Identification of an optimized glycolytic-related risk signature for predicting the prognosis in breast cancer using integrated bioinformatic analysis.
Aberrant metabolic disorders and significant glycolytic alterations in tumor tissues and cells are hallmarks of breast cancer (BC) progression. This study aims to elucidate the key biomarkers and pathways mediating abnormal glycolysis in breast cancer using bioinformatics analysis. Differential genes expression analysis, gene ontology analysis, Kyoto encyclopedia of genes and genomes analysis, gene set enrichment analyses, and correlation analysis were performed to explore the expression and prognostic implications of glycolysis-related genes. We effectively integrated 4 genes to construct a prognostic model of shorter survival in the high-risk versus low-risk group. The prognostic model showed promising predictive value and may be an integral part of the prognosis of BC. The survival analysis and receiver operating characteristic curves suggested that the signature showed a good predictive performance in both the The Cancer Genome Atlas training set and 2 gene expression omnibus validation sets. Multivariable analysis demonstrated that the 4-gene signature had an independent prognostic value. Furthermore, all calibration curves exhibited robust validity in prognostic prediction. We established an optimized 4-gene signature to clarify the connection between glycolysis and BC, and offered an attractive platform for risk stratification and prognosis predication of BC patients.


Contributions of lower extremity kinematics to trunk accelerations during moderate treadmill running.
Trunk accelerations during running provide useful information about movement economy and injury risk. However, there is a lack of data regarding the key biomechanical contributors to these accelerations. The purpose was to establish the biomechanical variables associated with root mean square (RMS) accelerations of the trunk. Eighteen healthy males (24.0 ± 4.2 yr; 1.78 ± 0.07 m; 79.7 ± 14.8 kg) performed treadmill running with high resolution accelerometer measurement at the lumbar spine and full-body optical motion capture. We collected 60 sec of data at three speeds (2.22, 2.78, 3.33 m ∙ s(-1)). RMS was calculated for medio-lateral (ML), anterio-posterior (AP), vertical (VT), and the resultant Euclidean scalar (RES) acceleration. From motion capture, we calculated 14 kinematic variables, including mean sagittal plane joint angles at foot contact, mid-stance, and toe-off. Principal components analysis (PCA) was used to form independent components comprised of combinations of the original variables. Stepwise regressions were performed on the original variables and the components to determine contributions to RMS acceleration in each axis. Significant speed effects were found for RMS-accelerations in all axes (p < 0.05). Regressions of the original variables indicated from 4 to 5 variables associated with accelerations in each axis (R2 = 0.71 to 0.82, p < 0.001). The most prominent contributing variables were associated with the late flight and early stance phase. PCA reduced the data into four components. Component 1 included all hip angles before mid-stance and component 2 was primarily associated with propulsion. Regressions indicated key contributions from components 1 and 2 to ML, VT, and RES acceleration (p < 0.05). The variables with highest contribution were prior to mid-stance and mechanically relate to shock absorption and attenuation of peak forces. Trunk acceleration magnitude is associated with global running variables, ranging from energy expenditure to forces lending to the mechanics of injury. These data begin to delineate running gait events and offer relationships of running mechanics to those structures more proximal in the kinetic chain. These relationships may provide insight for technique modification to maximize running economy or prevent injury.


Structures and rearrangement reactions of 4-aminophenol(H2O)1+ and 3-aminophenol(H2O)1+ clusters.
In this paper the structures of 4-aminophenol(H2O)1+ and 3-aminophenol(H2O)1+ clusters are investigated in molecular beam experiments by different IR/UV-double resonance techniques as well as the mass analyzed threshold ionization spectroscopy yielding both inter- and intramolecular vibrations of the ionic and neutral species. Possible structures are extensively calculated at the level of density functional theory (DFT) or at the ab initio level of theory. From the experimental and theoretical investigations it can be concluded that in the case of 4-aminophenol(H2O)1 one O-H...O hydrogen-bonded structure exists in the neutral cluster but two structures containing either an O-H...O or a N-H...O hydrogen-bonded arrangement are observed in the spectra of the ionic species. This observation is a result of an intramolecular rearrangement reaction within the ion which can only take place if high excess energies are used. A reaction path via the CH bonds is calculated and explains the experimental observations. In the case of 3-aminophenol(H2O)1+ only one O-H...O bound structure is observed both in the neutral and ionic species. Ab initio and DFT calculations show that due to geometrical and energetical reasons a rearrangement cannot be observed in the 3-aminophenol(H2O)1+ cluster ion.


Permanent urinary diversion in two Vietnamese pot-bellied pigs by extrapelvic urethral or urethropreputial anastomosis.
Permanent urinary diversion was performed in a Vietnamese pot-bellied pig to bypass apparent urethral obstruction at the level of the urethral recess and in a second pig to correct bleeding from perineal urethrostomy. In the first pig, extrapelvic anastomosis of the penile portion of the urethra to the pelvic portion of the urethra was performed. In the second pig, the penis was amputated and the pelvic portion of the urethra was anastomosed to the preputial epithelium, creating a urethropreputial conduit. Postoperatively, positive-contrast radiography demonstrated continuity of the anastomoses, and both pigs were able to urinate normally. The pig with the urethropreputial anastomosis developed hematuria and nocturia that were controlled by continuous administration of antibiotics and resolved following cleansing of the preputial diverticulum 1 year after surgery. Extrapelvic urinary diversion should be considered for permanent resolution of urethral obstruction in Vietnamese pot-bellied pigs; urethral anastomosis is preferable to urethropreputial anastomosis, because of the greater risk of ascending urinary tract infection associated with urethropreputial anastomosis.


Influence of shortened recovery between resistance exercise sessions on muscle-hypertrophic effect in rat skeletal muscle.
Resistance exercise training induces muscle hypertrophy, and recovery between sessions is one of the major determinants of this effect. However, the effect of the recovery period between sessions on muscle hypertrophy following resistance exercise training remains unclear. To elucidate the effect of recovery period on hypertrophy, in the present study, we investigated changes in protein degradation systems and hypertrophic responses in rat skeletal muscle to resistance training with variable recovery periods. In the conventional recovery group (exercised every 72 h) and a shorter recovery group (exercised every 24 h), 18 bouts of resistance exercise consisting of 50 repetitions of a 3-sec maximal isometric contraction caused muscle hypertrophy and slight activation of muscle protein degradation systems. By contrast, in an excessively shorter recovery group (exercised every 8 h), 18 bouts of resistance exercise did not cause hypertrophy and markedly activated protein degradation systems, accompanied by inflammatory responses. These observations indicate that excessive shortening of recovery between sessions does not cause skeletal muscle hypertrophy, likely due to the activation of proteolysis induced by inflammatory responses to resistance exercise training.


ICBP90 mediates Notch signaling to facilitate human hepatocellular carcinoma growth.
The Notch signaling pathway plays a key role in cell proliferation and development that is closely related to an inverted CCAAT box binding protein (ICBP90), but little is known about whether there is a correlation between Notch signaling and ICBP90. The aim of the current study was to elucidate this. MTT assay and flow cytometry were used to determine the proliferation, cell cycle and apoptosis of HepG2 or Hepa1-6 cells treated by N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a specific inhibitor of the Notch pathway. RT-PCR, Western Blot and in situ immunofluorescence staining were employed to examine expression of ICBP90 in the cells. DAPT caused inhibition of the activation of the Notch signaling pathway, followed by preventing the cells at the G0/G1 phases to enter S and G2/M phases. ICBP90 and Hes-1 proteins were highly expressed in the untreated cells. The reduced levels of Notch intracellular domain (NICD) protein were observed in the DAPT-treated cells, thereby bringing about the down-regulation of ICBP90 with the increment of the DAPT dose. Consistent with this, knockdown of the Hes-1 gene, which encodes a critical transcriptional factor in the Notch pathway, also led to the attenuation of ICBP90. On the contrary, Jagged-1, a Notch ligand, facilitated ICBP90 production. Adriamycin could result in the reduction of ICBP90, which was not accompanied with the alteration of Hes-1. ICBP90 was almost fully distributed within the nuclei, but Hes-1 was visible within both the cytoplasm and nuclei. Our novel findings strongly indicate that inactivation of the Notch signaling pathway impedes hepatocellular carcinoma progress via reduction of ICBP90.


Parasympathomimetic action of scorpion venom on the cardiovascular system.
Although the precise mechanism of the cardiovascular effects in man evoked by the venom of the yellow scorpion has yet to be completely elucidated, previous studies indicate that excessive adrenergic activity is present in many of the cases. This report describes two patients in whom yellow scorpion sting was followed by bradyarrhythmia with varying degrees of atrioventricular block which promptly regressed after the administration of atropine; this is consistent with a direct parasympathomimetic effect of the venom or with a central effect producing increased vagal tone. It is suggested that the cardiovascular actions of the venom may represent a wide spectrum of effects on the autonomic nervous system, ranging from the predominantly sympathomimetic to the predominantly parasympathomimetic.


Preventive effects of low molecular weight heparin on formation of deep vein thrombosis by reducing D dimer values in patients undergoing spinal surgery.
Deep vein thrombosis (DVT) is one of the most common complications for patients undergoing spinal surgery. This study aims to investigate preventive effects of low-molecular-weight heparin (LMWH) on the formation of DVT. This study involved 37 patients who underwent spinal surgery between April 2016 and April 2017. Patients were divided into LMWH group and Control group. Clinical parameters, including operation time, intra-operative blood loss, incision length, post-operative visual analogue scale (VAS), exercise-time leaving bed and post-operative extubation time, were collected. Blood routine analysis, including platelet count (PLT), red blood cell count (RBC), white blood cell count (WBC) and hemoglobin (HGB) were also conducted. Coagulation parameters, including prothrombin time-international normalized ratio (PT-INR), fibrinogen (FIB), activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time 1 (PT-1) and D-dimer (DD), were evaluated. The drainage fluid was collected. LMWH treatment significantly decreased operative time, blood loss and incision length compared to Control group at 1st, 3rd and 7th day post-operation (all p<0.05). LMWH treatment significantly increased WBC levels compared to Control group at 1st, 3rd and 7th day post-operation (p<0.05). LMWH treatment significantly decreased DD levels in the post-operative patients compared to Control group at 1st, 3rd and 7th day post-operation (p<0.05). However, LMWH treatment doesn't affect drainage amounts of patients. DD levels were positively correlated with WBC counts for the LMWH treated patients. Low molecular weight heparin effectively prevents the formation of DVT by reducing DD values in patients undergoing spinal surgery.


