Fusion Domains Guide the Oriented Insertion of Light-Driven Proton Pumps into Liposomes.
One major objective of synthetic biology is the bottom-up assembly of minimalistic nanocells consisting of lipid or polymer vesicles as architectural scaffolds and of membrane and soluble proteins as functional elements. However, there is no reliable method to orient membrane proteins reconstituted into vesicles. Here, we introduce a simple approach to orient the insertion of the light-driven proton pump proteorhodopsin (PR) into liposomes. To this end, we engineered red or green fluorescent proteins to the N- or C-terminus of PR, respectively. The fluorescent proteins optically identified the PR constructs and guided the insertion of PR into liposomes with the unoccupied terminal end facing inward. Using the PR constructs, we generated proton gradients across the vesicle membrane along predefined directions such as are required to power (bio)chemical processes in nanocells. Our approach may be adapted to direct the insertion of other membrane proteins into vesicles.


An import signal in the cytosolic domain of the Neurospora mitochondrial outer membrane protein TOM22.
TOM22 is an integral component of the preprotein translocase of the mitochondrial outer membrane (TOM complex). The protein is anchored to the lipid bilayer by a central trans-membrane segment, thereby exposing the amino-terminal domain to the cytosol and the carboxyl-terminal portion to the intermembrane space. Here, we describe the sequence requirements for the targeting and correct insertion of Neurospora TOM22 into the outer membrane. The orientation of the protein is not influenced by the charges flanking its trans-membrane segment, in contrast to observations regarding proteins of other membranes. In vitro import studies utilizing TOM22 preproteins harboring deletions or mutations in the cytosolic domain revealed that the combination of the trans-membrane segment and intermembrane space domain of TOM22 is not sufficient to direct import into the outer membrane. In contrast, a short segment of the cytosolic domain was found to be essential for the import and assembly of TOM22. This sequence, a novel internal import signal for the outer membrane, carries a net positive charge. A mutant TOM22 in which the charge of the import signal was altered to -1 was imported less efficiently than the wild-type protein. Our data indicate that TOM22 contains physically separate import and membrane anchor sequences.


Synthesis and preclinical evaluation of a heterodimeric radioligand targeting fibroblast activation protein and integrin-αvβ3.
Tumor progression is accompanied by intrinsic heterogeneity and different phenotypes, which implies a different expression of cell surface receptors. Fibroblast activation protein (FAP) and integrin αvβ3 are highly expressed in the cell surface of cancer-associated cells or cancer cells compared with normal cells. Therefore, a FAP/integrin αvβ3 bispecific heterodimer was developed for positron emission tomography (PET) diagnostic imaging and radiotherapy. The heterodimer DOTA-FAPI-RGD was labeled with the diagnostic radionuclide gallium-68 or the therapeutic radionuclide lutetium-177, with yields >80%, and high stability. The competitive displacement binding assay showed an IC50 = 6.8 ± 0.6 nM for DOTA-FAPI-RGD towards FAP and IC50 = 2.1 ± 0.4 nM towards integrin αvβ3. Radionuclide labeled DOTA-FAPI-RGD showed high specificity and rapid internalization into U87MG cells (FAP/αvβ3-positive) in vitro. Micro-PET and biodistribution studies of [68Ga]Ga-DOTA-FAPI-RGD in tumor-bearing mice demonstrated that a high and specific tumor uptake of the tracer and a fast body clearance, resulting in high contrast images. In addition to the imaging applications demonstrated in this study, the labeling of the heterodimeric ligand with the radionuclide lutetium-177 used in cancer treatment might allow the therapeutic application of this ligand.


Clinical value of combined detection of serum APE1-Aabs and CEACAM-1 in the diagnosis of colorectal cancer.
To analyze the clinical value of combined detection of serum APE1-Aabs and CEACAM-1 in pathological diagnosis of colorectal cancer. From December 2014 to July 2016, 60 patients with colorectal cancer and 50 healthy subjects were enrolled in this study. The levels of APE1-AAbs, CEACAM-1 and CEA in the serum were measured, and the clinical value of each index in the diagnosis of colorectal cancer was analyzed. The level of serum APE1-AAbs in colorectal cancer group was significantly higher than that in healthy control group (p < 0.05). The levels of serum CEACAM-1 and CEA in colorectal cancer patients were significantly higher than those in healthy control group (p < 0.05). The sensitivity and accuracy of APE1-AAbs and CEACAM-1 in the diagnosis of colorectal cancer were significantly higher than separate detection of APE1-AAbs, CEACAM-1 or CEA. Combined detection of serum APE1-AAbs and CEACAM-1 has the advantages of high sensitivity and good accuracy in the diagnosis of colorectal cancer, and it is worthy to be popularized in clinical practice.


[Effectiveness of sagittal top compression reduction technique in treatment of thoracolumbar vertebral fractures].
To investigate the effectiveness of sagittal top compression reduction technique in the treatment of thoracolumbar vertebral fractures. A retrospective analysis was conducted on the clinical data of 59 patients with thoracolumbar vertebral fractures who met the selection criteria and were admitted between November 2018 and January 2022. Among them, 34 patients were treated with sagittal top compression reduction technique (top pressure group), and 25 patients were treated with traditional reduction technique (traditional group). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, fracture segment, cause of injury, AO classification of thoracolumbar vertebral fractures, thoracolumbar injury classification and severity (TLICS) score, American Spinal Injury Association (ASIA) grading, surgical approach, preoperative vertebral body index, height ratio of the anterior margin of injured vertebra, injured vertebra angle, segmental kyphosis angle, visual analogue scale (VAS) score, and Oswestry disability index (ODI). The operation time, intraoperative blood loss, and incidence of complications between the two groups were recorded and compared. After operation, VAS score and ODI were used to evaluate effectiveness, and X-ray and CT examinations were performed to measure imaging indicators such as vertebral body index, height ratio of the anterior margin of injured vertebra, injured vertebra angle, and segmental kyphosis angle. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). No complication such as dural sac, nerve root, or vascular injury was found during operation, and all incisions healed by first intention. Patients in both groups were followed up 6-48 months, with an average of 20.6 months. No loosening, breakage, or failure of internal fixation occurred during follow-up. The imaging indicators, VAS score, and ODI of the two groups significantly improved at 1 week and last follow-up when compared to preoperative ones ( P<0.05). At last follow-up, the VAS score and ODI further significantly improved when compared to 1 week after operation ( P<0.05). At 1 week after operation and last follow-up, the vertebral body index, segmental kyphosis angle, injured vertebra angle, and ODI in the top pressure group were significantly better than those in the traditional group ( P<0.05). There was no significant difference in VAS score and height ratio of the anterior margin of injured vertebra between the two groups at 1 week after operation ( P>0.05), but the two indicators in the top pressure group were significantly better than those in the traditional group at last follow-up ( P<0.05). The treatment of thoracolumbar vertebral fractures with sagittal top compression reduction technique can significantly improve the quality of vertebral reduction, and is superior to traditional reduction techniques in relieving pain and improving spinal function.


Delayed administration of the human anti-RGMa monoclonal antibody elezanumab promotes functional recovery including spontaneous voiding after spinal cord injury in rats.
Spinal cord injury (SCI) often results in permanent functional loss due to a series of degenerative events including cell death, axonal damage, and the upregulation of inhibitory proteins that impede regeneration. Repulsive Guidance Molecule A (RGMa) is a potent inhibitor of axonal growth that is rapidly upregulated following injury in both the rodent and human central nervous system (CNS). Previously, we showed that monoclonal antibodies that specifically block inhibitory RGMa signaling promote neuroprotective and regenerative effects when administered acutely in a clinically relevant rat model of thoracic SCI. However, it is unknown whether systemic administration of RGMa blocking antibodies are effective for SCI after delayed administration. Here, we administered elezanumab, a human monoclonal antibody targeting RGMa, intravenously either acutely or at 3 h or 24 h following thoracic clip impact-compression SCI. Rats treated with elezanumab acutely and at 3 h post-injury showed improvements in overground locomotion and fine motor function and gait. Rats treated 24 h post-SCI trended towards better recovery demonstrating significantly greater stride length and swing speed. Treated rats also showed greater tissue preservation with reduced lesion areas. As seen with acute treatment, delayed administration of elezanumab at 3 h post-SCI also increased perilesional neuronal sparing and serotonergic and corticospinal axonal plasticity. In addition, all elezanumab treated rats showed earlier spontaneous voiding ability and less post-trauma bladder wall hypertrophy. Together, our data demonstrate the therapeutic efficacy of delayed systemic administration of elezanumab in a rat model of SCI, and uncovers a new role for RGMa inhibition in bladder recovery following SCI.


Neurogenesis of retinal ganglion cells is not essential to visual functional recovery after optic nerve injury in adult zebrafish.
Zebrafish central nervous system (CNS) possesses a strong neural regeneration ability to restore visual function completely after optic nerve injury (ONI). However, whether neurogenesis of retinal ganglion cell (RGC) contributes to functional recovery remains controversial. Our quantitative analysis of RGCs in different ONI models showed that almost all RGCs survived in optic nerve crush (ONC) model; while over 90% of RGCs survived in the first 2 weeks with 75% remaining after 7 weeks in optic nerve transection (ONT) model. Retrograde labeling from tectum revealed a surprising regeneration rate, with over 90% and over 50% of RGCs regrowing axons to tectum at the first week in ONC and ONT model respectively. In the latter one, the number of regenerative RGCs after 4 weeks had no significant difference from the control group. As for neurogenesis, newborn RGCs were rarely detected either by double retrograde labeling or BrdU marker. Since few RGCs died, microglia number showed a temporary increase at 3 days post injury (dpi) and a decrease at 14 dpi. Finally, myelin structure within retina kept integrity and optomotor response (OMR) test demonstrated visual functional restoration at 5 weeks post injury (wpi). In conclusion, our results have directly shown that RGC survival and axon regrowth are responsible for functional recovery after ONI in adult zebrafish.


