Molecular Mechanisms of Syndromic Cryptorchidism: Data Synthesis of 50 Studies and Visualization of Gene-Disease Network.
Background: Cryptorchidism is one of the most frequent congenital birth defects in male children and is present in 2-4% of full-term male births. It has several possible health effects including reduced fertility, increased risk for testicular neoplasia, testicular torsion, and psychological consequences. Cryptorchidism is often diagnosed as comorbid; copresent with other diseases. It is also present in clinical picture of several syndromes. However, this field has not been systematically studied. The aim of the present study was to catalog published cases of syndromes which include cryptorchidism in the clinical picture and associated genomic information. Methods: The literature was extracted from Public/Publisher MEDLINE and Web of Science databases, using the keywords including: syndrome, cryptorchidism, undescended testes, loci, and gene. The obtained data was organized in a table according to the previously proposed standardized data format. The results of the study were visually represented using Gephi and karyotype view. Results: Fifty publications had sufficient data for analysis. Literature analysis resulted in 60 genomic loci, associated with 44 syndromes that have cryptorchidism in clinical picture. Genomic loci included 38 protein-coding genes and 22 structural variations containing microdeletions and microduplications. Loci, associated with syndromic cryptorchidism are located on 16 chromosomes. Visualization of retrieved data is presented in a gene-disease network. Conclusions: The study is ongoing and further studies will be needed to develop a complete catalog with the data from upcoming publications. Additional studies will also be needed for revealing of molecular mechanisms associated with syndromic cryptorchidism and revealing complete diseasome network.


Lipoleiomyoma of broad ligament mimicking ovarian cancer in a postmenopausal patient: case report and literature review.
Lipoleiomyoma is a very rare tumor which is composed of adipocytes and smooth muscle cells. It is most commonly located in uterine corpus although cervical, ovarian, and retroperitoneal locations were also reported. Lipoleiomyoma located in broad ligament is extremely uncommon and only five cases were reported to date. Here, we report the sixth case of lipoleiomyoma of broad ligament which was diagnosed in a postmenopausal woman who was subjected to exploratory laparotomy with a preoperative diagnosis of a solid adnexal mass suggesting an ovarian malignancy.


Sarcoid-like reaction-computed tomography features in 12 patients.
The aim of the study was to analyze the computed tomography (CT) findings of sarcoid-like reaction caused by underlying malignancy or immune modulation. Twelve patients with pathologically proven sarcoidosis from underlying causes (malignancies, hepatitis C infection, and immune-modulatory treatment) in 2001 to 2011 were identified. All patients had chest CT scans, which were reviewed by 3 experienced thoracic radiologists. Medical records were also reviewed. Follow-up imaging, available in 11 patients, was assessed for response. All patients were white, 8 women and 4 men, with ages ranging from 26 to 72 years. Seven had underlying malignancy, 2 had inflammatory bowel disease, and 3 had liver disease caused by chronic hepatitis C viral infection. On CT, 92% (11/12) of patients had lymphadenopathy, 75% (9/12) had pulmonary nodules less than 5 mm, and 50% (6/12) had ground-glass opacity (GGO). In 42% (5/12) of patients, the dominant finding was discrete nodules (1-5 mm). In 33% (4/12) of patients, the dominant finding was ultrafine nodules with confluence, mimicking GGO. The most common distribution of lung nodules was perilymphatic, found in 78% (7 of the 9 patients with lung nodules). Follow-up was available in 10 patients, limited follow-up in 1, and no follow-up in 1. Six of the 11 patients who had follow-up had complete resolution of CT findings, 3 had partial resolution, and 2 had no resolution. Imaging features of patients with sarcoid-like reaction include lymphadenopathy, small nodules, and ultrafine nodules with confluence, mimicking GGO. Ultrafine nodules with confluence mimicking GGO were unexpectedly common in this series.


Surface ozone levels in the forest and vegetation areas of the Biga Peninsula, Turkey.
Spatial and temporal variability of surface ozone in the rural, mountainous and suburban sites of Biga Peninsula, at the northwest of Turkey which is about 300km southwest of Istanbul was investigated using passive samplers and continuous analyzers. A total 10 passive samplers and two continuous analyzers were used between 1.1.2013 and 31.12.2014. OX levels in the study region were examined to understand NOx dependent or independent contribution to ozone. The influences of the meteorological parameters on ozone levels were also examined by wind speed and ambient temperature. The results clearly show that mountainous areas have higher cumulative exposure to ozone than suburban locations. In order to understand the long range transport sources contributing to the high ozone levels in the region backward trajectories were computed using HYSPLIT model and then clustering of trajectories are performed. The results clearly show the characteristics of pollutant transport from north to Biga Peninsula. Additionally, AOT40 (Accumulated hourly O3 concentrations Over a Threshold of 40ppb) cumulative index was calculated using daytime hourly measurements. The results indicate that the ozone values in the study area are much higher than the critical levels for forest and vegetation based on EU Directive 2008/50/EC.


Using crystal structure prediction to rationalize the hydration propensities of substituted adamantane hydrochloride salts.
The crystal energy landscapes of the salts of two rigid pharmaceutically active molecules reveal that the experimental structure of amantadine hydrochloride is the most stable structure with the majority of low-energy structures adopting a chain hydrogen-bond motif and packings that do not have solvent accessible voids. By contrast, memantine hydrochloride which differs in the substitution of two methyl groups on the adamantane ring has a crystal energy landscape where all structures within 10 kJ mol(-1) of the global minimum have solvent-accessible voids ranging from 3 to 14% of the unit-cell volume including the lattice energy minimum that was calculated after removing water from the hydrated memantine hydrochloride salt structure. The success in using crystal structure prediction (CSP) to rationalize the different hydration propensities of these substituted adamantane hydrochloride salts allowed us to extend the model to predict under blind test conditions the experimental crystal structures of the previously uncharacterized 1-(methylamino)adamantane base and its corresponding hydrochloride salt. Although the crystal structure of 1-(methylamino)adamantane was correctly predicted as the second ranked structure on the static lattice energy landscape, the crystallization of a Z' = 3 structure of 1-(methylamino)adamantane hydrochloride reveals the limits of applying CSP when the contents of the crystallographic asymmetric unit are unknown.


Preparative purification of dipeptidyl peptidase IV.
Dipeptidyl-Peptidase IV was purified from pig kidney by ammonium sulfate fractionation, gel filtration, QAE-cellulose chromatography and affinity columns with Gly-Pro- and Concanavalin A-Sepharose. The specific activity of the purified enzyme is 41.8 units/mg. Polyacrylamide gel electrophoresis and silver staining show a single band. The enzyme preparation is free of aminopeptidase and dipeptidase activity, proved fluorimetrically and by gas chromatography/mass spectrometry. The most important procedure for removal of contaminating enzyme activities is a stepwise NaCl-gradient on a QAE-ZetaPrep ion exchange disk.


Association of Red Cell Index and Hospital Mortality in Chronic Obstructive Pulmonary Disease Patients Admitted to the Intensive Care Unit: A Retrospective Cohort Study.
This study aims to explore the association between red cell index (RCI) and hospital mortality in Chronic Obstructive Pulmonary Disease (COPD) patients in the intensive care unit. This was a retrospective cohort research. The study included 821 COPD patients. Clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database was conducted. Multivariate logistic regression analysis was used to assess the correlation between RCI and in-hospital mortality. Age, SOFA score, diabetes mellitus, cerebrovascular disease, congestive heart failure and mechanical ventilation were considered for subgroup analysis. This study comprised 821 patients, of which 16.5% (124/821) suffered hospital mortality. In the multivariate logistic regression model, RCI was positively associated with hospital mortality, each unit increase in RCI was associated with a 3% increase in hospital mortality (odds ratio [OR] =1.03; 95% confidence interval [95CI%] =1.01-1.06). Meanwhile, compare with the lowest RCI group, the highest RCI groups tended to have higher risks of hospital mortality (OR [95% CI] 2.33 [1.27-4.27]). Additionally, subgroup analysis result was persistent among all the groups. Higher RCI was positively associated with a higher risk of mortality in critically ill patients with COPD. Further investigation is necessary to confirm these findings.


Determination of Tear Production and Intraocular Pressure With Rebound Tonometry in Wild Humboldt Penguins ( Spheniscus humboldti ).
Tear production and intraocular pressures (IOPs) were determined in 38 and 102 wild Humboldt penguins (Spheniscus humboldti), respectively, from the Punta San Juan Marine Protected Area in Ica, Peru. Tear production was measured by Schirmer tear test, and IOP was measured with a TonoVet rebound tonometer. Adult (n = 90) and chick (n = 12) penguins were sampled from 2 different beaches (north and south facing) during 2 sampling years (2010 and 2011). Results showed a mean ± SD (range) of 9 ± 4 (2-20) mm/min for tear production and 28 ± 9 (3-49) mm Hg for IOP. Tear production in penguins differed between beach and sex, whereas IOP differed between age, year, and beach. The IOPs were negatively correlated with packed cell volume. Tear production and IOP values had greater variation in this population than it has in other avian species. Previous investigations of IOP and tear production in Spheniscus species were conducted with birds housed under professional care in artificial marine and freshwater environments. This is the first study, to our knowledge, investigating tear production and IOP in wild penguins and establishes valuable reference intervals for this species.


Lyme disease: recognition and management for emergency nurses.
Over the past ten years there has been a significant rise in the number of people who present to emergency departments with Lyme disease. Although some patients remain asymptomatic many present with a rash around a previous tick bite and others may present with a range of debilitating symptoms that can be problematic if left untreated. Due to the growing prevalence of Lyme disease in the UK and the US this article gives an overview of the vector-borne condition and provides emergency nurses with information about the pathophysiology, prevention, presenting signs and symptoms and management.


