Metabolic syndrome in patients with rheumatoid arthritis followed at a University Hospital in Northeastern Brazil.
Patients with rheumatoid arthritis (RA) are 30-60% more likely to develop cardiovascular disease (CV) than the general population. Metabolic syndrome (MS), defined by a number of cardiovascular risk factors, confers a greater risk of CVdisease and diabetes. The association of MS with RA is not yet fully understood and its prevalence varies from 19 to 63% across studies. To assess the prevalence of MS in a population of RA patients followed in a hospital in Northeastern Brazil and analyze associations of demographic and clinical factors with MS. Outpatients with RA were evaluated in a cross-sectional study regarding demographic, clinical, laboratory and anthropometric data. The criteria for defining MS were those adopted by NCEPIII (2005) and IDF (2006). 110 patients with RA were studied; 97.3% were female, with a mean age of 55.5 years (SD=12.9) and duration of illness of 11.2 years (SD=7.3). The MS prevalence from NCEPIII (2005) and IDF (2005) were, respectively, 50% and 53.4%. Advanced age (57.9±11.9 versus 52.9±13.5; p=0.04) and smoking load >20 packs/year (29% versus 9%, p=0.008) were associated with MS. The major components of the metabolic syndrome were abdominal obesity (98.1%), hypertension (80%) and low HDL cholesterol (72.2%). RA patients in a tertiary center in Northeastern Brazil showed high prevalence of MS. It is worth noting that almost all patients had MS and abdominal obesity, which has important practical implications. In addition to the components of MS, age and smoking were associated with this syndrome.


Azide Radical Initiated Ring Opening of Cyclopropenes Leading to Alkenyl Nitriles and Polycyclic Aromatic Compounds.
We report herein a radical-mediated amination of cyclopropenes. The transformation proceeds through a cleavage of the three-membered ring after the addition of an azide radical on the strained double bond and leads to tetrasubstituted alkenyl nitrile derivatives upon loss of N2 . With 1,2-diaryl substituted cyclopropenes, this methodology could be extended to a one-pot synthesis of highly functionalized polycyclic aromatic compounds (PACs). This transformation allows the synthesis of nitrile-substituted alkenes and aromatic compounds from rapidly accessed cyclopropenes using only commercially available reagents.


Nuclear translocation of PKC-α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs).
PI-PLCβ1 is involved in cell proliferation, differentiation, and myelodysplastic syndrome (MDS) pathogenesis. Moreover, the increased activity of PI-PLCβ1 reduces the expression of PKC-α, which, in turn, delays the cell proliferation and is linked to erythropoiesis. Lenalidomide is currently used in low-risk patients with MDS and del(5q), where it can suppress the del(5q) clone and restore normal erythropoiesis. In this study, we analyzed the effect of lenalidomide on 16 patients with low-risk del(5q) MDS, as well as del(5q) and non-del(5q) hematopoietic cell lines, mainly focusing on erythropoiesis, cell cycle, and PI-PLCβ1/PKC-α signaling. Overall, 11 patients were evaluated clinically, and 10 (90%) had favorable responses; the remaining case had a stable disease. At a molecular level, both responder patients and del(5q) cells showed a specific induction of erythropoiesis, with a reduced γ/β-globin ratio, an increase in glycophorin A, and a nuclear translocation of PKC-α. Moreover, lenalidomide could induce a selective G0/G1 arrest of the cell cycle in del(5q) cells, slowing down the rate proliferation in those cells. Altogether, our results could not only better explain the role of PI-PLCβ1/PKC-α signaling in erythropoiesis but also lead to a better comprehension of the lenalidomide effect on del(5q) MDS and pave the way to innovative, targeted therapies.-Poli, A., Ratti, S., Finelli, C., Mongiorgi, S., Clissa, C., Lonetti, A., Cappellini, A., Catozzi, A., Barraco, M., Suh, P.-G., Manzoli, L., McCubrey, J. A., Cocco, L., Follo, M. Y. Nuclear translocation of PKC-α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs).


