Neurohormonal activation late after cavopulmonary connection.
To determine whether patients with cavopulmonary connection have higher levels of vasoactive/water-salt regulating hormones and if so, whether hormone levels are related to postoperative haemodynamics and postoperative follow up. Cross sectional study. University hospital. 20 patients (New York Heart Association functional class I-II), mean age 11 years (range 4 to 22), were studied at a mean of 2 years (0.5 to 6) after a total cavopulmonary connection (TCPC, n = 12) or a bidirectional Glenn anastomosis (BDG, n = 8). Cardiac catheterisation was performed and blood samples were drawn. Control blood samples were drawn from 33 healthy children, mean age 12 years (6 to 16). Plasma levels of angiotensin II, renin, aldosterone, arginine, vasopressin, atrial natriuretic factor (ANF), brain natriuretic peptide (BNP). All neurohormones were significantly increased in both TCPC and BDG patients (p < 0. 05), with a fourfold increase in angiotensin II, renin, and aldosterone, and a twofold increase in vasopressin, ANF, and BNP (compared with healthy controls). There was no correlation between haemodynamic variables and hormone levels. Angiotensin II and renin were inversely correlated with time to follow up. All subjects over 15 years (n = 5) had normal neurohormonal levels. Neurohormones were raised for years after successful cavopulmonary operations but lower levels were observed with time on follow up. This supports the hypothesis that neurohormonal activation is primarily related to altered postoperative physiology and that adaptation takes place over time.


Selectivity of juxtaposition between cup-shaped lactotrophs and gonadotrophs from rat anterior pituitary in culture.
Semi-thin sections of three-dimensional reaggregates from adult female rat pituitary, cultured in serum-free defined medium, were stained for prolactin, gonadotropin, thyrotropin, growth hormone and S-100, using the double immunolabelling technique. The frequency of juxtaposition between lactotrophs and gonadotrophs was enumerated and compared with the expected frequency at random distribution of polygonal cell profiles in a hexagonal configuration. The proportions of lactotrophs and gonadotrophs in the aggregate sections were determined using stereometrical analysis. The observed frequency of juxtaposition did not differ significantly from the expected frequency. Hence, no reason was found to assume a selective adhesion between lactotrophs and gonadotrophs in adult female rat pituitary reaggregates. A constant proportion of lactotrophs was found to meet the criteria of a cup-shaped morphology, and 70% +/- 9% (mean +/- S.D.) of these so-called cup-shaped lactotrophs were found to be juxtaposed at their concave side to gonadotrophs. Administration of 0.01 nM 17 beta-oestradiol to the culture medium resulted in a significant reduction of the proportion of cup-shaped lactotrophs but did not affect the selectivity of juxtaposition to gonadotrophs. The selectivity of juxtaposition between cup-shaped lactotrophs and gonadotrophs may be the morphological correlate of the functional relationship between these cells, which are known to be involved in an intra-pituitary paracrine communication system.


The clinical nurse leader: prepared for an era of healthcare reform.
Passage of the 2010 Patient Protection and Affordable Care Act will require change in the healthcare systems. The clinical nurse leader must be prepared to lead and shape the changing environment to achieve maximum outcomes for patients and families. Movement toward integrated care delivery across the care continuum, the transition of the Centers for Medicare & Medicaid Services to a value-based funding model, and accountability for high-quality, cost-effective care are just some of the drivers of this new integrated healthcare system. Reimbursement models that reward those health systems that are able to meet benchmark performance standards will result in major shifts in how health systems operate. Expertise in care coordination across the healthcare continuum is essential for maximum reimbursement. Payment for value instead of volume delivered is a major reimbursement transition coming to the acute care setting, necessitating increased attention to mining data necessary to capture quality patient outcomes for maximum reimbursement. The clinical nurse leader is ideally suited to function within these integrated systems of the future, and possesses the skills needed to assist healthcare systems to meet this challenge.


Developmental expression of G alpha o and G alpha s isoforms in PC12 cells: relationship to neurite outgrowth.
Recent evidence suggests neuronal differentiation is associated with developmentally regulated changes in the expression of certain G-protein subtypes but the relationship of such changes to neuronal differentiation and/or neurite outgrowth is poorly understood. In this study, the appearance of the G-protein alpha o and alpha s subunit isoforms was characterized in NGF-induced differentiating pheochromocytoma (PC)12 cells and correlated with neurite outgrowth, which was assessed with direct morphometric measures at 24-h intervals for a 5-day period and at 24, 48 and 72 h following NGF removal. Significant increases were observed in alpha o1 immunoreactive levels and the ratio of alpha o1/alpha o2 immunoreactivities during NGF exposure but not in the levels of either the long or short isoform of alpha s. The former changes also correlated significantly with neurite length during NGF treatment. Furthermore, no significant changes were observed in the levels of alpha o or alpha s isoforms following NGF removal. These findings suggest that alpha o isoforms are involved in neuritic extension in PC12 cells.


Genome-Wide Expression Analysis of Root Tips in Contrasting Rice Genotypes Revealed Novel Candidate Genes for Water Stress Adaptation.
Root system architecture (RSA) is an important agronomic trait with vital roles in plant productivity under water stress conditions. A deep and branched root system may help plants to avoid water stress by enabling them to acquire more water and nutrient resources. Nevertheless, our knowledge of the genetics and molecular control mechanisms of RSA is still relatively limited. In this study, we analyzed the transcriptome response of root tips to water stress in two well-known genotypes of rice: IR64, a high-yielding lowland genotype, which represents a drought-susceptible and shallow-rooting genotype; and Azucena, a traditional, upland, drought-tolerant and deep-rooting genotype. We collected samples from three zones (Z) of root tip: two consecutive 5 mm sections (Z1 and Z2) and the following next 10 mm section (Z3), which mainly includes meristematic and maturation regions. Our results showed that Z1 of Azucena was enriched for genes involved in cell cycle and division and root growth and development whereas in IR64 root, responses to oxidative stress were strongly enriched. While the expansion of the lateral root system was used as a strategy by both genotypes when facing water shortage, it was more pronounced in Azucena. Our results also suggested that by enhancing meristematic cell wall thickening for insulation purposes as a means of confronting stress, the sensitive IR64 genotype may have reduced its capacity for root elongation to extract water from deeper layers of the soil. Furthermore, several members of gene families such as NAC, AP2/ERF, AUX/IAA, EXPANSIN, WRKY, and MYB emerged as main players in RSA and drought adaptation. We also found that HSP and HSF gene families participated in oxidative stress inhibition in IR64 root tip. Meta-quantitative trait loci (QTL) analysis revealed that 288 differentially expressed genes were colocalized with RSA QTLs previously reported under drought and normal conditions. This finding warrants further research into their possible roles in drought adaptation. Overall, our analyses presented several major molecular differences between Azucena and IR64, which may partly explain their differential root growth responses to water stress. It appears that Azucena avoided water stress through enhancing growth and root exploration to access water, whereas IR64 might mainly rely on cell insulation to maintain water and antioxidant system to withstand stress. We identified a large number of novel RSA and drought associated candidate genes, which should encourage further exploration of their potential to enhance drought adaptation in rice.


Innovations in the utilization of health information technology in psychiatric services.
There is ever-increasing activity in applying information technology to various areas of healthcare, including mental health. Examples of innovations include applications in screening, treatment, clinical decision support, communication and coordination, telemedicine, Internet-based education and services, public health research, training and education, and bioinformatics. Issues and challenges include protection of privacy, managing narrative free text, assessing the reliability of information found online, and mitigating impact on clinical workflow. While many of the innovations described will not be fully realized until national information systems reach a larger scale, many are having a positive impact on mental healthcare today.


[Subconjunctival nodule with Dirofilaria repens].
Dirofilaria repens infection, a zoonotic illness, is rarely seen in humans; it is more frequently met over the endemic areas of the Southern Europe and Sri Lanka. The authors report a case of dirofilaria conjunctivae in a 27 year old woman from Craiova; such infections are hardly to be found in our country. Our patient presented a mobile, bulbar, subconjunctival tumoral formation which was surgically removed; immature Dirofilaria repens was revealed into it. Case particularity was that the patient had not visited any of the endemic areas. Environmental changes with global warming can lead to some new unspecific diseases in our country.


Immune infiltration and a ferroptosis-related gene signature for predicting the prognosis of patients with cholangiocarcinoma.
Cholangiocarcinoma (CHOL) is a digestive tract tumor with high malignancy and poor prognosis and is extremely challenging to treat. At present, induced cell death holds great promise in tumor therapy. Ferroptosis is a recently proposed pattern of programmed cell death, and numerous studies have shown that it is intimately involved in tumors. However, the roles of differentially expressed ferroptosis-related genes (DEFRGs) in CHOL have not been investigated. Our study was based on The Cancer Genome Atlas (TCGA) database, and DEFRGs were obtained to construct a prognostic riskScore model of CHOL by univariate and multivariate Cox regression analyses. Subsequently, the model was evaluated by nomogram construction, survival analysis, receiver operating characteristic (ROC) analysis, and exploration of the immune microenvironment. The mRNA and protein expression levels of each gene in the model were validated by the Gene Expression Omnibus (GEO) database, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) staining. Our study found that the construction of a nomogram confirmed the predictive value of the model for overall survival (OS), and it was confirmed to have high diagnostic value by ROC analysis. Our experimental results were almost consistent with our bioinformatics results. In conclusion, we found that the prognostic model showed extremely high diagnostic and prognostic value and could predict the possibility of immunotherapy, thus providing a new direction for individualized treatment of patients with CHOL.