[Comparative study of 3 methods of evaluation of antiseptic products and disinfectants in quality control].
For choosing a protocol of determination of bactericidal activity of antiseptic and disinfectant products, we have compared a method using an MS2 Abbott system and the classic methods: membrane filtration and dilution-method by transfer loops. The bactericidal-activity of 12 antiseptic solutions are determined. The results shown that there was no significative difference between the automated system and AFNOR specifications. The dilution-method by transfer loops gave higher bactericidal concentrations than the two other methods.


Pathologic findings in fallopian tubes of women with chronic pelvic pain after Essure placement.
Pelvic pain has been associated with Essure, a permanent contraceptive implant. Here we describe histopathologic findings in long-term Essure users with chronic pelvic pain. We descriptively evaluated and compared histopathologic features of hysterectomy specimens removed for a primary diagnosis of chronic pelvic pain from women with (n = 3) and without (n = 3) prior placement of Essure coils (mean of 8.6 years prior). Interstitial fallopian tubes of Essure patients demonstrated fibrosis. Two cases had flattening of ampullary epithelial folds. Tubes of Essure users showed no acute inflammation, but 2/3 showed focal chronic inflammation. All patients had additional findings, such as endometriosis, adenomyosis or leiomyomas, that could be associated with pain. Given the minimal and bland inflammation in Essure cases, symptoms may more plausibly be ascribed to confounding gynecologic conditions or other mechanisms.


Mortality Prediction in Patients Undergoing Non-Invasive Ventilation in Intermediate Care.
Intermediate Care Units (ImCU) have become an alternative scenario to perform Non-Invasive Ventilation (NIV). The limited number of prognostic studies in this population support the need of mortality prediction evaluation in this context. The objective of this study is to analyze the performance of Simplified Acute Physiology Score (SAPS) II and 3 in patients undergoing NIV in an ImCU. Additionally, we searched for new variables that could be useful to customize these scores, in order to improve mortality prediction. Cohort study with prospectively collected data from all patients admitted to a single center ImCU who received NIV. The SAPS II and 3 scores with their respective predicted mortality rates were calculated. Discrimination and calibration were evaluated by calculating the area under the receiver operating characteristic curve (AUC) and with the Hosmer-Lemeshow goodness of fit test for the models, respectively. Binary logistic regression was used to identify new variables to customize the scores for mortality prediction in this setting. The study included 241 patients consecutively admitted to an ImCU staffed by hospitalists from April 2006 to December 2013. The observed in-hospital mortality was 32.4% resulting in a Standardized Mortality Ratio (SMR) of 1.35 for SAPS II and 0.68 for SAPS 3. Mortality discrimination based on the AUC was 0.73 for SAPS II and 0.69 for SAPS 3. Customized models including immunosuppression, chronic obstructive pulmonary disease (COPD), acute pulmonary edema (APE), lactic acid, pCO2 and haemoglobin levels showed better discrimination than old scores with similar calibration power. These results suggest that SAPS II and 3 should be customized with additional patient-risk factors to improve mortality prediction in patients undergoing NIV in intermediate care.


[Antiviral treatment of subacute sclerosing panencephalitis].
The natural outcome of SSPE which is as a rule unfavourable independently of the treatment given, and this indicates the necessity of studies on new methods of treatment. After failures of steroids, immunosuppressants and transfer factor the treatment with virostatic drugs seems to be most safe and justified. The paper contains preliminary results of clinical observations of 34 patients with SSPE treated with amantadine, ITF (a derivative of isothiazole) and isoprinosine. In some cases it was tried to correlate the results of treatment with those of immunological and electrophysiological investigations. The presented data are insufficient for a reliable conclusion to be drawn concerning the effect of various drugs on the course of SSPE, nevertheless, it seems that the best results with slowing down of the progression of the disease were observed in the group treated with isoprinosine.


A new species of Globicornis Latreille (Coleoptera: Dermestidae) from Baltic amber, with a key to fossil species.
Based on a well-preserved specimen from Eocene Baltic amber, the fourth fossil species belonging to the genus Globicornis Latreille (Coleoptera: Dermestidae: Megatominae), G. groehni sp. nov., is described and illustrated. A key to the species of Globicornis known from Baltic amber is also provided. The addition of this species further improves our knowledge about dermestids in Baltic amber, and moves us closer to the level of taxonomic coverage needed for detailed ecological studies based upon the coleopteran assemblage within the deposit.


'Wormy'form appendix.
Appendicitis and helminth infections are both common conditions in children. However, helminths (pinworms) infestation causing appendiceal luminal obstruction and presenting as appendicitis is uncommon.


Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line.
Surfactant protein D (SP-D), an innate immune molecule, has an indispensable role in host defense and regulation of inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis, oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7), and explains the underlying mechanisms. SP-D and a recombinant fragment of human SP-D (rhSP-D) induced G2/M phase cell cycle arrest, and dose and time-dependent apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz. activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2) showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SP-D in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis. The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from healthy controls was not affected. The study suggests involvement of SP-D in host's immunosurveillance and therapeutic potential of rhSP-D in the eosinophilic leukemia and cancers of other origins.


[Carbonyl stress and chronic renal failure].
Pathogenesis of many diseases and their complications is linked to oxidative stress. In the last two years, the attention has been paid also to carbonyl stress which is alosely related to oxidative stress. Carbonyl stress is characterized as an increase of reactive carbonyl compounds caused by their increased formation and/or decreased breakdown and excretion. Reactive carbonyl compounds can be formed from carbohydrates, lipids and amino acids both by oxidative and non-oxidative pathways, can be detoxified by several enzymes and excreated by kidneys depending on their function. Carbonyl compounds can form advanced glycation end-products (AGEs) and advanced lipoperoxidation end-products (ALEs), which are known to take part in the pathogenesis mainly of diabetic and uremic complications.


Antigen-presenting function of B lymphocytes.
Here we review our current results studying B cells as APC and the mechanisms by which processed antigen is transported to and held on the cell surface for recognition by the specific T cell along with the MHC class II molecules. These studies were carried out using the globular protein cytochrome c as antigen for which the T-cell antigenic determinant was localized to a C-terminal 10-amino acid peptide fragment. For certain analyses, native cytochrome c or antigenic peptide fragments were covalently coupled to antibodies directed toward B-cell surface structures, allowing the targeting of antigen to the APC surface. Our findings indicate that all B cells function as APC and that the APC function is not differentially regulated in defined B-cell subpopulations. Using cytochrome c-antibody conjugates, it was shown that the surface Ig plays two significant roles in augmenting the B-cell APC function following antigen binding: signalling for enhanced APC function and concentrating antigen for subsequent internalization and processing. Both IgM and IgD appear to function identically in facilitating antigen processing in both immune and nonimmune B-cell populations. Furthermore, the surface Ig does not appear to be specially differentiated to function in concentrating antigen, as antigen artificially bound to other B-cell surface structures including MHC class I and class II molecules is also effectively presented. Lastly, evidence is presented that a previously described B-cell activating factor activity is strongly associated with the membranes of activated but not unactivated helper T cells, providing a mechanism by which the T-cell helper function can be focused on the specific antigen-presenting B cell. Concerning the mechanism by which processed antigen is presented at the B-cell surface, evidence is presented suggesting a role of peptide-binding chaperone proteins which may function to transport peptide to the APC surface and facilitate its association with the appropriate Ia. One candidate protein, PBP72/74, is described which binds peptides but not native antigens, is a member of the hsp70 family and appears to play a role in antigen presentation by the ability of antisera raised against it to block APC functions. Peptide-antibody conjugates were used to explore the spacial restrictions on MHC-restricted peptide presentation and it was shown that peptides covalently coupled to antibodies specific for Ig, class I or class II molecules are effective antigens in vitro even in the absence of processing.(ABSTRACT TRUNCATED AT 400 WORDS)


Regulation by thyroid-stimulating hormone of sodium/iodide symporter gene expression and protein levels in FRTL-5 cells.
To investigate the mechanism of I- transport stimulation by TSH, we studied the effects of TSH on Na+/I- symporter (NIS) messenger RNA (mRNA) and protein levels in FRTL-5 cells and correlated these with I- transport activity. When 1 mU/ml TSH was added to quiescent FRTL-5 cells, a 12-h latency was observed before the onset of increased I- transport activity, which reached a maximum [approximately 27 times basal (5H medium) levels] at 72 h. In contrast, Northern blot analysis, using rat NIS complementary DNA as a probe, revealed that addition of TSH to these cells significantly increased NIS mRNA at 3-6 h, reaching a maximum after 24 h (approximately 5.9 times basal levels). Forskolin and (Bu)2cAMP mimicked this stimulatory effect on both the I- transport activity and mRNA levels. D-ribofranosylbenzimidazole, a transcription inhibitor, almost completely blocked TSH-induced stimulation of I- transport and NIS mRNA levels. Western blot analysis demonstrated that TSH increased NIS protein levels at 36 h, reaching a maximum at 72 h, in parallel with the kinetics of TSH-induced I- transport activity. However, it also showed that the amount of NIS protein already present in FRTL-5 cell membranes before the addition of TSH was about one third of the maximum level induced by TSH. These results indicate that stimulation of I- transport activity by TSH in thyrocytes is partly due to a rapid increase in NIS gene expression, followed by a relatively slow NIS protein synthesis. However, the existence of an abundant amount of protein in quiescent FRTL-5 cells with very low I- transport activity also suggests that this activity is controlled by another TSH-regulated factor(s).


Transgenic animal models for measuring mutations in vivo.
Transgenic animal models for measuring mutations provide a powerful tool for rapidly assessing tissue-specific mutations following in vivo treatment. These models are based on the insertion into the rodent genome of the Escherichia coli lacI (lac repressor) or lacZ (beta-galactosidase) genes that serve as targets for mutations. Following in vivo treatment of animals, genomic DNA is isolated from various tissues and the target gene is packaged into lambda-phage heads; the lambda-phage are used to infect E. coli in order to produce plaques. Mutations in the target gene are then detected using colorimetric or selective procedures. In this review methods are discussed for producing these transgenic models, the target genes used, gene rescue techniques, sequencing of isolated mutants, and parameters that affect dosing regimens and design of studies. We also present a summary of data published to date with these systems and present our conclusions and proposed directions for future research.