Hybrid Models Based on Fusion Features of a CNN and Handcrafted Features for Accurate Histopathological Image Analysis for Diagnosing Malignant Lymphomas.
Malignant lymphoma is one of the most severe types of disease that leads to death as a result of exposure of lymphocytes to malignant tumors. The transformation of cells from indolent B-cell lymphoma to B-cell lymphoma (DBCL) is life-threatening. Biopsies taken from the patient are the gold standard for lymphoma analysis. Glass slides under a microscope are converted into whole slide images (WSI) to be analyzed by AI techniques through biomedical image processing. Because of the multiplicity of types of malignant lymphomas, manual diagnosis by pathologists is difficult, tedious, and subject to disagreement among physicians. The importance of artificial intelligence (AI) in the early diagnosis of malignant lymphoma is significant and has revolutionized the field of oncology. The use of AI in the early diagnosis of malignant lymphoma offers numerous benefits, including improved accuracy, faster diagnosis, and risk stratification. This study developed several strategies based on hybrid systems to analyze histopathological images of malignant lymphomas. For all proposed models, the images and extraction of malignant lymphocytes were optimized by the gradient vector flow (GVF) algorithm. The first strategy for diagnosing malignant lymphoma images relied on a hybrid system between three types of deep learning (DL) networks, XGBoost algorithms, and decision tree (DT) algorithms based on the GVF algorithm. The second strategy for diagnosing malignant lymphoma images was based on fusing the features of the MobileNet-VGG16, VGG16-AlexNet, and MobileNet-AlexNet models and classifying them by XGBoost and DT algorithms based on the ant colony optimization (ACO) algorithm. The color, shape, and texture features, which are called handcrafted features, were extracted by four traditional feature extraction algorithms. Because of the similarity in the biological characteristics of early-stage malignant lymphomas, the features of the fused MobileNet-VGG16, VGG16-AlexNet, and MobileNet-AlexNet models were combined with the handcrafted features and classified by the XGBoost and DT algorithms based on the ACO algorithm. We concluded that the performance of the two networks XGBoost and DT, with fused features between DL networks and handcrafted, achieved the best performance. The XGBoost network based on the fused features of MobileNet-VGG16 and handcrafted features resulted in an AUC of 99.43%, accuracy of 99.8%, precision of 99.77%, sensitivity of 99.7%, and specificity of 99.8%. This highlights the significant role of AI in the early diagnosis of malignant lymphoma, offering improved accuracy, expedited diagnosis, and enhanced risk stratification. This study highlights leveraging AI techniques and biomedical image processing; the analysis of whole slide images (WSI) converted from biopsies allows for improved accuracy, faster diagnosis, and risk stratification. The developed strategies based on hybrid systems, combining deep learning networks, XGBoost and decision tree algorithms, demonstrated promising results in diagnosing malignant lymphoma images. Furthermore, the fusion of handcrafted features with features extracted from DL networks enhanced the performance of the classification models.


Analyzing person, situation and person × situation interaction effects: Latent state-trait models for the combination of random and fixed situations.
Latent state-trait (LST) models (Steyer, Ferring, & Schmitt, 1992) allow separating person-specific (trait) effects from (1) effects of the situation and person × situation interactions, and (2) random measurement error in purely observational studies. Typical LST applications use measurement designs in which all situations are sampled randomly and do not have to be known for any individual. Limitations of conventional LST models for only random situations are that traits are implicitly assumed to generalize perfectly across situations, and that main effects of situations are inseparable from person × situation interaction effects because both are measured by the same latent variable. In this article, we show how these limitations can be overcome by using measurement designs in which two or more random situations are nested within two or more fixed situations that are known for each individual. We present extended LST models for the combination of random and fixed situations (LST-RF approach) and show that the extensions allow (1) examining the extent to which traits are situation-specific and (2) isolating person × situation interactions from situation main effects. We demonstrate that the LST-RF approach can be applied with both homogenous and heterogeneous indicators in either the single- or multilevel structural equation modeling frameworks. Advantages and limitations of the new models as well as their relation to other approaches for studying person × situation interactions are discussed.


Cross-cultural factors in disclosure of intimate partner violence: an integrated review.
This paper is a report of an integrated review to identify cross-cultural factors that have an impact on women's disclosure of intimate partner violence, specifically related to Mexican-American women. Intimate partner violence was once recognized as a private matter. Disclosure is a complex concept; furthermore in our multi-cultural society, a woman's decision whether or not to disclose abuse can be attributed to several factors influenced by her culture. The World Wide Web and multiple databases including Academic Premier, Cumulative Index of Nursing and Allied Health Literature (CINAHL), PsychArticles, PsychInfo, Medline, Eric, MedicLatina, and Psychology and Behavioral Science Collection were searched for studies published between 1996 and 2007. A search was conducted using databases including the CINAHL, PsychINFO, MEDLINE, ERIC and MedicLatina. Both qualitative and quantitative studies published between May 1996 and July 2007 were included. Forty-two studies were included in the review. Appraisal of study quality was not undertaken. Fear was the most common cross-cultural factor interfering with disclosure. Most of the literature examines factors influencing and interfering with disclosure of abuse among white and African-American women. Only one study was found to include a sample of Mexican-American women. Increased efforts are needed to understand disclosure of intimate partner violence in minority women so that service providers can tailor services and ways to encourage disclosure with appropriate strategies based on women's culture. Further research is needed to understand the lived experiences of minority women, including Mexican-American women living in intimate partner violence.


IL-33 induces both regulatory B cells and regulatory T cells in dextran sulfate sodium-induced colitis.
Interleukin (IL)-33 is a member of the IL-1 family. Serum levels of IL-33 are increased in inflammatory bowel diseases (IBD), suggesting that IL-33 is involved in the pathogenesis of IBD, although its role is not clear. In this study, we investigated the role of IL-33 in the regulation of T-helper (Th) cell and B cell responses in mesenteric lymph nodes (MLN) in mice with dextran sulfate sodium (DSS)-induced colitis. Here, we showed that IL-33-treated mice were susceptible to DSS-induced colitis as compared with PBS-treated mice. The production of spontaneous inflammatory cytokines production by macrophages or dendritic cells (DC) in MLN significantly increased, and the responses of Th2, regulatory T cells (Treg) and regulatory B cells (Breg) were markedly upregulated, while Th1 responses were significantly downregulated in MLN of IL-33-treated mice with DSS-induced colitis. Our results demonstrate that IL-33 contributes to the pathogenesis of DSS-induced colitis in mice by promoting Th2 responses, but suppressing Th1 responses, in MLN. Moreover, IL-33 treatment increased Breg and Treg responses in MLN in mice with DSS-induced colitis. Therefore, modulation of IL-33/ST2 signaling is implicated as a novel biological therapy for inflammatory diseases associated with Th1 responses.


8-OH-DPAT abolishes the pulmonary C-fiber-mediated apneic response to fentanyl largely via acting on 5HT1A receptors in the nucleus tractus solitarius.
Intravenous bolus injection of morphine causes a vagal-mediated brief apnea (∼3 s), while continuous injection, via action upon central μ-opioid receptor (MOR), arrests ventilation (>20 s) that is eliminated by stimulating central 5-hydroxytryptamine 1A receptors (5HT(1A)Rs). Bronchopulmonary C-fibers (PCFs) are essential for triggering a brief apnea, and their afferents terminate at the caudomedial region of the nucleus tractus solitarius (mNTS) that densely expresses 5HT(1A)Rs. Thus we asked whether the vagal-mediated apneic response to MOR agonists was PCF dependent, and if so, whether this apnea was abolished by systemic administration of 8-hydroxy-2-(di-n-propylamino)tetral (8-OH-DPAT) largely through action upon mNTS 5HT(1A)Rs. Right atrial bolus injection of fentanyl (5.0 μg/kg, a MOR agonist) was performed in the anesthetized and spontaneously breathing rats before and after: 1) selective blockade of PCFs' conduction and subsequent bivagotomy; 2) intravenous administration of 5HT(1A)R agonist 8-OH-DPAT; 3) intra-mNTS injection of 8-OH-DPAT; and 4) intra-mNTS injection of 5HT(1A)R antagonist WAY-100635 followed by 8-OH-DPAT (iv). We found the following: First, fentanyl evoked an immediate apnea (2.5 ± 0.4 s, ∼6-fold longer than the baseline expiratory duration, T(E)), which was abolished by either blocking PCFs' conduction or bivagotomy. Second, this apnea was prevented by systemic 8-OH-DPAT challenge. Third, intra-mNTS injection of 8-OH-DPAT greatly attenuated the apnea by 64%. Finally, intra-mNTS microinjection of WAY-100635 significantly attenuated (58%) the apneic blockade by 8-OH-DPAT (iv). We conclude that the vagal-mediated apneic response to MOR activation depends on PCFs, which is fully antagonized by systemic 8-OH-DPAT challenge largely via acting on mNTS 5HT(1A)Rs.


American and Swedish children's acquisition of vowel duration: effects of vowel identity and final stop voicing.
Vowel durations typically vary according to both intrinsic (segment-specific) and extrinsic (contextual) specifications. It can be argued that such variations are due to both predisposition and cognitive learning. The present report utilizes acoustic phonetic measurements from Swedish and American children aged 24 and 30 months to investigate the hypothesis that default behaviors may precede language-specific learning effects. The predicted pattern is the presence of final consonant voicing effects in both languages as a default, and subsequent learning of intrinsic effects most notably in the Swedish children. The data, from 443 monosyllabic tokens containing high-front vowels and final stop consonants, are analyzed in statistical frameworks at group and individual levels. The results confirm that Swedish children show an early tendency to vary vowel durations according to final consonant voicing, followed only six months later by a stage at which the intrinsic influence of vowel identity grows relatively more robust. Measures of vowel formant structure from selected 30-month-old children also revealed a tendency for children of this age to focus on particular acoustic contrasts. In conclusion, the results indicate that early acquisition of vowel specifications involves an interaction between language-specific features and articulatory predispositions associated with phonetic context.


Inversion in Mg1-xNixAl2O4 Spinel: New Insight into Local Structure.
A wide variety of compositions adopt the isometric spinel structure (AB2O4), in which the atomic-scale ordering is conventionally described according to only three structural degrees of freedom. One, the inversion parameter, is traditionally defined as the degree of cation exchange between the A- and B-sites. This exchange, a measure of intrinsic disorder, is fundamental to understanding the variation in the physical properties of different spinel compositions. Based on neutron total scattering experiments, we have determined that the local structure of Mg1-xNixAl2O4 spinel cannot be understood as simply being due to cation disorder. Rather, cation inversion creates a local tetragonal symmetry that extends over sub-nanometer domains. Consequently, the simple spinel structure is more complicated than previously thought, as more than three parameters are needed to fully describe the structure. This new insight provides a framework by which the behavior of spinel can be more accurately modeled under the extreme environments important for many geophysics and energy-related applications, including prediction of deep seismic activity and immobilization of nuclear waste in oxides.