Linkage associations in hybridized Salvelinus genomes. The duplicate loci encoding pepidase-D and glucosephosphate isomerase and the unduplicated sorbitol dehydrogenase locus.
Electrophoresis was performed on parents and progeny of 21 families of tetraploid derivative Salvelinus species. Variable phenotypes were shown for the duplicate loci encoding the enzyme peptidase D in lake (S. namaycush) and brook trout (S. fontinalis) and in the fertile hybrid (splake) between them. Pairwise examinations of joint segregation between the duplicated PepD loci and 23 other biochemical loci were performed. Nonrandom assortment was found among progeny of parents doubly heterozygous for the PepD-1 and PepD-2 loci, the duplicate loci encoding glucosephosphate isomerase (Gpi-1 and Gpi-2) and the single locus encoding sorbitol dehydrogenase (Sdh). Two classical linkage groups were found among the uniquely marked loci; PepD-1 with Gpi-1 and PepD-2 with Gpi-2 with Sdh. Pseudolinkage among loci in the two different groups was found in males. The results are shown to fit a chromosomal model involving preferential tetravalent pairing of homoeologous chromosomes. The linkage of PepD and Gpi loci is consistent with that reported in a variety of vertebrate species and indicates the conservation of this linkage group over taxa separated by at least 300 million years of evolution.


Reaching Into the Unknown: Actions, Goal Hierarchies, and Explorative Agency.
Action is widely characterized as possessing a teleological dimension. The dominant way of describing goal-directed action and agency is in terms of exploitation, i.e., pursuing pre-specified goals using existing strategies. Recent theoretical developments emphasize the place of exploration, i.e., discovering new goals or acquiring new strategies. The exploitation-exploration distinction poses questions with regard to goals and agency: Should exploration, as some authors have suggested, be regarded as acting without a goal? We argue that recognizing the hierarchical nature of goals is crucial in distinguishing the two kinds of activity, because this recognition prevents the claim that exploration is goal-free, while allowing for a homogeneous account of both exploitative and explorative actions. An action typically causes relatively low-level/proximal (i.e., sensorimotor, immediate) and relatively high-level/distal (i.e., in the environment, at a wider timescale) outcomes. In exploitation, one relies on existing associations between low- and high-level states, whereas in exploration one does not have the ability or intention to control high-level/distal states. We argue that explorative action entails the capacity to exercise control within the low-level/proximal states, which enables the pursuit of indeterminate goals at the higher levels of a goal hierarchy, and the possibility of acquiring new goals and reorganization of goal hierarchies. We consider how the dominant models of agency might accommodate this capacity for explorative action.


Combination of Optimization and Metalated-Ligand Exchange: An Effective Approach to Functionalize UiO-66(Zr) MOFs for CO2 Separation.
The strategy to functionalize water-stable metal-organic frameworks (MOFs) in order to improve their CO2 uptake capacities for efficient CO2 separation remains limited and challenging. We herein present an effective approach to functionalize a prominent water-stable MOF, UiO-66(Zr), by a combination of optimization and metalated-ligand exchange. In particular, by systematic optimization, we have successfully obtained UiO-66(Zr) of the highest BET surface area reported so far (1730 m(2) g(-1) ). Moreover, it shows a hybrid Type I/IV N2 isotherm at 77 K and a mesopore size of 3.9 nm for the first time. The UiO-66 MOF underwent a metalated-ligand-exchange (MLE) process to yield a series of new UiO-66-type MOFs, among which UiO-66-(COONa)2 -EX and UiO-66-(COOLi)4 -EX MOFs have both enhanced CO2 working capacity and IAST CO2 /N2 selectivity. Our approach has thus suggested an alternative design to achieve water-stable MOFs with high crystallinity and gas uptake for efficient CO2 separation.


The in vitro growth pattern of human bone marrow in methylcellulose stimulated by different concentrations of conditioned medium.
The proliferation of human bone marrow in methylcellulose stimulated by various concentrations of conditioned medium (CM) and observed at various intervals was studied. The growth kinetics of granulocytic aggregates was found to differ from monocytic clusters and colonies. Granulocytic aggregates showed a consistent and reproducible dose-response relationship; at day 7, the maximum number of granulocytic aggregates was found at 4% CM. At higher levels, the total number of aggregates decreased, while the number of cells per aggregate increased. The number of macrophage aggregates was far less, depending on the CM concentration. Photographic interval studies showed that at high concentrations of CM, clusters and colonies were formed earlier, but also coalesce to form one colony. Our results suggest that the proliferation kinetics of granulocytic aggregates are complex and preclude simple statements about sensitivity to colony-stimulating activity.


Preparing the United States for Zika Virus: Pre-emptive Vector Control and Personal Protection.
Discovered in 1947 in a monkey in the Zika forest of Uganda, Zika virus was dismissed as a cause of a mild illness that was confined to Africa and Southeast Asia and transmitted by Aedes mosquitoes. In 2007, Zika virus appeared outside of its endemic borders in an outbreak on the South Pacific Island of Yap. In 2013, Zika virus was associated with a major neurological complication, Guillain-Barré syndrome, in a larger outbreak in the French Polynesian Islands. From the South Pacific, Zika invaded Brazil in 2015 and caused another severe neurological complication, fetal microcephaly. The mosquito-borne transmission of Zika virus can be propagated by sexual transmission and, possibly, by blood transfusions, close personal contacts, and organ transplants, like other flaviviruses. Since these combined mechanisms of infectious disease transmission could result in catastrophic incidences of severe neurological diseases in adults and children, the public should know what to expect from Zika virus, how to prevent infection, and what the most likely failures in preventive measures will be. With federal research funding stalled, a Zika vaccine is far away. The only national strategies to prepare the United States for Zika virus invasion now are effective vector control measures and personal protection from mosquito bites. In addition to a basic knowledge of Aedes mosquito vectors and their biting behaviors, an understanding of simple household vector control measures, and the selection of the best chemical and physical mosquito repellents will be required to repel the Zika threat.


The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.
IL-17-producing T lymphocytes have been recently shown to comprise a distinct lineage of proinflammatory T helper cells, termed Th17 cells, that are major contributors to autoimmune disease. We show here that the orphan nuclear receptor RORgammat is the key transcription factor that orchestrates the differentiation of this effector cell lineage. RORgammat induces transcription of the genes encoding IL-17 and the related cytokine IL-17F in naïve CD4(+) T helper cells and is required for their expression in response to IL-6 and TGF-beta, the cytokines known to induce IL-17. Th17 cells are constitutively present throughout the intestinal lamina propria, express RORgammat, and are absent in mice deficient for RORgammat or IL-6. Mice with RORgammat-deficient T cells have attenuated autoimmune disease and lack tissue-infiltrating Th17 cells. Together, these studies suggest that RORgammat is a key regulator of immune homeostasis and highlight its potential as a therapeutic target in inflammatory diseases.


Glycan cross-feeding activities between bifidobacteria under in vitro conditions.
Bifidobacteria colonize the gut of various mammals, including humans, where they may metabolize complex, diet-, and host-derived carbohydrates. The glycan-associated metabolic features encoded by bifidobacteria are believed to be strongly influenced by cross-feeding activities due to the co-existence of strains with different glycan-degrading properties. In this study, we observed an enhanced growth yield of Bifidobacterium bifidum PRL2010 when co-cultivated with Bifidobacterium breve 12L, Bifidobacterium adolescentis 22L, or Bifidobacterium thermophilum JCM1207. This enhanced growth phenomenon was confirmed by whole genome transcriptome analyses, which revealed co-cultivation-associated transcriptional induction of PRL2010 genes involved in carbohydrate metabolism, such as those encoding for carbohydrate transporters and associated energy production, and genes required for translation, ribosomal structure, and biogenesis, thus supporting the idea that co-cultivation of certain bifidobacterial strains with B. bifidum PRL2010 causes enhanced metabolic activity, and consequently increased lactate and/or acetate production. Overall, these data suggest that PRL2010 cells benefit from the presence of other bifidobacterial strains.


Mapping brain gene coexpression in daytime transcriptomes unveils diurnal molecular networks and deciphers perturbation gene signatures.
Brain tissue transcriptomes may be organized into gene coexpression networks, but their underlying biological drivers remain incompletely understood. Here, we undertook a large-scale transcriptomic study using 508 wild-type mouse striatal tissue samples dissected exclusively in the afternoons to define 38 highly reproducible gene coexpression modules. We found that 13 and 11 modules are enriched in cell-type and molecular complex markers, respectively. Importantly, 18 modules are highly enriched in daily rhythmically expressed genes that peak or trough with distinct temporal kinetics, revealing the underlying biology of striatal diurnal gene networks. Moreover, the diurnal coexpression networks are a dominant feature of daytime transcriptomes in the mouse cortex. We next employed the striatal coexpression modules to decipher the striatal transcriptomic signatures from Huntington's disease models and heterozygous null mice for 52 genes, uncovering novel functions for Prkcq and Kdm4b in oligodendrocyte differentiation and bipolar disorder-associated Trank1 in regulating anxiety-like behaviors and nocturnal locomotion.


[Efficacy of sleeve gastrectomy plus gastric remnant banding on weight reduction and remnant gastric dilatation: an animal experimental study].
To investigate the efficacy of sleeve gastrectomy plus gastric remnant banding on weight reduction and remnant gastric dilatation in SD rat model. Sleeve gastrectomy plus gastric remnant banding was performed in 20 male SD rats as the study group; sleeve gastrectomy was performed in 20 SD male rats as the control group, and laparotomy was performed in 10 SD male rats as the blank control group. Body weight was measured before the experiment, at day 1 and at 2-week intervals within 16 weeks after operation. The number of survival rats was 15 in the study group (15/20), 13 in the control group (13/20), and 10 in the blank control group (10/10). Postoperative body weight increased markedly in the blank control group, returned to the pre-operative level two weeks after operation in the control group, and four weeks after operation in the study group. Weight increase of the study group was significantly slower than that of the other two groups (P<0.01). Postoperative gastric dilation of the control group was more obvious as compared to the study group. Sleeve gastrectomy plus gastric remnant banding is safe and effective because of the restriction of postoperative gastric dilation.