Clinical characteristics of cytomegalovirus infection in rheumatic diseases: multicentre survey in a large patient population.
To survey and elucidate the clinical characteristics of CMV infection in rheumatic disease patients. A detailed questionnaire survey on CMV infection was carried out against rheumatic disease patients hospitalized in member hospitals, and the obtained clinical and/or laboratory data were analysed. Out of 7377 patients, 151 were diagnosed as having CMV infection. The underlying diseases ranged broadly, but SLE, microscopic polyangiitis, and dermatomyositis were the most common. Four were diagnosed histopathologically, and the others via positive CMV antigenaemia. In addition to oral corticosteroid for all but one patient, 81 were treated with pulsed methylprednisolone (MPSL), 64 with cyclophosphamide (CYC) and 36 with other immunosuppressants. Forty-four had a fatal outcome, for which presence of clinical symptoms, other infectious complications, lymphopenia, an older age (>59.3 yrs) and the use of pulsed MPSL were significant risk factors (P < 0.05) by univariate analysis. Multivariate analysis retained the first three (P < 0.05). The CMV antigenaemia count was significantly higher for the symptomatic than asymptomatic [10.1 (0.0-2998.0) vs 4.0 (1.3-1144.4)/10(5) PMNs, respectively, P < 0.05; threshold count: 5.6/10(5) PMNs]. No treatment benefit by anti-viral agent was observed as for survival. CMV infection was mostly diagnosed by antigenaemia, and occurred among patients under strong immunosuppressive therapy using pulsed MPSL and/or immunosuppressants. Lymphopenia, presence of symptoms and other infections are significant risk factors for a poor outcome and pulsed MPSL and an older age may predict it. Patients were prone to be symptomatic with anti-genaemia count over 5.6/10(5) PMNs.


Wrinkled Graphene Monoliths as Superabsorbing Building Blocks for Superhydrophobic and Superhydrophilic Surfaces.
Superhydrophobic and superhydrophilic surfaces are of great interest because of a large range of applications, for example, as antifogging and self-cleaning coatings, as antibiofouling paints for boats, in metal refining, and for water-oil separation. An aqueous ink based on three-dimensional graphene monoliths (Gr) can be used for constructing both superhydrophobic and superhydrophilic surfaces on arbitrary substrates with different surficial structures from the meso- to the macroscale. The surface wettability of a Gr-coated surface mainly depends on which additional layers (air for a superhydrophobic surface and water for a superhydrophilic surface) are adsorbed on the surface of the graphene sheets. Switching a Gr-coated surface between being superhydrophobic and superhydrophilic can thus be easily achieved by drying and prewetting with ethanol. The Gr-based superhydrophobic membranes or films should have great potential as efficient separators for fast and gravity-driven oil-water separation.


GEOGRAPHIC VARIATION WITHIN AN ISLAND: UNIVARIATE AND MULTIVARIATE CONTOURING OF SCALATION, SIZE, AND SHAPE OF THE LIZARD GALLOTIA GALLOTI.
Microgeographic variation of the vegetarian lizard Gallotia galloti within the island of Tenerife is described using univariate analysis, correlation, multiple group principal component analysis, canonical analysis, transects, and contours. The size varies locally in a mosaic pattern while head shape shows a WNW-ESE cline in the south. The scalation (scale and femoral pore counts) has two facets to its geographic variation, both of which are incongruent with the primary variation in the size and shape. The scalation shows categorical variation (stepped cline) between northern and southern populations and also a strong clinal relationship with altitude. The possible causes of this variation are considered and adaptation to current ecological conditions appears to be implicated for at least the altitudinal variation, although the pertinent factors are not obvious. It is apparent that vertebrate populations distributed across small islands do not necessarily offer the advantage of a discrete homogeneous unit for evolutionary studies but can offer the opportunity for studying microgeographic variation.


Structure-activity relationships and cellular mechanism of action of small molecules that enhance the delivery of oligonucleotides.
The pharmacological effects of antisense and siRNA oligonucleotides are hindered by the tendency of these molecules to become entrapped in endomembrane compartments thus failing to reach their targets in the cytosol or nucleus. We have previously used high throughput screening to identify small molecules that enhance the escape of oligonucleotides from intracellular membrane compartments and have termed such molecules OECs (oligonucleotide enhancing compounds). Here, we report on the structure-activity relationships of a family of OECs that are analogs of a hit that emerged from our original screen. These studies demonstrate key roles for the lipophilic aromatic groups, the tertiary nitrogen, and the carbamate moiety of the parent compound. We have also investigated the intracellular site of action of the OECs and have shown that activity is due to the release of oligonucleotides from intermediate endosomal compartments rather than from early endosomes or from highly acidic downstream compartments. At high concentrations of OECs toxicity occurs in a manner that is independent of caspases or of lysosomal cathepsins but instead involves increased plasma membrane permeability. Thus, in addition to describing specific characteristics of this family of OECs, the current study provides insights into basic mechanisms of oligonucleotide trafficking and their implications for oligonucleotide delivery.


[High glucose dialysate enhances peritoneal fibrosis through upregulating glucose transporters GLUT1 and SGLT1].
Objective: To investigate the role of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) in high glucose dialysate-induced peritoneal fibrosis. Methods: Thirty six male SD rats were randomly divided into 6 groups (6 in each):normal control group, sham operation group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorizin group (PD+Z group), PD+phloretin+phlorizin group (PD+T+Z group). Rat model of uraemia was established using 5/6 nephrotomy, and 2.5% dextrose peritoneal dialysis solution was used in peritoneal dialysis. Peritoneal equilibration test was performed 24 h after dialysis to evaluate transport function of peritoneum in rats; HE staining was used to observe the morphology of peritoneal tissue; and immunohistochemistry was used to detect the expression of GLUT1, SGLT1, TGF-β1 and connective tissue growth factor (CTGF) in peritoneum. Human peritoneal microvascular endothelial cells (HPECs) were divided into 5 groups:normal control group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorezin group (PD+Z group), and PD+phloretin+phlorezin group (PD+T+Z group). Real time PCR and Western blotting were used to detect mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF in peritoneal membrane and HPECs. Results:In vivo, compared with sham operation group, rats in PD group had thickened peritoneum, higher ultrafiltration volume, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly increased (all P<0.05); compared with PD group, thickened peritoneum was attenuated, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly decreased in PD+T, PD+Z and PD+T+Z groups (all P<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in peritoneum were positively correlated with the expressions of TGF-β1 and CTGF (all P<0.05). In vitro, the mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF were significantly increased in HPECs of peritoneal dialysis group (all P<0.05), and those in PD+T, PD+Z, and PD+T+Z groups were decreased (all P<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in HPECs were positively correlated with the expressions of TGF-β1 and CTGF (all P<0.05). Conclusion: High glucose peritoneal dialysis fluid may promote peritoneal fibrosis by upregulating the expressions of GLUT1 and SGLT1.


CE: Original Research: Identifying Hospitalized Patients at Risk for Harm: A Comparison of Nurse Perceptions vs. Electronic Risk Assessment Tool Scores.
: Objective: In many hospitals, nurse-led "safety huddles" are used to relay patient safety information, although whether this effectively identifies patients at risk for harm has not been determined. New electronic risk assessment tools are designed to identify patients at risk for harm during hospitalization, based on specific markers in the electronic health record. This study sought to compare the results of both methods. The findings may help to enhance decision making at the level of care delivery. A nonexperimental correlational study was conducted over a three-week period in 2015 in a large metropolitan acute care community hospital. Nurses on three units-a medical-surgical unit, a progressive care unit, and an orthopedic unit-constituted the convenience sample. Designated safety huddle leaders collected data using the daily census sheet to record the nurses' perceived risk of harm for each patient and the reason for risk concern. Separately, designated advanced practice nurses collected the electronic risk assessment tool's reports from the same units. Data were paired as they were entered into the database and analyzed to determine correlation. Perceptions of harm from the nurses, recorded as yes or no responses, were compared with the electronic tool's identification of high risk or moderate-to-low risk. In 746 data pairs, differences between the nurses' harm risk perceptions and the electronic tool's harm risk reports were statistically significant, supporting our prediction that there would be no correlation. The most significant difference was seen in instances when a nurse identified a patient as being at higher risk than the electronic tool did, often citing behavioral or psychosocial issues as the reason for concern. Nurses perceived harm risk differently than the electronic tool did. In situations when the electronic tool cited risk and the nurse perceived no risk, the risks were currently being addressed in the plan of care. In situations when the nurse perceived higher risk than the electronic tool did, the nurse often cited behavioral or psychosocial issues (which frequently lacked defined data points in the electronic health record and thus were not available to the tool). Changes in data mining algorithms must incorporate and weight the impact of psychosocial and behavioral elements together with other risk factors in order to provide meaningful practice recommendations.


Mechanisms of high salinity tolerance in plants.
Among abiotic stresses, high salinity stress is the most severe environmental stress, which impairs crop production on at least 20% of irrigated land worldwide. In response to high salinity stress, various genes get upregulated, the products of which are involved either directly or indirectly in plant protection. Some of the genes encoding osmolytes, ion channels, receptors, components of calcium signaling, and some other regulatory signaling factors or enzymes are able to confer salinity-tolerant phenotypes when transferred to sensitive plants. Overall, the susceptibility or tolerance to high salinity stress in plants is a coordinated action of multiple stress responsive genes, which also cross talk with other components of stress signal transduction pathways. High salinity exerts its negative impact mainly by disrupting the ionic and osmotic equilibrium of the cell. In saline soils, high levels of sodium ions lead to plant growth inhibition and even death; therefore, mechanisms of salinity tolerance involve sequestration of Na(+) and Cl(-) in vacuoles of the cells, blocking of Na(+) entry into the cell, Na(+) exclusion from the transpiration stream, and some other mechanisms that help in salinity tolerance. Understanding these mechanisms of stress tolerance, along with a plethora of genes involved in the stress signaling network, is important to improve high salinity stress tolerance in crops plants. This chapter first describes the adverse effect of salinity stress and general pathway for the plant stress response, followed by roles of various ion pumps, calcium, SOS pathways, ABA, transcription factors, mitogen-activated protein kinases, glycine betaine, proline, reactive oxygen species, and DEAD-box helicases in salinity stress tolerance. The cross-tolerance between stresses is also mentioned.