In vitro pharmacology of a novel non-peptide angiotensin II-receptor antagonist, E4177.
E4177, 3-[(2'-carboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl-3H- imidazo[4,5-b]pyridine, was characterized by in vitro autoradiography and by examining functional antagonism upon angiotensin II (Ang II)-induced contraction of isolated vessels. In rat adrenal cortex and liver, E4177 competitively inhibited the specific binding of 125I-[Sar1,Ile8]Ang II, with IC50 being (5.2 +/- 1.0) x 10(-8) M for the adrenal cortex and (1.2 +/- 0.3) x 10(-7) M for the liver. These IC50 values were similar to those for losartan, which showed an IC50 of (6.0 +/- 0.9) x 10(-8) M for the adrenal cortex and (1.3 +/- 0.5) x 10(-7) M for the liver. In contrast, E4177 and losartan had little effect on the binding to rat adrenal medulla where AT2-receptors predominate. These results indicate that E4177 is AT1-specific as is losartan. E4177 and losartan competitively antagonized the Ang II-induced contraction of human and rabbit arterial strips without any agonistic action. The obtained IC50 values indicated that E4177 was twice as potent as losartan in human arteries and three times more so in rabbit aortic strips. Responses to norepinephrine, serotonin, histamine or KCl were not affected by E4177. In addition, E4177 (10(-5) M) had no effect on angiotensin-converting enzyme activity. These data indicate that E4177 is a potent AT1 Ang II-receptor antagonist that may be clinically useful for the treatment of cardiovascular diseases such as hypertension.


The Expression and Diagnostic Value of LncRNA H19 in the Blood of Patients with Osteoarthritis.
To investigate the expression and diagnostic value of LncRNA H19 in the blood of patients with osteoarthritis. A total of 130 cases of patients with osteoarthritis admitted to Jinling Hospital, Nanjing, China from Jun 2016 to Jul 2017 were elected as the study group, and 100 patients who underwent physical examination in Jinling Hospital during the same period were selected as the control group. The differences in expression levels of LncRNA H19 between the two groups were compared, the diagnostic value of LncRNA H19 in osteoarthritis and its relationship with clinical characteristics of patients with osteoarthritis were analyzed. The expression level of LncRNA H19 increased in peripheral blood of patients with osteoarthritis (P<0.05). The AUC, critical value, sensitivity and specificity of the diagnosis of osteoarthritis were 0.891, 1.879, 96.00% and 85.73%, respectively. The expression level of LncRNA H19 was related to K-L grading, and the expression level of LncRNA H19 increased with K-L grading. Pearson correlation analysis showed that LncRNA H19 was negatively correlated with bone metabolism indexes PINP, N-MID, BGP, BALP and Lysholm score (P<0.05), and positively correlated with bone metabolism indexes β-CTX, VAS score and WOMAC score (P<0.05). LncRNA H19 is highly expressed in peripheral blood of patients with osteoarthritis, which is closely related to the occurrence and development of osteoarthritis and has a good diagnostic value for osteoarthritis.


Supercapacitors based on self-assembled graphene organogel.
Self-assembled graphene organogel (SGO) with 3-dimensional (3D) macrostructure was prepared by solvothermal reduction of a graphene oxide (GO) dispersion in propylene carbonate (PC). This SGO was used as an electrode material for fabricating supercapacitors with a PC electrolyte. The supercapacitor can be operated in a wide voltage range of 0-3 V and exhibits a high specific capacitance of 140 F g(-1) at a discharge current density of 1 A g(-1). Furthermore, it can still keep a specific capacitance of 90 F g(-1) at a high current density of 30 A g(-1). The maximum energy density of the SGO based supercapacitor was tested to be 43.5 Wh kg(-1), and this value is higher than those of the graphene based supercapacitors with aqueous or PC electrolytes reported previously. Furthermore, at a high discharge current density of 30 A g(-1), the energy and power densities of the supercapacitor were measured to be 15.4 Wh kg(-1) and 16,300 W kg(-1), respectively. These results indicate that the supercapacitor has a high specific capacitance and power density, and excellent rate capability.


Predicting the physiological role of circadian metabolic regulation in the green alga Chlamydomonas reinhardtii.
Although the number of reconstructed metabolic networks is steadily growing, experimental data integration into these networks is still challenging. Based on elementary flux mode analysis, we combine sequence information with metabolic pathway analysis and include, as a novel aspect, circadian regulation. While minimizing the need of assumptions, we are able to predict changes in the metabolic state and can hypothesise on the physiological role of circadian control in nitrogen metabolism of the green alga Chlamydomonas reinhardtii.


Anti-Thy-1 antibody responses evoked by Thy-1 antigen expressed in transfected mouse mastocytoma cells and rat fibroblast.
The mouse genomic Thy-1.1 gene was isolated from a phage library constructed from AKR/J (Thy-1.1) mouse DNA. Partial nucleotide sequence analysis of the coding region showed that it has only a single nucleotide difference from the Thy-1.2 gene, namely that amino acid 89 reads CGA (Arg) in Thy-1.1 and CAA (Glu) in Thy-1.2, corresponding to the amino acid substitutions previously identified. It was subcloned into an SV-40 derived vector for transfection. Transient transfection into HeLa cells gave 2% positive staining by immunofluorescence. The gene in this vector was also co-transfected into L cells and mastocytoma cells (both of Thy-1.2 strain origin) together with the Agpt gene. L-cell clones selected for transformation proved almost negative for Thy-1.1 expression, and any positive clones gradually lost Thy-1.1 antigen expression in culture. On the contrary, all clones of mastocytoma transformants gave a high level of expression after more than 3 months in culture. The mastocytoma transformants were used to study the immunogenicity of Thy-1.1 molecules expressed on transfected cells. They evoked clear anti-Thy-1.1 plaque-forming cell (PFC) responses both in vivo and in vitro. The mastocytoma transformants also proved able to induce a T-dependent anti-Thy-1.1 antibody response in a cell transfer experiment. The immunogenicity of Thy-1.2 molecules on rat fibroblasts was also studied after transfection with a Thy-1.2 gene cosmid. Although Thy-1.2 expression was very low, these transfectants elicited a clear anti-Thy-1.2 PFC response from AKR spleen cells hyperimmunized against CBA thymocytes.


Reflections during a study on family therapy with drug addicts.
This article presents ideas and reflections emerging during a project on family therapy with drug abusers. Initially inspired by the writings of Stanton and Todd on the subject, the project developed into a recursive and self-reflective process, characterized by increasing doubts about the usefulness of categorization of families, of pre-planning therapy, and of the therapist as an "expert." The limitations of approaches that emphasize the importance of understanding the family structure as the basis for changing it are discussed, particularly with respect to how they decrease therapist flexibility and may block the family's finding their own solution. Alternative approaches to practice and research are also discussed, bearing on ideas particularly formulated by theoreticians and practitioners inspired by second-order cybernetics.


Assessing colonoscopy training outcomes using quality indicators.
Training numbers for colonoscopy vary among specialties. Tracking colonoscopy quality indicators for program graduates may provide reliable outcome data to improve educational programs and establish training requirements. The purpose of this study was to measure specific colonoscopy quality indicators for a family medicine graduate to determine if outcome can be used to assess the quality of procedure training and contribute to more objective means of establishing training numbers. We present a case series of the first 800 colonoscopies performed by a newly credentialed family physician who had performed 101 procedures during residency training. Procedure reports and medical records were reviewed for all patients receiving a colonoscopy by this physician from September 2003 to September 2007. Selected quality indicators were compared to recommended colonoscopy standards. The overall reach-the-cecum rate was 98.6%. Adenomas were detected in 21.6% of females and 33.7% of males. All polyps measuring less than 2 cm were removed. Epinephrine was used for 3 patients with hemostasis after polypectomy. There were no perforations. Quality indicators for colonoscopy were met after 101 supervised procedures. Postgraduate tracking of nationally recognized colonoscopy quality indicators can provide valuable outcome data to improve residency training and assist in establishing uniform training requirements among specialties.


Severe granulocytopenia secondary to chlorpromazine despite concurrent lithium treatment: a case report.
Severe chlorpromazine-induced granulocytopenia where the white-cell count decreases to below 1,000/mm3 rarely occurs and lithium is known to cause leucocytosis. The use of lithium in the prevention of granulocytopenia induced by drugs is still controversial. This report describes a patient with bipolar disorder suffering from severe granulocytopenia and severe respiratory infection after receiving chlorpromazine 50 to 150 mg per day along with long term lithium therapy. Bone-marrow aspiration and biopsy revealed inhibited maturation of myeloid series in the promyelocyte stage. The findings were consistent with a drug-induced effect. White-cell count return to normal after the discontinuation of chlorpromazine. It was proved in this case that combined lithium therapy had no effect in preventing agranulocytosis induced by chlorpromazine.


Inflammatory myelopathy presenting as a cystic intramedullary spinal cord lesion.
A case of subacute progressive spinal tetraparesis had myelographic evidence of cervical spinal cord swelling and a delayed metrizamide computed tomographic myelogram (MCTM) suggested cavitation within the swollen spinal cord. Surgical exploration of the cervical cord revealed inflammatory changes only. No syrinx or intramedullary tumour was found. The accumulation of metrizamide within the spinal cord, as demonstrated by MCTM, did not represent a syrinx or a cystic tumour, but more likely an area of inflammation. Because inflammatory myelopathy may simulate an intramedullary tumor or syrinx, careful analysis of all clinical and radiological information is necessary to help make a correct diagnosis.


Infection of the Circulifer haematoceps cell line Ciha-1 by Spiroplasma citri: the non-insect-transmissible strain 44 is impaired in invasion.
Successful transmission of Spiroplasma citri by its leafhopper vector requires a specific interaction between the spiroplasma surface and the insect cells. With the aim of studying these interactions at the cellular and molecular levels, a cell line, named Ciha-1, was established using embryonic tissues from the eggs of the S. citri natural vector Circulifer haematoceps. This is the first report, to our knowledge, of a cell line for this leafhopper species and of its successful infection by the insect-transmissible strain S. citri GII3. Adherence of the spiroplasmas to the cultured Ciha-1 cells was studied by c.f.u. counts and by electron microscopy. Entry of the spiroplasmas into the insect cells was analysed quantitatively by gentamicin protection assays and qualitatively by double immunofluorescence microscopy. Spiroplasmas were detected within the cell cytoplasm as early as 1 h after inoculation and survived at least 2 days inside the cells. Comparing the insect-transmissible GII3 and non-insect-transmissible 44 strains revealed that adherence to and entry into Ciha-1 cells of S. citri 44 were significantly less efficient than those of S. citri GII3.