Photoelectron spectroscopic study of the anionic transition metalorganic complexes [Fe(1,2)(COT)](-) and [Co(COT)](-).
The gas-phase, iron and cobalt cyclooctatetraene cluster anions, [Fe(1,2)(COT)](-) and [Co(COT)](-), were generated using a laser vaporization source and studied using mass spectrometry and anion photoelectron spectroscopy. Density functional theory was employed to compute the structures and spin multiplicities of these cluster anions as well as those of their corresponding neutrals. Both experimental and theoretically predicted electron affinities and photodetachment transition energies are in good agreement, authenticating the structures and spin multiplicities predicted by theory. The implied spin magnetic moments of these systems suggest that [Fe(COT)], [Fe(2)(COT)], and [Co(COT)] retain the magnetic moments of the Fe atom, the Fe(2) dimer, and the Co atom, respectively. Thus, the interaction of these transition metal, atomic and dimeric moieties with a COT molecule does not quench their magnetic moments, leading to the possibility that these combinations may be useful in forming novel magnetic materials.


Phenotypic detection of AmpC β-lactamases, extended-spectrum β-lactamases and metallo-β-lactamases in Enterobacteriaceae using a resazurin microtitre assay with inhibitor-based methods.
Dissemination of antibiotic resistance in Enterobacteriaceae mediated by AmpC β-lactamase, extended-spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) is clinically significant. A simple and relatively quick method for the detection of these resistance phenotypes would greatly improve chemotherapeutic recommendation. This technology would provide valuable input in our surveillance of resistance on a global stage, particularly if the methodology could be applicable to resource-poor settings. A resazurin microtitre plate (RMP) assay incorporating cloxacillin, clavulanic acid and EDTA for the rapid phenotypic identification of AmpC, ESBL and MBL and the co-existence of β-lactamases has been developed. A total of 47 molecularly characterized Enterobacteriaceae clinical isolates producing AmpCs, ESBLs, co-producers of ESBL and AmpC, MBLs and co-producers of ESBL and MBL were phenotypically examined using the RMP assay. The ceftazidime- and cefotaxime-based RMP assays successfully detected all 16 AmpC, 14 ESBL and 9 MBL producers, 6 ESBL-AmpC co-producers and 2 ESBL-MBL co-producers without false-positive results. The ceftazidime-based assay was more reliable in detecting AmpC alone, while the cefotaxime-based assay performed better in identifying co-producers of ESBL and AmpC. There was no difference in the detection of ESBL and MBL producers. The findings of the present study suggest that use of the RMP assay with particular β-lactamase inhibitors explicitly detects three different β-lactamases, as well as co-existence of β-lactamases, within 6 h of initial isolation of the pathogen. This assay is applicable to carry out in any laboratory, is cost-effective and is easy to interpret. It could be implemented in screening patients and controlling infection and for surveillance purposes.


The everyday risk work of Dutch child-healthcare professionals: inferring 'safe' and 'good' parenting through trust, as mediated by a lens of gender and class.
Amidst intensifying policy concerns with children's wellbeing and development, healthcare professionals are required not only to assess risk of abuse and neglect, but to manage risk of 'poor parenting' more broadly. Drawing on 15 in-depth interviews and non-participant observations of 61 professional-family interactions, across four preventative public health services for children in the Netherlands, we explored how professionals accomplished such risk work amid intractable uncertainties. Building inferences from brief encounters with families, professionals gauged the extent to which they trusted parents to care 'appropriately'. This trust developed most readily with parents experienced as 'familiar' by the largely middle-class female professionals. Harnessing Schutzian phenomenology, we analyse the related manifestations of social structure within the interactional-dynamics and lifeworlds of risk assessment. We argue that social structures of gender, class and ethnicity can be seen as influential both through the differing potential for 'we-relationships' to be formed and via the generalising and stereotyped knowledge applied in their absence.


Differential microRNA regulation correlates with alternative polyadenylation pattern between breast cancer and normal cells.
Alternative polyadenylation (APA) could result in mRNA isoforms with variable lengths of 3' UTRs. Gain of microRNA target sites in the 3' UTR of a long mRNA isoform may cause different regulation from the corresponding short isoform. It has been known that cancer cells globally exhibit a lower ratio of long and short isoforms (LSR); that is, they tend to express larger amounts of short isoforms. The objective of this study is to illustrate the relationship between microRNA differential regulation and LSR. We retrieved public APA annotations and isoform expression profiles of breast cancer and normal cells from a high-throughput sequencing method study specific for the mRNA 3' end. Combining microRNA expression profiles, we performed statistical analysis to reveal and estimate microRNA regulation on APA patterns in a global scale. First, we found that the amount of microRNA target sites in the alternative UTR (aUTR), the region only present in long isoforms, could affect the LSR of the target genes. Second, we observed that the genes whose aUTRs were targeted by up-regulated microRNAs in cancer cells had an overall lower LSR. Furthermore, the target sites of up-regulated microRNAs tended to appear in aUTRs. Finally, we demonstrated that the amount of target sites for up-regulated microRNAs in aUTRs correlated with the LSR change between cancer and normal cells. The results indicate that up-regulation of microRNAs might cause lower LSRs of target genes in cancer cells through degradation of their long isoforms. Our findings provide evidence of how microRNAs might play a crucial role in APA pattern shifts from normal to cancerous or proliferative states.


Impaired apoptosis in mitogen-stimulated lymphocytes of patients with multiple sclerosis.
We investigated the sensitivity to cell death of peripheral blood mononuclear cells (PBMCs) from patients with multiple sclerosis (MS). PBMCs from MS patients, following PHA stimulation, were less sensitive to cell death than those from healthy donors (mean +/- s.e.m., 22.5 +/- 1.9 in MS patients vs 36.5 +/- 2.8 in healthy controls; p = 0.0003). However, when Fas-agonist antibody was added, the increase in respect to apoptosis induced by mitogen alone was even higher in MS patients than in controls. In addition, PHA-activated PBMCs from MS patients showed higher surface expression of Fas than controls, while Bcl-2 expression was decreased. This finding raised the question of whether an impaired generation of apoptotic signals may be contributing to the immune component of MS.


Immunochemical characterization and tissue distribution of glutaredoxin (thioltransferase) from calf.
Glutaredoxin catalyzes glutathione-dependent disulfide oxidoreduction reactions in a coupled system with NADPH, GSH and glutathione reductase and has an active site disulfide/dithiol with the sequence -Cys-Pro-Tyr-Cys-. Calf thymus glutaredoxin (thioltransferase), which contains two additional structural half-cystine residues, was purified to homogeneity, using a modification of the previously described isolation procedure. This method involved a pI-shift of glutaredoxin, obtained after oxidation of the fully reduced form with hydroxyethyl-disulfide, followed by CM-Sepharose chromatography. On both SDS- and IEF-gels the protein migrated as one band (M(r) 12,000). The pure protein was used to affinity-purify rabbit antiglutaredoxin antibodies obtained by immunization with the oxidized form of glutaredoxin. Using these antibodies the distribution of glutaredoxin was mapped in calf organs and tissues by Western blots and by immunohistochemistry. Glutaredoxin was demonstrated in all organs investigated. Western blots showed the presence of weak additional high molecular weight bands of unknown identity in certain organs. The immunohistochemical analyses revealed that glutaredoxin is highly expressed in a wide variety of cell types, both epithelial and mesenchymal. The distribution and occurrence in the calf organs was similar to that previously described for thioredoxin in the rat. There were some exceptions: e.g., follicular cells in the ovary did not contain immunohistochemically demonstrable glutaredoxin but expressed thioredoxin. Particularly striking were observations of strong glutaredoxin immunoreactivity in oocytes in the ovary and the pattern of glutaredoxin in epithelial tissue of the skin and tongue reflecting differential expression during cell differentiation. The distribution demonstrated that glutaredoxin serves functions apart from the originally described role as hydrogen donor for ribonucleotide reductase which only occurs in replicating cells. Such functions should relate particularly to glutathione-catalyzed protein disulfide oxidoreductions and cellular signalling by redox regulating mechanisms.


Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation.
Here we discuss studies of the structure, folding, oligomerization and amyloid fibril formation of several proline mutants of human stefin B, which is a protein inhibitor of lysosomal cysteine cathepsins and a member of the cystatin family. The structurally important prolines in stefin B are responsible for the slow folding phases and facilitate domain swapping (Pro 74) and loop swapping (Pro 79). Moreover, our findings are compared to β₂-microglobulin, a protein involved in dialysis-related amyloidosis. The assessment of the contribution of proline residues to the process of amyloid fibril formation may shed new light on the critical molecular events involved in conformational disorders.


DNA disentangling by type-2 topoisomerases.
A type-2 topoisomerase cleaves a DNA strand, passes another through the break, and then rejoins the severed ends. Because it appears that this action is as likely to increase as to decrease entanglements, the question is: how are entanglements removed? We argue that type-2 topoisomerases have evolved to act at "hooked" juxtapositions of strands (where the strands are curved toward each other). This type of juxtaposition is a natural consequence of entangled long strands. Our model accounts for the observed preference for unlinking and unknotting of short DNA plasmids by type-2 topoisomerases and well explains experimental observations.


Biliary strictures: endoscopic assessment and management.
The diagnosis of biliary strictures can be challenging. Endoscopy has an established role in the diagnosis and therapy of biliary strictures. However, the diagnostic yield from conventional endoscopic retrograde cholangiopancreatography tissue sampling is modest. Improvements in existing technologies as well as the implementation of novel technologies and techniques have the potential to improve the diagnostic performance of endoscopy and expand its therapeutic role. Recent studies have enabled greater clarity about the role of preoperative biliary drainage and the choice of stents in this setting as well as the utility of metal stents in benign and malignant disease.


[New ways in the surgery of acute appendicitis?].
Acute appendicitis is still one of the most common abdominal emergencies necessitating operative treatment. For the past century, the conventional management of appendicitis has been open appendectomy. Since the introduction of laparoscopic appendectomy, it has been performed with increased frequency. Clinical trials evaluating outcomes comparing open appendectomy with laparoscopic appendectomy indicate that laparoscopic appendectomy is associated with lower complication rate and lower mortality and is to be considered the procedure of choice for patients with suspected acute appendicitis. Ever since Kalloo's first report on transgastric peritoneoscopy in a porcine model in 2004, this dramatic surgical revolution has prompted many surgeons and endoscopists to study this new technique. This complex technique involves breaching the wall of a hollow organ to gain access into the peritoneum: Natural Orifice Translumenal Endoscopic Surgery (NOTES). In recent years, several NOTES experiments have been carried out in animal models and even on humans, including appendectomy. NOTES may help to reduce surgical pain and shorten recovery time. The concept of NOTES has generated intensive interest in the medical community as well as in the group of patients. Although the novel procedure is still far from being mature and many technical problems have to be overcome and more clinical studies have to be done before its widespread application in human appendectomy, NOTES is a promising procedure for the future.