Virilizing hepatoblastoma: precocious sexual development and partial response of pulmonary metastases to cis-platinum.
A 42/3 year old boy with hepatoblastoma presented with precocious sexual development and an abdominal mass. During the course of disease, serial endocrinologic laboratory investigations were done, along with alpha-fetoprotein levels. A significant correlation is noted in these values at diagnosis, postsurgery, and later during a relapse. Ectopic production of chorionic gonadotropins by the tumor is evident. After extensive surgical resection, chemotherapy was started because of metastases. Although the primary tumor failed to respond, the pulmonary metastatic disease showed a greater than 50 percent response rate with cis-platinum.


Movement-related potentials with reference to isometric force output in discrete and repetitive tasks.
This study investigates whether different speed and accuracy constraints in discrete and repetitive index finger isometric force-production tasks influence the characteristics of the movement-related potentials (MRP) preceding and accompanying these tasks. Three components of MRP (Bereitschaftspotential, BP, motor potential, MP, and movement-monitoring potential, MMP) associated with isometric force output were identified and examined. Our principal finding for the MRP amplitude showed that only MMP, not BP and MP, was enhanced at higher rates of force development for both speed and accuracy tasks. That is to say, there was a high correlation between MMP peak amplitude and the rate of force development for both repetitive and discrete force-production tasks. Additionally, the amplitude of MMP was consistently higher for fast, rather than accurate, force outputs. Moreover, the results from analysis of MRP onset times suggest that, in general, the MRP begin earlier for the fast force output than for the accurate force output.


Influencing factors of prognosis in children with pulmonary atresia with intact ventricle septum after transthoracic balloon dilation of pulmonary valve and construction of a nomograph prediction model.
This study aimed to identify factors that affect the prognosis of children with pulmonary valve atresia and intact ventricular septum treated with transthoracic balloon dilation of the pulmonary valve. The study included 148 participants who were followed up for 5 years. Of these, 10 died, while 138 survived. Independent sample t-test and χ2 test were used to analyze clinical data of children in the death and survival groups. It was found that height, weight, body surface area, arterial oxygen saturation, degree of tricuspid regurgitation, pulmonary valve cross valve pressure difference, ICU length of stay, length of stay, reoperation intervention, and complications were statistically significant (P<0.05). ROC curve analysis of the measurement indicators with statistically significant differences showed that height, weight, body surface area, arterial oxygen saturation, ICU length of stay, and length of stay had AUCs ranging from 0.723 to 0.870. Logistic regression analysis revealed that the degree of tricuspid regurgitation, pulmonary valve cross valvular pressure difference, ICU length of stay, reoperation intervention, and complications were independent risk factors that affect the prognosis of patients with PA/IVS undergoing transthoracic balloon dilation of pulmonary valve. The study proposed a nomogram prediction model using R language software 4.0 "rms" package, which was validated using calibration curve and decision curve. The model had a C-index of 0.667 (95% CI: 0.643-0.786) and high degree of fit. This study provides clinicians with a prediction model to identify children with poor prognosis after treatment with transpulmonary valve balloon dilatation. .


Immune Control Despite Protracted Lymphopenia After Chemoradiation in an Elite Controller.
Elite controllers are human immunodeficiency virus-1-positive individuals capable of sustaining undetectable viral loads without treatment. We present the case of an elite controller diagnosed with extensive stage small cell lung cancer who maintained a viral load of <20 copies/mL despite the development of severe treatment-related lymphopenia.


[Effects of surface-active substances with antistatic properties on several immunity indices].
In experiments performed on rats, it was established that the antibodies' formation was stimulated as a result of a combination of staphylococcal anatoxin or E. coli vaccine immunization with the administration of the non-ionogenic surface-active substances (SAS) Stearox-920 and OC-20. Those SAS proved to have immunostimulating properties, and Stearox-920 was more effective. Another experimental study revealed a growing bactericide activity of the skin, which could be seen from the rate of its self-cleaning from the standard E. coli suspension.