Validity of activity-based devices to estimate sleep.
The aim of this study was to examine the feasibility of sleep estimation using a device designed and marketed to measure core physical activity. Thirty adolescent participants in an epidemiological research study wore 3 actigraphy devices on the wrist over a single night concurrent with polysomnography (PSG). Devices used include Actical actigraph, designed and marketed for placement around the trunk to measure physical activity, in addition to 2 standard actigraphy devices used to assess sleep-wake states: Sleepwatch actigraph and Actiwatch actigraph. Sleep-wake behaviors, including total sleep time (TST) and sleep efficiency (SE), were estimated from each wrist-device and PSG. Agreements between each device were calculated using Pearson product movement correlation and Bland-Altman plots. Statistical analyses of TST revealed strong correlations between each wrist device and PSG (r = 0.822, 0.836, and 0.722 for Sleepwatch, Actiwatch, and Actical, respectively). TST measured using the Actical correlated strongly with Sleepwatch (r = 0.796), and even stronger still with Actiwatch (r = 0.955). In analyses of SE, Actical correlated strongly with Actiwatch (r = 0.820; p < 0.0001), but not with Sleepwatch (0.405; p = 0.0266). SE determined by PSG correlated somewhat strongly with SE estimated from the Sleepwatch and Actiwatch (r = 0.619 and 0.651, respectively), but only weakly with SE estimated from the Actical (r = 0.348; p = 0.0598). The results from this study suggest that a device designed for assessment of physical activity and truncal placement can be used to measure sleep duration as reliably as devices designed for wrist use and sleep wake inference.


Ion-pairing chromatography on a porous graphitic carbon column coupled with time-of-flight mass spectrometry for targeted and untargeted profiling of amino acid biomarkers involved in Candida albicans biofilm formation.
Candida albicans, the most common fungal pathogen related to colonization and biofilm formation on the surfaces of indwelling medical devices, shows high resistance to the most commonly used antifungal drugs. In this study, an ion-pairing chromatography-porous graphitic carbon column coupled with a time-of-flight mass spectrometry (IP-PGC-TOF/MS) system was developed for targeted and untargeted profiling of metabolites involved in biofilm and planktonic growth of C. albicans. Using untargeted profiling analysis, 16 differential metabolites were screened and identified as potential biomarkers, most of which were amino acids or related compounds. Based on untargeted profiling analysis, targeted quantitative analysis of 22 amino acids was established and carefully evaluated using stable isotope-labeled internal standards. Among them, 9 amino acids that were not screened by untargeted profiling were further characterized as new biomarkers. Finally, a total of 25 potential biomarkers were screened using the combined targeted and untargeted strategy, among which 16 were characterized for the first time. Our results confirmed that amino acid metabolism and polyamine metabolism were at a high level in biofilms, except for some new biomarkers including ornithine, arginine and proline that were directly related to ornithine. Further experiments were carried out on the ornithine decarboxylase-negative (spe1Δ) mutant, and the results showed that the consumption of ornithine for putrescine biosynthesis has a significant impact on biofilm formation and may prove to be a drug target for resolving drug resistance of C. albicans. This study provides a systematic view of changes in amino acid metabolism during C. albicans biofilm formation by a combination of targeted and untargeted profiling using an original IP-PGC-TOF/MS method. It is a feasible approach for characterizing subtle variations and screening novel biomarkers from the microbial metabolome.


Genetic and phenotypic variation in sources of preweaning lamb mortality.
Information on causes of mortality to 8 wk weaning for 16,881 lambs of 10 line-breed groups by 594 sires born over a 5-yr period was analyzed by least squares procedures to estimate sire variance and covariance components within line and year-season. Heritability estimates were approximately 5% for total mortality in the binomial scale and near 10% when converted to a normal scale. Average heritability estimates in the binomial and normal scale were, respectively, 4 and 12% for perinatal and 3 and 7% for postnatal mortality. The heritability estimates for respiratory problems were inconsistent; binomial-scale estimates ranged from 0 to 7% in different populations. Regression adjustment for effects of variation in litter size and birth weight caused only minor changes in the heritability estimates. Comparison of covariances among half-sibs vs full-sibs indicated very large maternal effects on perinatal mortality but smaller and less consistent effects on sources of postnatal mortality. Phenotypic correlations among sources of mortality indicated a 26% greater influence of postnatal than perinatal mortality on variation in total mortality, but both the genetic and phenotypic correlations between those two components were slightly negative. These results suggest that the use of family and progeny test selection for transmitted effects on both perinatal and postnatal lamb viability should be effective.


A Novel Nonsense INS Mutation Causes Inefficient Preproinsulin Translocation Into the Endoplasmic Reticulum.
Preproinsulin (PPI) translocation across the membrane of the endoplasmic reticulum (ER) is the first and critical step of insulin biosynthesis. Inefficient PPI translocation caused by signal peptide (SP) mutations can lead to β-cell failure and diabetes. However, the effect of proinsulin domain on the efficiency of PPI translocation remains unknown. With whole exome sequencing, we identified a novel INS nonsense mutation resulting in an early termination at the 46th residue of PPI (PPI-R46X) in two unrelated patients with early-onset diabetes. We examined biological behaviors of the mutant and compared them to that of an established neonatal diabetes causing mutant PPI-C96Y. Although both mutants were retained in the cells, unlike C96Y, R46X did not induce ER stress or form abnormal disulfide-linked proinsulin complexes. More importantly, R46X did not interact with co-expressed wild-type (WT) proinsulin in the ER, and did not impair proinsulin-WT folding, trafficking, and insulin production. Metabolic labeling experiments established that, despite with an intact SP, R46X failed to be efficiently translocated into the ER, suggesting that proinsulin domain downstream of SP plays an important unrecognized role in PPI translocation across the ER membrane. The study not only expends the list of INS mutations associated with diabetes, but also provides genetic and biological evidence underlying the regulation mechanism of PPI translocation.


MEK-ERK Activity Regulates the Proliferative Activity of Fetal Hepatoblasts Through Accumulation of p16/19(cdkn2a).
Hepatoblasts are somatic progenitor cells in the fetal liver, which retain a high proliferative capacity and differentiate into both hepatocytes and cholangiocytes in vivo. Although efficient expansion of hepatoblasts in vitro has been difficult without genetic modification, we have previously demonstrated that the interaction with mesenchymal cells is important for expansion of hepatoblasts in vitro. In this study, we show cell signaling pathways regulating the long-term proliferative ability of hepatoblasts. Individual primary hepatoblasts derived from mouse fetal livers formed large colonies when cocultured with mesenchymal feeder cells; however, secondary colony formation was unsuccessful, indicating that in vitro culture could induce short-term, but not long-term, proliferation. When the MEK inhibitor, PD0325901, was added to these cultures, hepatoblasts formed large colonies containing many Ki-67-positive cells. Expression of p16/19(cdkn2a), a cyclin-dependent kinase inhibitor, was induced after 3-6 days culture of hepatoblasts, whereas PD0325901 significantly suppressed this expression. Consistent with these observations, fetal hepatoblasts derived from p16/19(cdkn2a) knockout mice showed long-term proliferation without PD0325901, suggesting that MEK activity induced cell cycle arrest through accumulation of p16/19(cdkn2a). In transplantation assays, we could demonstrate that in vitro expanded hepatoblasts could proliferate and differentiate into hepatocytic and cholangiocytic cells in injured livers. It should also be noted that ERK in primary hepatoblasts was not highly activated during fetal liver development. Collectively, all these findings suggest that the MEK/ERK-independent pathway in the fetal liver is involved in hepatoblast proliferation to avoid accumulation of cyclin-dependent kinase inhibitor.


Deficiency of Jamc Leads to Congenital Nuclear Cataract and Activates the Unfolded Protein Response in Mouse Lenses.
The malfunction of junctional adhesion molecule C (JAM-C) has been reported to induce congenital cataract in humans and mice; however, specific characters and the mechanism of this cataract are still unclear. This study aimed to characterize abnormal lens development in Jamc knockout mice and clarify the underlying mechanism. Jamc knockout mice backcrossed onto the C57BL/6 genetic background were used for this research. Slit-lamp and darkfield images showed the cataract phenotype of Jamc-/- mice. Hematoxylin and eosin staining was performed to visualize the morphological and histological features. RNA sequencing was applied to detect differentially expressed genes. Quantitative RT-PCR, western blot, and immunofluorescence were used to determine the level of unfolded protein response (UPR)-related genes. TUNEL staining was utilized to label cell death. Jamc knockout mice exhibited nuclear cataract with abnormal lens morphology and defective degradation of nuclei and organelles in lens fiber cells. Compared with wild-type control mice, the expression level of BiP, CHOP, TRIB3, and CHAC1, genes involved in endoplasmic reticulum stress and the UPR, were highly upregulated in Jamc-/- lenses, suggesting that abnormal lens development was accompanied by UPR activation. Moreover, increased cell death was also found in Jamc-/- lenses. Congenital nuclear cataract caused by Jamc deficiency is accompanied by defective degradation of nuclei and organelles in lens fiber cells, lens structure disorder, and UPR activation, suggesting that JAM-C is required for maintaining normal lens development and that UPR activation is involved in cataract formation in Jamc-deficient lenses.


Associations between pet ownership and self-reported health status in people suffering from chronic fatigue syndrome.
This study explored the association between pet ownership and self-reported health in people suffering from chronic fatigue syndrome (CFS). One hundred and ninety-three (193) people with medically diagnosed CFS completed a postal survey designed to collect information on illness severity, physical and psychologic health, and pet ownership practices. Most of the participants were female (72.0%), over 45 years of age (57.1%) and married (41.1%) with no children (63.1%). Pets were owned by 58.3% of the sample, with dogs and cats being the most commonly kept types of companion animal. The general health of the participants was discovered to be poor, as assessed by scores on the Chalder Fatigue Questionnaire (CFQ), General Health Questionnaire-12 (GHQ-12), and Short-Form-36 (SF-36) health survey. Pet ownership was not significantly associated with scores on the CFQ, GHQ-12, or SF-36 scales, although pet owners considered their animals to offer them a range of health benefits, notably those associated with mental well-being. Overall, findings suggest no statistically significant association between pet ownership and self-reported health in people with CFS. Nonetheless, people suffering from this condition believe that their pets have the potential to enhance quality of life. Although animals should not be regarded as a panacea for people with long-term conditions such as CFS, they may, nonetheless, serve a valuable, and currently underutilized, role in promoting well-being, whether in their own right, or in conjunction with more traditional forms of therapy.