Ecotypic and genotypic effects on regrowth and heading date in switchgrass (Panicum virgatum).
Switchgrass (Panicum virgatum L.) is a native perennial grass species with great potential for bioenergy and forage. However, knowledge about its genetics and biology related to breeding is still in its infancy. Studying the diversity of switchgrass germplasm will shed light on variability, response to environmental conditions, adaptability, breeding, etc. Thirty-six switchgrass accessions/cultivars were used to study the ecotypic and genotypic effects on regrowth, heading date, and vegetative growth period. The R-360 honeycomb design was used for planting these accessions in 2007. Data on regrowth and heading dates were recorded in 2008, 2010, and 2011. Vegetative growth period was calculated by subtracting the regrowth date from the heading date. It was found that the lowland started regrowing earlier (77 ± 0.4 days of the year, DOY) than the upland ecotype (82 ± 0.3 DOY). The upland had earlier heading date (160 ± 0.4 DOY) than the lowland ecotype (173 ± 0.5 DOY). Vegetative growth period was about 18 days longer in the lowland (89 ± 0.6 days) than the upland ecotype (71 ± 0.4 days). For switchgrass (i.e., all accessions), biomass yield was related positively to growth period and heading date; however, biomass was only weakly related to regrowth. Therefore, when targeting biomass in the breeding program, growth period may be a quick and reliable reference in both ecotypes to quickly estimate biomass potential while regrowth and heading date may be better used as a parameter for accessions within an ecotype.


Measurement of normalized spectral responsivity of digital imaging devices by using a LED-based tunable uniform source.
We present an instrumentation solution for measurement of normalized spectral responsivity of digital imaging sensors and cameras. The instrument consists of multiple light-emitting diodes (LEDs), a single-grating monochromator, and a small-size integrating sphere. Wavelength tuning is achieved by a proper selection of LED in accordance with the monochromator setting in a range from 380 to 900 nm. High spectral purity with a bandwidth of 5 nm is realized without using double gratings and order-sorting filters. Experimental characteristics and calibration of the instrument are described with the related error and uncertainty sources. The performance is demonstrated by measuring a monochrome charge-coupled device and a trichromatic complementary metal-oxide-semiconductor device. The measurement uncertainty is evaluated to be less than 1% (k=2) except several wavelengths with low LED power.


[Diagnosis and treatment of olfactory cleft diseases].
To discuss the diagnosis and treatment of the diseases originated in the olfactory cleft. Eight consecutive patients with the diagnosis of olfactory cleft diseases, encountered between December, 2003 and May, 2006, were included in this retrospective study. On the basis of case reports, the related anatomy, diagnosis and treatment of olfactory cleft diseases were discussed. For the 8 patients with olfactory cleft diseases, the clinical and pathological diagnosis were as follows: adenocarcinoma, squamous cell carcinoma, inverted papilloma, glioma with cerebrospinal fluid (CSF) rhinorrhea, pyocyst of the superior turbinate, angiofibrosteoma, neurofibroma and hemangioma. All patients were treated by endoscopic surgery. Postoperative radiotherapy was given to two patients with malignant tumour. The diseases in the olfactory cleft are not uncommon, which are often overlooked. In order to avoid misdiagnosis, (1) it is important to pay attention to this specific anatomic area; (2) the particularity of olfactory cleft diseases should be emphasized, especially in the cases of huge tumors. In that cases, the primary sites of olfactory cleft tumors can not be correctly judged preoperatively by CT scans, which can only be found during endoscopic surgery. For the treatment of olfactory cleft diseases, surgery under endoscope is the treatment of choice. If the tumor is malignant, postoperative radiotherapy should be added.


Pluripotency of Wolbachia against Arboviruses: the case of yellow fever.
Background: Yellow fever outbreaks have re-emerged in Brazil during 2016-18, with mortality rates up to 30%. Although urban transmission has not been reported since 1942, the risk of re-urbanization of yellow fever is significant, as Aedes aegypti is present in most tropical and sub-tropical cities in the World and still remains the main vector of urban YFV. Although the YFV vaccine is safe and effective, it does not always reach populations at greatest risk of infection and there is an acknowledged global shortage of vaccine supply. The introgression of Wolbachia bacteria into Ae. aegypti mosquito populations is being trialed in several countries ( www.worldmosquito.org) as a biocontrol method against dengue, Zika and chikungunya. Here, we studied the ability of Wolbachia to reduce the transmission potential of Ae. aegypti mosquitoes for Yellow fever virus (YFV). Methods: Two recently isolated YFV (primate and human) were used to challenge field-derived wild-type and Wolbachia-infected ( wMel +) Ae. aegypti mosquitoes. The YFV infection status was followed for 7, 14 and 21 days post-oral feeding (dpf). The YFV transmission potential of mosquitoes was evaluated via nano-injection of saliva into uninfected mosquitoes or by inoculation in mice. Results: We found that Wolbachia was able to significantly reduce the prevalence of mosquitoes with YFV infected heads and thoraces for both viral isolates. Furthermore, analyses of mosquito saliva, through indirect injection into naïve mosquitoes or via interferon-deficient mouse model, indicated Wolbachia was associated with profound reduction in the YFV transmission potential of mosquitoes (14dpf). Conclusions: Our results suggest that Wolbachia introgression could be used as a complementary strategy for prevention of urban yellow fever transmission, along with the human vaccination program.


Development and evaluation of the British English coordinate response measure speech-in-noise test as an occupational hearing assessment tool.
The studies described in this article outline the design and development of a British English version of the coordinate response measure (CRM) speech-in-noise (SiN) test. Our interest in the CRM is as a SiN test with high face validity for occupational auditory fitness for duty (AFFD) assessment. Study 1 used the method of constant stimuli to measure and adjust the psychometric functions of each target word, producing a speech corpus with equal intelligibility. After ensuring all the target words had similar intelligibility, for Studies 2 and 3, the CRM was presented in an adaptive procedure in stationary speech-spectrum noise to measure speech reception thresholds and evaluate the test-retest reliability of the CRM SiN test. Studies 1 (n = 20) and 2 (n = 30) were completed by normal-hearing civilians. Study 3 (n = 22) was completed by hearing impaired military personnel. The results display good test-retest reliability (95% confidence interval (CI) < 2.1 dB) and concurrent validity when compared to the triple-digit test (r ≤ 0.65), and the CRM is sensitive to hearing impairment. The British English CRM using stationary speech-spectrum noise is a "ready to use" SiN test, suitable for investigation as an AFFD assessment tool for military personnel.


Palpable Penile Metastases: A Bizarre Presentation of Rectal Adenocarcinoma.
Metastasis to the penis is an uncommon occurrence, with only about 370 cases reported in the literature to date. The majority of the primary tumors are genitourinary in origin. We report on a patient with undiagnosed disseminated rectal adenocarcinoma, who first presented with lesions of the corporal bodies. A review of the literature indicates that corporeal metastasis as an initial presentation of malignancy is an extremely rare occurrence and carries a very poor prognosis.


Highly salted food and mountain herbs elevate the risk for stomach cancer death in a rural area of Japan.
Although many case-control and experimental studies have shown that highly salted foods are risk factors for stomach cancer, only a few cohort studies have supported the relationship. In a cohort study conducted in a rural area of Japan, 8035 residents aged over 30 years (approx. 55% were female) filled out a questionnaire. Seventy-six of them died from stomach cancer during an 11-year follow-up period. In the questionnaire, intake frequencies of 29 food items, smoking and drinking habits were investigated. Tsukemono (pickled vegetables) and tsukudani (foods deep boiled in soy sauce) are highly salted foods in the area. Frequency of each food item intake was classified into three levels, and age- and sex-adjusted risks were calculated using proportional hazard models. In the final model obtained by backward elimination, frequent intake of tsukemono and tsukudani and that of mountain herbs remained as significant risk factors. Compared with the least frequent intake, risk (95% confidence interval) of the most frequent intake was 5.4 (1.8-16.3) for highly salted foods (P for trend < 0.01) and 3.7 (1.4-9.6) for mountain herbs (P for trend = 0.04). Highly salted foods and mountain herbs were important risk factors for death from stomach cancer.


The role of p53 in tumor progression.
p53 mutation is a common event in tumors. The evidence that such mutation is an important step in the sequence of genetic changes which underly tumor progression is outlined. Such evidence includes the study of human tumors, animal tumor models and cell culture. In several instances, p53 mutation seems to be a late event. This is by no means a universal finding, and important reservations are stated concerning the role of p53 mutation in tumor progression.


Sclerosis in non-Hodgkin's lymphomata.
A total of 242 cases of non-Hodgkin's lymphoma arising primarily in lymph nodes are reported. Lymph nodes have been classified histologically and the incidence of sclerosis in each group assessed. Two types of fibrosis were found, one composed of fibrous bands from 10 mum to several hundred mum thick within the node and invaded perinodal tissue. The other type was a fine compartmentalizing fibrosis sometimes simulating the pattern of metastatic carcinoma in part of a node, the rest of the node being typical of malignant lymphoma. Both types of fibrosis were present in some nodes. Fibrous bands were present in all histological types, with the exception of the diffuse lymphocytic well differentiated group. Fine compartmentalizing fibrosis was seen only in association with areas of undifferentiated large celled lymphoma. The presence of sclerosis is shown to correlate with a better prognosis when compared with non-sclerosing tymours of similar histological type. That sclerosing lymphomata are more slowly progressive is borne out by the fact that two-thirds of the patients with sclerotic nodes presented with localized disease compared with less than half of the patients whose nodes showed no sclerosis.


Apple HyperCard: videodisc authoring system and illustration medium.
The following article describes the Apple Macintosh Program HyperCard as an interactive videodisc authoring system and illustration medium for creating medical instructional materials.