In situ analysis of myelin basic protein gene expression in myelin-deficient oligodendrocytes: antisense hnRNA and readthrough transcription.
Mice homozygous for the recessive mutation myelin deficient (mld) exhibit a severe deficit in the synthesis of myelin basic protein (MBP). The primary defect in mld mice is an unusual rearrangement of the MBP gene. The mld MBP locus consists of two tandem MBP genes that span approximately 90 kb of DNA; the upstream gene contains an extensive inversion of its 3' region, while the downstream gene appears identical to the wild-type gene. In this report, the aberrant expression of the mld MBP locus was examined by in situ hybridization with MBP genomic and cDNA probes. In situ hybridization with a single-stranded genomic probe from the inverted region of the mld MBP gene revealed that primary transcripts initiating from the upstream MBP promoter elongate through the inverted region generating abundant antisense MBP heterogeneous nucleus RNA (hnRNA) transcripts in mld oligodendrocytes. Little or no antisense MBP RNA was detected in cytoplasmic regions in mld brain sections indicating that the antisense MBP hnRNA transcripts are not processed and transported out of the nucleus. Furthermore, we provide evidence that these abnormal transcripts elongate through the downstream MBP gene's promoter region, suggesting that transcription of the downstream mld MBP gene is inhibited by readthrough transcripts that originate at the upstream promoter.


Profiling of the most reliable mutations from sequenced SARS-CoV-2 genomes scattered in Uzbekistan.
Due to rapid mutations in the coronavirus genome over time and re-emergence of multiple novel variants of concerns (VOC), there is a continuous need for a periodic genome sequencing of SARS-CoV-2 genotypes of particular region. This is for on-time development of diagnostics, monitoring and therapeutic tools against virus in the global pandemics condition. Toward this goal, we have generated 18 high-quality whole-genome sequence data from 32 SARS-CoV-2 genotypes of PCR-positive COVID-19 patients, sampled from the Tashkent region of Uzbekistan. The nucleotide polymorphisms in the sequenced sample genomes were determined, including nonsynonymous (missense) and synonymous mutations in coding regions of coronavirus genome. Phylogenetic analysis grouped fourteen whole genome sample sequences (1, 2, 4, 5, 8, 10-15, 17, 32) into the G clade (or GR sub-clade) and four whole genome sample sequences (3, 6, 25, 27) into the S clade. A total of 128 mutations were identified, consisting of 45 shared and 83 unique mutations. Collectively, nucleotide changes represented one unique frameshift mutation, four upstream region mutations, six downstream region mutations, 50 synonymous mutations, and 67 missense mutations. The sequence data, presented herein, is the first coronavirus genomic sequence data from the Republic of Uzbekistan, which should contribute to enrich the global coronavirus sequence database, helping in future comparative studies. More importantly, the sequenced genomic data of coronavirus genotypes of this study should be useful for comparisons, diagnostics, monitoring, and therapeutics of COVID-19 disease in local and regional levels.


Efficient decolorization and detoxification of textile industry effluent by Salvinia molesta in lagoon treatment.
Salvinia molesta, an aquatic fern was observed to have a potential of degrading azo dye Rubine GFL up to 97% at a concentration of 100mg/L within 72h using 60±2g of root biomass. Both root as well as stem tissues showed induction in activities of the enzymes such as lignin peroxidase, veratryl alcohol oxidase, laccase, tyrosinase, catalase, DCIP reductase and superoxide dismutase during decolorization of Rubine GFL. FTIR, GC-MS, HPLC and UV-visible spectrophotometric analysis confirmed phytotransformation of the model dye into smaller molecules. Analysis of metabolites revealed breakdown of an azo bond of Rubine GFL by the action of lignin peroxidase and laccase and formation of 2-methyl-4-nitroaniline and N-methylbenzene-1, 4-diamine. Anatomical tracing of dye in the stem of S. molesta confirmed the presence of dye in tissues and subsequent removal after 48h of treatment. The concentration of chlorophyll pigments like chlorophyll a, chlorophyll b and carotenoid was observed during the treatment. Toxicity analysis on seeds of Triticum aestivum and Phaseolus mungo revealed the decreased toxicity of dye metabolites. In situ treatment of a real textile effluent was further monitored in a constructed lagoon of the dimensions of 7m×5m×2m (total surface area 35m(2)) using S. molesta for 192h. This large scale treatment was found to significantly reduce the values of COD, BOD5 and ADMI by 76%, 82% and 81% considering initial values 1185, 1440mg/L and 950 units, respectively.


Rice Rhizospheric Effects on the Bioavailability of Toxic Trace Elements during Land Application of Biochar.
Land application of biochar, the product of organic waste carbonization, can improve soil fertility as well as sequester carbon to mitigate climate change. In addition, biochar can greatly influence the bioavailability of toxic trace elements (TTEs) in soils resulting from its large internal surface areas, abundance in organic carbon, and ability to modify soil pH. Most research to date employs batch leaching tests to predict how biochar addition impacts TTE bioavailability, but these ex situ tests rarely considered the rhizospheric effect which might offset or intensify the changes induced by organic residue addition. This is especially so in rice rhizospheres because of strong clines in localized redox conditions. In this study, we adopted in situ high-resolution (HR) diffusive gradients in thin films (DGT) as well as rhizo-bag porewater sampling experiments to depict an overall picture of the difference in TTE (As, Cd, Cu, Ni, and Pb) bioavailability between the rice rhizosphere and bulk soils during land application of biochar. Porewater sampling experiments revealed that biochar additions stimulated TTE release due to the increase of dissolved organic carbon (DOC) and H+ concentrations. In the rhizosphere, although biochar still promoted As, Cd, and Ni release into porewaters, the rhizospheric effect was one of dampening/reduction compared with the bulk soil. When we focused on the localized changes of TTE bioavailability in the rhizosphere using an in situ HR-DGT approach, on the contrary, flux maxima of Cd, Cu, and Ni occurred near/on the root surface, and hot spots of As can be observed at peripheries of the rooting zone, which demonstrated the high heterogeneity and complexity of the rhizosphere's influence on TTE bioavailability.


Vascular effects of prazosin on normothermic and hypothermic perfusion in the isolated rat kidney.
To investigate whether alpha-adrenergic mechanisms would participate in the vascular response to normothermic or hypothermic perfusion of the isolated rat kidney, four groups of rats were studied. They were perfused for 15 min at 37 degrees C with either normal saline (group I) or prazosin (group II) or at 32 degrees C with saline (group III) or prazosin (group IV). Both in group I and in group III perfusate flow tended to fall with time, although this was significant in group I only. In group II prazosin prevented the drop in flow rates; in group IV this drug even increased flow. At all times flow rates in group IV were significantly higher than in group II. It is concluded that at normothermic perfusion an alpha-adrenergic mechanism is activated that slowly constricts the renal vessels. At 32 degrees C intense alpha-adrenergic vasoconstriction occurs; enhanced flow rates at this temperature may be explained by shunting through intrarenal arteriovenous anastomoses.


Association between ACE and AGT polymorphism and cardiovascular risk in acromegalic patients.
Whether the renin-angiotensin-aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly. The study included one hundred and seventeen acromegalic patients (62 F/55 M, age: 50.2 ± 12.3 years) and 106 healthy controls (92 F/14 M, age: 41.4 ± 11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype. The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism [48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotype]compared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers [40 (16-60) vs. 12 (5-36) µg/L, p < 0.05]. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p < 0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow Apeak values than T allele carriers (0.94 ± 0.46 vs. 0.73 ± 0.20; p = 0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms. Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.


Oligonucleotide microarrays: immobilization of phosphorylated oligonucleotides on epoxylated surface.
A facile and efficient method for direct immobilization of phosphorylated oligonucleotides on an epoxy-activated glass surface is described. The new immobilization strategy has been analyzed for its performance in DNA microarray under both microwave and thermal conditions. It reflects high immobilization efficiency ( approximately 23%), and signal-to-noise ratio ( approximately 98) and resulted in high hybridization efficiency ( approximately 36%) in comparison to those obtained with standard methods, viz., NTMTA ( approximately 9.76%) and epoxide-amine ( approximately 9.82%). The probes immobilized through the new strategy were found to be heat-stable, since the performance of microarray decreased by only approximately 7% after subjecting it to 20 PCR-like heat cycles, suggesting that the chemistry could be used in integrated PCR/microarray devices. The immobilization of probes following the proposed chemistry resulted in spots of superior quality in terms of spot morphology, spot homogeneity, and signal reproducibility. The constructed microarrays have been successfully used for the discrimination of nucleotide mismatches. In conclusion, these features make the new immobilization strategy ideal for facile, efficient, and cost-effective manufacturing of DNA microarrays.


Evidence for a chemical-thermal structure at base of mantle from sharp lateral P-wave variations beneath Central America.
Compressional waves that sample the lowermost mantle west of Central America show a rapid change in travel times of up to 4 s over a sampling distance of 300 km and a change in waveforms. The differential travel times of the PKP waves (which traverse Earth's core) correlate remarkably well with predictions for S-wave tomography. Our modeling suggests a sharp transition in the lowermost mantle from a broad slow region to a broad fast region with a narrow zone of slowest anomaly next to the boundary beneath the Cocos Plate and the Caribbean Plate. The structure may be the result of ponding of ancient subducted Farallon slabs situated near the edge of a thermal and chemical upwelling.


Partial hydrodynamic representation of quantum molecular dynamics.
A hybrid method is proposed to propagate system-bath quantum dynamics that use both basis functions and coupled quantum trajectories. In it, the bath is represented with an ensemble of Bohmian trajectories while the system degrees of freedom are accounted through reduced density matrices. By retaining the Hilbert space structure for the system, the method is able to capture interference processes that are challenging to describe in Bohmian dynamics due to singularities that these processes introduce in the quantum potential. By adopting quantum trajectories to represent the bath, the method beats the exponential scaling of the computational cost with the bath size. This combination makes the method suitable for large-scale ground and excited state fully quantum molecular dynamics simulations. Equations of motion for the quantum trajectories and reduced density matrices are derived from the Schrödinger equation and a computational algorithm to solve these equations is proposed. Through computations in two-dimensional model systems, the method is shown to offer an accurate description of subsystem observables and of quantum decoherence, which is difficult to obtain when the quantum nature of the bath is ignored. The scaling of the method is demonstrated using a model with 21 degrees of freedom. The limit of independent trajectories is recovered when the mass of bath degrees of freedom is much larger than the one of the system, in agreement with mixed quantum-classical descriptions.