Thermal inactivation kinetics of β-galactosidase during bread baking.
In this study, β-galactosidase was utilized as a model enzyme to investigate the mechanism of enzyme inactivation during bread baking. Thermal inactivation of β-galactosidase was investigated in a wheat flour/water system at varying temperature-moisture content combinations, and in bread during baking at 175 or 205°C. In the wheat flour/water system, the thermostability of β-galactosidase increased with decreased moisture content, and a kinetic model was accurately fitted to the corresponding inactivation data (R2=0.99). Interestingly, the residual enzyme activity in the bread crust (about 30%) was hundredfold higher than that in the crumb (about 0.3%) after baking, despite the higher temperature in the crust throughout baking. This result suggested that the reduced moisture content in the crust increased the thermostability of the enzyme. Subsequently, the kinetic model reasonably predicted the enzyme inactivation in the crumb using the same parameters derived from the wheat flour/water system. However, the model predicted a lower residual enzyme activity in the crust compared with the experimental result, which indicated that the structure of the crust may influence the enzyme inactivation mechanism during baking. The results reported can provide a quantitative understanding of the thermal inactivation kinetics of enzyme during baking, which is essential to better retain enzymatic activity in bakery products supplemented with heat-sensitive enzymes.


24-hour electrocardiogram before and during cisapride treatment in neonates and infants.
We studied prospectively the effects of cisapride on heart rate and rhythm using standard ECG and 24-hour ECG recordings in term and preterm neonates and infants. We studied subjects with gastroesophageal reflux disease (apparent life-threatening events, apneas, bradycardias) before and 3 days after starting cisapride (0.8 mg/kg/day in 4 doses). We performed standard ECGs for determination of corrected Q-T interval (QTc) and Q-T dispersion (QTd) and 24-hour ECG recordings for analysis of heart rate, heart rate variability, and heart rhythm. Fourteen term and 17 preterm subjects (gestational age range 28-36 weeks) were studied at a median chronological age of 29 (range 3-132) days. Cisapride significantly increased the QTc in preterm infants (before vs. after: 408 +/- 7 vs. 433 +/- 7 ms, p = 0.001). Two preterm and 1 term infant had a QTc >450 ms before cisapride. Four preterm (4/15 = 27%) and 2 term (2/13 = 15%) subjects had a QTc >450 ms on cisapride. After cisapride the QTd remained normal, and no relevant arrhythmias were documented on Holter recordings. Cisapride significantly decreased peak and mean heart rates of all study subjects without affecting the heart rate variability, while it increased the minimal heart rate of preterm infants only (before vs. after: 66 +/- 5 vs. 78 +/- 5 bpm, p = 0.02). The maximally measured R-R intervals (pauses) decreased after cisapride in preterm infants (before vs. after: 1.33 +/- 0.2 s vs. 1.05 +/- 0.2 s, p = 0.04). Although cisapride did cause a significant prolongation of the ventricular action potential duration in preterm infants, the QTd remained unaffected, and no clinically relevant arrhythmias were documented in this small sample. On the other hand, cisapride had a direct lowering effect on the maximal and mean heart rates of both term and preterm infants, while the drug increased the minimal heart rate and reduced the severity of bradycardia episodes in preterm infants.


Diagnosis and management of orbital inflammation and infections secondary to foreign bodies: a clinical review.
Orbital inflammation and secondary infections may be caused by many types of foreign bodies, including organic and inorganic matter, non-autogenous surgical implants and allografts, and surgical hardware and materials utilized in reconstructive surgery. In penetrating injury patients, the nature of the foreign body determines the clinical behavior; inert objects such as steel and glass may not cause significant inflammation to warrant their removal. Removal of organic foreign bodies, however, is mandatory since these objects usually lead to secondary infection with abscess and fistula formation. This paper reviews salient points related to history-taking and physical examination, diagnostic workup, and medical and surgical treatment in foreign body-induced orbital inflammation and infections. It is emphasized that practically every case of orbital trauma should be approached with a high index of suspicion for penetrating injury with possible intraorbital foreign body. The investigational tools to detect orbital foreign bodies, including ultrasonography, computed tomography and magnetic resonance imaging, are reviewed. The principles of the management, including antimicrobial therapy, surgical indications and techniques, are also discussed.


Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)-Is There Still Room for Optimism?
Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with peculiar functionalities that distinguish them from the bulk of tumor cells, most notably their tumor-initiating potential and drug resistance. Given these properties, it appears logical that CSCs have become an important target for many pharma companies. Antibody-drug conjugates (ADC) have emerged over the last decade as one of the most promising new tools for the selective ablation of tumor cells. Three ADCs have already received regulatory approval and many others are in different phases of clinical development. Not surprisingly, also a considerable number of anti-CSC ADCs have been described in the literature and some of these have entered clinical development. Several of these ADCs, however, have yielded disappointing results in clinical studies. This is similar to the results obtained with other anti-CSC drug candidates, including native antibodies, that have been investigated in the clinic. In this article we review the anti-CSC ADCs that have been described in the literature and, in the following, we discuss reasons that may underlie the failures in clinical trials that have been observed. Possible reasons relate to the biology of CSCs themselves, including their heterogeneity, the lack of strictly CSC-specific markers, and the capacity to interconvert between CSCs and non-CSCs; second, inherent limitations of some classes of cytotoxins that have been used for the construction of ADCs; third, the inadequacy of animal models in predicting efficacy in humans. We conclude suggesting some possibilities to address these limitations.


Outcomes of Dissection Angles as Predictor of Restenosis after Drug-Coated Balloon Treatment.
The predictors of restenosis after endovascular therapy (EVT) with paclitaxel drug-coated balloons (DCBs) have not been clearly established. The present study aimed to investigate the association of post-procedural dissection, as evaluated using intravascular ultrasound (IVUS), with the risk of restenosis following femoropopliteal EVT with paclitaxel DCBs. In the present single-center retrospective study, 60 de novo femoropopliteal lesions (44 patients) that underwent EVT with DCBs, without bail-out stenting, were enrolled. The primary outcome was 1-year primary patency. Risk factors for restenosis were evaluated using a Cox proportional hazards regression model and random survival forest analysis. The 1-year primary patency rate was 57.2% [95% confidence interval, 45%-72%]. IVUS-evaluated post-procedural dissection was significantly associated with the risk of restenosis (P=0.002), with the best cutoff point of 64º [range, 39º-83º]. The random survival forest analysis showed that the variable importance measure of IVUS-evaluated dissection was significantly lower than that of the reference vessel diameter (P<0.001), not different from that of the lesion length (P=0.41), and significantly higher than that of any other clinical feature (all P<0.05). IVUS-evaluated post-procedural dissection was associated with 1-year restenosis following femoropopliteal EVT with DCB.


Deficits of reach-to-grasp coordination following stroke: Comparison of instructed and natural movements.
The present work evaluates whether stroke-induced deficits of reach-to-grasp movements, established by typical laboratory paradigms, transfer unconditionally to more natural situations. Sixteen patients with a stroke to the motor-dominant left hemisphere and 16 age- and gender-matched healthy control subjects executed grasping movements with their left (ipsilesional, non-dominant) hand. All movements started in the same position, were aimed at the same object positioned in the same location, and were followed by forward displacement of that object along the same path. Twenty movements were performed as a repetitive, externally triggered task executed for their own sake (context L, as in typical laboratory tasks). Twenty movements were performed as part of a self-initiated action sequence aimed at winning a reward (context E, similar to many everyday situations). The kinematics and dynamics of the transport, grasp and manipulation component of each reach-to-grasp movement were quantified by 41 parameters. Analyses of variance yielded a significant effect of Context for 29 parameters, a significant effect of Group for 9 parameters (mostly related to the coupling of hand transport and grip aperture), and a significant interaction for 5 parameters (all related to the coupling of hand transport and grip aperture). The interaction reflected the fact that stroke patients' movement parameters were more abnormal in context E than in context L. Our data indicate that unilateral stroke degrades the grasp-transport coupling, and that stroke-related motor deficits may be more pronounced in a natural than in a laboratory context. Thus, for stroke patients, assessments and rehabilitation regimes should mainly use activities that are as natural as possible.


[Coagulation screening tests of low-weight newborn infants--deviations and dynamics].
A prospective study was performed in 1993 in our hospital, including newborns with low birth weight and a control group of term infants. It aims to give information about their coagulation status and its dynamics. Abnormalities in the carried out screening tests were noticed in both groups during the first day of life. After the performed vit. K prophylaxis PT had almost the same dynamics in the two groups and almost reached the normal values in adults. aPTT remains highly prolonged in the group of low birth weight infants. Comparing the haemostasiological test levels between the group of low birth weight newborns, having received a prophylactic dose of vit. K i.m. and the corresponding group without vit. K prophylaxis, we established the faster normalizing of these levels in the first group.


Squamous cell carcinoma arising from a fibroepithelial polyp.
Fibroepithelial polyps (FEPs) are among the most common benign skin lesions treated frequently without submitting for histologic examination since malignant degeneration is exceedingly rare. In this case report, we describe an aggressive gross squamous cell carcinoma mass arising from a large pedunculated-type FEP located at the lower limb, which, to our knowledge, has not been reported yet.


Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.
Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.


Guidance on the assessment of exposure of operators, workers, residents and bystanders in risk assessment of plant protection products.
This guidance is designed to assist risk assessors and applicants when quantifying potential non-dietary, systemic exposures as part of regulatory risk assessment for plant protection products (PPPs). It is based on the Scientific Opinion on 'Preparation of a Guidance Document on Pesticide Exposure Assessment for Workers, Operators, Residents and Bystanders' developed by the EFSA Panel on Plant Protection Products and their Residue (PPR) in 2010. Highlighting some inconsistencies between the approaches adopted by regulatory authorities, the PPR Panel proposed a number of changes to the practices in use (i.e. use of deterministic methods for individual PPPs; need to perform an acute risk assessment for PPPs that are acutely toxic; use of appropriate percentile for acute or longer term risk assessments). In the first version of the guidance, issued in 2014, several scenarios for outdoor uses were included, with an annexed calculator, as well as recommendations for further research. The guidance has been updated in 2021 with the inclusion of additional scenarios and revision of default values, on the basis of the evaluation of additional evidence. To support users in performing the assessment of exposure and risk, an online calculator, reflecting the guidance content, has been further developed.