[MIDCAB procedure by original stabilizer and usual devices].
The key of MIDCAB is how to stabilize the left anterior descending artery. We introduce our MIDCAB procedure by using our original stabilizer and usual devices in this paper. Between March 1997 and August 1997, 13 patients underwent left internal thoracic artery to left anterior descending artery revascularization without extracorporeal circulation, and one case underwent right internal thoracic artery to right coronary artery. In all cases, we exposed the internal thoracic artery through a 8 cm anterior fifth space thoracotomy. One case of MIDCAB to right coronary artery was added an inferior hemisternotomy for anastomosis to the right coronary artery. The internal thoracic artery was harvested by using the Kent retractor. The anastomosis were done by using our original stabilizer and retract O tapes. In our method, there was no mortality and no postoperative cardiac event. There were 5 postoperative complications, one was reoperation due to bleeding from a branch of the internal thoracic artery, two cases were wound infection. Cerebral infarction, bleeding due to urinary bladder tumor and lumbar compression fracture was seen in one case each. MIDCAB procedure was performed safety and effectively by using our original stabilizer and usual devices.


Unusually Short-Lived Solvent-Dependent Excited State in a Half-Sandwich Ru(II) Complex Induced by Low-Lying 3MC States.
A ruthenium complex with a half-sandwich geometry ([(p-cymene)Ru(Cl)(curcuminoid)]) was synthesized, characterized, and investigated regarding its ultrafast photophysics. These photophysical investigations of the complex revealed a weak and short-lived emission from the initially populated 1MLCT state and solvent-dependent photoinduced dynamics, where the secondarily populated 3MC state is stabilized by nonpolar solvents. Overall the decay of the 3dd-MC state to the ground state is completed within picoseconds. This short excited-state lifetime is in stark contrast to the typically observed long-lived 3MLCT states with lifetimes of nanoseconds or microseconds in unstrained, octahedral ruthenium complexes but is in good agreement with the findings for distorted octahedral complexes. This is pointing to the half-sandwich geometry as a new and easy approach to study these otherwise often concealed dd states.


SMALL POPULATION GENETIC VARIABILITY AT LOCI UNDER STABILIZING SELECTION.
Genetic variability at a locus under stabilizing selection in a finite population is investigated using analytic methods and computer simulations. Three measures are examined: the number of alleles k, heterozygosity H, and additive genetic variance Vg. A nearly-neutral theory results. The composite parameter S = NVM /Vs (where N is the population size, VM the variance of new mutant allelic effects and Vs the weakness of stabilizing selection) figures prominently in the results. The equilibrium heterozygosity is similar to that of strictly neutral theory, H = 4Nμc / (1 + 4Nμc ), except that μc = μe=μ/1+cS where c is about 0.5. Simulations corroborate Vg=4μVs1+1/S except for very low N. Genetic variability attains similar equilibrium values at both a "lone" locus and at an "embedded" locus. This agrees with my earlier work concerning molecular clock rates. These results modify the neutralist interpretation of data concerning genetic variability and genetic distances between populations. Low H values are proportional not to N but to N. This may explain the narrow observed range of H among species. Heterozygosities need not be highly correlated to genetic variances. Genetic variances are not highly dependent on population size except in very small populations which are difficult to sample without bias because the smallest populations go extinct the fastest. Nearly neutral evolution will not be easily distinguished from strictly neutral theory under the Hudson-Kreitman-Aguade inter-/intraspecific variation ratio test, since a similar effective mutation rate holds for genetic distances and D = 2μc t, where μe=μ/1+S. As with strictly neutral theory, comparisons across loci should show D and H to be positively correlated because of the shared μc . But unlike neutral theory, for a given locus, comparisons across species should show D and H to be negatively correlated. There is no obvious threshold of population size below which genetic variability inevitably declines. Extinction depends on both genetic variation and natural selection. Neither theory nor observation presently indicates the measure of genetic variability (k, H, VG or other) that best indicates vulnerability of a small population to extinction.


IL-37d Negatively Regulates NLRP3 Transcription via Receptor-mediated Pathway and Alleviates DSS-induced Colitis.
Interleukin-37 (IL-37) is a new negative immune regulator. It has 5 splicing forms, IL-37a-e, and most research mainly focuses on IL-37b functions in diverse diseases. Our previous research found that IL-37d inhibits lipopolysaccharide-induced inflammation in endotoxemia through a mechanism different from that of IL-37b. However, whether IL-37d plays a role in colitis and the underlying mechanisms is still obscure. Herein, we identified whether IL-37d regulates NLRP3 inflammasome activity and determined its effect on colitis. NLRP3 inflammasome in macrophages from IL-37d transgenic (IL-37dtg) and control wild type (WT) mice were activated by lipopolysaccharide and adenosine 5'-triphosphate. The expression of NLRP3 inflammasome components and its downstream effector, IL-1β, were detected by real-time polymerase chain reaction, western blot, and ELISA. The models of alum-induced peritonitis and dextran sodium sulfate (DSS)-induced colitis were used to investigate the function of IL-37d on regulating the activity of NLRP3 inflammasome in vivo. Our results showed that the activation of NLRP3 inflammasome in macrophage and alum-induced peritonitis was inhibited by IL-37d. Strikingly, IL-37d suppressed NLRP3 expression at the priming step via inhibiting NF-κB activation by transcriptional profiling. Moreover, the recombinant protein IL-37d attenuated NLRP3 inflammasome activation and the production of IL-1β, which could be reversed by IL-1R8 knockdown. Finally, IL-37d transgenic mice resisted DSS-induced acute colitis and NLRP3 inflammasome activation. Interleukin-37d inhibits overactivation of the NLRP3 inflammasome through regulating NLRP3 transcription in an IL-1R8 receptor-mediated signaling pathway.


Multiple control and dynamic response of the Xenopus melanotrope cell.
Some amphibian brain-melanotrope cell systems are used to study how neuronal and (neuro)endocrine mechanisms convert environmental signals into physiological responses. Pituitary melanotropes release alpha-melanophore-stimulating hormone (alpha-MSH), which controls skin color in response to background light stimuli. Xenopus laevis suprachiasmatic neurons receive optic input and inhibit melanotrope activity by releasing neuropeptide Y (NPY), dopamine (DA) and gamma-aminobutyric acid (GABA) when animals are placed on a light background. Under this condition, they strengthen their synaptic contacts with the melanotropes and enhance their secretory machinery by upregulating exocytosis-related proteins (e.g. SNAP-25). The inhibitory transmitters converge on the adenylyl cyclase system, regulating Ca(2+) channel activity. Other messengers like thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH, from the magnocellular nucleus), noradrenalin (from the locus coeruleus), serotonin (from the raphe nucleus) and acetylcholine (from the melanotropes themselves) stimulate melanotrope activity. Ca(2+) enters the cell and the resulting Ca(2+) oscillations trigger alpha-MSH secretion. These intracellular Ca(2+) dynamics can be described by a mathematical model. The oscillations travel as a wave through the cytoplasm and enter the nucleus where they may induce the expression of genes involved in biosynthesis and processing (7B2, PC2) of pro-opiomelanocortin (POMC) and release (SNAP-25, munc18) of its end-products. We propose that various environmental factors (e.g. light and temperature) act via distinct brain centers in order to release various neuronal messengers that act on the melanotrope to control distinct subcellular events (e.g. hormone biosynthesis, processing and release) by specifically shaping the pattern of melanotrope Ca(2+) oscillations.


Self-Assembled 3D Hierarchical Porous Bi2MoO6 Microspheres toward High Capacity and Ultra-Long-Life Anode Material for Li-Ion Batteries.
Three-dimensional (3D) hierarchical porous Bi2MoO6 microspheres (HPBMs) were successfully prepared and used as the anode material in Li-ion batteries (LIBs) for the first time. The HPBMs showed a high capacity (>830 mAh·g-1, 734.5 mAh·cm-2), high rate capability (20 A·g-1, 177.7 mAh·g-1), and superior long cycle life (>2700 cycles) in the temperature range 5-55 °C without adding any other conductive carbon materials, such as graphene and carbon nanotubes. This can be reasonably attributed to their substantially high surface area, 3D hierarchical porous structure, and homogeneous conductive matrix composed of metallic nanoparticles. HPBMs surprisingly showed a high reversible discharge capacity of 537.2 mAh·g-1 (475.4 mAh·cm-2) and an average discharge voltage >3.0 V even when coupled with LiCoO2 in a full cell. The results highlight the feasibility of HPBMs as anode material for LIBs.


Homochiral BINAPDA-Zr-MOF for Heterogeneous Asymmetric Cyanosilylation of Aldehydes.
A new homochiral BINAPDA-Zr-MOF was prepared by a new chiral organic linker of (R)-4,4'-(6,6'-dichloro-2,2'-diethoxyl-[1,1'-binaphthalene]-4,4'-diyl)dibenzoic acid (R-L) and ZrCl4 under solvothermal conditions. Its structure was determined by Pawley refinement on the basis of the measured PXRD pattern determined for BINAPDA-Zr-MOF, and it showed that the obtained chiral MOF crystallized in the F23 space group with the same topological structure as that of UiO-66. The obtained BINAPDA-Zr-MOF can be a very active catalyst to catalyze aldehyde cyanosilylation. In addition, the chiral BINAPDA-Zr-MOF was a typical solid catalyst, which was proved by a hot leaching test; moreover, it could be reused at least five times without loss of its catalytic activity and enantioselectivity.


Multiplexed integrating plasmids for engineering of the erythromycin gene cluster for expression in Streptomyces spp. and combinatorial biosynthesis.
Bacteria in the genus Streptomyces and its close relatives are prolific producers of secondary metabolites with antibiotic activity. Genome sequencing of these bacteria has revealed a rich source of potentially new antibiotic pathways, whose products have never been observed. Moreover, these new pathways can provide novel genes that could be used in combinatorial biosynthesis approaches to generate unnatural analogues of existing antibiotics. We explore here the use of multiple orthologous integrating plasmid systems, based on the int/attP loci from phages TG1, SV1, and ϕBT1, to express the polyketide synthase (PKS) for erythromycin in a heterologous Streptomyces host. Streptomyces strains containing the three polyketide synthase genes eryAI, eryAII, and eryAIII expressed from three different integrated plasmids produced the aglycone intermediate, 6-deoxyerythronolide B (6-dEB). A further pair of integrating plasmids, both derived from the ϕC31 int/attP locus, were constructed carrying a gene cassette for glycosylation of the aglycone intermediates, with or without the tailoring gene, eryF, required for the synthesis of erythronolide B (EB). Liquid chromatography-mass spectrometry of the metabolites indicated the production of angolosaminyl-6-dEB and angolosaminyl-EB. The advantages of using multiplexed integrating plasmids for engineering expression and for combinatorial biosynthesis were demonstrated.