Solo Single-Incision Laparoscopic Resectional Roux-en-Y Gastric Bypass for Morbid Obesity with Metabolic Syndrome.
With the advancement of laparoscopic devices and surgical technology, the era of minimal invasive surgery has progressed to reduced-port surgery, and finally to single-incision laparoscopic surgery (SILS). Several reports show successful application of SILS to various types of bariatric surgery. Oftentimes, this requires a skilled and experienced scopist to perform the procedure. To overcome the technical difficulties of single-incision Roux-en-Y gastric bypass, a manual scope holder was used instead of an assistant scopist, greatly stabilizing the field of view. This allows the surgery to be performed at any time without being influenced by the need of a highly experienced scopist. In this report, we describe in detail the world's first solo single-incision laparoscopic resectional Roux-en-Y gastric bypass.


Can Medical Nutrition Therapy Affect Feto-Maternal Outcomes in Gestational Glucose Intolerance: An Open-Label Pilot Randomized Control Trial in World's Diabetes Capital.
Gestational diabetes is defined as the carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Gestational glucose intolerance (GGI) is used to indicate pregnant women whose 2-h postprandial glucose is > 120 mg/dl and below 140 mg/dl (Diabetes in Pregnancy Study Group of India, DIPSI criteria). This study was planned to see whether intervention in GGI group helps to improve feto-maternal outcomes. This open-label randomized control trial was conducted in Department of Obstetrics and Gynaecology of King George's Medical University, Lucknow. Inclusion criteria were all the antenatal women attending the antenatal clinic and diagnosed as GGI, and exclusion criteria were overt diabetes. Total of 1866 antenatal women were screened, and among them, 220 (11.8%) women were diagnosed as gestational diabetes; 412 (22.1%) women were diagnosed as GGI. The mean fasting blood sugars in the women with GGI who had medical nutrition therapy were much lower than the women with GGI who did not have any intervention. The present study showed the women with GGI had higher complications like polyhydramnios, PPROM, foetal growth restriction, macrosomia, preeclampsia, preterm labour and vaginal candidiasis more in the women with GGI as compared to euglycaemic women. The present study of nutritional intervention in GGI group has shown trend towards lesser complication if we start medical nutrition therapy reflected by delayed development of GDM and less neonatal hypoglycaemia and hyperbilirubinemia.


Validation by CT scan of quadriceps muscle thickness measurement by ultrasound in acute kidney injury.
Accelerated muscle wasting still represents a major issue in critically ill patients. However, a key problem in the intensive care unit is the lack of adequate tools for bedside evaluation of muscle mass. Moreover, when acute kidney injury (AKI) coexists, fluid overload and/or rapid fluid shifts due to renal replacement therapies that frequently occur and may interfere with muscle mass assessment. The purpose of this study is to validate muscle ultrasound (US) by a gold standard (muscle CT scan) for the assessment of quadriceps muscle thickness in critically ill patients with AKI. Quadriceps rectus femoris thickness and quadriceps vastus intermedius thickness of critically ill patients with AKI were blindly assessed at the same leg sites by both US and computed tomography (CT) scan. Using bivariate mixed-model linear regression analysis, we estimated, average difference in thickness between measurement sites, agreement (differential and proportional bias) of US compared to CT, and precision of the two methods, and eventually performed Bland-Altman analysis for repeated measurements on pooled results. We analyzed 233 couples of measurements (30 patients). Average muscle thickness ranged between 1.0 and 1.6, depending on the measurement site. When comparing US to CT, both the observed differential bias (between + 0.04 and + 0.26 cm depending on the muscle site) and the proportional bias (between 82 and 98% of the reference values, depending on the muscle site) were not statistically significant. However, precision analysis showed that US scan tended to be slightly less precise in comparison to CT. Bland-Altman analysis on pooled results showed that the 95% limits of agreement between the US and CT were narrow, ranging from - 0.34 to + 0.36 cm. In critically ill patients with AKI, quadriceps muscle thickness assessment based on US is unbiased, although it occurs with a minor loss of precision compared to CT.