Spatial patterns of atmospherically deposited organic contaminants at high elevation in the southern Sierra Nevada mountains, California, USA.
Atmospherically deposited contaminants in the Sierra Nevada mountains of California, USA have been implicated as adversely affecting amphibians and fish, yet little is known about the distributions of contaminants within the mountains, particularly at high elevation. The hypothesis that contaminant concentrations in a high-elevation portion of the Sierra Nevada decrease with distance from the adjacent San Joaquin Valley was tested. Air, sediment, and tadpoles were sampled twice at 28 water bodies in 14 dispersed areas in Sequoia and Kings Canyon National Parks (2,785-3,375 m elevation; 43-82 km from Valley edge). Up to 15 chemicals were detected frequently in sediment and tadpoles, including current- and historic-use pesticides, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. Only beta-endosulfan was found frequently in air. Concentrations of all chemicals detected were very low, averaging in the parts-per-billion range or less in sediment and tadpoles, and on the order of 10 pg/m3 for beta-endosulfan in air. Principal components analysis indicated that chemical compositions were generally similar among sites, suggesting that chemical transport patterns were likewise similar among sites. In contrast, transport processes did not appear to strongly influence concentration differences among sites, because variation in concentrations among nearby sites was high relative to sites far from each other. Moreover, a general relationship for concentrations as a function of distance from the valley was not evident across chemical, medium, and time. Nevertheless, concentrations for some chemical/medium/time combinations showed significant negative relationships with metrics for distance from the Valley. However, the magnitude of these distance effects among high-elevation sites was small relative to differences found in other studies between the valley edge and the nearest high-elevation sites.


The ability of macular parameters and circumpapillary retinal nerve fiber layer by three SD-OCT instruments to diagnose highly myopic glaucoma.
To compare the ability of circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macular parameters obtained by three spectral-domain optical coherence tomography (SD-OCT) instruments to detect highly myopic glaucoma. In this study, 84 glaucomatous eyes, 53 normal eyes with high myopia, and 86 normal eyes (not highly myopic) were enrolled. Each participant was imaged using Cirrus, RTVue, and 3D OCT to evaluate the average and quadrant cpRNFL thicknesses. The macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL/IPL), and mRNFL + GCL/IPL (GCC) thicknesses were analyzed. The areas under the receiver operating characteristic curves (AUCs) were compared between the instruments. In addition, the best parameters for the AUC were compared between the cpRNFL parameters and macular parameters in each instrument. These analyses revealed similar AUCs for the average cpRNFL and GCC thicknesses between the instruments. RTVue displayed a significantly higher AUC in the nasal cpRNFL thickness than both Cirrus (P = 0.0004) and 3D OCT (P = 0.0006). 3D OCT showed higher AUCs than Cirrus in the mRNFL parameters. There were no significant differences between the best cpRNFL parameters and macular parameters in each instrument. The average cpRNFL and GCC thicknesses that were measured using these OCT instruments exhibited similar abilities for diagnosing highly myopic glaucoma, and RTVue exhibited better diagnostic abilities than Cirrus and 3D OCT for nasal cpRNFL. 3D OCT had better ability than Cirrus in the mRNFL. Both cpRNFL and GCC in each instrument were comparable, and their measurements offered good ability for diagnosing glaucoma with high myopia. (http://www.umin.ac.jp/ctr/index/htm9, UMIN000006900.).


Frequent type 2 neurofibromatosis gene transcript mutations in sporadic intramedullary spinal cord ependymomas.
To further investigate the role of Type 2 neurofibromatosis (NF2) gene transcript mutations in the sporadically occurring counterparts of NF2-associated tumors. Reverse transcription-polymerase chain reaction followed by agarose gel electrophoresis, single strand conformation polymorphism analysis, and automated deoxyribonucleic acid sequence analysis were used to screen for mutations in the NF2 gene transcript in seven unrelated patients with sporadic intramedullary spinal cord ependymomas. Five of seven intramedullary spinal cord ependymomas harbored detectable mutations. All of these mutations occurred in the region of the transcript that is homologous to known cytoskeletal proteins and resulted in significant truncation of the predicted protein product. Mutations of the NF2 transcript occur in the majority of sporadic intramedullary spinal cord ependymomas. These mutations are frequent in a region of the transcript that is homologous to a family of cytoskeletal proteins, and they probably render the protein product inactive. These results add to the body of knowledge concerning the role of the NF2 gene transcript in tumorigenesis.


Long-term outcomes after an arterial switch operation for simple complete transposition of the great arteries.
Although coronary artery obstruction, aortic insufficiency (AI), and pulmonary stenosis (PS) have been reported after arterial switch operation (ASO), limited long-term studies on ASO exist. Our study aimed to examine long-term outcomes after ASO for simple complete transposition of the great arteries (TGA). All 108 patients with simple complete TGA who underwent ASO at Seoul National University Children's Hospital between 1987 and 2004 were enrolled. We retrospectively reviewed the patients' medical records and the results of various functional and imaging studies. Among 108 cases of ASO for simple TGA, 96 have been followed-up through the present time (mean follow-up duration was 11.7+/-8.6 years: range= 4 to 23 years). The 20-year rates of freedom from significant AI, PS, and coronary obstruction were 78.6%, 67.8%, and 95.8%, respectively. AI showed a tendency to progress as follow-up time increased in 21.4% of the population studied (p=0.014); however, AS, PS, and PI showed no such progression. Late coronary artery occlusion was not associated with the initial coronary arterial pattern. Re-operations were done for 13 patients (13.5%) at an average of 8+/-4.3 years after ASO. The survival rate was 96%, while the re-operation-free was 90% at 10 years and 83% at 20 years. Most patients showed normal physical growth with good activity {98%; New York Heart Association (NYHA) class 1 activity} and normal development (96%). Although most patients showed normal physical growth and development after successful ASO, meticulous long-term follow-up is necessary because of progressive AI and coronary complications.


Chorioamnionitis and diagnostic value of C-reactive protein, erythrocyte sedimentation rate and white blood cell count in its diagnosis among pregnant women with premature rupture of membranes.
Several laboratory parameters have been used in these studies to diagnose chorioamnionitis leading to controversies to some extent. The aim of this study was to assess the diagnostic value of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) count in chorioamnionitis among pregnant women with premature rupture of membranes (PROM). In a cross-sectional diagnostic test research, 71 patients presented with PROM before the 37th week of gestation were enrolled. A blood sample was taken from all the patients. Hematologic automatic blood cell counter was used to count the blood cells and their differentiation. ESR and CRP were also measured using the same blood sample at the laboratory. Sensitivity, specificity, correct classification rate and likelihood ratios were calculated. Receiver operating curves were plotted and area under curve was estimated along with its 95% confidence interval. A total of 71 patients were studied. None of the patients had a positive drug history or a history of hypertension before the 20th week of gestation or during her previous pregnancy. Contrary to ESR, WBC count and CRP results didn't provide minimum acceptable diagnostic accuracy measures for diagnosis of chorioamnionitis. The sensitivity and specificity of a positive ESR test at a cutoff value of 52 were 66.7 and 60%, respectively. The area under curve was calculated to be 0.62. The findings of the present study were not supportive of using CRP, WBC as a reliable diagnostic test to identify chorioamnionitis in women with PROM. The results of CRP and WBC were not acceptable but ESR diagnostic value was minimally acceptable.


[Tuberculous spondylitis after intravesical BCG instillation: a case report].
We report a case of tuberculous spondylitis after intravesical bacillus Calmette-Guerin (BCG) instillation. A 71-year-old man was administered BCG (80 mg per week) for 8 weeks for prophylactic treatment of bladder cancer. After the first instillation he experienced miction pain, pollakisuria, and febrile episodes. Two months after the completion of BCG instillation, he complained to back pain and spinal X-ray showed a lytic lesion of Th7 vertebra. Diagnosis of metastatic transitional cell carcinoma was made based on MRI and bone scan. But pathological findings at laminectomy revealed tuberculous spondylitis. Antituberculous therapy (SM, RFP, and INH) was instituted and anterior supine fusion was performed. Now he is free from bladder cancer and tuberculous infection. Intravesical BCG instillation is effective for superficial bladder cancer, but it should be kept in mind that complications related to this treatment could occur and the adequate antituberculosis treatment has to be insisted if indicated.


[Interaction of prostaglandin E2 with receptors and their effect on adenylate cyclase activity in human thyroid tissue].
The investigations have been performed on thyroid tissue excised from patients suffering from euthyroid goiter and thyrotoxicosis. The study of thyroid thyrotoxic tissue has revealed the decrease in the number of free receptors to 3H-PGE2 caused by the enhanced production of receptor-endogenous PGE2 complexes whose level in thyrotoxic tissue was significantly higher than in euthyroid tissue. PGE2 and GppNHp had a pronounced stimulating effect on adenylate cyclaze activity both in euthyroid and thyrotoxic tissues, with enzyme sensitivity to stimulating effects considerably increased in the latter case.


The influence of demographic characteristics, living conditions, and trauma exposure on the overall health of a conflict-affected population in Southern Sudan.
There remains limited evidence on how armed conflict affects overall physical and mental well-being rather than specific physical or mental health conditions. The aim of this study was to investigate the influence of demographic characteristics, living conditions, and violent and traumatic events on general physical and mental health in Southern Sudan which is emerging from 20 years of armed conflict. A cross-sectional survey of 1228 adults was conducted in November 2007 in the town of Juba, the capital of Southern Sudan. Multivariate linear regression analysis was used to investigate the associations and relative influence of variables in three models of demographic characteristics, living conditions, and trauma exposure, on general physical and mental health status. These models were run separately and also as a combined model. Data quality and the internal consistency of the health status instrument (SF-8) were assessed. The variables in the multivariate analysis (combined model) with negative coefficients of association with general physical health and mental health (i.e. worse health), respectively, were being female (coef. -2.47; -2.63), higher age (coef.-0.16; -0.17), absence of soap in the household (physical health coef. -2.24), and experiencing within the past 12 months a lack of food and/or water (coef. -1.46; -2.27) and lack of medical care (coef.-3.51; -3.17). A number of trauma variables and cumulative exposure to trauma showed an association with physical and mental health (see main text for data). There was limited variance in results when each of the three models were run separately and when they were combined, suggesting the pervasive influence of these variables. The SF-8 showed good data quality and internal consistency. This study provides evidence on the pervasive influence of demographic characteristics, living conditions, and violent and traumatic events on the general physical and mental health of a conflict-affected population in Southern Sudan, and highlights the importance of addressing all these influences on overall health.