Comparison of Efficacy of Intraoperative Indocyanine Green Videoangiography in Clipping of Anterior Circulation Aneurysms with Postoperative Digital Subtraction Angiography.
The aim of this study is to assess the efficacy of intraoperative indocyanine green videoangiography (ICG-VA) using postoperative digital subtraction angiography (DSA) in clipped anterior circulation aneurysms. A prospective study was conducted for 1 year which included thirty patients of anterior circulation aneurysm treated by clipping of aneurysm. Intraoperative ICG-VA was performed on all the patients. Postoperative DSA was performed to assess the efficacy of ICG-VA. Intraoperative ICG-VA revealed the occlusion of aneurysm in all the thirty patients. Postoperative DSA revealed aneurysm neck remnant in two patients and demonstrated no branch occlusion. Intraoperative ICG-VA is useful in assessing the completeness of clipping of cerebral aneurysms and ensures patency of branch vessels, thus providing a better postoperative outcome. It replaces the need for invasive postoperative angiographic imaging in a selected group of patients and is also cost effective.


Bovine leukemia virus-induced lymphocytosis and increased cell survival mainly involve the CD11b+ B-lymphocyte subset in sheep.
In this study, we show that bovine leukemia virus (BLV)-induced persistent lymphocytosis (PL) results from the in vivo expansion of the CD11b+ B-lymphocyte population. This subset shares phenotypic characteristics with murine and human B-1 cells. BLV interactions with the sheep B-1-like subset were explored. We found that B-1- and B-2-like cells are initially infected to similar extents. However, in long-term-infected sheep, the viral load is higher in B-1-like cells and only B-1- and not B-2-like cells show increased ex vivo survival compared to that in uninfected sheep. Ex vivo viral expression was found in both B-1- and B-2-like cells, indicating that both cell types support viral replication. Finally, cycloheximide and a protein kinase C inhibitor (H7) that blocks the ex vivo activation of viral expression did not affect the increased survival in B-1-like cells, suggesting that resistance to apoptosis is acquired in vivo. Collectively, these results indicate a peculiar susceptibility of sheep B-1-like cells to BLV transforming effects and further support the involvement of increased survival in BLV pathogenesis.


Ultrathin Functional Polymer Modified Graphene for Enhanced Enzymatic Electrochemical Sensing.
Grafting thin polymer layers on graphene enables coupling target biomolecules to graphene surfaces, especially through amide and aldehyde linkages with carboxylic acid and primary amine derivatives, respectively. However, functionalizing monolayer graphene with thin polymer layers without affecting their exceptional electrical properties remains challenging. Herein, we demonstrate the controlled modification of chemical vapor deposition (CVD) grown single layer graphene with ultrathin polymer 1,5-diaminonaphthalene (DAN) layers using the electropolymerization technique. It is observed that the controlled electropolymerization of DAN monomer offers continuous polymer layers with thickness ranging between 5⁻25 nm. The surface characteristics of pure and polymer modified graphene was examined. As anticipated, the number of surface amine groups increases with increases in the layer thickness. The effects of polymer thickness on the electron transfer rates were studied in detail and a simple route for the estimation of surface coverage of amine groups was demonstrated using the electrochemical analysis. The implications of grafting ultrathin polymer layers on graphene towards horseradish peroxidase (HRP) enzyme immobilization and enzymatic electrochemical sensing of H₂O₂ were discussed elaborately.


Bone and gallium scan findings in malignant fibrous histiocytoma. Case report with radiographic and pathologic correlation.
Malignant fibrous histiocytoma (MFH) is the most common soft tissue malignancy in adults. The Ga-67 citrate scan findings of an extremity-located MFH, the most common location of this neoplasm, have never been published in English language journals to the best of the authors' knowledge. Ga-67 citrate and Tc-99m MDP scans of the thigh mass accurately depicted the tumor's local extent, including the presence of central ischemic necrosis within the tumor, and the absence of adjacent osseous involvement and distant metastases, as correlated with computed tomography, angiography, and pathologic examinations.


The effect of ionizing radiation on metoprolol.
The influence of ionising radiation on physico-chemical properties of metoprolol tartrate (MT) in solid phase was studied. The compound was irradiated by radiation produced by a beam of high-energy electrons in an accelerator, in doses from 25 to 400 kGy, and the possible changes in the samples were detected by organoleptic analysis (colour, forms, clarity), chromatographic and spectrometric methods. Already at the standard sterilisation dose of 25 kGy, the presence of free radicals (0.3764 × 10(16) spin/g) and a decrease in the melting point by 1°C were noted. At higher doses of irradiation products of radiolysis appeared (100 kGy) and the colour was changed from white to pale cream (200 kGy). Our observation was that with increasing mass loss of MT after irradiation with 100, 200 and 400 kGy, the concentration of free radicals increased from 1.0330 to 1.6869 × 10(16) spin/g. The radiolytic yield of total radiolysis was 4.54 × 10(7) mol/J for 100 kGy, 7.42 × 10(7) mol/J for 200 kGy and 4.74 × 10(7) mol/J for 400 kGy. No significant changes were observed in the character of FT-IR spectra, but in UV an increase in intensity of the band at the analytical wavelength was noted. As follows from the results MT shows high radiochemical stability for the typical sterilisation doses 25-50 kGy, and will probably be able to be sterilised by radiation in the dose of 25 kGy.


Development of a novel smart scaffold for human skeletal muscle regeneration.
Skeletal muscle defects are notoriously difficult to manage and the current methods used are associated with many limitations. Engineered skeletal muscle tissue has the potential to provide a solution that circumvents these disadvantages. Our previous work has identified a novel three-dimensionally aligned degradable phosphate glass fibre scaffold that can support myoblast differentiation and maturation. This current study has further developed the scaffold by encasing the fibres within a collagen gel to produce a smart composite scaffold that provides key biomimetic cues and supports the formation of a tissue that may be implanted in vivo. The constructs formed were approximately 30 mm long and microscopic examination confirmed favourable unidirectional cell alignment. There was good cell survival, and gene expression studies demonstrated upregulation of the myogenic regulatory factors and developmental and adult myosin heavy chain isoforms indicating myofibre formation and maturation respectively. Compared with the three-dimensional glass fibre scaffolds, the composite scaffolds had later gene upregulation, however, the use of collagen gels reinforced with degradable aligned glass fibres offers the opportunity to create a tissue analogue that can be easily manipulated. Furthermore, the glass fibre ends could support tendon/bone formation, and the channels formed as the fibres degrade could allow for vascular ingrowth.


Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation.
The metabolism of the spleen tyrosine kinase inhibitor N4-(2,2-dimethyl-3-oxo-4-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethyoxyphenyl)-2,4-pyrimidinediamine (R406) and its oral prodrug N4-(2,2-dimethyl-4-[(dihydrogenphosphonoxy)methyl]-3-oxo-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethyoxyphenyl)-2,4-pyrimidinediamine disodium hexahydrate (R788, fostamatinib) was determined in vitro and in humans. R788 was rapidly converted to R406 by human intestinal microsomes, and only low levels of R788 were observed in plasma of human subjects after oral administration of (14)C-R788. R406 was the major drug-related compound in plasma from human subjects, and only low levels of metabolites were observed in plasma. The plasma metabolites of R406 were identified as a sulfate conjugate and glucuronide conjugate of the para-O-demethylated metabolite of R406 (R529) and a direct N-glucuronide conjugate of R406. Elimination of drug-related material into the urine accounted for 19% of the administered dose, and the major metabolite in urine from all the human subjects was the lactam N-glucuronide of R406. On average, 80% of the total drug was recovered in feces. Two drug-related peaks were observed; one peak was identified as R406, and the other peak was identified as a unique 3,5-benzene diol metabolite of R406. The 3,5-benzene diol metabolite appeared to result from the subsequent O-demethylations and dehydroxylation of R529 by anaerobic gut bacteria because only R529 was converted to this metabolite after the in vitro incubation with human fecal samples. These data indicate that the major fecal metabolite of R406 observed in humans is a product of a hepatic cytochrome P450-mediated O-demethylation and subsequent O-demethylations and dehydroxylation by gut bacteria.


International summit on the nutrition of adolescent girls and young women: consensus statement.
An international summit focusing on the difficult challenge of providing adequate nutrition for adolescent girls and young women in low- and middle-income countries was held in Portland, Oregon in 2015. Sixty-seven delegates from 17 countries agreed on a series of recommendations that would make progress toward improving the nutritional status of girls and young women in countries where their access to nutrition is compromised. Delegate recommendations include: (1) elevate the urgency of nutrition for girls and young women to a high international priority, (2) raise the social status of girls and young women in all regions of the world, (3) identify major knowledge gaps in the biology of adolescence that could be filled by robust research efforts, (4) and improve access to nutrient-rich foods for girls and young women. Attention to these recommendations would improve the health of young women in all nations of the world.


Transgender Healthcare and Medical Education: An Inductive Thematic Analysis of Digital Discourse.
Introduction Transgender and gender-diverse (TGD) patients face significant healthcare disparities informed by discrimination, social stigma, and socioeconomic inequality. This is further exacerbated by a paucity of transgender health content in medical education, contributing to a large proportion of providers being ill-equipped to manage TGD patients' health concerns. Method This paper uses the framework approach for an inductive thematic analysis of online discussion forums concerning transgender health and medical education. Online text from anonymous participants was chosen for their authentic accounts of healthcare experiences and to ensure responses are less restrained in discussing sensitive topics. Results Three major themes were identified from the data: desire for more knowledgeable providers, negative healthcare experiences and attitudes, and recommendations for transgender health education. Three subcategories emerged from the latter theme that further illuminated participant recommendations for inclusive healthcare. Conclusions As a result of the unique healthcare concerns faced by TGD patients, providing materials to educate students and providers is crucial to meet the needs of the TGD patient population. Participant reports align with previous literature in recommending curricular reforms in medical school, promoting career options for TGD-identifying people in healthcare, and cultivating a more inclusive clinical culture.