Focussed ion beam machined cantilever aperture probes for near-field optical imaging.
Near-field optical probe is the key element of a near-field scanning optical microscopy (NSOM) system. The key innovation in the first two NSOM experiments (Pohl et al., 1984; Lewis et al., 1984) is the fabrications of a sub-wavelength optical aperture at the apex of a sharply pointed transparent probe tip with a thin metal coating. This paper discusses the routine use of focussed ion beam (FIB) to micro-machine NSOM aperture probes from the commercial silicon nitride cantilevered atomic force microscopy probes. Two FIB micro-machining approaches are used to form a nanoaperture of controllable size and shape at the apex of the tip. The FIB side slicing produces a silicon nitride aperture on the flat-end tips with controllable sizes varying from 120 nm to 30 nm. The FIB head-on drilling creates holes on the aluminium-coated tips with sizes down to 50 nm. Nanoapertures in C and bow tie shapes can also be patterned using the FIB head-on milling method to possibly enhance the optical transmission. A transmission-collection NSOM system is constructed from a commercial atomic force microscopy to characterize the optical resolution of FIB-micro-machined aperture tips. The optical resolution of 78 nm is demonstrated by an aperture probe fabricated by FIB head-on drilling. Simultaneous topography imaging can also be realized using the same probe. By mapping the optical near-field from a bow-tie aperture, optical resolution as small as 59 nm is achieved by an aperture probe fabricated by the FIB side slicing method. Overall, high resolution and reliable optical imaging of routinely FIB-micro-machined aperture probes are demonstrated.


Socio-economic mobility among patients with schizophrenia or major affective disorder. A 17-year retrospective follow-up.
Social mobility among patients with schizophrenia or major affective disorder was compared with that among the general population. Mobility was studied retrospectively from 1970 to 1987. Socio-economic status (SES) was defined by occupation as in the population census (upper white-collar, lower white-collar, blue-collar, entrepreneur, farmer, unemployed). All patients aged 30-60 years at discharge (2901 men and 3620 women) in 1987-88 in Finland were included in the study. The SES structure of the general population was used for comparisons. Among patients with schizophrenia there was a constant downward drift, commonly to unemployment. This risk was higher among men than women. In the youngest age group a marked decline from the parents' social status was observed. Among patients with major affective disorder the distribution of SES in 1970 was similar to that of the general population. By 1987, a downward drift was again observed, mainly to unemployment regardless of the initial SES group. The number of patients in occupational categories were usually 30-50% lower than expected. Schizophrenic patients had a high risk of social drop-out. Among patients with major affective disorder the downward drift was much less.


Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy.
Radiation-induced tinnitus is a side effect of radiotherapy in the inner ear for cancers of the head and neck. Effective dose constraints for protecting the cochlea are under-reported. The aim of this study is to determine the cochlea dose limitation to avoid causing tinnitus after head-and-neck cancer (HNC) intensity-modulated radiation therapy (IMRT). In total 211 patients with HNC were included; the side effects of radiotherapy were investigated for 422 inner ears in the cohort. Forty-nine of the four hundred and twenty-two samples (11.6%) developed grade 2+ tinnitus symptoms after IMRT, as diagnosed by a clinician. The Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) criteria were used for tinnitus evaluation. The logistic and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models were used for the analyses. The NTCP-fitted parameters were TD 50 = 46.31 Gy (95% CI, 41.46-52.50), γ 50 = 1.27 (95% CI, 1.02-1.55), and TD 50 = 46.52 Gy (95% CI, 41.91-53.43), m = 0.35 (95% CI, 0.30-0.42) for the logistic and LKB models, respectively. The suggested guideline TD 20 for the tolerance dose to produce a 20% complication rate within a specific period of time was TD 20 = 33.62 Gy (95% CI, 30.15-38.27) (logistic) and TD 20 = 32.82 Gy (95% CI, 29.58-37.69) (LKB). To maintain the incidence of grade 2+ tinnitus toxicity <20% in IMRT, we suggest that the mean dose to the cochlea should be <32 Gy. However, models should not be extrapolated to other patient populations without further verification and should first be confirmed before clinical implementation.


European multicenter trials of curosurf for treatment of neonatal respiratory distress syndrome.
Curosurf, a preparation of polar lipids and hydrophobic proteins isolated from porcine lungs by liquid-gel chromatography, is currently used in European multicenter trials for prevention and treatment of neonatal respiratory distress syndrome (RDS). In babies requiring artificial ventilation with 60-100% oxygen, tracheal instillation of a single dose of Curosurf (200 mg/kg) leads to a dramatic improvement of gas exchange and reduced mortality, without increasing the incidence of neurodevelopmental handicap among survivors. Several factors, including high ventilator pressure and oxygen requirements, have a negative impact on the therapeutic response, suggesting that the patients should be treated at a comparatively early stage of the disease. Clinical trials testing this hypothesis, as well as the effect of multiple treatment doses, are in progress.