Treatment of hairy-cell leukemia: current views.
Although hairy-cell leukemia (HCL) is uncommon, remarkable progress has been made in the treatment of patients with this disease. Because of their unique mechanisms of action, the purine analogs, 2'-deoxycoformycin (2'-DCF) and 2-chlorodeoxyadenosine (2-CdA), are naturally targeted to lymphocytes and are cytotoxic to both resting and dividing cells. Both of these agents induce durable complete remissions (CRs) in the overwhelming majority of patients. Remarkably, equally high rates of durable CR are achieved in both untreated and previously treated patients. Furthermore, patients with large tumor burdens fare as well as those with minimal disease. Therefore, these agents have emerged as the treatments of choice for all patients with hairy-cell leukemia and have supplanted earlier treatments such as splenectomy and interferon-alpha (IFN-alpha). Since a single 7-day cycle of 2-CdA leads to excellent outcomes and is associated with few toxicities other than culture-negative fever, this agent is particularly attractive and may offer some advantages. However, given the indolent natural history of HCL, long-term follow-up study will be required to determine if one purine analog offers a survival advantage over the other.


Extended antibiotic prophylaxis after pancreatoduodenectomy reduces postoperative abdominal infection in high-risk patients: Results from a retrospective cohort study.
Preoperative biliary stenting before pancreatoduodenectomy is associated with a greater risk of bacteribilia and thus could lead to more frequent and severe surgical site infections. We hypothesized that an extended antibiotic prophylaxis could reduce the risk of surgical site infections for these high-risk patients compared with standard antibiotic prophylaxis. All consecutive patients who underwent pancreatoduodenectomy between January 1, 2010 and December 31, 2016 were included in a tricentric retrospective cohort and classified according to the risk of surgical site infections (high or low) and the type of antibiotic prophylaxis (standard or extended). Extended antibiotic prophylaxis was defined by the use of high-rank β-lactams >2 days after surgery. Standard antibiotic prophylaxis concerned all single dose of low-rank β-lactams antibiotic prophylaxis. The primary outcome was postoperative surgical site infections. Three hundred and eight patients were included; 146 (47%) were high-risk patients, and 81 (55%) received extended antibiotic prophylaxis, mostly composed of piperacilline-tazobactam and gentamicin. There were significantly fewer surgical site infections in high-risk patients receiving extended antibiotic prophylaxis versus standard antibiotic prophylaxis (odds ratio = 0.4; 95% confidence interval, 0.2-0.8; P = .011), even after adjusting on age, sex, and duration of the surgical procedure (adjusted odds ratio = 0.3; 95% confidence interval, 0.1-0.7; P = .0071). There was no statistical difference in 28-day mortality (P = .32) or 90-day mortality (P = .13). Microorganisms identified in bile culture were more often sensitive to antibiotic prophylaxis in high-risk extended antibiotic prophylaxis group than in high-risk standard antibiotic prophylaxis group (64% versus 38%; P = .01). Extended antibiotic prophylaxis is associated with a reduced risk of surgical site infections for high-risk patients with no significant reduction on 28-day mortality. Additional studies are required to determine the optimal duration of extended antibiotic prophylaxis for these patients.


Effects of Changes in Body Fat Mass as a Result of Regular Exercise on Hemoglobin A1c in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis.
An increase in visceral fat is associated with an increase in insulin resistance, so reducing body fat mass through exercise may help alleviate type 2 diabetes mellitus (T2DM). The current meta-analysis evaluated the effect of changes in body fat via an intervention of regular exercise on hemoglobin A1c (HbA1c) in patients with T2DM. The inclusion criteria were randomized controlled trials involving adults with T2DM, intervention involving exercise alone, an overall duration of intervention ≥12 weeks, and reporting HbA1c and body fat mass. The mean differences (MDs) were defined as the MD between the exercise group and the control group, and the MDs in HbA1c (in percentage) and body fat mass (in kilograms) were calculated. All MDs in HbA1c were pooled as overall effects. A meta-regression analysis was performed to evaluate the relationship between the MD in the body fat mass (in kilograms) and the MD in HbA1c. Twenty studies (1,134 subjects) were analyzed. The pooled MD in HbA1c (in percentage) decreased significantly (-0.4; 95% confidence interval [-0.5, -0.3]) but contained significant heterogeneity (Q = 52.7, p < .01; I2 = 41.6%). A meta-regression analysis showed that a decrease in the MD in body fat mass was significantly associated with a decrease in the MD in HbA1c (R2 = 80.0%) and heterogeneity decreased (Q = 27.3, p = .61; I2 = 11.9%), and a reduction in body fat mass of 1 kg was estimated to decrease the HbA1c (%) by approximately 0.2. The current study suggested that a decrease in HbA1c due to regular exercise depends on a reduction in body fat mass in patients with T2DM.


Infants' developing understanding of social gaze.
Young infants are sensitive to self-directed social actions, but do they appreciate the intentional, target-directed nature of such behaviors? The authors addressed this question by investigating infants' understanding of social gaze in third-party interactions (N = 104). Ten-month-old infants discriminated between 2 people in mutual versus averted gaze, and expected a person to look at her social partner during conversation. In contrast, 9-month-old infants showed neither ability, even when provided with information that highlighted the gazer's social goals. These results indicate considerable improvement in infants' abilities to analyze the social gaze of others toward the end of their 1st year, which may relate to their appreciation of gaze as both a social and goal-directed action.


Errors introduced by a quarter-wave plate in photoelastic multimode optical fiber sensors.
The errors that are introduced by a quarter-wave plate are theoretically evaluated for photoelastic multimode fiber sensors with different configurations. The results indicate that, for the orthogonal and parallel fiber sensors, the error is proportional to the change in the differential retardation of the quarter-wave plate, whereas the error is proportional to the square of the change for the pi/4 fiber sensor.


Pruritus and behavior of pigs infested by itch mites, Sarcoptes scabiei (Acari: Sarcoptidae).
Effects of infestation by Sarcoptes scabiei (De Geer) on pruritus and other behaviors of pigs for 9-13 wks after weaning were evaluated. Regardless of the dose of mites inoculated, pigs fed ad lib. spent approximately 60% of their time at rest. Within their average day, pigs spent more time eating in morning and evening, were more active and pruritic at midday, and rested more and spent the least time drinking water at night. Mite infestations increased total activity and time spent scratching and rubbing. Infested pigs sprayed with water rubbed and scratched 4-10 times more frequently than those left undisturbed or disturbed by other means. Pigs receiving inoculating doses of 1,000 mites became more pruritic than pigs receiving 100 mites, and both groups developed more pruritus than non-infested control pigs.


Risk factors of placental abruption.
Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. In a retrospective case - control study birth records included 78 cases with placental abruption and 780 randomly selected controls were investigated. Statistical analysis for comparing the studied risk factors between groups was performed using Pearson's Chi-square test along with presenting relevant odds ratio (OR). From 7301 deliveries included in the study, 78 (1%) was complicated placental abruption. Women aged 35 or more likely for experiencing (OR = 3.650, 95% confidence interval [CL] = 1.57-6.83) and those who had a previous cesarean section (OR = 2.65, 95% CL = 3.91- 33.41) were in higher risk for placental abruption ([50 cases] 64% vs. [28 cases] 36% P < 0.01). The results indicate that among the placental abruption is one of the most common causes of bleeding during the pregnancy and one of the major obstetrical emergency.


Roles of protein phosphatase 1 and 2A in an IL-6-mediated autocrine growth loop of human myeloma cells.
Deregulation of IL-6 production is one of the major causes for human multiple myeloma. Exogenous IL-6 stimulated the proliferation of fresh human myeloma cells and the myeloma cell line, U266, which produced IL-6 spontaneously. Anti-IL-6 antibody and IL-6 antisense oligonucleotide suppressed the IL-6 stimulated myeloma cell proliferation, indicating that IL-6 induced the myeloma cell proliferation via an autocrine loop. Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, inhibited the U266 cell proliferation at a concentration of less than 1 ng/ml. At this concentration, okadaic acid suppressed the IL-6-induced IL-6 gene expression of myeloma cells. It seems that the okadaic acid blocked the myeloma cell proliferation by reducing IL-6 synthesis in myeloma cells. In addition, IL-6 itself also regulated IL-6 receptor expression. Analysis by FACScan and RT-PCR showed that anti-IL-6 antibody treatment up-regulated IL-6 receptor expression. Interestingly, the presence of okadaic acid induced the up-regulation of IL-6 receptor expression as well as the down-regulation of IL-6-induced gp130 phosphorylation in the myeloma cells. Taken together, these data suggest that protein phosphatase 1 and 2A are involved in IL-6-mediated autocrine growth of human myeloma cells by modulating IL-6 signaling and IL-6 receptor expression in myeloma cells.


Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs.
We evaluated four potential gallium-68 (68Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([15O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study. Following an evaluation of myocardial blood flow with [15O]water PET, the pigs (total n=14) underwent a dynamic 90-min PET study with one of four 68Ga-labeled BAPEN derivatives (n=3-5 per tracer) either at rest or under adenosine stress. Serial arterial blood samples were collected during the imaging for the measurements of total radioactivity, radiometabolites, plasma protein binding and blood-to-plasma ratio for the 68Ga chelates. Time-activity curves of the left ventricular blood pool and myocardium were derived from PET images, and metabolite-corrected arterial input function was used for kinetic modeling. Also, ex vivo biodistribution of 68Ga radioactivity was analyzed. All four 68Ga tracers showed undesirably slow myocardial accumulation over time, but their in vivo stability, clearance from blood and the kinetics of the myocardium uptake varied. [68Ga][Ga-(sal)2BAPDMEN]1+ showed the highest myocardial uptake in PET images and tissue samples (myocardium-to-blood ratio 7.63±1.89, myocardium-to-lung ratio 3.03±0.33 and myocardium-to-liver ratio 1.80±0.82). However, there was no correlation between the myocardial perfusion measured with [15O]water and the net uptake rates or K1 values of the 68Ga chelates. Our results revealed that myocardial accumulation of the 68Ga chelates proposed for myocardial perfusion imaging with PET was slow and not determined by myocardial perfusion in a large animal model. These findings suggest that the studied tracers are not suitable for clinical imaging of myocardial perfusion.