[Epidemiologic study of tear film lipid layer thickness measurement in the population of Taishitun Community in Beijing].
Objective: To investigate the distribution of tear film lipid layer thickness (LLT) and the relationship between symptoms and signs of dry eye and tear film LLT in the population of Taishitun Community in Beijing. Methods: A cross-sectional study. From May 2016 to August 2016, three streets of Taishitun Community were randomly selected as survey districts and 540 persons were taken as investigation subjects. Every participant completed 6 items of dry eye examinations as follows: questionnaire (Ocular Surface Disease Index, OSDI), measurement of tear film LLT, tear film break-up time (TBUT), corneal and conjunctival staining, SchirmerⅠtest and the infrared meibomian photography. According to their age, all participants were divided into four groups: junior group (<18 years old), youth group (18 to 40 years old), middle-aged group (41 to 59 years old) and the elderly group (over 60 years old). With the OSDI criteria, no dry eye symptom group (score, <12 points), mild to moderate dry eye symptom group (score, 12 to 32) and severe dry eye symptom group (score, 33-100) were included. With the statistical methods of variance analysis and multivariate Logistic regression analysis, distribution of the variables of LLT and the relationship between dry eye symptoms and LLT were studied. Results: A total of 473 residents finally participated in this study, and the response ratio was 87.6%. The values of LLT were normally distributed. The average LLT was (59.87±18.50) nm [(60.16±19.15) nm in males and (59.67±18.57) nm in females], and the comparison of LLT with different genders was not statistically significant (t=0.198, P=0.843). The tear film LLT of four different age groups had statistical significance (F=15.092, P<0.05), and increased with age [(56.10±18.33) nm in the junior group, (54.60±16.29) nm in the youth group, (60.61±19.18) nm in the middle-aged group and (73.25±14.58) nm in the elderly group]. The LLT was inversely proportional to the severity of dry eye symptoms. With a thinner LLT, the symptoms of the subjects turned severe. In the elderly with different degrees of symptoms, the LLT was significantly different (F=0.019, P<0.05), while in the youth and middle-aged groups with different degrees of symptoms, the LLT was not significantly different (F=0.096, P>0.05. F=0.538, P>0.05). In the OSDI symptom questionnaire, only blurred vision and decreased visual acuity were related to the tear film LLT (P<0.05). There was no significant correlation between the TBUT, SchirmerⅠtest result, meibomian gland loss rate and the tear film LLT (P>0.05). Conclusions: In Taishitun Community of Beijing, the values of tear film LLT had a normal distribution. The LLT was positively correlated with age, but inversely correlated with the severity of the symptoms of dry eye. There was no significant correlation between the LLT and the TBUT, SchirmerⅠtest result and meibomian gland loss rate.(Chin J Ophthalmol, 2017, 53: 495-501).


Refining the Pulmonary and Functional Competencies in a Male Patient With Guillain-Barré Syndrome.
Guillain-Barré syndrome (GBS) is the most prevalent form of autoimmune-related acute demyelinating polyneuropathy that affects people of any age group. Its global prevalence is 1.9 per 100,000 people. Acute or subacute symmetrical motor and sensory neuropathy involving several peripheral nerves is referred to as GBS. It typically occurs after an infection caused by a virus, but infrequently with surgery or vaccination. There are different variants of GBS, like acute sensory axonal neuropathy, acute motor axonal neuropathy, and Miller-Fisher syndrome. Motor paralysis that affects distal muscles more than proximal muscles and is more pronounced and symmetrical may be a presenting symptom of GBS. Over the course of several days, it starts in the legs and progresses to the arms, face, and eyes. Reflexes may be missing, bifacial weakness may be present, severe cases result in respiratory paralysis, and autonomic abnormalities may be rare. Patients with GBS exhibit anti-ganglioside antibodies that seem to react with antigens found in some previous infectious pathogens' lipopolysaccharides. These antibodies target gangliosides, like GM1, which are dispersed within the myelin of the peripheral nervous system. There are three phases: acute, plateau, and recovery. Only plasmapheresis and intravenous immunoglobulin have shown effective recovery. A 24-year-old male presented with weakness of the bilateral lower limb associated with fever and breathlessness. The range of motion of hip flexion was reduced to 45 degrees, and muscle power was also reduced. For hip flexors, it was 3/5; for knee flexors and extensors, it was 4/5; and for ankle plantar flexors and dorsiflexors, it was 2/5. Investigations like a complete blood count (CBC), cerebrospinal fluid (CSF) examination, and nerve conduction velocity (NCV) were done. Post-diagnosis, the patient received an intravenous immunoglobulin (IVIG) dose; the same was managed by neurophysiotherapy, and after treatment, the patient was functionally independent. According to the findings of our study, neurorehabilitation resulted in favorable outcomes, shortened the length of the hospital stay, and enabled him to return to his desk job.


Molecular cloning of the human 2,3-bisphosphoglycerate mutase cDNA and revised amino acid sequence.
The human erythrocyte 2,3-bisphosphoglycerate mutase (BPGM) is a multifunctional enzyme which controls the metabolism of 2,3-diphosphoglycerate (DPG), the main allosteric effector of haemoglobin. Several cDNA banks were constructed from reticulocyte mRNA either by conventional cloning methods in plasmid pBR322 and screening with specific mixed oligonucleotide probes, or in the expression vector lambda gt 11. The largest cDNA isolated was 1673 bases, and encodes for a protein of 258 amino acids; it contains a large 3' untranslated region (785 bases). It is slightly smaller than the size of the intact mRNA estimated by Northern blot (1800 bases). Our sequence data indicate differences with the previously published amino acid sequence involving 21% of the residues. They were entirely confirmed by the amino acid composition of the tryptic peptides derived from purified BPGM. The revised amino acid sequence of the human BPGM is presented.


Design, synthesis, and in vitro evaluation of novel antifungal triazoles containing substituted 1,2,3-triazole-methoxyl side chains.
In order to develop new triazole derivatives, we optimized the lead compound a6 by structural modifications to obtain a series of (2R,3R)-3-((1-substituted-1H-1,2,3-triazol-4-yl) methoxy)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol, compounds 5-36. Most of the target compounds exhibited excellent in vitro antifungal activity against Candida albicans 10231 and Candida glabrata 537 with MIC ≤ 0.125 µg/mL. Of particular note, compounds 6, 22, 28, 30 and 36 were highly active against Candida neoformans 32609 with MIC ≤ 0.125 µg/mL and showed broad-spectrum antifungal activity including against fluconazole-resistant Candida auris 891. In addition, compounds 6 and 22 demonstrated inhibitory effects on filamentation in the azole-resistant C. albicans isolate. Moreover, compounds 6 and 22 were minimally toxic to HUVECs and possessed weak inhibitory effects on the human CYP3A4 and CYP2D6. SARs and docking study further indicated that ortho-substituted groups in the terminal phenyl ring can promote the compounds to improve their antifungal activity.


[Caregiver burden in caring for elders before and after long-term care service in Korea].
Purposes of this study were: evaluation of family burden of caring for elders who receive long term care services, and examination of differences in burden before and after the introduction of long term care service in Korea. Data were collected by questionnaires from 416 caregivers of elders who were registered with the Long Term Care Insurance Corporation in six cities. Data were collected in September, 2010 and analyzed using descriptive statistics, paired t-test, and ANOVA with the Scheffe test, and stepwise multiple regression. Family burden decreased significantly after long-term care service was initiated. Subjective burden decreased from 2.93 to 2.69 (t=11.78, p<.001), and objective burden, from 3.40 to 3.10 (t=12.73, p<.001). Stepwise multiple regression analysis revealed that factors affecting subjective burden were family relations (F=13.60, p=.003), age (F=5.47, p=.019), job (F=6.98, p=.008), and education (F=4.59, p=.032), and that factors affecting objective burden were living together (F=17.66, p<.001), job (F=13.34, p=.003), monthly income (F=6.61, p=.010), and type of service (F=6.62, p=.010). The results of this first study to investigate caregiver burden after the Korean Long-term Care Insurance System was begun provide positive information for the development of strategies to decrease family burden in long term care.


[Preoperative chemoradiotherapy as neoadjuvant therapy for 35 patients with locally advanced lower rectal carcinoma].
To explore the effect of combined preoperative chemotherapy with radiotherapy on locally advanced lower rectal carcinoma. Thirty- five patients with locally advanced lower rectal carcinoma were received a new regimen of combined preoperative chemotherapy with radiotherapy. Routine fr action of radiation was given with total dose of 46 Gy,2 Gy per fraction,five ti mes a week. Patients received oxaliplatin 130 mg/m(2) (infusion) on day 1, plus leu novorin 200 mg/m(2) and 5- FU 500 mg/m(2)(intravenous bolus) from day 1 to day 3 eve ry 3 weeks for total two cycles before irradiation. Operation was performed 4 to 6 weeks later after neoadjuvant therapy. After neoadjuvant therapy,all patients underwent surgical resection with complete pathologic response in 7 patients,average tumor size decrease of in 34.4%, tumor stage decrease in 65.7% o f patients and nodal- negative change rate of 55.6%. Radical resection was per formed in 34 patients,in whom 18 patients received abdominoperineal resection(AP R) and 16 patients received sphincter- preserving surgery with 45.7% of anal preservation rate. One patient received palliative resection. No local recurrence occurred in all patients who received radical resection,but two cases had liver metastasis. Combined preoperative chemotherapy with radiotherapy is a better neoadjuvant therapy for lower advanced rectal cancer,which can decrease tumor stage,improve resectability and anal sphincter preservation rate,therefore ,this new neoadjuvant therapy with tolerable toxicity will has a promising application in the clinical setting.