Sequence of the pearl oyster carbonic anhydrase-related protein and its evolutionary implications.
Carbonic anhydrases are conserved in vertebrates and invertebrates, and a noncatalytic carbonic anhydrase-related protein VIII (CARP VIII) has been found in deuterostomes and the phylum Placozoa. I isolated a cDNA encoding a noncatalytic CARP from the mantle of the pearl oyster Pinctada fucata. The polypeptide (CARP-1) predicted from the nucleotide sequence shares 44-60% identity with known CARP VIII sequences, and its phylogenetic analysis showed that P. fucata formed a single group with deuterostome invertebrates. However, since CARP VIII sequences are not identified in protostomes, these results suggest that CARP-1 may have originated in molluscs independently from deuterostome CARP VIII sequences.


Deformities of the hand and wrist with ulnar deficiency.
Deformities of the hand and wrist in 26 upper limbs of 20 patients with ulnar deficiency were studied. In eight limbs the ulna was totally absent. In the remainder it was severely or moderately hypoplastic. Abnormalities of the digits were present in all affected limbs. There was ectrodactyly in 25 hands. The thumb was hypoplastic in 21 hands and totally absent in five. Digital deformities also included syndactyly (14 hands) and delta phalanx (six hands). Early syndactyly release, pollicization, and rotational osteotomy of the metacarpals improved hand function in many of these patients. In only three of 26 limbs was there more than 20 degrees of fixed ulnar deviation at the wrist. In 16 patients the distal ulnar "anlage" was not removed. None of these patients developed ulnar deviation of the wrist or progressive deformity at the wrist during growth. Resection of the distal ulnar "anlage" does not appear to be warranted, unless there is progressive deformity of the wrist or elbow or increased bowing of the radius.


Interleukin-1 beta and interferon-gamma induce proliferation and apoptosis in cultured Schwann cells.
This study reports that in Schwann cell tissue culture the administration of the two pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma), at different dosages, singly or in combination, can induce apoptosis and/or mitosis. Schwann cell apoptosis was maximal within 24 h of stimulation with 50 U/ml of IFN-gamma, while proliferation was at its peak within 24 h with 10 U/ml IL-1 beta, and both processes decreased progressively by 48 and 72 h. Moreover, the combination of the two cytokines did not show any synergistic effect. These data can be interpreted as a possible involvement of pro-inflammatory cytokines not only in myelin disruption but also in promoting remyelination.


Isolation and biochemical characterization of cell wall tight protein complex involved in self-flocculation of Kluyveromyces bulgaricus.
Flocculation of yeasts is a cell-cell aggregation phenomenon which is driven by interactions between cell wall lectins and cell wall heteropolysaccharides. In Sabouraud medium, Kluyveromyces bulgaricus was highly flocculent. Incubation of flocculent K. bulgaricus cells with EDTA or Hecameg led to extracts showing hemagglutinating and flocculating properties. Purification of the extracts by native PAGE gave two bands which allowed flocculation of deflocculated K. bulgaricus. Both bands with specific reflocculating activity were composed of five subunits, of which only three possessed weak reflocculating activity upon deflocculated yeast. The mixture of these three proteins allow the recovery of initial specific reflocculating activity of the complex. These three proteins, denoted p28, p36 and p48, presented, in their first 15 amino acids, homologies with glycolysis enzymes, i.e., 3-phosphoglycerate mutase, glyceraldehyde-3-phosphate dehydrogenase and enolase, respectively. However, no such enzymatic activity could be detected in the crude extract issued from treatment with EDTA and Hecameg of flocculent yeast cells. When yeasts had grown in glucose poor medium, flocculation was drastically affected. The EDTA and Hecameg crude extracts showed weak reflocculating activity. After PAGE, the protein complexes did not appear in the EDTA extract, but they did appear in the Hecameg crude extract. These results suggest that: (i) self-flocculation of K. bulgaricus depends on the expression of different floc-forming protein complex, (ii) these proteins are galactose specific lectins showing homologies in their primary structure with glycolysis enzymes.