EPIDEMIOLOGIC RESEARCH REGARDING THE IMPACT OF RISK FACTORS ON HEALTH-RELEATED QUALITY OF LIFE IN CANCER PATIENTS.
To assess the health-related quality of life in cancer patients and the relative and attributable risks for the degree of dissatisfaction related to intrinsic and extrinsic factors. Our research included 128 cancer patients treated at the Surgical Clinic II of the Iasi Regional Cancer Institute between December 2014 and June 2015. Thus, data were collected by using an inquiry sheet derived from the SF-36 questionnaire, which included closed and open questions about the quality of life, socioemographic data and such risk factors as smoking, alcohol use, related diseases and risk behaviours. Results: The patient sample had a mean age of 60.85 years, 51.6% of them lived in urban areas, were high school graduates, and of low economic status. As to the behavioural risk factors we found that over 80% of the patients were non-smokers, did not use alcohol, and were normal weighted. Pain was experienced by 70.7% of the cancer patients and depression affected 74% of the study cases. Patients were asked to self-assess their own health status on a scale of 0 (worst) to 100 (the best health status). Our study showed a poor health status (mean score 65) in the study cancer patients. The relative and attributable risks for the degree of dissatisfaction related to intrinsic and extrinsic factors were calculated and ranked factors in decreasing order: smoking, depression, pain, alcohol use, male gender, obesity, low income. We found that prolonged'suffering affects the psyche and causes depression and that the patients of low financial status, most of them living in villages, have difficulty in accessing medical care. The obtained data about the quality of life in relation with risk factors are in agreement with the data in the literature.


Sexes in gynodioecious Geranium sylvaticum do not differ in their isotopic signature or photosynthetic capacity.
In gynodioecious plants, females are expected to produce more or better seeds than hermaphrodites in order to be maintained within the same population. Even though rarely measured, higher seed production can be achieved through differences in physiology. In this work, we measured sexual dimorphism in several physiological traits in the gynodioecious plant Geranium sylvaticum. Photosynthetic rate, stomatal conductance, transpiration rate, WUE and isotopic signatures were measured in plants growing in two habitats differing in light availability. Females have been reported to produce more seeds than hermaphrodites. However, we did not observe any significant difference in seed output between the sexes in these experimental populations. Similarly, the sexes did not differ in any physiological trait measured. Seed production was strongly limited by light availability. Likewise, differences between plants growing in full light versus low light were detected in most physiological parameters measured. Our results show that the sexes in G. sylvaticum do not show any evidence of sexual dimorphism in physiology, which concurred with a lack of sexual differences in seed output.


Tuning of Thiyl/Thiolate Complex Near-Infrared Chromophores of Platinum through Geometrical Constraints.
The chemistry of radical-ligand complexes of the transition metals has developed into a vibrant field of research that spans from fundamental studies on the relationship between the chemical and electronic structures to applications in catalysis and functional materials chemistry. In general, fine-tuning of the relevant properties relies on an increasingly diversifying pool of radical-proligand structures. Surprisingly, the variability of the conformational freedom and the number of distinct bonding modes supported by many radical proligands is limited. This work reports on the angular constraints and relative geometric alignment of metal and ligand orbitals as key parameters that render a series of chemically similar thiyl/thiolate complexes of platinum(II) electronically and spectroscopically distinct. The use of conformational flexible thiophenols as primary ligand scaffolds is essential to establishing a defined radical-ligand [(areneS)2PtII]•+ core whose electronic structure is modulated by a series of auxiliary coligands at platinum.


Synthesis of (phosphonomethyl)phosphinate pyrophosphate analogues via the phospha-Claisen condensation.
Pyrophosphate analogues are of great importance especially for the design of biologically active molecules. The phospha-Claisen condensation allows for the rapid synthesis of (phosphonomethyl)phosphinate pyrophosphate analogues and building blocks that can be employed in numerous applications.


Induction of apoptosis by eicosapentaenoic acid in esophageal squamous cell carcinoma.
Eicosapentaenoic acid (EPA) suppresses the proliferation of cell lines derived from colon, pancreatic, breast and other cancers. Few reports have described the effect of EPA on esophageal cancer cell lines. We investigated the effect of EPA on the proliferation of the esophageal squamous cell carcinoma cell lines TE11 and KYSE180 with a WST-1 assay. Apoptosis was evaluated with a DNA fragmentation assay. Levels of apoptosis-related proteins (caspase-3, -7, -9 and poly (ADP-ribose) polymerase (PARP)) and cleaved caspase-3, -7, -9 and PARP were evaluated by western blot analysis. After exposure to EPA for 24 h, KYSE180 and TE11 cell proliferation was suppressed in a dose-dependent manner (p<0.05). In addition, caspase -3, -7, -9 and PARP were activated. EPA (0.1 μM, 1 μM, 10 μM) induced apoptosis in a dose-dependent manner, as detected by the DNA fragmentation assay. EPA shows potential as a new treatment for esophageal cancer.


Anomalous dielectric and thermal properties of Ba-doped PbZrO3 ceramics.
The dielectric and thermal properties of an antiferroelectric (AFE) material characterised by an intermediate ferroelectric (FE) phase between the AFE and paraelectric phase in zero field are studied by means of a generalised Landau-Kittel model of AFEs. A temperature-dependent coupling of the two sublattices is introduced in accordance with the Rae-Dove (RD) model of re-entrant phase transitions. The sublattice polarisation components are calculated as functions of temperature and the applied electric field by minimising numerically the free energy. The calculated dielectric susceptibility shows anomalies at the boundaries of the intermediate FE phase, characteristic for first-order phase transitions. It is shown that this behaviour is in qualitative agreement with the measured dielectric constant in Ba-doped PbZrO3 ceramics. The model also predicts a negative adiabatic electrocaloric temperature change ΔT in a broad temperature range in the AFE phase, in qualitative agreement with experiments. The dipolar heat capacity is also predicted to be negative in the intermediate phase in zero field, in analogy with the results of the RD model.


[Flow cytometry estimate of s phase cell cycle and prognosis of osteosarcoma in children and adolescents].
Flow cytometry analysis has been used to measure the S phase in paraffin embedded osteosarcoma tissues of 22 children and adolescents who were surgically treated. The aim of this study was the assessment of S phase cell cycle in relation to survival, localization of tumour and histopathological grading. Our findings demonstrate the usefulness of flow cytometry determination of S phase cell cycle as a prognostic factor. Higher percentage of S phase cells predict worse prognosis.


Performance of growing cattle grazing stockpiled Jesup tall fescue with varying endophyte status.
The objective of this study was to evaluate the performance of growing cattle when intensively grazing stockpiled endophyte-infected (E+), endophyte-free (E-), and nontoxic endophyte-infected (EN) tall fescue during the winter. The experiment was conducted over 5 consecutive winters. In each year, plots (1 ha each, 4 per treatment) were harvested for hay in August, fertilized in September, and forage was allowed to accumulate until grazing was initiated in early December. Each year, 48 Angus-cross tester cattle (4 per plot) were given a daily allotment of forage, under strip-grazing (frontal grazing) management, with a target residual height of 5 cm. Steers were used the first year, and heifers were used in subsequent years. The grazing periods for determination of pasture ADG were 86 d (yr 1), 70 d (yr 2), 86 d (yr 3), 72 d (yr 4), and 56 d (yr 5). Pasture ADG of cattle did not differ among treatments (P = 0.13) and were 0.51, 0.59, and 0.56 kg/d (SEM 0.03) for E+, E-, and EN, respectively. Serum prolactin concentrations of heifers grazing E+ were less (P < 0.05) than those grazing E- and EN during all years except yr 2. In yr 2, E+ and E- did not differ (P = 0.11). Serum prolactin of heifers grazing E- and EN did not differ (P > 0.20) except in yr 4. During yr 4, serum prolactin of heifers grazing E- was greater (P = 0.05) than that of heifers grazing EN. Serum urea-N concentrations (SUN) tended to differ among treatments (P = 0.10) and there was a treatment x year interaction (P = 0.05). During yr 1 through 3, SUN did not differ (P > 0.15) among treatments. However, as the stands aged, E- had a greater invasion of other plant species, which increased the CP content of the sward, thus causing heifers grazing E- during yr 5 to have greater (P < 0.01) SUN than heifers grazing E+ and EN, which did not differ (P = 0.89). Forage disappearance (DM basis) did not differ (P = 0.75) among treatments and was 4.7, 4.7, and 5.0 kg/animal daily (SEM 0.27) for E+, E-, and EN, respectively. Body weight gain per hectare was greater (P = 0.04) for E+ (257 kg) than for E- (220 kg) or EN (228 kg). In most years, animal grazing days on E+ were greater than those on E- or EN. However, in yr 5, animal grazing days did not differ (P > 0.20) among treatments. The use of stockpiled E+ as a source of low-cost winter feed is a viable option for producers, whereas grazing of EN may be more beneficial during the spring and fall, when more severe negative effects of ergot alkaloids have been observed.


[Prevention of dialysis-induced leukopenia and hypoxemia by using low-molecular dextran].
In 10 patients with end stage renal failure on chronic haemodialysis the effect was studied of the low molecular dextran (filling the dialyser) on the peripheral blood leucocyte count and some gasometric and ventilatory parameters during and after haemodialysis (HD). When the dialyser was filled with dextran neither the leucocyte count nor the arterial PaO2 were altered but on the 10th minute of HD without dextran both those values fell. The decrease of the ventilation rate (VE), of the alveolar oxygen tension (PAO2) as well as of the index of oxygen utilisation (VIO2/VE) within the first hour of HD with or without dextran might be due to the absorption of the CO2 by dialysing fluid.