Behavioral responses in people affected by alcohol use disorder and psychiatric comorbidity: correlations with addiction severity.
In this study, we investigated in people suffering from alcohol use disorder (AUD) with or without dual diagnosis (concomitant psychiatric disability) how they feel their dependence condition. We predicted that AUD people with a dual diagnosis could feel potentiated their addiction. Alcohol habits and psychiatric conditions of 183 AUD men and 62 AUD women were measured by using the DSM-5, the severity of alcohol dependence questionnaire (SADQ), the alcohol anamnesis and psychiatric examination by the symptom check list 90-R (SCL-90-R). We have shown that alcohol drinking does not correlate with both psychiatric examination and self-reported psychopathology. SADQ shows that severe alcohol dependence correlates with highest psychiatric symptoms and with the levels of alcohol consumption. This finding suggests that high SADQ scores may represent a tool to early disclose only patients with dual diagnosis. SADQ may provide information to address pharmacological interventions because revealing aspects of the dark side of addiction potentiated by AUD associated psychopathology.


Supercritical fluid extraction and high-performance liquid chromatographic determination of phloroglucinols in St. John's Wort (Hypericum perforatum L.).
A small-scale supercritical fluid extraction (SFE) method was developed for the selective extraction of phloroglucinols from St. John's wort (SJW) leaf/flower mixtures using supercritical carbon dioxide (CO(2)). The extraction efficiency was investigated as influenced by pressure, temperature, time, and modifier. The optimized condition of SFE was carried out at 3.80 x 10(4) kpa (5500 psi) and 50 degrees C. Samples were held in static extraction for 10 min, followed by a dynamic extraction for 90 min at the flow rate of 1 mL/min. A simple and sensitive HPLC method was developed for the analysis of hyperforin and adhyperforin, the major phloroglucinols, in the SFE extract of SJW.


Role of exercise and metabolism in heart failure with normal ejection fraction.
Left ventricular dysfunction associated with metabolic disorders has a number of features that might shed light on the integrity of heart failure with normal ejection fraction. First, although these patients may be dyspneic and have a normal ejection fraction, their diastolic dysfunction is not isolated. Both experimental models and sensitive new parameters in humans have shown abnormal systolic function, even though the less sensitive parameters (such as ejection fraction) become abnormal only with stress. Moreover, the mechanistic contributors to myocardial dysfunction, including structural changes and metabolic influences on the cardiac myocyte, interstitial fibrosis, vascular disease, and altered loading, are likely to influence systolic as much as diastolic function. The responses of systolic and diastolic heart failure to exercise training show analogies, particularly with respect to the importance of peripheral adaptation, as well as a similar training response. Together, these features are more supportive of a continuum of pathophysiology between systolic and diastolic heart failure, rather than the 2 representing discreet phenomena.


Differential expression of interleukin-1 beta and interleukin-6 in human fetal serum and meconium-stained amniotic fluid.
The study was designed to investigate the expression of the inflammatory cytokines interleukin-1 beta and interleukin-6 in meconium-stained amniotic fluid and in fetal cord serum. Amniotic fluid and fetal cord serum specimens were collected from 10 and 9 women with meconium-stained and clear amniotic fluid, respectively, during Caesarean operation at labor The mean concentrations of interleukin-1 beta found in clear and meconium-stained amniotic fluid were 10.0 and 54.5 pg/ml, respectively, and the difference was not statistically significant. On the other hand, the concentrations of interleukin-6 in meconium-stained amniotic fluid (774 pg/ml) was significantly higher than that found in clear amniotic fluid (149 pg/ml) (P = 0.0036). The differences of levels of both interleukin-1 beta and interleukin-6 in fetal cord serum specimens were not significant between neonates born to mothers with either clear or meconium-stained amniotic fluid (P = 0.8702 and 0.2987, respectively). The results of this study suggest that the production of at least one of the inflammatory cytokines, interleukin-6, is associated with the meconium found in amniotic fluid.


Exploring the factors influencing consumer behaviours and practices towards sustainable WEEE management in Putrajaya, Malaysia.
The disposal practises and preferences of household waste from electrical and electronic equipment disposal (WEEE) are essential components in material flow analysis (MFA). Nevertheless, the synergistic of consumers' behaviours and preferences with the disposal of different WEEE has yet to be investigated in depth. This study examined several consumer features of WEEE management using a quantitative questionnaire survey, including consumers' disposal behaviours and preferences. As a Malaysian federal government administrative centre, and model of a contemporary and sustainable Malaysian city, Putrajaya was chosen as the study area. Using stratified random sampling, the questionnaire was distributed through face-to-face and online surveys among households across 20 precincts within Putrajaya. From June 2021 to January 2022, 500 surveys were distributed over seven months, and IBM SPSS Statistic version 26 was used to analyse the data. The result shows that 80% of respondents have a good knowledge of WEEE management and are fully aware of the dangerous materials they have in their WEEE. 75% said they would recycle their WEEE, but only 44% said they would separate it from other household wastes. It was also shown that 88% of the household were willing to pay a collection fee of at least RM 10 for each collection. This analysis found that Extended Producer Responsibility (EPR) mechanisms can assist in overcoming weaknesses in WEEE management by including beneficial schemes to incentivise consumers to improve current waste policies. In the meantime, governments, media, and local non-governmental organisations may help by increasing awareness of effective and sustainable WEEE management.


Neuroimaging of opioid exposure: a review of preclinical animal models to inform addiction research.
Opioid use results in thousands of overdose deaths each year. To address this crisis, we need a better understanding of the neurobiological mechanisms that drive opioid abuse. The noninvasive imaging tools positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and manganese-enhanced magnetic resonance imaging (MEMRI) can be used to identify how brain activity responds to acute opioid exposure and adapts to chronic drug treatment. These techniques can be performed in humans and animal models, and brain networks identified in animals closely map to the human brain. Animal models have the advantage of being able to systematically examine the independent effects of opioid exposure in a controlled environment accounting for the complex factors that drive opioid misuse in humans. This review synthesizes literature that utilized noninvasive neuroimaging tools (PET, fMRI, and MEMRI) measuring brain activity correlates in animals to understand the neurobiological consequences of exposure to abused opioids. A PubMed search in September 2023 identified 25 publications. These manuscripts were divided into 4 categories based on the route and duration of drug exposure (acute/chronic, active/passive administration). Within each category, the results were generally consistent across drug and imaging protocols. These papers cover a 20-year range and highlight the advancements in neuroimaging methodology during that time. These advances have enabled researchers to achieve greater resolution of brain regions altered by opioid exposure and to identify patterns of brain activation across regions (i.e., functional connectivity) and within subregions of structures. After describing the existing literature, we suggest areas where additional research is needed.


Monitoring and evaluation of removal of pathogens at municipal wastewater treatment plants.
The concentrations and removal of Cryptosporidium, Giardia, and microbial indicators, including somatic coliphages and fecal coliforms were investigated through the wastewater treatment processes at three municipal wastewater treatment plants in Beijing, China. The experimental results showed that the concentrations of Cryptosporidium in untreated wastewater, primary treatment effluent, secondary treatment effluent, tertiary treatment effluent were 33-600, 67-333, 0-9 and 0-0.4 oocysts L(-1), and that of Giardia were 130-3,600, 533-2,033, 0-32 and 0-2.1 cysts L(-1), respectively. The reduction ratios of Cryptosporidium and Giardia by the primary treatment process were 0.12 log and 0.18 log, respectively. Oxidation ditch process had higher reduction efficiency to Cryptosporidium and Giardia than anaerobic-anoxic-oxic process and conventional activated sludge process, probably because of longer retention time and higher sludge concentration. Membrane ultrafiltration had a notably better efficiency to reduce microorganisms, especially Cryptosporidium and Giardia, than conventional flocculation sedimentation and sand filtration process, as the tertiary treatment. Comparing with total coliforms, fecal coliforms and heterotrophic bacteria, concentration of somatic coliphages was correlated better with that of Cryptosporidium and Giardia in untreated wastewater and secondary treatment effluent.


[Establishment of animal models of endometriosis in rhesus monkeys].
To establish animal models of endometriosis in rhesus monkeys and study the invasion mechanism of endometriosis. Five female healthy rhesus monkeys with regular menstrual cycles were selected, of whom 4 were used for endometriosis model establishment and 1 for control. During the period of days 8-15 of menstruation, or 3-5 days after the midcycle estrogen peak, the endometrium was implanted into the pelvic cavity other than the uterus in the experimental group, and in the control group, the greater omentum was implanted instead. Exploratory laparotomy or laparoscopy was performed during the period between days 8 and 15 of menstruation in the second and the fourth month respectively after the implantation for observing the occurrence of endometriosis. In the experimental group, the implanted endometrium survived in the receptor site in 3 monkeys, 2 of whom were found to have chocolate cyst after the operation. Laparoscopy was again performed in the 2 monkeys with endometriosis 4 months after the operation, showing pelvic adhesion and growth of ectopic endometrium similar to the changes as observed two months after the operation. In comparison with the control, deteriorated mental states and dietary changes, along with body weight losses, occurred in the 3 models of endometriosis, and 2 of them later died of intussusception. Animal models of endometriosis can be established successfully in rhesus monkeys on the basis of the implantation theory, which, however, is influenced by individual differences between the animals. Heredity is an important factor in pathogenesis of endometriosis, and ectopic growth of the endometrium may severely impact the body function.


The LHRH neuronal system in female rats: relation to the medial preoptic nucleus.
Previously we have found that small lesions confined to the medial preoptic nucleus (MPN) or the suprachiasmatic nucleus (SCN) blocked the cyclic release of gonadotropins in the female rat, inducing a persistent estrous state. Since the MPN is located just caudal to the organum vasculosum of the lamina terminalis (OVLT) where LHRH cell bodies are most concentrated, we applied an immunocytochemical technique to examine the possibility that the lesions had simply disrupted LHRH neurons or fibers. Using a new anti-LHRH provided by Dr. V. D. Ramirez, we found that the distribution pattern of immunoreactive LHRH cell bodies and fibers was similar to that previously reported, although the staining was more intense and extensive with low background. There was no concentration of LHRH cell bodies and fibers in the MPN or SCN and, in fact, these nuclei generally showed a lower density of stained elements than did surrounding tissue. In persistent estrous animals with lesions confined to the MPN there was no detectable reduction of stained fibers in the median eminence. These results, along with the results of other workers, suggest that persistent estrus following lesions of the MPN or SCN is not due to reduction of LHRH neurons or fibers. Rather, they support the hypothesis that these nuclei are critical for triggering the ovulatory release of LHRH.