Polyribosomes from Peas: II. Polyribosome Metabolism during Normal and Hormone-induced Growth.
Polyribosomes as large as 10-mers (strands of messenger RNA bearing 10 ribosomes) were isolated from etiolated pea (Pisum sativum L. var. Alaska) stem tissue during all stages of development when methods were used which essentially eliminated ribonuclease activity during extraction. Actively growing tissue, harvested from the apical 10 mm, yielded many large polyribosomes and a low (<20%) proportion of monosomes. Similar tissue, allowed to age by applying lanolin to decapitated apices, showed a progressive decrease in number of larger polyribosomes and an increase in the proportion of monosomes. Hormone treatments, which prolonged growth and delayed aging, delayed the loss in large polyribosomes and the increase in proportion of monosomes. Growth-stimulating hormones, added to previously aged tissue, stimulated the production of many large polyribosomes in pre-existing cells.It is suggested that (a) large polyribosomes occur in all regions of the pea stem, (b) changes in polyribosome distribution appear to precede changes in growth rate, (c) loss of larger polyribosomes is closely related to a decrease in mRNA templates followed more gradually by loss of ribosomes, (d) hormone-stimulated continuation of growth is accomplished through maintenance of available mRNA.Methods are described, involving detailed analysis of polysome distribution, which, although they cannot be used to measure changes in initiation of ribosomes on to mRNA, do permit measurement of the amount of polysomal-associated mRNA present in tissues at different stages of growth. These analyses lead to the further suggestion that hormone stimulation of growth of previously nongrowing tissue is accomplished primarily through an increase in available mRNA prior to synthesis of ribosomes.


Effects of very low fluences of high-energy protons or iron ions on irradiated and bystander cells.
In space, astronauts are exposed to radiation fields consisting of energetic protons and high atomic number, high-energy (HZE) particles at very low dose rates or fluences. Under these conditions, it is likely that, in addition to cells in an astronaut's body being traversed by ionizing radiation particles, unirradiated cells can also receive intercellular bystander signals from irradiated cells. Thus this study was designed to determine the dependence of DNA damage induction on dose at very low fluences of charged particles. Novel techniques to quantify particle fluence have been developed at the NASA Space Radiation Biology Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The approach uses a large ionization chamber to visualize the radiation beam coupled with a scintillation counter to measure fluence. This development has allowed us to irradiate cells with 1 GeV/nucleon protons and iron ions at particle fluences as low as 200 particles/cm(2) and quantify biological responses. Our results show an increased fraction of cells with DNA damage in both the irradiated population and bystander cells sharing medium with irradiated cells after low fluences. The fraction of cells with damage, manifest as micronucleus formation and 53BP1 focus induction, is about 2-fold higher than background at doses as low as ∼0.47 mGy iron ions (∼0.02 iron ions/cell) or ∼70 μGy protons (∼2 protons/cell). In the irradiated population, irrespective of radiation type, the fraction of damaged cells is constant from the lowest damaging fluence to about 1 cGy, above which the fraction of damaged cells increases with dose. In the bystander population, the level of damage is the same as in the irradiated population up to 1 cGy, but it does not increase above that plateau level with increasing dose. The data suggest that at fluences of high-energy protons or iron ions less than about 5 cGy, the response in irradiated cell populations may be dominated by the bystander response.


Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35.
Leukotriene C4 (LTC4) synthase catalyzes the conjugation of LTA4 with reduced GSH to form LTC4, the parent of the receptor active cysteinyl leukotrienes implicated in the pathobiology of bronchial asthma. Previous cloning of the cDNA for human LTC4 synthase demonstrated significant homology of its amino acid sequence to that of 5-lipoxygenase activating protein (FLAP) but none to that of the GSH S-transferase super-family. Genomic cloning from a P1 library now reveals that the gene for LTC4 synthase contains five exons (ranging from 71 to 257 nucleotides in length) and four introns, which in total span 2.52 kilobase pairs in length. The intron/exon junctions of LTC4 synthase align identically with those of FLAP; however, the small size of the LTC4 synthase gene contrasts with the > 31-kilobase pair size reported for FLAP. Confirmation of the LTC4 synthase gene size to ensure that no deletions had occurred during the cloning was obtained by two overlapping polymerase chain reactions from genomic DNA, which provided products of the predicted sizes. Primer extension analysis with poly(A)+ RNA from culture-derived human eosinophilic granulocytes or the KG-1 myelogenous cell line revealed multiple transcriptional start sites with prominent signals at 66, 69, and 96 base pairs 5' of the ATG translation start site. The 5'-flanking region revealed a GC-rich promoter sequence consistent with an SP-1 site and consensus sequences for AP-1 and AP-2 enhancer elements, 24, 807, and 877 bp, respectively, 5' from the first transcription initiation site. Southern blot analysis of a genomic DNA (with full-length cDNA as well as 5' and 3' oligonucleotide probes) confirmed the size of the gene and indicated a single copy gene in normal human genomic DNA. Fluorescent in situ hybridization mapped LTC4 synthase to chromosomal location 5q35, which is in close proximity to the cluster of genes for cytokines and receptors involved in the regulation of cells central to allergic inflammation and implicated in bronchial asthma.


[Analysis on the diagnosis of suspected occupational diseases in Guangzhou from 2014 to 2019].
Objective: To understand the diagnosis of suspected occupational diseases reported in Guangzhou from 2014 to 2019, so as to provide theoretical basis and technical support for the supervision of suspected occupational disease reports. Methods: By cluster sampling, the suspected occupational disease report card, occupational disease report card and pneumoconiosis report card reported by Guangzhou from January 1, 2014 to December 31, 2019 in the occupational disease and occupational health information monitoring system were collected for matching analysis to understand the diagnosis of suspected occupational disease patients. Results: From 2014 to 2019, a total of 1426 suspected occupational cases in 7 categories and 32 species were reported in Guangzhou. The average number of reported cases per year was about 240. The main diseases of suspected occupational diseases were suspected occupational noise deafness (68.44%, 976/1426) , suspected occupational chronic benzene poisoning (16.48%, 235/1426) , suspected occupational other pneumoconiosis (4.84%, 69/1426) , suspected occupational silicosis (3.23%, 46/1426) and suspected occupational welder pneumoconiosis (1.82%, 26/1426) . The diagnostic rate required to enter the occupational disease diagnostic program is 36.61% (522/1426) , and the diagnostic rate is 59.20% (309/522) . In 2019, the diagnosis rate of suspected occupational diseases was the lowest (23.92%, 61/255) , Huadu District was the lowest (8.33%, 9/108) , suspected occupational pneumoconiosis was the lowest (28.03%, 44/157) , the diagnosis rate of suspected occupational diseases reported by the Centers for Disease control and prevention was the lowest (17.43%, 19/109) , and the diagnosis rate of suspected occupational diseases reported by outpatient treatment was the lowest (22.22%, 2/9) . The suspected occupational diseases reported by institutions outside Guangzhou did not enter the occupational disease diagnosis procedure. Suspected occupational skin diseases, suspected occupational diseases caused by physical factors and suspected occupational tumors were diagnosed, and the diagnosis rate of occupational disease prevention and control institutions was the highest (94.87%, 37/39) . Conclusion: The main types of suspected occupational diseases reported during these six years are noise deafness, chronic benzene poisoning and pneumoconiosis. The overall diagnosis rate and diagnosis rate of suspected occupational diseases are not high. It is suggested to improve the network direct reporting system of suspected occupational diseases and strengthen the follow-up management and supervision of suspected occupational diseases.


Perceived fairness of pay among people with and without disabilities: a propensity score matched analysis of working Australians.
Equity and fairness at work are associated with a range of organizational and health outcomes. Past research suggests that workers with disabilities experience inequity in the workplace. It is difficult to conclude whether the presence of disability is the reason for perceived unfair treatment due to the possible confounding of effect estimates by other demographic or socioeconomic factors. The data source was the Household, Income, and Labor Dynamics in Australia (HILDA) survey (2001-2012). Propensity for disability was calculated from logistic models including gender, age, education, country of birth, and father's occupational skill level as predictors. We then used nearest neighbor (on propensity score) matched analysis to match workers with disabilities to workers without disability. Results suggest that disability is independently associated with lower fairness of pay after controlling for confounding factors in the propensity score matched analysis; although results do suggest less than half a standard deviation difference, indicating small effects. Similar results were apparent in standard multivariable regression models and alternative propensity score analyses (stratification, covariate adjustment using the propensity score, and inverse probability of treatment weighting). Whilst neither multivariable regression nor propensity scores adjust for unmeasured confounding, and there remains the potential for other biases, similar results for the two methodological approaches to confounder adjustment provide some confidence of an independent association of disability with perceived unfairness of pay. Based on this, we suggest that the disparity in the perceived fairness of pay between people with and without disabilities may be explained by worse treatment of people with disabilities in the workplace.