Comparison of oral Candida species prevalence and carriage among gutka-chewers and betel-quid chewers.
To compare prevalence and carriage of Candida species among gutka-chewers and betel-quid-chewers. The cross-sectional case-control study was conducted between January and December, 2015 at the Oral Surgery department of Abbasi Shaheed Hospital and the Dental department of Jinnah Postgraduate Medical Centre, Karachi, and comprised oral yeast samples of gutka-chewers, betel-quid-chewers, and non-chewers. A standardised questionnaire was used to gather demographic data and oral hygiene maintenance information. Oral Candida strains were collected, cultured and identified using standard techniques and yeast identification system. In all groups, unstimulated whole salivary flow rate was determined. Lesions on the tongue and oral mucosa were clinically investigated and numbers of missing teeth were recorded. SPSS 20 was used for data analysis. Of the total 185 samples, 50(27%) were from gutka-chewers, 50(27%)betel-quid-chewers, and 85(46%) non-chewers. Oral Candida carriage was comparable among betel-quid-chewers (18 [36%])and gutka-chewers (20 [40%]), but it was significantly higher than the non-chewers (11 [12.9%]) (p<0.05).Candida species were isolated from 45 (90%) of gutka-chewers and 45 (90%) of BQ-chewers. Among the groups, Candida albicans was the most commonly isolated yeast species (38% in gutka-chewers and 12.9% non-chewers). Mean numbers of missing teeth were significantly higher among BQ-chewers (6.8±0.4 teeth [range: 5-10]) (p<0.01) and gutka-chewers 6.8±0.6 teeth (range: 5-10) (p<0.01) than non-chewers (2.2±0.3 teeth [range: 0-3 teeth]). There was no significant difference in unstimulated whole salivary flow rate and the number of missing teeth among gutka-chewers and betel-quid-chewers (p>0.05). Prevalence and carriage of Candida species were comparable between betel-quid-chewers and gutka-chewers compared to non-chewers.


Nitratireductor rhodophyticola sp. nov., isolated from marine red algae.
Two Gram-stain-negative, strictly aerobic bacteria, strains L1-7-SET and R6, isolated from marine red algae, were characterized. They shared 99.9 % 16S rRNA gene sequence similarity and a 100 % digital DNA-DNA hybridization (DDH) value, representing members of a single species. Cells of strains L1-7-SET and R6 were catalase- and oxidase-positive motile rods with a single polar flagellum. Strains L1-7-SET and R6 optimally grew at 30-35 °C, pH 7.0-8.0 and with 1.0-2.0 % (w/v) NaCl. Ubiquinone-10 was the sole isoprenoid quinone and C19 : 0 cyclo ω8c and summed feature 8 (comprising C18 : 1 ω7c and/or C18 : 1 ω6c) were detected as the major cellular fatty acids. The DNA G+C contents of strains L1-7-SET and R6 were both 61.62 mol%. The polar lipids of strain L1-7-SET consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and two unidentified polar lipids. Phylogenetic analyses based on 16S rRNA gene and 120 protein marker sequences revealed that strains L1-7-SET and R6 formed a phyletic lineage within the genus Nitratireductor and they were most closely related to Nitratireductor aquibiodomus NL21T and Nitratireductor kimnyeongensis KY 101T with both 98.8 % 16S rRNA gene sequence similarities. Digital DDH values between strain L1-7-SET and the type strains of N. aquibiodomus and N. kimnyeongensis were 60.3 and 29.5 %, respectively. The phenotypic, chemotaxonomic and molecular features support that strains L1-7-SET and R6 represents a novel species of the genus Nitratireductor, for which the name Nitratireductor rhodophyticola sp. nov. is proposed. The type strain is L1-7-SET (=KACC 19076T=KCTC 92231T=JCM 31802T).


Synergistic Effect of SH003 and Doxorubicin in Triple-negative Breast Cancer.
Triple-negative breast cancer (TNBC) is highly aggressive, resulting in poor prognosis. Chemotherapy of TNBC relies on anti-cancer agents with strong cytotoxicity, but it causes several side effects with recurrence. While combinational approaches of chemotherapeutics have been highlighted as a new treatment strategy for TNBC to reduce side effects, combinations of anti-cancer agents with herbal medicines have not been reported. We recently reported that newly modified traditional Chinese medicine named SH003 inhibited TNBC growth. Considering a combinational strategy for TNBC treatment, we further studied synergistic effects of SH003 with various anti-cancer drugs in TNBC treatment. Here, we demonstrate that SH003 shows a synergistic effect with doxorubicin on TNBC treatment. Our in vitro cell viability assays revealed that SH003 and doxorubicin showed a synergistic effect in the well-defined TNBC cell line, MDA-MB-231. Moreover, we found that the combinational treatment caused Caspase-dependent apoptotic cell death. Our in vivo mouse xenograft tumor growth assays confirmed that combinational treatment of SH003 with doxorubicin repressed MDA-MB-231 tumor growth with no weight loss. Therefore, we conclude that the combinational treatment of SH003 with doxorubicin shows the synergism in TNBC treatment, and suggest that SH003 can be used together with conventional anti-cancer drugs in chemotherapeutic approaches. Copyright © 2016 John Wiley & Sons, Ltd.


The 308-nm excimer laser stimulates melanogenesis via the wnt/β-Catenin signaling pathway in B16 cells.
Background: The mechanism of the 308-nm excimer laser in vitiligo treatment has not yet been adequately studied. In this study, we explored the role of the 308-nm excimer laser in treatment of vitiligo and the molecular mechanisms underlying melanin biosynthesis in melanocytes after 308-nm excimer laser radiation. Materials and methods: The B16 cells were irradiated at doses of 0 mJ/cm2, 100 mJ/cm2, 300 mJ/cm2 and 600 mJ/cm2 using a 308-nm excimer laser and then cultured for an additional 24, 48 or 72 hours. Melanogenesis and tyrosinase activity in cells were measured by biochemical methods. The expression of tyrosinase, MITF, Wnt3α and β-catenin was analyzed by Western blotting. Results: Cell irradiation with the 308-nm excimer laser not only significantly elevated the melanin content (p < .01) but also stimulated the activity of tyrosinase (p < .01). The expressions of tyrosinase and MITF were also significantly increased in cells after 308-nm excimer laser irradiation. We also defined the signaling pathway by which the 308-nm excimer laser stimulates melanin biosynthesis. Increased Wnt3α and β-catenin expression was observed by Western blot analysis. Conclusion: Activation of the Wnt/β-catenin pathway likely led to the activation of MITF and tyrosinase transcription, as well as, the subsequent induction of melanin synthesis.


Phylogenomic insights into the diversification of salamanders in the Isthmura bellii group across the Mexican highlands.
Mountain formation in Mexico has played an important role in the diversification of many Mexican taxa. The Trans-Mexican Volcanic Belt in particular has served as both a cradle of diversification and conduit for dispersal. We investigated the evolutionary history of the Isthmura bellii group of salamanders, a widespread amphibian across the Mexican highlands, using sequence capture of ultraconserved elements. Results suggest that the I. bellii group probably originated in southeastern Mexico in the late Miocene and later dispersed across the Trans-Mexican Volcanic Belt and into the Sierra Madre Occidental. Pre-Pleistocene uplift of the Trans-Volcanic Belt likely promoted early diversification by serving as a mesic land-bridge across central Mexico. These findings highlight the importance of the Trans-Volcanic Belt in generating Mexico's rich biodiversity.


Prognostic analyses of genes associated with anoikis in breast cancer.
Breast cancer (BRCA) is the most diagnosed cancer worldwide and is responsible for the highest cancer-associated mortality among women. It is evident that anoikis resistance contributes to tumour cell metastasis, and this is the primary cause of treatment failure for BRCA. However, anoikis-related gene (ARG) expression profiles and their prognostic value in BRCA remain unclear. In this study, a prognostic model of ARGs based on The Cancer Genome Atlas (TCGA) database was established using a least absolute shrinkage and selection operator analysis to evaluate the prognostic value of ARGs in BRCA. The risk factor graph demonstrated that the low-risk group had longer survival than the high-risk group, implying that the prognostic model had a good performance. We identified 11 ARGs that exhibited differential expression between the two risk groups in TCGA and Gene Expression Omnibus databases. Through Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analyses, we revealed that the screened ARGs were associated with tumour progression and metastasis. In addition, a protein-protein interaction network showed potential interactions among these ARGs. Furthermore, gene set enrichment analysis suggested that the Notch and Wnt signalling pathways were overexpressed in the high-risk group, and gene set variation analysis revealed that 38 hallmark genes differed between the two groups. Moreover, Kaplan-Meier survival curves and receiver operating characteristic curves were used to identify five ARGs (CD24, KRT15, MIA, NDRG1, TP63), and quantitative polymerase chain reaction was employed to assess the differential expression of these ARGs. Univariate and multivariate Cox regression analyses were then performed for the key ARGs, with the best prediction of 3 year survival. In conclusion, ARGs might play a crucial role in tumour progression and serve as indicators of prognosis in BRCA.


Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors.
Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics is conferred by the enzymatic modification of the antibiotic. Therefore, a deeper knowledge of the aminoglycoside-modifying enzymes and their interactions with the antibiotics and solvent is of paramount importance in order to facilitate the design of more effective and potent inhibitors and/or novel semisynthetic aminoglycosides that are not susceptible to modifying enzymes.


The Unfolded Protein Response Supports Plant Development and Defense as well as Responses to Abiotic Stress.
The unfolded protein response (UPR) is a stress response conserved in eukaryotic organisms and activated by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Adverse environmental conditions disrupt protein folding in the ER and trigger the UPR. Recently, it was found that the UPR can be elicited in the course of plant development and defense. During vegetative plant development, the UPR is involved in normal root growth and development, the effect of which can be largely attributed to the influence of the UPR on plant hormone biology. The UPR also functions in plant reproductive development by protecting male gametophyte development from heat stress. In terms of defense, the UPR has been implicated in virus and microbial defense. Viral defense represents a double edge sword in that various virus infections activate the UPR, however, in a number of cases, the UPR actually supports viral infections. The UPR also plays a role in plant immunity to bacterial infections, again through the action of plant hormones in regulating basal immunity responses.