The promises and perils of pragmatism: commentary on Fins, Bacchetta, and Miller.
Fins, Bacchetta, and Miller's clinical pragmatism has several appealing features: an emphasis on dialogue, a commitment to consensus, a focus on particular individuals rather than persons in general, and a strong interest in the process as well as the product of moral decision making. Nevertheless, for all its protests to the contrary, clinical pragmatism has a tendency to privilege medical facts over nonmedical values, to conflate appropriate medical decisions with right moral decisions, and to conceive problems at the bedside in terms of "getting" patients and families to "go along" with the treatment plans of clinicians. In sum, there is within clinical pragmatism the potential for physicians to take back some of the power they ceded to patients during the height of the patients' rights and autonomy movement. Provided that clinicians guard against the temptation to use clinical pragmatism manipulatively, however, the method promises, more than most other methods of moral problem solving, to help increasingly diverse individuals make good moral decisions about patients' care under conditions of enormous uncertainty.


Alopecia in a black Labrador retriever associated with focal sub-follicular panniculitis and sebaceous adenitis.
A 6-year-old entire male black Labrador retriever was presented with nonpruritic multicentric, well-demarcated alopecia of 12-weeks duration. Skin biopsies from the margins of alopecic regions showed sebaceous adenitis and sub-follicular panniculitis. Biopsies from alopecic areas showed severe follicular atrophy with residual fibrous tracts, loss of sebaceous glands and lymphohistiocytic panniculitis beneath individual atrophic hair follicle groups. These features differed from previous reports of pilosebaceous diseases of dogs and appeared to extend the spectrum of inflammatory patterns in presumed immune-mediated adnexal diseases of this species. During the 12-month follow-up, there was partial hair regrowth without treatment but alopecia was permanent in the centre of larger lesions.


[The implementation and management of disease risk reduction claims in the European Union and the United States].
The improvement of food labeling can improve consumers' health awareness, reduce the burden of chronic diseases on the health and economy, and promote the development of the healthy food industry. Disease Risk Reduction Claim has been developed in European Union and the U.S. for over 20 years, with mature management methods and experience, but it is still lacking in China. Learning and drawing on the international management experience of food disease risk reduction claims can assist China to establish food disease risk reduction claims and improve the food health claims and labeling system.


Pure Testicular Seminoma Relapsing Late with Somatic Type Malignancy.
Background. Somatic type malignancy (STM) occurs in 2% of all germ cell tumours (GCTs). The prognosis is unfavourable and the origin is poorly understood. Pathogenetic hypotheses involve direct transformation of teratoma, origin from totipotent cancer cells, or derivation from yolk sac tumour elements. Case Presentation. A 31-year-old patient was cured from testicular seminoma clinical stage IIc by orchiectomy and cisplatin-based chemotherapy. Nine years later, he experienced a late relapse with a mass sized 5 × 6 cm located at the former metastatic site. As no remission occurred after chemotherapy with three cycles of cisplatin, ifosfamide and etoposide, the mass was surgically resected. Histologically, the specimen consisted of neurofibroma with areas of malignant peripheral nerve sheath tumour and spots with mature bone formation. FISH analysis disclosed isochromosome 12p in the majority of evaluated cells suggesting somatic type malignancy (STM) of GCT. The patient is well 1 year after surgery. Conclusion. The pathogenesis of this STM remains enigmatic. The origin from GCT was evidenced by documentation of isochromosome 12p. Unrecognized teratomatous elements in the primary and totipotent cancer cells surviving the first chemotherapy could be hypothesized to represent the origin. STM developing from seminoma cells would be another novel hypothesis.


Recent trends in ILO conventions related to occupational safety and health.
The present study was conducted to analyze the ratification status of International Labour Organization (ILO) conventions related to occupational safety and health (OSH) by ILO member states in terms of national indicators (length of ILO membership and national income status) and regional affiliation. 17 conventions designated as OSH-related by the 2003 International Labour Conference were examined. In general, countries with longer ILO membership ratified higher numbers of conventions related to OSH. With some variation, long-membership countries had the largest number of ratifications, followed by middle- and short-membership countries in all regions. There were also incremental increases in the number of ratifications for OSH-related conventions according to the national income status. Common regional characteristics that could not be explained by the factors studied also existed. Future efforts to increase ratification at an international level will need to consider the factors influencing ratification practice among the member states.


Children and adolescents with low back pain: a descriptive study of physical examination and outcome measurement.
A retrospective, cohort study of children and adolescents with low back pain (LBP) referred to physical therapy. To describe the clinical presentation, examination findings, and classification of children and adolescent patients with LBP, and to explore the concurrent validity of the Oswestry questionnaire as a disability measure in this group. Little information is available regarding the clinical presentation, physical examination findings, and outcome assessment in children and adolescents with LOP. Charts were reviewed for historical, diagnostic, physical examination,and outcome information. Diagnoses given by the referring physicians were recorded. A treatment-based classification was made for each subject. Descriptive statistics were calculated for all variables. The validity of the Oswestry questionnaire was examined. The children and adolescents included in this study represented 5% (n = 25) of all cases of LOP referred to physical therapy. A greater percentage of patients had difficulty with extension than with flexion range of motion (ROM). Initial pain scores were lower if a specific pathology was present (P = .001). Initial pain and Oswestry scores were poorly correlated (r = 0.16). Forty-four percent (n = 11) of patients scored under the floor value of 12% on the Oswestry. The referral rate of children and adolescents with LBP seems to be low. Compared to adults, children and adolescents appear more likely to have a specific diagnosis given to them by their physician. The physical examination findings appear to indicate that spinal stabilization approaches may be beneficial for many patients. The Oswestry questionnaire may not be a valid tool for documenting changes in disability in these patients. Further research is needed on the conservative management of children and adolescents with LBP.


Dual inhibition of BTLA and PD-1 can enhance therapeutic efficacy of paclitaxel on intraperitoneally disseminated tumors.
Expression of immune checkpoints in the tumor microenvironment is one mechanism underlying paclitaxel (PTX) chemoresistance. This study aimed to investigate whether the addition of checkpoint blockade to PTX can improve the therapeutic efficacy against apparently disseminated intraperitoneal tumors. We analyzed the in vivo expression of various immune checkpoints in CD3+CD8+ cytotoxic T cells from tumor-bearing mice treated with or without PTX and validated the tumor-killing activities of selected checkpoint-expressing T-cell subpopulations ex vivo. The regulation of selected checkpoints was investigated in vitro. The therapeutic effects of inhibition of a targeted checkpoint pathway with antibodies added to PTX therapy were examined. CD3+CD8+ T cells expressed with herpes virus entry mediator (HVEM), programmed cell death 1 (PD-1), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in tumor-bearing hosts treated with PTX had effective tumoricidal activities. In addition to PTX and cytokines, B and T lymphocyte attenuator (BTLA) or homologous to lymphotoxin, exhibits inducible expression and competes with herpes simplex virus (HSV) glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT) interacting with HVEM can regulate the expression of PD-1 on CD3+CD8+ T cells. Interleukin (IL)-15 increased the percentage of HVEMhighgranzyme B (GZMB)+ cells among CD3+CD8+ T cells, which was suppressed by the BTLA/HVEM signal. LIGHT induced the percentage of HVEM+GZMB+ cells but not HVEMhighGZMB+ cells among CD3+CD8+ T cells. Expression of IL-15, BTLA, or LIGHT was detected in CD19+ B cells and regulated by damage-associated molecular patterns/Toll-like receptor interactions. In the tumor-bearing hosts treated with PTX, certain proportions of BTLA+ B or PD-1+ T lymphocytes were still noted. When dual inhibition of BTLA and PD-1 was added to PTX, the antitumor effects on intraperitoneally disseminated tumors can be significantly improved. Dual blockade of BTLA on B cells and PD-1 on cytotoxic T cells may have clinical potential for enhancing the efficacy of PTX in the treatment of tumors with intraperitoneal spread, including epithelial ovarian carcinomas.


THE EFFECT OF INTRA(CEREBRO)VENTRICULAR RESERPINE ON THE ACETYLCHOLINE CONTENT OF THE HEART, ILEUM AND HYPOTHALAMUS OF THE DOG.
The effect of injection of reserpine into the cerebral ventricles on the acetylcholine contents of the sino-atrial node, ileum and hypothalamus of the dog was studied in ten dogs. Another group of five dogs served as a control. The effect of intravenous administration of reserpine, in the same dose as given intracerebroventricularly, was also studied on the acetylcholine content of these tissues in five dogs. General sedation, bradycardia, miosis, salivation, emesis and purgation were looked for. Tissues were removed 1 hr after administration of reserpine for estimation of acetylcholine content, which was increased in all the tissues studied. The increase in the peripheral tissues was greater than in the hypothalamus. The increase in the acetylcholine content was not quantitatively related to the other effects of reserpine. The increase in the acetylcholine content of the sino-atrial node and the ileum and also the peripheral effects observed on intracerebroventricular administration of reserpine can be attributed to its central action. With the same dose of reserpine given intravenously the acetylcholine content of the sino-atrial node was significantly increased, while that of the hypothalamus and ileum was not.


PGP9.5 methylation as a marker for metastatic colorectal cancer.
Recently, it has been proven that protein gene product 9.5 (PGP9.5) hypomethylation might play an important role in re-expression of the PGP9.5 gene in gallbladder cancer. We previously examined the expression of PGP9.5 in primary colorectal cancer using immunohistochemistry and found that PGP9.5 expression is related to tumor progression and may be useful as a marker for invasive colorectal cancer. These results prompted us to examine the methylation status of the PGP9.5 gene in colorectal cancer. The methylation status of the PGP9.5 gene in primary tumors derived from 49 patients with colorectal cancer using a quantitative methylation-specific polymerase chain reaction (qMSP) and the association between the methylation status and the clinicopathological findings was evaluated. An aberrant methylation of the PGP9.5 gene was detected in 36 out of 49 (73%) primary colon cancer samples. Subsequently, clinicopathological data were tested for their association with the methylation results. Lymph node metastasis was significantly associated with a lower frequency of methylation (p=0.029). These findings indicated that PGP9.5 was less frequently methylated in metastatic colorectal cancer, suggesting that PGP9.5 hypomethylation might play an important role in re-expression of the PGP9.5 gene in colorectal cancer.