Major acute-phase reactant synthesis during chronic inflammation in amyloid-susceptible and -resistant mouse strains.
Hepatic levels of mRNA specific for total serum amyloid A (SAA), the SAA1 and SAA2 isotypes, serum amyloid P (SAP), C-reactive protein (CRP), and fibronectin, as well as the plasma concentrations of SAA and SAP were examined in amyloid-resistant (A/J) and amyloid-susceptible (CBA/J) mice during azocasein-induced chronic inflammation. In both strains hepatic SAA and SAP mRNA levels and plasma SAA and SAP protein concentrations increased dramatically during the early stages of inflammation; this was followed by a decrease to concentrations that were maintained at levels considerably higher than background. The ratios of SAA1 and SAA2 mRNA and plasma protein were 1:1 throughout. This indicated that there was no preferential accumulation of mRNA specifying a particular isotype and no preferential synthesis or clearance of a particular isotype during chronic inflammation and the early stages of amyloidogenesis in either strain. Similarly, hepatic SAP mRNA levels in both strains increased dramatically during the early stages of inflammation and were subsequently maintained at elevated levels. Plasma SAP concentrations increased rapidly during the first three days of the study in both A/J and CBA/J mice; however, during the later stages of inflammation, A/J plasma SAP levels decreased to a steady-state concentration that was approximately half that observed in CBA/J mice. Our results identify differences in the hepatic mRNA and plasma protein levels of the major mouse acute-phase reactants (APR) in the amyloid-resistant A/J and amyloid-susceptible CBA/J mouse strains. These findings are consistent with circulating inflammatory APR concentrations contributing, together with other factors, to the onset and pathogenesis of secondary amyloidosis.


[Assortative mating in temperament and intelligence, and the role of marital satisfaction].
Assortative mating is the mating of pairs that are more similar in some trait than would be expected from random mating. It takes place when sexually reproducing organisms tend to mate with individuals that are like themselves in some respect (positive assortative mating) or dissimilar (negative assortative mating). The present study measures verbal and nonverbal intelligence, along with several temperamental traits, testing the similarity, complementarity, social homogamy, and convergence hypotheses. The role of marital satisfaction was also analyzed. The sample comprised 357 adults (age range 19-69), who completed verbal aptitude, inductive reasoning, and temperament tests. The findings show that couples are similar in almost all the measured traits, even after controlling for age and educational level. Differences were observed in the couples' degree of similarity depending on the duration of their relationship. Further, only similarity in verbal intelligence for males and in impulsivity for females was associated with marital satisfaction in long-term couples.


Characterization of mouse Bmp5 regulatory injury element in zebrafish wound models.
Many key signaling molecules used to build tissues during embryonic development are re-activated at injury sites to stimulate tissue regeneration and repair. Bone morphogenetic proteins provide a classic example, but the mechanisms that lead to reactivation of BMPs following injury are still unknown. Previous studies have mapped a large "injury response element" (IRE) in the mouse Bmp5 gene that drives gene expression following bone fractures and other types of injury. Here we show that the large mouse IRE region is also activated in both zebrafish tail resection and mechanosensory hair cell injury models. Using the ability to test multiple constructs and image temporal and spatial dynamics following injury responses, we have narrowed the original size of the mouse IRE region by over 100 fold and identified a small 142 bp minimal enhancer that is rapidly induced in both mesenchymal and epithelial tissues after injury. These studies identify a small sequence that responds to evolutionarily conserved local signals in wounded tissues and suggest candidate pathways that contribute to BMP reactivation after injury.


Consumer-based research: using focus groups as a method for evaluating quality of care.
In response to the consumer movement, health care organizations have become interested in obtaining feedback through face-to-face contacts with the people using their products and services. Focus groups are one qualitative research method of obtaining rich information within a social context. The article discusses the purpose, design, and methodology of focus groups, and a case example is given. Focus groups can add to existing knowledge about how well services are being delivered or what new products might be developed in the future.


Increased intracellular gamma-aminobutyric acid selectively lowers the level of the larger of two glutamate decarboxylase proteins in cultured GABAergic neurons from rat cerebral cortex.
The regulation of glutamate decarboxylase (GAD; EC 22.214.171.124) was studied by using cultures of cerebral cortical neurons from rat brain grown in serum-free medium. About 50% of the neurons in the cultures were gamma-aminobutyric acid (GABA)ergic as determined by two double-staining procedures. Immunoblotting experiments with four anti-GAD sera that recognize the two forms to varying degrees, demonstrated that the cultures contained the two forms of GAD that are present in rat brain (apparent molecular masses = 63 and 66 kDa). GAD activity was reduced by 60-70% when intracellular GABA levels were increased by incubating the cultures with the GABA-transaminase inhibitor gamma-vinyl-GABA for greater than 5-10 h or with 1 mM GABA itself. Neither baclofen nor muscimol (100 microM) affected GAD activity. Immunoblotting experiments showed that only the larger of the two forms of GAD (66 kDa) was decreased by elevated GABA levels. These results, together with previous results indicating that the smaller form of GAD is more strongly regulated by pyridoxal 5'-phosphate (the cofactor for GAD), suggest that the two forms of GAD are regulated by different mechanisms.


Titanium surface hydrophilicity enhances platelet activation.
Titanium implant surface modification is a key strategy used to enhance osseointegration. Platelets are the first cells that interact with the implant surface whereupon they release a wide array of proteins that influence the subsequent healing process. This study therefore investigated the effect of titanium surface modification on the attachment and activation of human platelets. The surface characteristics of three titanium surfaces: smooth (SMO), micro-rough (SLA) and hydrophilic micro-rough (SLActive) and the subsequent attachment and activation of platelets following exposure to these surfaces were determined. The SLActive surface showed the presence of significant nanoscale topographical features. While attached platelets appeared to be morphologically similar, significantly fewer platelets attached to the SLActive surface compared to both the SMO and SLA surfaces. The SLActive surface however induced the release of the higher levels of chemokines β-thromboglobulin and platelet factor 4 from platelets. This study shows that titanium surface topography and chemistry have a significant effect on platelet activation and chemokine release.


[Primary investigation on fumigation and moxibustion in treatment ulcer and sore of yin syndrome].
To explore the fumigation and moxibustion therapy in treatment of ulcer and sore of yin syndrome. The fumigation and moxibustion therapy is the combination of fumigation and moxibustion, in which, smoking fumigation is provided with warming effect and the actions as moxibustion. This therapy works on the efficacy of both fumigation and moxibustion. In treatment, different herbal medicines can be selected flexibly, acting on dispersing yin and rescuing yang. The fumigation and moxibustion therapy can drain toxin and remove ulcer and sore. It contributes to the treatment of boils and chronic sores of yin syndrome and promotes wound healing.


Differences in Brachypelma albopilosa (Theraphosidae) hemolymph proteome between subadult and adult females.
The changes in the hemolymph proteome of mygalomorph Brachypelma albopilosa females were examined for the first time in relation to their developmental stage (subadult and adult period). Seven distinct subunits of hemocyanin (a, b, c, d, e, f, and g chains), as well as actin were clearly identified and their sequence partly characterized using a combination of one- and two-dimensional gel electrophoresis and mass spectrometry. The different structures determined along with possible post-translational modifications may reflect a role of hemocyanin in molting, immunity, and reproduction. In addition, despite no precise identification, additional peptide sequences from eight protein bands (four bands >200 kDa and four bands in the 95-200 kDa mass range) were determined. As reported in other spider species, the putative corresponding structures are the coagulogen protein and/or lipoproteins (HDL-1, HDL-2, VHDL) for which quantitative differences between adult and subadult individuals could be related to the molting process and/or cuticle lipid and protein composition according to the developmental stage.


The effects of berberine on the magnitude of the acute inflammatory response induced by Escherichia coli lipopolysaccharide in broiler chickens.
One hundred twenty-six 19-d-old male broiler chickens were used to determine the effects of berberine on the magnitude of the acute inflammatory response induced by Escherichia coli lipopolysaccharide (LPS). The birds were weighed and randomly allotted to 1 of 3 treatments at d 19 (3 treatments x 7 replicates x 6 birds). The treatments comprised a control group in which saline was injected at d 21, an LPS-treated group in which LPS (3 mg/kg of BW) was injected at d 21, and finally a berberine and LPS-treated group in which berberine (15 mg/kg of BW) was orally administered from d 19 to d 24 with LPS injection (3 mg/kg of BW) at d 21. Injection of LPS alone decreased (P < 0.01) weight gain, feed intake, and feed conversion compared with the control and the berberine-administered group. Relative liver weight was increased (P < 0.05) in the LPS-treated group 72 h postinjection compared with the control and the berberine-treated group. Total counts of white blood cells and lymphocytes were also increased (P < 0.05) in the LPS-treated group 72 h postinjection. The heterophil concentration of the LPS-treated group was greater (P < 0.05) than that of both the control and the berberine-administered group 24 h postinjection. Broilers in the LPS-treated group had greater (P < 0.05) total serum protein compared with birds in the control and the berberine-administered group both 24 and 72 h postinjection. In addition, the plasma interleukin-6 level of the LPS-treated group was significantly elevated (P < 0.01) at 24 h compared with that of the control and the berberine-administered group. Our results indicate that LPS injection initiated a series of physiological changes typical of an acute phase response in broiler chickens. These effects were largely mitigated by oral administration of berberine.


Imaging mouse retinal ganglion cells and their loss in vivo by a fundus camera in the normal and ischemia-reperfusion model.
To visualize retinal ganglion cells (RGCs) and their gradual loss in the living mouse. With the use of B6.Cg-Tg(Thy1-CFP)23Jrs/J mice, which express cyan fluorescent protein (CFP) in RGCs, and a commercially available mydriatic retinal camera attached with a 5 million-pixel digital camera to visualize RGCs in vivo, the authors recorded fundus photographs longitudinally in the ischemia reperfusion model group and the untreated group to evaluate longitudinal changes in the number of RGCs in experimental models. Moreover, RGCs expressing CFP were evaluated histologically by a retrograde-labeling method and retinal whole mount or sections. The authors devised an in vivo imaging technique using a conventional retinal camera and visualized RGCs at the single-cell level. In the ischemia reperfusion model, a longitudinal reduction in the number of RGCs was demonstrated in each mouse eye. The number of RGCs and the fluorescence intensity of the nerve fiber decreased considerably during the first week. The percentages of RGCs decreased to 34.2% +/- 7.5%, 24.1% +/- 9.1%, 23.0% +/- 9.3%, and 22.2% +/- 8.4% (mean +/- SD, n = 5) of the percentages before injury at 1, 2, 3, and 4 weeks after injury, respectively (P < 0.001). In this transgenic mouse, 97% of CFP-expressing cells were RGCs and 73% of RGCs expressed CFP. This in vivo technique allows noninvasive, repeated, and longitudinal evaluation of RGCs for investigation of retinal neurodegenerative diseases and new therapeutic modalities for them.