Inhibitive Properties of Benzyldimethyldodecylammonium Chloride on Microbial Corrosion of 304 Stainless Steel in a Desulfovibrio desulfuricans-Inoculated Medium.
Biocides are frequently used to control sulfate-reducing bacteria (SRB) in biofouling. The increasing restrictions of environmental regulations and growing safety concerns on the use of biocides result in efforts to minimize the amount of biocide use and develop environmentally friendly biocides. In this study, the antimicrobial activity and corrosion inhibition effect of a low-toxic alternative biocide, benzyldimethyldodecylammonium chloride (BDMDAC), on a 304 stainless steel substrate immersed in a Desulfovibrio desulfuricans (D. desulfuricans)-inoculated medium was examined. Potentiodynamic polarization curves were used to analyze corrosion behavior. Biofilm formation and corrosion products on the surfaces of 304 stainless steel coupons were examined using scanning electron microscopy (SEM), energy-dispersive X-ray spectrum, and confocal laser scanning microscopy (CLSM). Results demonstrated that this compound exhibited satisfactory results against microbial corrosion by D. desulfuricans. The corrosion current density and current densities in the anodic region were lower in the presence of BDMDAC in the D. desulfuricans-inoculated medium. SEM and CLSM analyses revealed that the presence of BDMDAC mitigated formation of biofilm by D. desulfuricans.


Wedge resection in rhinosurgery: a review of the literature and long-term results in a hundred cases.
First a historical review is given of the development of the concept of wedge resection of the bony nasal pyramid since Joseph, 1907. In a second part the technical details about wedge resection are described for different types of nasal deformities. In a third part long-term results in 100 patients, 18 months after septorhinoplasty are presented. In 61 patients unilateral and in 39 patients bilateral wedge resections were performed as one step of rhinoplasty. The long-term results were good in 93 patients, there was undercorrection in six cases, whereas one patient had an overcorrected nose. These results are better than the long-term results following classic osteotomies alone. Thus the wedge resection, for the indications as defined in this study, is a very useful step in the concept of corrective and aesthetic septorhinoplasty.


Inhibition of Proteasome Activity Induces Aggregation of IFIT2 in the Centrosome and Enhances IFIT2-Induced Cell Apoptosis.
IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), one of the most highly responsive interferon-stimulated genes, inhibits the proliferation and migration of cancer cells and regulates viral replication. IFIT2 has been demonstrated to be a cytoskeleton-associated protein that becomes enriched in the mitotic spindle of cells. However, the molecular mechanisms by which IFIT2 executes biological functions are largely unclear. The findings of this study showed that inhibiting the activation of proteasome led to the enrichment of IFIT2 and induced the aggregation of IFIT2 protein in the centrosome. Microtubule inhibitor colchicine and dynein inhibitor ciliobrevin inhibited the proteasome inhibitor-induced aggregation of IFIT2 protein in the centrosome. Intriguingly, IFIT2 and proteasome inhibitor worked together to induce the apoptosis of cancer cells. The results of the present study revealed that the inhibition of proteasome activity blocked the degradation of IFIT2 and promoted the aggregation of IFIT2 in the centrosome, which in turn induced cell apoptosis. In short, IFIT2 may be a potential target for cancer therapeutics.


Case of glioblastoma patient treated with tumor treating fields therapy at recurrence degenerating to sarcoma.
Optune® treatment is a US FDA-approved treatment for glioblastoma (GBM) that employs alternating electric fields. Tumor treating field (TTF) therapy can exert its effects on GBM via cell cycle mitosis disruption and cytokinesis. We describe a patient with recurrent GBM who had disease progression following standard surgical treatment and concomitant chemoradiotherapy, and was found to have sarcomatous transformation after initiation of TTF therapy with bevacizumab. Upon tumor progression, repeat surgical resection revealed transformation into a GFAP-negative, reticulin-positive sarcoma with rhabdomyoid features. The possibility of a causal connection between TTF therapy and sarcomatous transformation needs to be further evaluated. No such case of apparent sarcoma formation in the CNS following chemoradiotherapy and/or TTF treatment for GBM has been reported.


Spinach or carrots can supply significant amounts of vitamin A as assessed by feeding with intrinsically deuterated vegetables.
The vitamin A value of spinach and carrots needs to be measured directly. The objective was to determine the vitamin A value of intrinsically labeled dietary spinach and carrots in humans. Spinach and carrots were intrinsically labeled by growing these plants in 25 atom% 2H2O nutrient solution. Growth in this medium yielded a range of trans beta-carotene (tbeta-carotene) isotopomers with a peak enrichment at molecular mass plus 10 mass units. Seven men with a mean (+/-SD) age of 59.0 +/- 6.3 y and a body mass index (in kg/m2) of 25.7 +/- 1.5 consumed puréed spinach (300 g, 20.8 micromol tbeta-carotene equivalents) or carrots (100 g, 19.2 micromol tbeta-carotene equivalents) with a standardized liquid diet (no extra fiber) in random order 4 mo apart. Seven women with a mean (+/-SD) age of 55.5 +/- 6.3 y and a body mass index of 26.4 +/- 4.2 consumed puréed spinach only (300 g, 20.0 micromol tbeta-carotene equivalents). A reference dose of [13C8]retinyl acetate (8.9 micromol) in oil was given to each subject 1 wk after each vegetable dose. Blood samples were collected over 35 d. Areas under the curve for total labeled serum beta-carotene responses were 42.4 +/- 8.5 nmol.d per micromol spinach beta-carotene and 119.8 +/- 23.0 nmol.d per micromol carrot beta-carotene (P < 0.01). Compared with the [13C8]retinyl acetate reference dose, spinach tbeta-carotene conversion to retinol was 20.9 +/- 9.0 to 1 (range: 10.0-46.5 to 1) and carrot tbeta-carotene conversion to retinol was 14.8 +/- 6.5 to 1 (range: 7.7-24.5 to 1) by weight. Spinach and carrots can provide a significant amount of vitamin A even though the amount is not as great as previously proposed. Food matrices greatly affect the bioavailability of plant carotenoids, their efficiency of conversion to vitamin A, or both.


Nongenetic implications of childbearing after age thirty-five.
A comprehensive review of the effects of advanced maternal age on nongenetic aspects of delayed childbearing is presented. Implications for fertility are assessed. Antepartum complications including hypertension, diabetes, placental abnormalities, and maternal mortality are reviewed. Labor patterns and neonatal outcome are evaluated with respect to age and parity. Recent well-controlled studies using multivariate regression analysis show that prenatal diagnosis, recognition, and management of high-risk pregnancy, antenatal and intrapartum fetal monitoring, and advances in perinatal medicine have dramatically reduced the problems associated with age. A management plan is presented.


MATERNAL EFFECTS ON OFFSPRING SIZE: VARIATION THROUGH EARLY DEVELOPMENT OF CHINOOK SALMON.
We performed two breeding experiments with chinook salmon (Oncorhynchus tshawytscha) to explore maternal effects on offspring size. We estimated the magnitude of maternal effects as the differences between sire-offspring and dam-offspring regression slopes. Early in life, offspring size is largely influenced by maternal size, but this influence decreases through early development, with the maternal effect becoming negative at intermediate offspring ages (corresponding to a period of reduced growth of progeny hatching from large eggs) and converging on zero as offspring age. Also, egg size was positively correlated with early survival, but negatively correlated with maternal fecundity.


Student mental health services and departments of psychiatry.
The authors suggest that the potential usefulness of a college mental health service as a site for teaching, training, and research has been understimated by departments of psychiatry. College health services can provide an opportunity for both trainees and investigators to deal with concepts of psychotherapeutic intervention, a developmental perspective, and a community mental health orientation.


Self-control depletion and sleep duration: the mediating role of television viewing.
Sleep insufficiency has been related to self-control failure: people fail to go to bed in time and end up sleep deprived. The role of state self-control in predicting bedtime and sleep duration has not yet been investigated. Based on research claiming an overlap between depleted self-control resources and fatigue, self-control depletion may foster earlier bedtimes. Conversely, self-control depletion also increases the propensity to procrastinate bedtime by giving in to the immediate gratification of late night entertainment. This study therefore looked at procrastinatory television viewing and its intermediary role in the association between state self-control and bedtime. The implications for sleep duration are examined. Firstyear students (N = 234) participated in an online survey. Using Day Reconstruction Method, they charted their activities and experiences during the preceding day and subsequent bedtime behavior. Self-control depletion was directly related to earlier bedtimes, which we explained by its similarity to fatigue. This was associated with longer sleep duration. Self-control depletion was indirectly related to later bedtimes because it increased the propensity to procrastinate by watching television. This was associated with shorter sleep duration. This study exposes a dual pathway between self-control depletion and sleep duration, whereby procrastinatory television viewing may reduce sleep duration.


Electrophysiological characterization of a large set of novel variants in the SCN5A-gene: identification of novel LQTS3 and BrS mutations.
SCN5A encodes for the α-subunit of the cardiac voltage-gated sodium channel Nav1.5. Gain-of-function mutations in SCN5A are related to congenital long QT syndrome (LQTS3) characterized by delayed cardiac repolarization, leading to a prolonged QT interval in the ECG. Loss-of-function mutations in SCN5A are related to Brugada syndrome (BrS), characterized by an ST-segment elevation in the right precordial leads (V1-V3). The aim of this study was the characterization of a large set of novel SCN5A variants found in patients with different cardiac phenotypes, mainly LQTS and BrS. SCN5A variants of 13 families were functionally characterized in Xenopus laevis oocytes using the two-electrode voltage-clamp technique. We found in most of the cases, but not all, that the electrophysiology of the variants correlated with the clinically diagnosed phenotype. A susceptibility to develop LQTS can be suggested in patients carrying the variants S216L, K480N, A572D, F816Y, and G983D. However, taking the phenotype into account, the presence of the variants in genomic data bases, the mutational segregation, combined with our in vitro and in silico experiments, the variants S216L, S262G, K480N, A572D, F816Y, G983D, and T1526P remain as variants of unknown significance. However, the SCN5A variants R568H and A993T can be classified as pathogenic LQTS3 causing mutations, while R222stop and R2012H are novel BrS causing mutations.