A bifunctional thymidylate synthetase-dihydrofolate reductase in protozoa.
Thymidylate synthetase and dihydrofolate reductase exist as a bifunctional protein in a number of species of protozoa which span diverse groups of the subkingdom. The enzymes copurify upon gel filtration and on affinity chromatography columns specific for dihydrofolate reductase. The bifunctional protein has been found in species of Crithidia, Leishmania, Trypanosoma, Plasmodium, Eimeria, Tetrahymena and Euglena. For reasons unknown, neither enzyme could be detected in Entamoeba histolytica or E. invadens. Since neither enzyme has yet been found as a separate protein in protozoa, it is likely that the bifunctional protein is widespread among these primitive eukaryotes. In most cases, the apparent size of the native protein is approximately twice that of the subunit possessing thymidylate synthetase. Further, with one exception, the subunit sizes are close to the sum of the subunit sizes of the separate enzymes found in other sources.


Phonon interference effects in molecular junctions.
We study coherent phonon transport through organic, π-conjugated molecules. Using first principles calculations and Green's function methods, we find that the phonon transmission function in cross-conjugated molecules, like meta-connected benzene, exhibits destructive quantum interference features very analogous to those observed theoretically and experimentally for electron transport in similar molecules. The destructive interference features observed in four different cross-conjugated molecules significantly reduce the thermal conductance with respect to linear conjugated analogues. Such control of the thermal conductance by chemical modifications could be important for thermoelectric applications of molecular junctions.


Postnatal development of renal tubular amino acid reabsorption in canine pups.
The renal clearance of amino acids in canine pups 5 days and 3, 8, and 12 weeks of age was studied. The 5-day-old pups had incomplete reabsorption of most amino acids. At 3 weeks, fractional reabsorption of 16 of 21 amino acids was complete; between 3 and 8 weeks, an adult pattern of reabsorption was present. Seemingly, a rapid development of amino acid transport precedes anatomic development or functional maturation of other transport systems.


Reduction in clinically important deterioration in chronic obstructive pulmonary disease with aclidinium/formoterol.
'Clinically important deterioration' (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations. ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg. This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD. A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV1; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George's Respiratory Questionnaire (SGRQ) total score (≥4 units). A 'sustained' CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time. CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18. AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05). Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01). AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05). AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies. Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011. Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.


Chronic pain: a review.
Chronic pain has been increasing in prevalence. It is considered the most underestimated health care problem impacting quality of life. A number of epidemiological studies conducted in different parts of the world, reported prevalence rates of chronic pain ranging from 12-80%. Chronic pain has detrimental effects on physical and mental health, daily activities, family relationships, employment, and economic well-being of the sufferers and family caregivers. Since the epidemiological studies about chronic pain in Lebanon are limited, the aim of this article is to help understand the magnitude of the problem and to depict strategies for the prevention and management of chronic pain. The article provides a review of the literature on the prevalence of chronic pain and the factors associated with it in adults.


Bioinformatics-driven, rational engineering of protein thermostability.
A longstanding goal in protein engineering is to identify specific sequence changes that endow proteins with desired functional properties. As opposed to traditional rational and random protein engineering techniques, we have employed a bioinformatic approach to identify specific sequence changes that influence key functional properties of a protein within a defined superfamily. Specifically, we have used the Bayesian sequence-based algorithms PROBE and Classifier to identify a strand-turn-strand motif that contributes to thermophilicity among members of the serine protease subtilase superfamily. By replacing a 16 amino acid sequence in the mesophilic subtilisin E (from Bacillus subtilis) with a bioinformatics-generated thermophilic model sequence, the melting temperature of subtilisin E was increased by 13 degrees C. While wild-type subtilisin E was inactive at 90 degrees C, the mutant retained a substantial fraction of its function, with ca. one-third of the activity that it has at 45 degrees C.


Individual CD34+CD38lowCD19-CD10- progenitor cells from human cord blood generate B lymphocytes and granulocytes.
Identification of human hematopoietic stem cells and analysis of molecular mechanisms regulating their function require biological assays that permit differentiation in all hematopoietic lineages simultaneously. In this study, we established conditions that permit the joint expression of the B-lymphoid and myeloid potential from cord blood-derived CD34+CD38lowCD19-/CD10- primitive progenitors that lack B-specific markers and transcripts. When cocultured during 6 weeks with the murine stromal cells MS-5 in the absence of exogenous human cytokines, CD34+CD38low-CD19-CD10- cells generated a high number of CD19+ B cells. Virtually all of these cells expressed a CD34-CD10+- CD19+cIgM- phenotype of late pro-B cells and transcripts of Pax-5, lambda-like, and mu chain were detected. We further show that 7% of CD34+CD38lowCD19- cells from cord blood, when grown individually with MS-5 cells, generated both CD19+ and CD11b+ cells after 6 weeks. Efficient B-cell differentiation was also observed in vivo after transplantation of human cord blood-derived unfractionated mononuclear cells or CD34+CD19+CD10- cells into immune-deficient mice. In contrast to the in vitro situation, all stages of B-cell differentiation were observed in vivo, including pro-B, pre-B, and sIgM+ B cells. Interestingly, human progenitors with the ability to differentiate along both B-lymphoid and granulocytic pathways were also detected among human CD34+CD38low cells in the marrow of chimeric mice 6 to 7 weeks after transplantation. Both in vitro and in vivo systems will offer an invaluable tool to further identify the lymphoid and myeloid potentialities of primitive progenitor cells isolated from fetal as well as adult human hematopoietic tissues and characterize stromal-derived signals that regulate their function.


Type 1 regulatory T cells and regulatory B cells induced by tolerogenic dendritic cells.
Dendritic cells (DC) are professional antigen-presenting cells that are capable of both activating immune responses and inducing tolerance. Several studies have revealed efficiency of therapeutic vaccination with tolerogenic DC (tolDC) in inhibition of experimental autoimmunity. The purpose of this study was to compare four different protocols for generation of tolDC - the antidiabetic drug troglitazone (TGZ DC), NF-κB inhibitor BAY 11-7082 (BAY DC), prostaglandin D2 metabolite 15d-PGJ2 (PGJ DC) and a combination of dexamethasone and 1α,25-dihydroxyvitamin D3 (DexVD3 DC) regarding phenotype, cytokine production and T cell stimulatory capacity. TGZ DC and BAY DC had a phenotype comparable to immature DC, while DexVD3 DC were more macrophage like. Analysis of cytokine production using cell culture supernatants from all DC populations revealed that DexVD3 DC were efficient producers of IL-10 and produced less pro-inflammatory cytokines. T cells primed with DexVD3 DC showed reduced proliferation, and further analyses of these T cells revealed that functionally effective type 1 regulatory T cells (Tr1) but not FoxP3(+) Treg were induced. Furthermore, DexVD3 DC promoted the induction of regulatory B cells (Breg). Together, these results indicate that DexVD3 DC have the best potential to be used in a tolerogenic antigen-presenting cell-based immunotherapy setting.


[An acute recurrence of focal-segmental glomerulosclerosis in a kidney transplanted from mother to son with a rapid decline in kidney function].
A case is presented of a 19-year-old man suffering from focal-segmental glomerulosclerosis with terminal chronic renal failure to whom a kidney taken from his mother was transplanted. There was high blood-group and tissue compatibility between mother and son. The initial result was good, the transplanted kidney functioned well-diuresis of 3300 ml with high proteinuria. Gradually the diuresis fell to 100-200 ml. From the 29th day following the transplantation pulse urbason therapy was applied for 3 days but without effect. This led to the resumption of hemodialysis and removal of the transplanted kidney. The microscopic examination of the kidney revealed massive focal-segmental glomerulosclerosis which had led to terminal chronic renal failure. The rapid severe relapse of the disease in the transplanted kidney is explained with the malignancy of the disease and the very high compatibility between donor and recipient. It is recommended that renal transplantation in patients with focal-segmental glomerulosclerosis should not be performed with a kidney taken from a parent.


Deep sequence modelling for predicting COVID-19 mRNA vaccine degradation.
The worldwide coronavirus (COVID-19) pandemic made dramatic and rapid progress in the year 2020 and requires urgent global effort to accelerate the development of a vaccine to stop the daily infections and deaths. Several types of vaccine have been designed to teach the immune system how to fight off certain kinds of pathogens. mRNA vaccines are the most important candidate vaccines because of their capacity for rapid development, high potency, safe administration and potential for low-cost manufacture. mRNA vaccine acts by training the body to recognize and response to the proteins produced by disease-causing organisms such as viruses or bacteria. This type of vaccine is the fastest candidate to treat COVID-19 but it currently facing several limitations. In particular, it is a challenge to design stable mRNA molecules because of the inefficient in vivo delivery of mRNA, its tendency for spontaneous degradation and low protein expression levels. This work designed and implemented a sequence deep model based on bidirectional GRU and LSTM models applied on the Stanford COVID-19 mRNA vaccine dataset to predict the mRNA sequences responsible for degradation by predicting five reactivity values for every position in the sequence. Four of these values determine the likelihood of degradation with/without magnesium at high pH (pH 10) and high temperature (50 degrees Celsius) and the fifth reactivity value is used to determine the likely secondary structure of the RNA sample. The model relies on two types of features, namely numerical and categorical features, where the categorical features are extracted from the mRNA sequences, structure and predicted loop. These features are represented and encoded by numbers, and then, the features are extracted using embedding layer learning. There are five numerical features depending on the likelihood for each pair of nucleotides in the RNA. The model gives promising results because it predicts the five reactivity values with a validation mean columnwise root mean square error (MCRMSE) of 0.125 using LSTM model with augmentation and the codon encoding method. Codon encoding outperforms Base encoding in MCRMSE validation error using the LSTM model meanwhile Base encoding outperforms codon encoding due to less over-fitting and the difference between the training and validation loss error is 0.008.