Genetic correlations among sex-limited traits in beef cattle.
Data from a comprehensive germ plasm evaluation program were used to estimate genetic correlations of reproductive and maternal traits of beef females with growth and carcass traits of their steer paternal half-sibs. The data set consisted of 187 sires with approximately four female and five male progeny each. Heritability estimates for age at puberty, weight at puberty, conceptions/service, gestation length, calving difficulty, progeny birth weight, progeny preweaning daily gain and mature weight measured on females were .613 +/- .177, .700 +/- .114, .026 +/- .126, .298 +/- .175, .217 +/- .175, .374 +/- .174, .094 +/- .161, and .540 +/- .150, respectively. Postweaning daily gain, carcass weight, fat trim weight and retail product weight measured on male half-sibs had estimated heritabilities of .363 +/- .090, .441 +/- .093, .502 +/- .093 and .451 +/- .093, respectively. The estimated genetic correlations suggest that selection for postweaning daily gain would result in increased age and weight at puberty, increased mature weight, improved fertility, reduced maternal gestation length, reduced maternal calving difficulty, increased maternal birth weight and reduced maternal preweaning gain. Predicted correlated responses to selection for reduced fat trim at a constant age were increased age and weight at puberty, increased mature weight, reduced maternal fertility, reduced maternal preweaning gain and increased maternal gestation length, birth weight and calving difficulty. Consequences of selection for increased age constant retail product weight or carcass weight appear to be increased age and weight at puberty, increased mature weight, improved fertility, increased maternal gestation length and maternal birth weight but reduced maternal difficulty and reduced maternal preweaning gain.


Successful treatment with allogenic hematopoietic stem cell transplantation of a severe congenital neutropenia patient harboring a novel ELANE mutation.
We report a 4-year-old boy with severe congenital neutropenia (SCN), who was successfully treated with hematopoietic stem cell transplantation (HSCT). The patient had frequently developed bacterial infections since 6 months of age, and showed severe neutropenia below 100/μl at 1 year and 4 months of age. The patient harbored a heterozygous missense mutation in ELANE exon 3 (p.Q73P, g.2253 A>C). This was a novel de novo mutation, and he was thus diagnosed as having SCN. Because of failure to respond to granulocyte colony-stimulating factor treatment and repeated admissions due to bacterial infections, allogeneic HSCT was performed from a serologically matched unrelated donor following the conditioning regimen: fludarabine/melphalan/anti-thymocyte globulin and a low dose of total body irradiation. Tacrolimus and a short course of methotrexate were used for graft-versus-host disease prophylaxis. Engraftment was achieved at day 12, and the patient maintained normal hematopoiesis for over 15 months after HSCT. We concluded that HSCT is a useful treatment for SCN patients, especially those who are at high risk for leukemic transformation. However, a larger number of SCN patients and longer follow-up are necessary to identify appropriate conditioning regimens and long-term prognosis.


TIMP3 promotes the maintenance of neural stem-progenitor cells in the mouse subventricular zone.
Adult neural stem cells (NSCs) in the mouse subventricular zone (SVZ) serve as a lifelong reservoir for newborn olfactory bulb neurons. Recent studies have identified a slowly dividing subpopulation of embryonic neural stem-progenitor cells (NPCs) as the embryonic origin of adult NSCs. Yet, little is known about how these slowly dividing embryonic NPCs are maintained until adulthood while other NPCs are extinguished by the completion of brain development. The extracellular matrix (ECM) is an essential component of stem cell niches and thus a key determinant of stem cell fate. Here we investigated tissue inhibitors of metalloproteinases (TIMPs)-regulators of ECM remodeling-for their potential roles in the establishment of adult NSCs. We found that Timp2, Timp3, and Timp4 were expressed at high levels in slowly dividing NPCs compared to rapidly dividing NPCs. Deletion of TIMP3 reduced the number of adult NSCs and neuroblasts in the lateral SVZ. In addition, overexpression of TIMP3 in the embryonic NPCs suppressed neuronal differentiation and upregulated the expression levels of Notch signaling relating genes. These results thus suggest that TIMP3 keeps the undifferentiated state of embryonic NPCs, leading to the establishment and maintenance of adult NSCs.


Videolaparoscopic treatment of Spigelian hernias.
Because treatment for Spigelian hernia is rarely discussed in the literature, this report presents two cases observed in a recent 6-month period by the U.O.A. Independent General Surgery Department, Hospital of Este. Both patients had laparoscopic treatment using a polypropylene prosthesis, which confirms the technological validity of the surgical method. The described cases are emblematic, because the intervention permitted a resolution of associated pathologies (gallbladder gallstones and umbilical hernia), which confirms both the efficacy of the surgical technique and of the high diagnostic precision of laparoscopy, as it is described by several sources. The validity of the technique is also confirmed by the quick recovery of patients and by the reduced hospitalization time, especially in elderly patients and in precarious general conditions.


Morphology-Controlled 9,10-Diphenylanthracene Nanoblocks as Electrochemiluminescence Emitters for MicroRNA Detection with One-Step DNA Walker Amplification.
The electrochemiluminescence (ECL) properties of polycyclic aromatic hydrocarbons (PAHs) are excellent on account of the high photoluminescence quantum yield. However, the poor solubility and radical instability of PAHs in the aqueous solution severely restricted further biological application. Here 9,10-diphenylanthracene (DPA) nanoblocks (NBs) with good dispersibility and stability in aqueous solution were prepared according to morphology-controlled technology employing water-soluble polymers as a protectant. Furthermore, an ECL "off-on" switch biosensor was developed based on a novel ECL ternary system with DPA NBs as luminophore, dissolved O2 as coreactant, and Pt-Ag alloy nanoflowers as the coreaction accelerator, which achieved a high-intense initial ECL signal. Subsequently, the Fc-DNA as ECL signal quencher was assembled on the electrode surface to quench the initial ECL signal for a "signal-off" state. Meanwhile, DNA swing arm was modified on the electrode surface for one-step DNA walker amplification. Interestingly, in the presence of miRNA-141 and T7 Exo, the one-step DNA walker amplification was executed to recover a strong ECL signal as a "signal-on" state by the digestion of Fc-DNA. Thus the developed ECL "off-on" switch biosensor possesses a detection limit down to 29.5 aM for ultrasensitive detection of miRNA-141, which is expected to be applicable to the detection of miRNA in clinic tumor cells.


Saccharides and temperature dual-responsive hydrogel layers for harvesting cell sheets.
Saccharides and temperature dual-responsive hydrogels have been prepared based on PNIPAAm copolymers containing phenylboronic acid (PBA) groups and used for harvesting cell sheets. The cell sheet could be released from the hydrogel layer at 37 °C simply by increasing sugar concentration, and could be more efficiently released at a lower temperature and elevated sugar concentration.


Macrolide resistance: an increasing concern for treatment failure in children.
Antimicrobial treatment of pediatric respiratory tract infections has evolved during the past 30 years as a result of antimicrobial resistance. The focus of antimicrobial therapy in these conditions has shifted from penicillins to other agents because of the dramatic increase in antimicrobial resistance among common respiratory pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. It is important for clinicians to understand how resistance develops so that they can help prevent this phenomenon from occurring with other antimicrobials. This article reviews the published literature on resistance to macrolide antimicrobials among common pediatric respiratory tract pathogens and clinical and bacteriologic outcomes of infections with these pathogens. Resistance among common pediatric respiratory tract pathogens to macrolides occurs through two main mechanisms, alteration of the target site and active efflux. Although resistance patterns vary by geographic region, the widespread use of macrolides has contributed to the emergence of both types of macrolide-resistant organisms. Conditions that favor the selection and proliferation of resistant strains include children with repeated, close contact who frequently receive antimicrobial treatment or prophylaxis, such as children who attend day care. Recent US surveillance data show that 20 to 30% of S. pneumoniae are resistant to macrolides, with approximately two-thirds of macrolide-resistant strains associated with an efflux mechanism and the remainder associated with a ribosomal methylase. Additionally, although less well-known, virtually all strains of H. influenzae have an intrinsic macrolide efflux pump. As resistance to macrolides has increased, clinical failures have resulted, and these agents are no longer considered appropriate for empiric first line antimicrobial therapy of acute otitis media and sinusitis unless patients are truly penicillin-allergic. Therefore, other antimicrobials are recommended for the empiric treatment of children with respiratory tract infections, including higher doses of amoxicillin and amoxicillin/clavulanate (90 mg/kg/day amoxicillin), cefuroxime axetil and intramuscular ceftriaxone. As resistance to macrolides increases and clinical failures in children become more common with this class of antimicrobials, judicious use of antimicrobials is needed. This includes limiting antimicrobial use for viral infections and using the most effective agents when antimicrobials are clinically indicated, such as higher doses of amoxicillin and amoxicillin/clavulanate. Application of these principles may prevent proliferation and further development of resistance.


Stabilizing bromelain for therapeutic applications by adsorption immobilization on spores of probiotic Bacillus.
Bromelain, a protease from pineapple plant can be applied as oral drug for the treatment of inflammation and certain diseases. Unlike most conventional supports, immobilization on edible support will make the enzyme suitable for therapeutic use. In this study, spores of probiotic Bacillus sp was used for the adsorption of bromelain. Effect of pH, temperature and enzyme concentration on bromelain immobilization was studied, followed by characterization of the enzymes. Maximum bromelain coupling (%) (50.607 ± 4.194) was obtained when immobilization was carried out at pH 6.0, 24 °C for 150 min. The immobilized enzyme showed optimum activity at pH 8 and 80 °C, while the free enzyme had 6 and 60 °C as its optimum pH and temperature, respectively. Bromelain Vmax increased after immobilization while Km decreased. Activation energy, Ea was 26.513 kJ/mol and 20.942 kJ/mol for the free and immobilized enzymes, respectively. The immobilized bromelain also showed significantly greater storage and thermal stability than the free bromelain. At 80 °C, the free bromelain lost all its activity after 50 min while the immobilized enzyme lost only 46.89% activity. Bromelain was successfully immobilized on Bacillus spores with improved catalytic and non-catalytic properties and this holds great potential for its growing therapeutic applications.