The association between adverse pregnancy outcomes and maternal human papillomavirus infection: a systematic review protocol.
Human papillomavirus (HPV) is the most prevalent genital infection, especially in young women of reproductive age. In vitro and animal model experiments provide compelling evidence of the harmful effect of HPV on pregnancy outcomes, but results from epidemiologic studies are inconclusive. We aim to determine the strength of the relationship between adverse pregnancy outcomes (APO) and HPV infection and assess its consistency across studies, by systematically reviewing the literature. The search strategy has been developed on the basis of the PICOS framework: Population (pregnant women); Exposure (HVP infection confirmed by HPV testing); Comparator (pregnant women without HPV infection); Outcomes (miscarriage, spontaneous preterm birth, low birth weight, preterm premature rupture of membranes, pregnancy-induced hypertensive disorders and intrauterine growth restriction) and Study design (observational studies). We will search three information sources: (1) electronic databases (MEDLINE, EMBASE, and EBM Reviews databases); (2) Grey literature (Google Scholar and Web of Science conference proceedings); and (3) citing and cited articles of included studies. Two reviewers (JN, NZ) will independently and in duplicate screen identified articles, select eligible studies, and extract data. Discrepancies will be resolved by consensus and otherwise by discussion with the other authors (MHM, HT). Quality of included studies will be assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. We will narratively synthesize extracted data whether meta-analysis is conducted or not. Meta-analysis of each outcome will be performed, and where appropriate, an average measure of association will be computed. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess and grade the strength of confidence in cumulative estimate. Comprehensive and high-quality evidence of a negative effect of HPV on pregnancy outcomes might be an additional motivation for HPV vaccination. Absence of such relationship could dispel anxiety and reassure HPV-infected pregnant women and clinicians. Findings of a poor level of confidence will allow identification of current knowledge gaps on HPV-pregnancy outcome relationship that need further research. PROSPERO CRD42016033425.


Effect of different dialyzer membranes on cutaneous microcirculation during hemodialysis.
Biocompatibility profiles of synthetic membranes may vary. In this prospective crossover study, we examined the effect of various membranes on cutaneous microcirculation during HD. 11 HD patients without cardiovascular complications were enrolled in this study. They were dialyzed using three types of membrane in a randomized order: ethylene-vinyl alcohol copolymer (EVAL), vitamin E-bonded cellulose (VE-C) and polysulfone (PS). The transcutaneous oxygen tension (TcPO2) was examined on the dorsum of foot to assess the cutaneous microcirculation. Serum biochemical parameters were also measured. The TcPO2 as a percentage of the predialysis level decreased from the beginning of HD, and significant differences were observed after 15 min of HD between EVAL and the other 2 membranes (98 +/- 6% (mean +/- SD) for EVAL versus 89 +/- 7% for VE-C (p < 0.01) and 88 +/- 10% for PS (p < 0.01)). Furthermore, there were significant differences at 30 and 60 min between EVAL and PS (30 min: 93 +/- 9% for EVAL versus 85 +/- 7% for PS (p < 0.05); 60 min: 92 +/- 10% for EVAL versus 79 +/- 10% for PS (p < 0.01)). The serum level of thiobarbituric acid reactants (TBARs), a marker of lipid peroxidation, increased significantly at the end of HD relative to that at the beginning of HD when using a PS membrane (from 1.9 +/- 0.5 to 2.1 +/- 0.5 nmol/ml, p < 0.05). Our results indicate that an EVAL membrane is superior to PS and VE-C membranes in terms of its smaller influence on cutaneous microcirculation. The repeated occurrence of microcirculatory disturbance during HD sessions may cause chronic endothelial dysfunction and even cardiovascular complications in HD patients.


Combining distinctive and novel loci doubles BP reduction, reverses diastolic dysfunction and mitigates LV hypertrophy.
Diastolic dysfunction often represents the onset of diastolic heart failure (DHF). We previously showed in principle that diastolic function in Dahl salt-sensitive rats (DSS) can be genetically determined by quantitative trait loci (QTLs) that also modulate blood pressure (BP). We analyzed cardiac phenotypes of four 'single' congenic strains by echocardiography, in which a specific DSS chromosome segment was replaced by its normotensive Lewis homologue. Two of the strains permanently lowered BP, and but attenuated diastolic dysfunction only in rats at 10 weeks of age, not at 15 weeks fed on a 2% NaCl diet starting from 8 weeks of age. We then combined multiple QTLs by integrating several 'single' congenic strains. As a result, BP was greatly reduced. Cardiac dysfunction and LV hypertrophy were continuously improved from 10 to 15 weeks, although the degree and timing of the improvement varied among different congenic combinations. Distinct QTLs exist that simultaneously modulate BP and diastolic function. These QTLs, in combination, synergistically lowered BP and permanently alleviated or reversed diastolic dysfunction. The genes that are contained in the congenic strains affecting diastolic function are not known for their specific influence on BP. Novel long-term strategies of prognosis, diagnosis and therapy for hypertensive DHF appear from this work.


Medical Event: Accidental Oral Administration of 177Lu-PSMA to a Patient With Hyperthyroidism.
A 74-year-old woman with hyperthyroidism was referred for radioiodine therapy. The patient was accidentally given 60 mCi of Lu-PSMA orally instead of I. Upon discovery of this medical event, we immediately started radiation protective actions including hydration, antiemetics, and laxatives. The patients did not have any symptoms. Static acquisition was performed from the abdominal-pelvic and head and neck regions at 20 and 90 hours after ingestion, which showed prominent intestinal activity and mild systemic activity in the kidneys, bladder, salivary, and lacrimal glands.


Neighborhood Collective Efficacy: A Longitudinal Social Determinant of Access to Medical Care Among Recently Immigrated Latina Young Adults.
The present longitudinal study examined changes in perceived access to health care among a recently immigrated cohort of Latina young adults who were assessed annually during their first 3 years in the United States. A parallel process growth model of perceived access to health care and neighborhood collective efficacy was examined, accounting for socioeconomic indicators and immigration status. Five hundred thirty Latina young adults (ages 18-23) participated at baseline assessment, and approximately 95% were retained over three annual assessment time points. Participants' mean level of perceived access to health care increased during their initial 3 years in the United States. Women who reported more of an increase in perceived access to health care tended to also indicate increased neighborhood collective efficacy relative to their peers during their first 3 years in the United States. Findings offer important information about the individual- and community-level factors that influence recently immigrated Latinas' health care access.


A controlled sequential morphologic study of hyperacute cardiac allograft rejection in the rat.
A series of heterotopic cardiac allografts from ACI strain rat donors to ACI skin-presensitized Lewis strain recipients was examined by light and electron microscopy at intervals from 1 minute to 24 hours for a sequential morphologic study of hyperacute rejection. Syngeneic Lewis hearts grafts in ACI skin-presensitized Lewis recipients provided controls. Extensive platelet aggregation throughout the vasculature of the allografts in the presence of a largely intact endothelium was the initial morphologic event, which was present by 1 minute posttransplant and absent in all syngeneic controls. This was followed by widespread endothelial damage. Endothelial damage preceded neutrophil margination and emigration in the graft. Neutrophil degranulation or evidence of phagocytosis was not observed within the 1st hour. At 6 and 24 hours, degranulated forms were common and apparent extrusion of granule contents with progressive ischemic injury. Segmental occlusion of the vasculature by platelet plugs and progressive disruption and loss of capillaries combined with an increase in permeability may result in myocardial ischemia. Neutrophil-derived agents do not appear to be of major significance in hyperacute rejection during the early posttransplant phase, but may play a role in mediating myocardial injury if the allograft survives for alonger period. However, on morphologic grounds, it is suggested that microcirculatory hypoperfusion with resultant ischemia is a major determinant of myocardial damage and graft function. No significant change was noted over the observation period in peripheral neutrophil or platelet counts when compared to syngeneic controls, and a slight reudction in specific cytotoxic antibody titer in the allografts was immediate but very transient.


Hepatic Meteorin-like and Krüppel-like Factor 3 are Associated with Weight Loss and Liver Injury.
Laparoscopic adjustable gastric banding (LAGB) was found to be effective in reducing body weight and improving insulin resistance in patients with obesity and non-alcoholic fatty liver disease (NAFLD). The adipokine/myokine meteorin-like (METNRL) is an important regulator of whole-body energy expenditure. Krüppel-like factor 3 (KLF3), a regulator of METRNL expression in eosinophils, inhibits the beiging of adipose tissue in mice and therefore regulates adipose tissue development. Thirty-three obese patients undergoing LAGB were included in the study. The hepatic and adipose tissue expression of METNRL and KLF3 was determined before (t0) and 6 months after (t6) LABG. The human liver cancer cell line (HepG2) was stimulated with cytokines and fatty acids and METNRL and KLF3 expressions were analyzed. LAGB-associated weight loss was correlated with decreased hepatic METNRL expression. The expression of METNRL and KLF3 in hepatic-and adipose tissues correlated before and after LAGB. Individuals with augmented LAGB-induced weight loss (>20 kg) showed lower hepatic METNRL and KLF3 expression before and after LAGB than patients with <20 kg weight loss. METNRL and KLF3 levels were higher in patients with higher NAFLD activity scores. HepG2 stimulation with interleukin-1β, tumor necrosis factor-α, palmitic acid but not interleukin-6, oleic acid, or lipopolysaccharide, induced the expression of one or both investigated adipokines. The novel description of METRNL and KLF3 as hepatokines could pave the way to target their production and/or signaling in obesity, NAFLD, and related disorders. Both proteins may act as possible biomarkers to estimate weight loss after bariatric surgery.


Rules for optimization of biocatalysis in organic solvents.
General rules for the optimization of different biocatalytic systems in various types of media containing organic solvents are derived by combining data from the literature, and the logarithm of the partition coefficient, log P, as a quantitative measure of solvent polarity. (1) Biocatalysis in organic solvents is low in polar solvents having a log P < 2, is moderate in solvents having a log P between 2 and 4, and is high in a polar solvents having a log P > 4. It was found that this correlation between polarity and activity parallels the ability of organic solvents to distort the essential water layer that stabilizes the biocatalysts. (2) Further optimization of biocatalysis in organic solvents is achieved when the polarity of the microenvironment of the biocatalyst (log P(i)) and the continuous organic phase (log P(cph)) is tuned to the polarities of both the substrate (log P(s)) and the product (log P(p)) according to the following rules: |log P(i) - log P(s)| and |log P(cph) - log P(p)| should be minimal and |log P(cph) - log P(s)| and |log P(i) - log P(p)| should be maximal, with the exception that in the case of substrate inhibition log P(i), should be optimized with respect to log P(s) In addition to these simple optimization rules, the future developments of biocatalysis in organic solvents are discussed.


