g) SGAWPC whose data were recorded regularly during puberty were selected. Growth standards for growth and maturity during puberty were Tanner and Whitehouse and Spanish Hernandez and Sobradillo charts. In pubertal growth spurt, 'take-off' occurred later than in the reference populations with a height SDS deficiency of -2.3 and -2.2 for boys and -2.0 and -1.9 for girls, compared with Spanish and Tanner references, respectively. Peak height velocity was normal in chronology and intensity, but the total pubertal gain was smaller. However, considering their growth from the same chronological age at which the reference populations took off until adulthood, the total gain was not significantly different in the three cohorts (32.5 +/- 5.4 cm vs 30.9 +/- 4.4 in boys, and 23.3 +/- 4.1 vs 25.7 +/- 5.4 cm in girls - Spanish reference - and 27.2 +/- 6.3 vs 27.6 +/- 3.5 cm in boys - Tanner charts), except in the case of girls (21.1 +/- 3.9 vs 25.3 +/- 4.1 cm, p <0.005 - Tanner charts). Adult height was significantly reduced (161.9 +/- 3.9 cm in males and 147.0 +/- 2.6 cm in females). Therefore, although the pubertal growth was smaller in these children, puberty probably did not modify their short final height.


Necrotizing lymphadenitis in systemic lupus erythematosus: is it Kikuchi-Fujimoto disease?
Kikuchi-Fujimoto disease (KFD; also called Kikuchi disease) is a rare disorder clinically characterized by lymphadenopathy along with constitutional symptoms and several systemic features which may closely mimic infections, malignancies, and autoimmune diseases. Systemic lupus erythematosus (SLE) is an autoimmune disorder which may have several clinical manifestations similar to KFD. Association of KFD with SLE is only rarely described, and whether this is a chance incidence or Kikuchi disease is a localized manifestation of SLE per se remains a matter of debate. We report here coexistence of these two diseases in 1 patient.


Role of Doppler Ultrasound in Assessing the Severity of Peripheral Arterial Diseases of the Lower Limb.
Peripheral arterial disease is defined as a clinical disorder in which there is a stenosis or occlusion of the arteries of the limbs. The most common etiology is ischemia due to occlusive disease. The objective of this study is to assess the severity of lower-limb peripheral arterial diseases based on various Doppler parameters. This descriptive cross-sectional study comprised 55 patients with clinical signs and symptoms of lower-limb peripheral arterial disease. Both inpatients and outpatients attending the authors' institute were taken up for the study. In this study, Doppler sonography was performed using 3-12 MHz linear array and 1-7 MHz curvilinear array transducers (SAMSUNG RS80A Ultrasound System). Out of 55 patients, Doppler sonography demonstrated echogenic plaques in 32 patients and corkscrew collaterals in 15 patients. Monophasic waveform with peak systolic velocity ratio of >2:1 was found in 42 patients, which is consistent with significant stenoses. Our study shows that Duplex Doppler sonography aided by color Doppler sonography can accurately locate the site and severity of stenosis/occlusion. It is safe, cost-effective, repeatable, and noninvasive.


Molecular characterization of aflatoxigenic and non-aflatoxigenic Aspergillus flavus isolates collected from corn grains.
Twelve species from six fungal genera were found to be associated with corn (Zea mays L.) grain samples collected from three main regions of Saudi Arabia. The average frequencies of the most common genera were Aspergillus (11.4%), Fusarium (9.5%), Penicillium (5.1%), and Alternaria (5.8%). Fifteen isolates of Aspergillus flavus were screened by HPLC for their ability to produce aflatoxins (AF). The percentage of aflatoxigenic A. flavus isolates was 53%. Eight isolates produced AF, at concentrations ranging 0.7-2.9 ppb. Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) molecular markers were used to genetically characterize isolates of A. flavus and to discriminate between the aflatoxigenic and non-aflatoxigenic isolates. RAPD and ISSR analysis revealed a high level of genetic diversity in the A. flavus population, which was useful for genetic characterization. The clustering in the RAPD and ISSR dendrograms obtained was unrelated to geographic origin. The RAPD and ISSR markers could not discriminate between aflatoxigenic and non-aflatoxigenic isolates, but the ISSR primers were somewhat better.