Ultrasonographic features of splenic lymphosarcoma in dogs: 12 cases (1980-1986).
The ultrasonographic appearance of the spleen and adjacent organs in 12 dogs with splenic lymphosarcoma was reviewed. Poorly marginated hypoechoic to anechoic nodules (4 mm to 3 cm in diameter) were found in all dogs. The anechoic nodules did not result in reflective shadowing or acoustic enhancement of the underlying tissues. The remainder of the splenic parenchyma appeared relatively hypoechoic when compared with the liver or renal cortices in 9 dogs. Recognition of this ultrasonographic pattern appears to be a useful diagnostic tool. Needle aspiration guided ultrasonographically will then enable histologic confirmation of lymphosarcoma.


Corrosion behavior of Au and Ag modified Cu-Ni-Mn alloys.
The linear electrochemical polarization method was used to provide quantitative in vitro measurements of corrosion rates as a function of exposure time for Cu-Ni-Mn, Cu-Ni-Mn-Au, Cu-Ni-Mn-Ag, and Cu-Ni-Mn-Au-Ag alloys in artificial saliva. Both Au and Ag additives to dental-cast Cu-Ni-Mn alloys lowered the corrosion rate significantly.


Barriers and Strategies for Transition from Student to Successful Hospital Pharmacist.
Many health care professionals experience a process of transition when entering the workforce. Various barriers have been documented in the literature, including a lack of confidence, challenging interactions with patients and colleagues, workload, increased responsibility, and a fear of making mistakes. Strategies to overcome these barriers, such as orientation and support programs, have been proposed. However, evidence for the transition of students into successful hospital pharmacists is limited. To identify key barriers to the transition from student to successful hospital pharmacist and to outline strategies to overcome these barriers. An electronic survey was distributed to Lower Mainland Pharmacy Services (LMPS) pharmacists, and subsequent one-on-one interviews were completed with a subgroup of new pharmacists. A total of 137 LMPS pharmacists (about 32% of potential respondents) responded to the survey, and 3 of these also participated in an interview. A performance score (used to quantify the transition experience) was calculated for 113 respondents, and there was a correlation between performance score and role satisfaction (r = 0.550, p < 0.001). Performance score was also correlated with years spent working as a hospital pharmacist (r = 0.333, p < 0.001) and with highest level of pharmacy education (r = 0.210, p = 0.026). Work in a specialty area and presence of an orientation program were additional factors associated with higher average performance scores. The greatest need for transitional support was during the first year of work, with trainers and social supports being identified as the most helpful resources. Various perspectives were offered during the interviews, with multiple barriers and strategies proposed. Among respondents to this survey, the key barriers faced during the transition from student to successful hospital pharmacist were limited time working as a hospital pharmacist, lack of additional pharmacy education, lack of knowledge, rotation among multiple areas, uncertainty about role identity, and limited university preparation. Given that successful transition is associated with subsequent job satisfaction, workplace strategies such as limiting the number of practice areas, developing an orientation program, and providing continued support during the first year of work should be encouraged.


The incorporation of acetate-1-C14 into cholesterol and fatty acids by surviving tissues of normal and scorbutic guinea pigs.
The synthesis of cholesterol and fatty acids from acetate-l-C(14) by the isolated liver, adrenal, and aorta of scorbutic and pair-fed control guinea pigs has been studied. It was found that ascorbic acid deficiency does not affect the rate of incorporation of C(14)-acetate into cholesterol and fatty acids by the tissues investigated, under our experimental conditions. The relatively high metabolic activity of the artery with regard to cholesterogenesis and lipogenesis was noted. The elevation of serum cholesterol and hexosamine in scurvy has been confirmed.


The Effect of Lipopolysaccharide on Ischemic-Reperfusion Injury of Heart: A Double Hit Model of Myocardial Ischemia and Endotoxemia.
Myocardial ischemia may coincide and interact with sepsis and inflammation. Our objective was to examine the effects of bacterial endotoxin on myocardial functions and cell injury during acute ischemia. Rabbits were pretreated with incremental doses of E. Coli lipopolysaccharide (LPS) or normal saline. Myocardial ischemia was induced by 50-minute occlusion of left anterior descending artery. S-TNFaR was additionally used to block the effects LPS. Ventricular contractility as it was measured by dp/dt during systole decreased from 2445± 1298 to 1422 ± 944 mm Hg/s, P = .019. Isovolumetric relaxation time as an index of diastolic function was prolonged from 50±18 ms to 102± 64 ms following ischemia. Pretreatment with low concentrations of LPS (<1 μg) had no effect on dp/dt, while at higher concentrations it suppressed both contractility and prolonged IVRT. Cell injury as measured by cardiac troponin I level increased to 15.1± 3.2 ng/dL following ischemia and continued to rise with higher doses of LPS. While blocking TNFa did not improve the myocardial contractility after ischemia, it eliminated additional deleterious effects of LPS. Lower doses of LPS had no deleterious effect on myocardial function, whereas higher doses of this endotoxin cause cardiac dysfunction and increased extent of injury.


Lupus Podocytopathy: A Rare Cause of Nephrotic Syndrome in Patients with Systemic Lupus Erythematosus.
Lupus podocytopathy, a unique form of lupus nephritis, mimics minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) and represents approximately 1% of lupus nephritis biopsies. Lupus podocytopathy is characterized by diffuse epithelial cell foot process effacement without immune complex deposition or with only mesangial immune complex deposition. We present the case of a young woman with systemic lupus erythematosus (SLE) who presented with nephrotic syndrome and acute kidney injury (AKI) and was subsequently diagnosed with lupus podocytopathy.


RhizoTubes as a new tool for high throughput imaging of plant root development and architecture: test, comparison with pot grown plants and validation.
In order to maintain high yields while saving water and preserving non-renewable resources and thus limiting the use of chemical fertilizer, it is crucial to select plants with more efficient root systems. This could be achieved through an optimization of both root architecture and root uptake ability and/or through the improvement of positive plant interactions with microorganisms in the rhizosphere. The development of devices suitable for high-throughput phenotyping of root structures remains a major bottleneck. Rhizotrons suitable for plant growth in controlled conditions and non-invasive image acquisition of plant shoot and root systems (RhizoTubes) are described. These RhizoTubes allow growing one to six plants simultaneously, having a maximum height of 1.1 m, up to 8 weeks, depending on plant species. Both shoot and root compartment can be imaged automatically and non-destructively throughout the experiment thanks to an imaging cabin (RhizoCab). RhizoCab contains robots and imaging equipment for obtaining high-resolution pictures of plant roots. Using this versatile experimental setup, we illustrate how some morphometric root traits can be determined for various species including model (Medicago truncatula), crops (Pisum sativum, Brassica napus, Vitis vinifera, Triticum aestivum) and weed (Vulpia myuros) species grown under non-limiting conditions or submitted to various abiotic and biotic constraints. The measurement of the root phenotypic traits using this system was compared to that obtained using "classic" growth conditions in pots. This integrated system, to include 1200 Rhizotubes, will allow high-throughput phenotyping of plant shoots and roots under various abiotic and biotic environmental conditions. Our system allows an easy visualization or extraction of roots and measurement of root traits for high-throughput or kinetic analyses. The utility of this system for studying root system architecture will greatly facilitate the identification of genetic and environmental determinants of key root traits involved in crop responses to stresses, including interactions with soil microorganisms.


Computed tomographic features of central descending transtentorial herniation--case report.
Computed tomographic (CT) features of central descending transtentorial herniation (DTH) were identified in a patient who presented with subarachnoid hemorrhage. The main features were symmetrical deformity of the brainstem and downward displacement of the third ventricle. The authors believe these findings will contribute significantly to the establishment of CT diagnostic criteria for central DTH.


Rethinking an effective AV fistula-graft screening program. An "A B C".
The goal of a vascular access screening program is to detect and preemptively correct hemodynamically significant stenosis, however, a practice pattern allowing to implement such a program still remains to be defined. Achieving balance between the increase in access-related procedures by adopting an aggressive screening program, and the risks associated with the absence of any screening program, i.e., failure or abandonment of the arterio-venous access with need for central venous catheter placement, can be extremely challenging. All major guidelines agree about the role of arterio-venous access monitoring, but the way surveillance should be managed is still a controversial issue. Preserving long-term vascular access function should be a goal for all hemodialysis teams, yet it ideally requires a multidisciplinary effort with a monitoring program, calling for a great deal of involvement by hemodialysis health professionals. In this context, the engagement of skilled nurses and the role of patient empowerment with collaborative decision-making may be the key to a successful vascular access screening program. Screening programs should be personalized, shared with the patients, and tailored according to vascular access type and site. In the near future, new devices and the use of artificial intelligence may allow to support interpretation of complex data and lead to the development of prediction models for vascular access failure.


Correlation between MTP -493G>T polymorphism and non-alcoholic fatty liver disease risk: a meta-analysis.
Several studies have found that microsomal transfer protein (MTP) may be important in the development and progression of non-alcoholic fatty liver disease (NAFLD). In this meta-analysis, we evaluated the relationships between a common polymorphism (-493G>T, rs1800591 G>T) in the MTP gene and NAFLD risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Eleven case-control studies were included in this meta-analysis. A total of 636 NAFLD patients and 918 healthy control subjects were examined in this meta-analysis. Our results indicate that the MTP -493G/T polymorphism increases the risk of NAFLD (G allele vs T allele: OR = 1.39, 95%CI = 1.17-1.65, P < 0.001; GG + GT vs TT: OR = 1.46, 95%CI = 1.02-2.09, P = 0.038, respectively). Subgroup analyses indicated that the MTP -493G/T polymorphism was associated with an increased risk of NAFLD in population-based, hospital-based, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and large sample-size subgroups under the allele and dominant models (all P < 0.05). However, we found no association between non-PCR-RFLP polymorphism and small sample-size subgroups (all P > 0.05). Our findings indicate that the MTP -493G/ T polymorphism may contribute to the development of NAFLD. Thus, the MTP -493G/T polymorphism may be a biomarker for the early detection of NAFLD.