Comparing two measures of leaf photorespiration rate across a wide range of light intensities.
Suppression of photorespiration by low O2 concentrations (Method 1) and simultaneous measurements of gas exchange and chlorophyll fluorescence (Method 2) are often used to estimate leaf photorespiration rate (Rp) of C3 plants. However, it is largely unknown whether Method 1 and Method 2 can be used equivalently in estimating Rp. Using a field experiment on two wheat cultivars (T. aestivum JM22 and T. aestivum Z39-118) whose leaf gas exchange and chlorophyll fluorescence at low and normal O2 concentrations (2% versus 21% O2) were simultaneously measured across a wide range of light intensities (I), this study assessed the impacts of the two measures on Rp and its response under changing irradiance conditions. All the above quantities increased with the increasing I until reaching the cultivar-specific maximum values and the corresponding saturation light intensities. However, there were significant differences between Rp estimated by Method 1 and Method 2 at the I range from 150 to 2000 μmol m-2 s-1 for T. aestivum JM22 and from 150 to 1000 μmol m-2 s-1 for T. aestivum Z39-118. These findings demonstrated that the two methods cannot be used equivalently under changing irradiance conditions.


Aggregation process on complex networks.
We study the dynamics of the aggregation of particles and the evolution of the mass distribution, on a complex network which is built following the Watts-Strogatz model. The particles perform random walks following the links on the network, and aggregate when they meet other particles. On disordered networks the density of particles decays as t(-1), while on regular networks it decays as t(-1/2). For intermediate levels of network disorder the dynamics follows that of regular networks at intermediate density, and for low density the disorder of the network becomes relevant and the density decays as t(-1). The crossover time between these two regimes scales with network disorder as t approximately p(-2). We study also an annealed model for the aggregation process, in which the quenched disorder of the network is replaced by stochastic long range jumps in the particle dynamics. The annealed model is found to obey a different scaling with network disorder, with a crossover time t approximately p(-1).


The use of focus groups to assist in the design and implementation of a new nursing practice model.
Focus groups facilitate change in healthcare institutions by providing comparative perceptions of all levels of healthcare staff in the environment, obtaining impressions of new options for healthcare delivery for which no information is available, and stimulating new ideas to improve cost-effective quality care. The authors discuss their experience using this data gathering and evaluation approach during the planning and implementation of a new nursing practice model. Factors to consider when using focus groups are offered, and lessons learned from the experience are presented.


Stereotyped behavioral responses to an auditory stimulus in the course of repeated treatment with methamphetamine plus scopolamine and methamphetamine in rats.
The present experiment was designed to study the effects of an auditory stimulus with 300 Hz, 100 dB on gradual emergence of behavioral sensitization in the course of repeated administration of methamphetamine (MAP) in combination with scopolamine (SCOP) and MAP. Repeated intraperitoneal injection of MAP (4.0 mg/kg) plus SCOP (0.5 mg/kg) induced significantly progressive and enduring enhancement of stereotyped behavior, resulting in intense, focussed stereotypy intermingled with gnawing and licking compared to repeated MAP treatment. Vigorous stereotyped behavior induced by repeated MAP plus SCOP was progressively attenuated by the tone, resulting in attenuation of the development of behavioral sensitization. Conversely, the tone had no invariable effects on behavioral sensitization induced by repeated MAP treatment. The present findings indicate that repeated MAP plus SCOP treatment progressively induced attenuating effects of tone as low as 300 Hz on MAP plus SCOP-induced intense stereotypy and vigorous behavioral sensitization. These findings suggest that a reciprocal balance between dopaminergic and cholinergic inhibitory systems may be involved in producing behavioral sensitization, and in the attenuating effects of the tone on MAP plus SCOP-induced vigorous behavioral sensitization.


A critical analysis of hardiness.
Hardiness is a construct with widespread appeal to nurse researchers. Of 97 papers reviewed, 35 were written by nurses. Because of its popularity, there is a pressing need to analyze hardiness carefully. This critical analysis of hardiness describes Kobasa's work as the foundation of hardiness research, provides a review of hardiness in the nursing literature, and recommends future hardiness research.


Incidental pancreatic cysts found by magnetic resonance imaging and their relationship with pancreatic cancer.
We examined whether the presence of pancreatic cysts could be a risk for pancreatic cancer by comparing the incidence and characteristics of cysts found by magnetic resonance (MR) imaging in patients with and without pancreatic cancer. Half-Fourier rapid acquisition with relaxation enhancement images and MR cholangiopancreatography were performed in 116 patients with pancreatic cancer (PC group) and 1226 with nonpancreatic disease (NP group). Incidence and characteristics of cysts were analyzed. Pancreatic cysts were detected in 65 patients (56%) of the PC group and in 123 patients (10%) of the NP group. According to the multivariate analysis, cyst presence was a significant risk factor for pancreatic cancer (odds ratio [OR], 10.27; P < 0.01), especially cysts larger than 10 mm (OR, 4.718; P < 0.01). When the definition of cyst presence in the PC group was restricted to the 33 cases with cysts considered to have existed before the development of cancer, the incidence was still high (OR, 2.976; P < 0.01) and size remained significant (OR, 4.428; P < 0.01). Patients with pancreatic cysts, especially larger than 10 mm, were considered to be at an increased risk of pancreatic cancer over the entire pancreas.


Portable equipment for taking dramatic sun-damage revealing photos at skin cancer prevention outreach events.
In recent years, appearance-based interventions have gained popularity as a means to improve public awareness about skin cancer and sun protective behaviors. Although numerous reports discuss the use of ultraviolet (UV) camera devices for this purpose,studies on the use of portable imaging devices in community outreach events do not presently exist. In this report, we discuss how we successfully utilize portable imaging devices at community outreach events. We also discuss the advantages and disadvantages of our portable devices in comparison to traditional UV cameras. Portable imaging devices are easy to use and have allowed us to increase our involvement in community outreach events targeting a wide range of participants.


Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer's Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil.
The pan Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor fasudil acts as a vasodilator and has been used as a medication for post-cerebral stroke for the past 29 years in Japan and China. More recently, based on the involvement of ROCK inhibition in synaptic function, neuronal survival, and processes associated with neuroinflammation, it has been suggested that the drug may be repurposed for neurodegenerative diseases. Indeed, fasudil has demonstrated preclinical efficacy in many neurodegenerative disease models. To facilitate an understanding of the wider biological processes at play due to ROCK inhibition in the context of neurodegeneration, we performed a global gene expression analysis on the brains of Alzheimer's disease model mice treated with fasudil via peripheral IP injection. We then performed a comparative analysis of the fasudil-driven transcriptional profile with profiles generated from a meta-analysis of multiple neurodegenerative diseases. Our results show that fasudil tends to drive gene expression in a reverse sense to that seen in brains with post-mortem neurodegenerative disease. The results are most striking in terms of pathway enrichment analysis, where pathways perturbed in Alzheimer's and Parkinson's diseases are overwhelmingly driven in the opposite direction by fasudil treatment. Thus, our results bolster the repurposing potential of fasudil by demonstrating an anti-neurodegenerative phenotype in a disease context and highlight the potential of in vivo transcriptional profiling of drug activity.


Oncogenes and tumor-suppressor genes.
The functional role of oncogenes in human lung carcinogenesis has been investigated by transfer of activated oncogenes into normal cells or an immortalized bronchial epithelial cell line, BEAS-2B. Transfection of v-Ha-ras, Ki-ras, or the combination of myc and raf into BEAS-2B cells produced tumorigenic cell lines, while transfection of raf or myc alone produced nontumorigenic cell lines. In addition to studying the pathogenic role of oncogenes, we are attempting to define negative growth-regulating genes that have tumor-suppressive effects for human lung carcinomas. Our strategy to identify tumor-suppressor genes involves loss of heterozygosity studies, monochromosome-cell fusion, and cell-cell fusion studies. Loss of heterozygosity studies have revealed consistent allelic DNA sequence deletions on chromosome 17p in squamous cell carcinomas, while large cell carcinomas and adenocarcinomas retained this locus. Mutations in p53, a tumor-suppressor gene located on chromosome 17p, have been observed. Cell-cell hybrid clones produced from fusion of nontumorigenic BEAS-2B cells with tumorigenic HuT292DM cells generally are nontumorigenic. The mechanistic role of the known tumor-suppressor genes Rb-1 and p53 in the development of human lung carcinomas is being investigated in this epithelial cell model of human bronchogenic carcinogenesis.


Isolation and Characterization of Lactoferrin Peptides with Stimulatory Effect on Osteoblast Proliferation.
Lactoferrin is reported to be a potential food protein with osteogenic activity. However, the activity of lactoferrin peptides is questionable. In the present study, we isolated and characterized peptides from lactoferrin with stimulatory effect on osteoblast proliferation. Peptides from the lactoferrin pepsin hydrolysate were purified using cation-exchange and gel-filtration chromatography. Effects of different hydrolysates and peptides on the proliferation of osteoblast MC3T3-E1 cells were compared by MTT assay. Results showed that fraction P5-a from Superdex Peptide 10/300 GL gel chromatography showed better activity. Tricine-sodium dodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry confirmed that two peptides components of P5-a corresponded to fractions of 20-78 and 191-277 amino acids in Bos taurus lactoferrin molecule (GI: 221706349). These results will provide some theoretical and practical data for the preparation and application of osteogenic peptides in functional food industry.


Regret and Therapeutic Decisions in Multiple Sclerosis Care: Literature Review and Research Protocol.
Background: Decisions based on erroneous assessments may result in unrealistic patient and family expectations, suboptimal advice, incorrect treatment, or costly medical errors. Regret is a common emotion in daily life that involves counterfactual thinking when considering alternative choices. Limited information is available on care-related regret affecting healthcare professionals managing patients with multiple sclerosis (MS). Methods: We reviewed identified gaps in the literature by searching for the combination of the following keywords in Pubmed: "regret and decision," "regret and physicians," and "regret and nurses." An expert panel of neurologists, a nurse, a psychiatrist, a pharmacist, and a psychometrics specialist participated in the study design. Care-related regret will be assessed by a behavioral battery including the standardized questionnaire Regret Intensity Scale (RIS-10) and 15 new specific items. Six items will evaluate regret in the most common social domains affecting individuals (financial, driving, sports-recreation, work, own health, and confidence in people). Another nine items will explore past and recent regret experiences in common situations experienced by healthcare professionals caring for patients with MS. We will also assess concomitant behavioral characteristics of healthcare professionals that could be associated with regret: coping strategies, life satisfaction, mood, positive social behaviors, occupational burnout, and tolerance to uncertainty. Planned Outcomes: This is the first comprehensive and standardized protocol to assess care-related regret and associated behavioral factors among healthcare professionals managing MS. These results will allow to understand and ameliorate regret in healthcare professionals. Spanish National Register (SL42129-20/598-E).