Synthesis, characterization and in vitro biocompatibility study of Au/TMC/Fe3O4 nanocomposites as a promising, nontoxic system for biomedical applications.
The unique properties and applications of iron oxide and Au nanoparticles have motivated researchers to synthesize and optimize a combined nanocomposite containing both. By using various polymers such as chitosan, some of the problems of classic core-shell structures (such as reduced saturation magnetization and thick coating) have been overcome. In the present study, chitosan and one of its well-known derivatives, N-trimethylchitosan (TMC), were applied to construct three-layer nanocomposites in an Au/polymer/Fe3O4 system. It was demonstrated that replacement of chitosan with TMC reasonably improved the properties of the final nanocomposites including their size, magnetic behavior and thermal stability. Moreover, the results of the MTT assay showed no significant cytotoxicity effect when the Au/TMC/Fe3O4 nanocomposites were applied in vitro. These TMC-containing magnetic nanoparticles are well-coated by Au nanoparticles and have good biocompatibility and can thus play the role of a platform or a label in various fields of application, especially the biomedical sciences and biosensors.


Mononuclear Co(II) polypyridyl complexes: synthesis, molecular structure, DNA binding/cleavage, radical scavenging, docking studies and anticancer activities.
Mononuclear Co(II) complexes [CoII(L)Cl2]; 1, [CoII(L)(bpy)Cl]PF6; 2, [CoII(L)(phen)Cl]PF6; 3 and [CoII(L)(pic)Cl]; 4, (where L = N,N-bis(pyridin-2-ylmethyl)aniline, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, pic = picolinic acid) were systematically synthesized and characterized by different analytical and spectroscopic methods. All the complexes were structurally identified by single-crystal X-ray diffraction analysis. Penta-coordinated complex 1 adopted a distorted trigonal bipyramidal geometry, whereas hexacoordinated complexes 2-4 have distorted octahedral geometry. The interactions of salmon sperm DNA (ss-DNA) with our synthesized complexes 1-4 were investigated by absorbance and fluorescence spectroscopy. All the complexes are very susceptible to DNA binding and exhibited binding affinities (Kb) in the order of ∼104 M-1, indicating their strong interaction with ss-DNA. The Stern-Volmer constant (Ksv) ranged from 0.46 ± 0.01 × 104 to 1.08 ± 0.04 × 104 M-1, suggesting weak or moderate binding with DNA. Agarose gel electrophoresis revealed the DNA cleavage activity in vitro for 2-4, which could efficiently cleave the supercoiled plasmid DNA without any external agents; however, with the addition of H2O2, the cleavage property was enhanced. Live-cell imaging and other biochemical assays demonstrated the ability of Co(II) complexes 1-4 to induce significant cytotoxicity in A549 lung cancer cells with IC50 values of 32.14 ± 1.3 μM, 3.14 ± 0.16 μM, 15.78 ± 0.72 μM and 18.45 ± 0.92 μM, and in MDA-MB-231 breast cancer cells with IC50 values of 20.42 ± 0.92 μM, 0.41 ± 0.02 μM, 2.31 ± 0.12 μM and 9.67 ± 0.35 μM, respectively.


Gold(I)-N-Heterocyclic Carbene Synthons in Organometallic Synthesis.
The prominent role of gold-N-heterocyclic carbene (NHC) complexes in numerous research areas such as homogeneous (photo)catalysis, medicinal chemistry and materials science has prompted organometallic chemists to design gold-based synthons that permit access to target complexes through simple synthetic steps under mild conditions. In this review, the main gold-NHC synthons employed in organometallic synthesis are discussed. Mechanistic aspects involved in their synthesis and reactivity as well as applications of gold-NHC synthons as efficient pre-catalysts, antitumor agents and/or photo-emissive materials are presented.


Laparoscopic partial sleeve duodenectomy (PSD) for nonampullary duodenal neoplasms: avoiding a whipple by separating the duodenum from the pancreatic head.
To learn the clinical outcome of patients undergoing laparoscopic partial sleeve duodenectomy (PSD) for lesions, which require sleeve resection of the duodenum. Traditionally, these lesions require en bloc excision of the head of the pancreas performed in an open fashion. A retrospective review of medical records of patients with nonampullary large or circumferential duodenal lesions, which were not amenable to endoscopic or local resection for complete removal, was performed. Characteristics, complications, and technical details were analyzed. Ten patients (5 men and 5 women; mean age, 70 years) with duodenal lesions including adenoma (n = 5), adenocarcinoma (n = 2), lymphangiolipoma (n = 1), leiomyoma (n = 1), and neuroendocrine tumor (n = 1) were included. All patients underwent a laparoscopic approach with either a proximal PSD (n = 3) or distal PSD (n = 7) after separation of the duodenum from the pancreatic head. Reconstruction was carried out by a side-to-side duodenojejunostomy (n = 7), end-to-side duodenojejunostomy (n = 2), or gastrojejunostomy (n = 1). Mean length of stay was 5.6 days, and complications were 20%. Laparoscopic PSD seems to be a safe and easily applicable technique for treatment of duodenal lesions not involving the ampulla, which requires separation of the duodenum from the pancreas head with sleeve resection of the duodenum and subsequent reconstruction.


Regulation of summer dormancy by water deficit and ABA in Poa bulbosa ecotypes.
Survival of many herbaceous species in Mediterranean habitats during the dry, hot summer depends on the induction of summer dormancy by changes in environmental conditions during the transition between the winter (growth) season to the summer (resting) season, i.e. longer days, increasing temperature and drought. In Poa bulbosa, a perennial geophytic grass, summer dormancy is induced by long days, and the induction is enhanced by high temperature. Here the induction of summer dormancy in a Mediterranean perennial grass by water deficit under non-inductive photoperiodic conditions is reported for the first time. Plants grown under 22/16 degrees C and non-inductive short-day (9 h, SD) were subjected to water deficit (WD), applied as cycles of reduced irrigation, or sprayed with ABA solutions. They were compared with plants in which dormancy was induced by transfer from SD to inductive long-day (16 h, LD). Responses of two contrasting ecotypes, from arid and mesic habitats were compared. Dormancy relaxation in bulbs from these ecotypes and treatments was studied by comparing sprouting capacity in a wet substrate at 10 degrees C of freshly harvested bulbs to that of dry-stored bulbs at 40 degrees C. Endogenous ABA in the bulbs was determined by monoclonal immunoassay analysis. Dormancy was induced by WD and by ABA application in plants growing under non-inductive SD. Dormancy induction by WD was associated with increased levels of ABA. Bulbs were initially deeply dormant and their sprouting capacity was very low, as in plants in which dormancy was induced by LD. Dormancy was released after 2 months dry storage at 40 degrees C in all treatments. ABA levels were not affected by dormancy relaxation. Summer dormancy in P. bulbosa can be induced by two alternative and probably additive pathways: (1) photoperiodic induction by long-days, and (2) water deficit. Increased levels of endogenous ABA are involved in both pathways.


Is Religion Taboo in Gerontology?: Systematic Review of Research on Religion in Three Major Gerontology Journals, 1985-1991.
The authors conducted a systematic review of research on religion in three major gerontology journals and found that from 1985 to 1991, 78 of 2,127 (3.6%) quantitative studies included a religious variable. In most cases (71%), measures consisted only of a single question, usually on religious denomination. Only 18% of the studies with a religious variable cited previously published religious research. There was a greater proportion of studies with a religious variable in the gerontology literature than in the psychiatry literature (χ2 = 5.01, df = 1, P = 0.025). Publications in gerontology were also significantly more likely than psychiatry to use a multidimensional measure.


Power and sample size calculations in case-control studies of gene-environment interactions: comments on different approaches.
Power and sample size considerations are critical for the design of epidemiologic studies of gene-environment interactions. Hwang et al. (Am J Epidemiol 1994;140:1029-37) and Foppa and Spiegelman (Am J Epidemiol 1997;146:596-604) have presented power and sample size calculations for case-control studies of gene-environment interactions. Comparisons of calculations using these approaches and an approach for general multivariate regression models for the odds ratio previously published by Lubin and Gail (Am J Epidemiol 1990; 131:552-66) have revealed substantial differences under some scenarios. These differences are the result of a highly restrictive characterization of the null hypothesis in Hwang et al. and Foppa and Spiegelman, which results in an underestimation of sample size and overestimation of power for the test of a gene-environment interaction. A computer program to perform sample size and power calculations to detect additive or multiplicative models of gene-environment interactions using the Lubin and Gail approach will be available free of charge in the near future from the National Cancer Institute.