Auditing SNOMED relationships using a converse abstraction network.
In SNOMED CT, a given kind of attribute relationship is defined between two hierarchies, a source and a target. Certain hierarchies (or subhierarchies) serve only as targets, with no outgoing relationships of their own. However, converse relationships-those pointing in a direction opposite to the defined relationships-while not explicitly represented in SNOMED's inferred view, can be utilized in forming an alternative view of a source. In particular, they can help shed light on a source hierarchy's overall relationship structure. Toward this end, an abstraction network, called the converse abstraction network (CAN), derived automatically from a given SNOMED hierarchy is presented. An auditing methodology based on the CAN is formulated. The methodology is applied to SNOMED's Device subhierarchy and the related device relationships of the Procedure hierarchy. The results indicate that the CAN is useful in finding opportunities for refining and improving SNOMED.


Thermal stability and melt rheology of poly(p-dioxanone).
Melt viscosities of poly(p-dioxanone) (PPDO) samples having different molecular weights were studied using a controlled-strain rotational rheometer under a nitrogen atmosphere. First, PPDO's thermal stability was evaluated by recording changes in its viscosity with time. The result, that samples' viscosities decreased with time when heated, demonstrated that PPDO is thermally unstable: its degradation activation energy, obtained by using a modified MacCallum equation, was a relatively low 71.8 kJ/mol K. Next, viscoelastic information was acquired through dynamic frequency measurements, which showed a shear thinning behavior among high molecular weight PPDOs, but a Newtonian flow behavior in a low molecular weight polymer (Mw = 18 kDa). Dynamic viscosity values were transferred to steady shear viscosities according to the Cox-Merz rule, and zero shear viscosities were derived according to the Cross model with a shear thinning index of 0.80. Then flow activation energy (48 kJ/mol K) was extrapolated for PPDO melts using an Arrhenius type equation. This activation energy is independent of polymer molecular weight. A linear relationship between zero shear viscosity and molecular weight was obtained using a double-logarithmic plot with a slope of 4.0, which is near the usually observed value of 3.4 for entangled linear polymers. Finally, the rheological behaviors of PPDO polymer blends having bimodal molecular weight distributions were investigated, with the results indicating that the relationship between zero shear viscosity and low molecular weight composition fraction can be described with a Christov model.


Regulation of odorant receptors: one allele at a time.
The odorant receptors (ORs) make up the largest gene family in mammals. Each olfactory sensory neuron chooses just one OR from the more than 1000 possibilities encoded in the genome and transcribes it from just one allele. This process generates great neuronal diversity and forms the basis for the development and logic of the olfactory circuit between the nose and the brain. The mechanism behind this monoallelic regulation has been the subject of intense speculation and increasing experimental investigation, yet remains enigmatic. Recent genetic experiments have brought the outlines of the process into sharper relief, identifying a feedback mechanism in which the first odorant receptor expressed, generates a signal that stabilizes its choice, thus maintaining singular selection. In the absence of this signal, the olfactory neuron re-enters the selection process and switches to choose an alternate OR. Irreversible genetic changes in the nuclei of olfactory neurons do not accompany OR selection, which must therefore be initiated by an epigenetic process that may involve a stochastic mechanism.


[Value of readout-segmented echo-planar diffusion imaging on 3.0 T MRI for predicting the early efficacy of concurrent radiochemotherapy of advanced stage nasopharyngeal carcinoma patients].
Objective: To discuss the value of RESOLVE for predicting early therapeutic effect of concourrent radiochemotherapy in advanced stage nasopharngeal carcinoma patients. Methods: Sixty-eight patients with nasopharyngeal carcinoma were confirmed by pathology in Henan Cancer Hospital from June 2014 to January 2016.All patients underwent RESLOVE(b value=800 s/mm(2)) with a 3.0 T MRI scanner.The ADC value and the area of the tumor was measured before treatment and 2 weeks after treatment independently performed by two radiologists with 5 years experiences and the agreement evaluation was performed using ANOVA analysis.The correlation among pretreatment ADC value, pathology type, gender, tumor area and the tumor regression rate were analyzed using Spearman rank correlation test.The difference between pretreatment ADC value was compared in CR group and non-CR group by independent sample t test.ROC curve was drawn and the maximum Youden index value was the cutoff calculating the ADC value and predicting the sensitivity, specificity and area under the curve. Results: (1)The agreement between 2 radiologist was excellent. The ICC values of the ADC and the area of the tumor before treatment and the area of the tumor after treatment were 0.89, 0.92 and 0.95, respectively. (2)The pretreatment ADC values of the CR group and the non-CR group were (0.877±0.103)×10(-3) mm(2)/s and (0.779±0.078)×10(-3) mm(2)/s, respectively. There was statistical difference t value=2.874, P value=0.005.(3)ROC curve showed that the sensitivity and specificity of the pretreatment ADC value in predicting CR was 85.2% and 71.0%, with the cut-off value of 0.792×10(-3) mm(2)/s, and the area under curve was 0.778.(4)There was apparently correlation beween the pretreatment ADC value and the tumor regression rate(r=0.333, P=0.006). There was no correlation among pretreatment ADC value, pathology type, gender and tumor area (P>0.05). Conclusion: There is important value using the pretreatment ADC value measured by RESOLVE for predicting the early effect of concurrent radiochemotherapy in advanced stage nasopharngeal carcinoma patients.


Clinical significance of B cell-activating factor in autoimmune pancreatitis.
Overexpression of B Cell-activating factor (BAFF) is involved in autoimmunity, but little is known about its role in autoimmune pancreatitis (AIP). The aim of this study was to investigate the role of BAFF in the diagnosis and pathogenesis of AIP. Patients with AIP (n = 19) were compared with 2 disease control groups (chronic pancreatitis [n = 17] and pancreatic cancer [n = 15]) and a healthy subject group (n = 19). Serum BAFF levels were assessed using an enzyme-linked immunosorbent assay. The expressions of BAFF and BAFF receptor in the pancreatic tissue of patients with AIP were estimated using immunohistochemistry. Mean serum BAFF levels were higher in the patients with AIP than in the patients with chronic pancreatitis, the patients with pancreatic cancer, and the healthy subjects (P < 0.0001 for all groups). Using the cutoff value of 1389 pg/mL, the sensitivity and specificity to differentiate AIP from disease and healthy controls were 89.5% and 92.2%, respectively. Glucocorticoid therapy decreased serum BAFF levels below 1389 pg/mL in all patients with AIP (P < 0.0001). B Cell-activating factor and BAFF receptor were expressed on cells infiltrating the pancreas of patients with AIP. B Cell-activating factor could be a novel marker for diagnosis and treatment response in AIP and may contribute to its pathogenesis.


Notch signaling pathway: a new target for neuropathic pain therapy.
The Notch gene, a highly evolutionarily conserved gene, was discovered approximately 110 years ago and has been found to play a crucial role in the development of multicellular organisms. Notch receptors and their ligands are single-pass transmembrane proteins that typically require cellular interactions and proteolytic processing to facilitate signal transduction. Recently, mounting evidence has shown that aberrant activation of the Notch is correlated with neuropathic pain. The activation of the Notch signaling pathway can cause the activation of neuroglia and the release of pro-inflammatory factors, a key mechanism in the development of neuropathic pain. Moreover, the Notch signaling pathway may contribute to the persistence of neuropathic pain by enhancing synaptic transmission and calcium inward flow. This paper reviews the structure and activation of the Notch signaling pathway, as well as its potential mechanisms of action, to provide novel insights for future treatments of neuropathic pain.


Comparative Transcriptomic Analysis of Temozolomide Resistant Primary GBM Stem-Like Cells and Recurrent GBM Identifies Up-Regulation of the Carbonic Anhydrase CA2 Gene as Resistance Factor.
About 95% of patients with Glioblastoma (GBM) show tumor relapse, leaving them with limited therapeutic options as recurrent tumors are most often resistant to the first line chemotherapy standard Temozolomide (TMZ). To identify molecular pathways involved in TMZ resistance, primary GBM Stem-like Cells (GSCs) were isolated, characterized, and selected for TMZ resistance in vitro. Subsequently, RNA sequencing analysis was performed and revealed a total of 49 differentially expressed genes (|log2-fold change| > 0.5 and adjusted p-value < 0.1) in TMZ resistant stem-like cells compared to their matched DMSO control cells. Among up-regulated genes, we identified carbonic anhydrase 2 (CA2) as a candidate gene correlated with glioma malignancy and patient survival. Notably, we describe consistent up-regulation of CA2 not only in TMZ resistant GSCs on mRNA and protein level, but also in patient-matched clinical samples of first manifest and recurrent tumors. Co-treatment with the carbonic anhydrase inhibitor Acetazolamid (ACZ) sensitized cells to TMZ induced cell death. Cumulatively, our findings illustrate the potential of CA2 as a chemosensitizing target in recurrent GBM and provide a rationale for a therapy associated inhibition of CA2 to overcome TMZ induced chemoresistance.


Latitude, migration, and the prevalence of multiple sclerosis.
Prevalence of multiple sclerosis (MS) was determined in three groups of Caucasians in King and Pierce Counties (Washington) and in Los Angeles County (California): natives (born in study state), migrants from high-risk states (North), and migrants from low risk states (South). A diagnosis of definite or probable MS (excluding migrants with onset before migration) was established in 1816 of the persons found. The prevalence in Los Angeles County natives and in migrants from the South to either Los Angeles County or King-Pierce Counties were relatively low, while prevalence in King-Pierce Counties among natives and migrants from the North were high. The prevalence in migrants from the North to Los Angeles was intermediate. The results suggest that some degree of protection is provided to migrants by residence in low-prevalence areas, either early or later in life.