Immune response to Candida albicans is preserved despite defect in O-mannosylation of secretory proteins.
The PMT gene family in Candida albicans encodes five isoforms of the protein mannosyltransferases that initiate O-mannosylation of secretory proteins. Mutations at the Pmt level have been associated with differences in pathogenicity, e.g. in contrast to pmt5/pmt5, pmt2/PMT2 mutants showed poor virulence. Our objective was to determine whether these differences were related to the capacity of pmt2/PMT2 and pmt5/pmt5 to (i) express differences in selected virulence factors, and (ii) stimulate the natural immune system. The results show that pmt mutants (i) form hyphae in serum, (ii) show defective production of proteases but not of phospholipases with respect to the parental strain, (iii) undergo mycelial transition in the kidneys of hematogenously infected animals, (iv) are phagocytosed and killed by macrophages similar to the parental strain, although neutrophils are unable to destroy pmt5/pmt5, (v) engage TLR4 and stimulate MyD88 leading to NF-kappaB activation, and (vi) stimulate cytokine production by macrophages. Collectively our findings suggest that the defect in protein O-mannosylation in C. albicans cause attenuation of the virulence although the antigenic factors that retain the capacity to stimulate an efficient immune response are preserved.


Epilogue as prologue. The skin: continual source of biologic problems and discoveries.
In much the same way as the survival of many species depends upon their abundant production of such genetic materials as pollens and spermatozoa, so does scientific progress depend upon a continual, lavish production of basic scientific works. In stimulating assembling, and disseminating various scientific studies related to the skin, the Montagna Symposia on the Biology of Skin have ensured progress not only in the understanding and management of skin was, is, and probably will always will be one of the richest sources of basic biologic information. No scientific discovery is wasted, no accurate clinical observation useless. No one can foresee when or how some seemingly irrelevant discovery in pure science or some seemingly insignificant clinical observation will yield fruits of incalculable practicable value. We cite here a few examples of some of the best results from apparently unrelated research and isolated clinical findings. In dermatologic research, the circular rhythm from patient with cutaneous disease to laboratory and from laboratory back to patient creates a centrifugal force that often spins off valuable discoveries.


[Cyclosporine as drug resistance modifiers; mechanism and clinical investigation].
Multidrug resistance(MDR), mediated by P-glycoprotein, is a well-understood mechanism of resistance to anticancer drugs. P-glycoprotein is thought to act as an efflux pump with broad specificity for variety of anticancer drugs. Cyclosporine and its analogue, SDZ PSC 833, have demonstrated ability to inhibit P-glycoprotein mediated transport function, restore accumulation defects for anticancer drugs, and reverse resistance in vitro and in vivo. The clinical trials of these drugs are on going. P-glycoprotein may also play a pivotal role in the evolution of pharmacological defence mechanisms, protecting organisms from cytotoxic agents. Approach to overcome resistance may result in serious challenges to the host's natural defenses. Clinical trials of MDR modulators, such as cyclosporine or SDZ PSC 833, should be designed with caution and with careful consideration for potential pharmacokinetic and pharmacodynamic interaction.


[Isolation and detection of murine transplantable breast tumor antigen by McAb F36/22].
A transplantable murine breast tumor antigen (called JC tumor) has been recognized by the detection of McAb F36/22 with the method of immunoblotting. JC tumor antigen was isolated by Sepharose-CL-4B, then was purified by McAb F36/22 affinity chromatography. Solid phase RIA detection demonstrated that the specific activity of the antigen which was purified by 188.4 times was 148,000 cpm/mg protein. SDS-PAGE and immunoblot analysis revealed that the tumor antigen possessed a molecular weight of 60kd. Competitive binding RIA indicated that JC tumor antigen inhibited the combining of ductal carcinoma antigen with McAb F36/22. It implied that some groups (antigen determinant) on JC tumor antigen were the same as or similar to those on ductal cancer antigen.


Improved ensemble of differential evolution variants.
In the field of Differential Evolution (DE), a number of measures have been used to enhance algorithm. However, most of the measures need revision for fitting ensemble of different combinations of DE operators-ensemble DE algorithm. Meanwhile, although ensemble DE algorithm may show better performance than each of its constituent algorithms, there still exists the possibility of further improvement on performance with the help of revised measures. In this paper, we manage to implement measures into Ensemble of Differential Evolution Variants (EDEV). Firstly, we extend the collecting range of optional external archive of JADE-one of the constituent algorithm in EDEV. Then, we revise and implement the Event-Triggered Impulsive (ETI) control. Finally, Linear Population Size Reduction (LPSR) is used by us. Then, we obtain Improved Ensemble of Differential Evolution Variants (IEDEV). In our experiments, good performers in the CEC competitions on real parameter single objective optimization among population-based metaheuristics, state-of-the-art DE algorithms, or up-to-date DE algorithms are involved. Experiments show that our IEDEV is very competitive.