Variability in the expression of a beta 2-microglobulin epitope on hepatocytes in chronic type C hepatitis on treatment with interferon.
Cytotoxic CD8+ T lymphocytes recognize viral antigens in the context of human leukocyte antigen class I molecule coexpression by target cells. Analysis of beta 2-microglobulin reactivity is useful in evaluating changes in human leukocyte antigen class I antigen distribution. In this study we analyzed liver biopsy specimens obtained from 15 patients with chronic active hepatitis type C who underwent a clinical trial with recombinant interferon-alpha 2b. We comparatively studied by immunohistochemical analysis the expression of human leukocyte antigen class I antigens in frozen liver samples obtained before entry in the protocol and in specimens taken 8 mo after initiation of treatment. Six normal liver samples were used as controls. For immunohistochemical analysis, a panel of several human leukocyte antigen class I monoclonal antibodies, specific for beta 2-microglobulin or different heavy-chain determinants, was used. In addition, we included a novel monoclonal antibody (HP-1H8), characterized in this report, which is specific for a distinct beta 2-microglobulin epitope. On entry, mean serum ALT was 240 +/- 89 IU/L and mean Knodell's index was 9.9 +/- 2.4, whereas at the time of the second biopsy mean values had diminished to 45 +/- 22 IU/L and 4.7 +/- 3.0, respectively. Liver sections from controls and patients expressed human leukocyte antigen class I light- and heavy-chain determinants in hepatocytes, biliary duct epithelium, sinusoidal lining cells and lymphocytes. Remarkably, the beta 2-microglobulin epitope recognized by the HP-1H8 monoclonal antibody was undetectable on hepatocytes from normal livers but clearly evident on hepatocytes from patients with chronic active hepatitis C before interferon treatment. Positive staining was more intense in areas of piecemeal and lobular necrosis. Double immunostaining with a CD2 monoclonal antibody demonstrated that labeling with HP-1H8 was predominantly associated with T-cell infiltration. Interestingly, the reactivity of HP-1H8 with hepatocytes was diminished or disappeared in specimens obtained during interferon treatment; the pattern of reactivity then resembled that of samples from normal controls. Our data indirectly suggest that, in addition to the increased expression of human leukocyte antigen class I molecules on hepatocytes in viral infections, conformational changes may take place in these antigens. These changes can be revealed by immunostaining with the HP-1H8 monoclonal antibody. Interferon therapy could down-regulate this expression through its effect in reducing the histological activity resulting from the lysis of virus-infected hepatocytes by cytotoxic T cells.


Generation of an induced pluripotent stem cell line from a long QT syndrome patient carrying KCNH2/1956C > A mutation.
Long QT syndrome (LQT) is an inherited primary arrhythmic disorder characterized by prolonged QT interval on the surface electrocardiogram and life-threatening arrhythmia. In this study, a skin biopsy was obtained from an LQT type 2 (LQT2) patient, who carried a nonsense mutation (c.1956C > A; p.Y652X) in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. The skin fibroblasts were reprogrammed by non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical embryonic stem cell-like morphology, exhibited normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.


Serum potassium in elderly heart failure patients as a predictor of readmission within 1 year.
Blood potassium levels are associated with adverse outcomes in patients with congestive heart failure (HF). However, it is unclear whether there are differences in outcome events in elderly patients with different blood potassium levels at the time of emergency readmission within 1 year. This study used data from patients hospitalized with HF, integrating electronic medical records from the PhysioNet restricted health data database and external outcome data. We conducted a retrospective study of HF patients aged 60 years and older, using baseline data, comorbidities, laboratory tests, and medication use as covariates to analyze the effect of serum potassium levels on outcome events, with the primary outcome being readmission within 1 year. A priori was used to calculate the sample size, and this retrospective cohort study included a total of 788 elderly HF patients, of whom 20.3% had hypokalaemia (K+ < 3.5 mmol/L) and 14.7% had hyperkalemia (K+ > 4.7 mmol/L). According to a multivariate Cox regression model, patients with hyperkalemia had a shorter time interval between readmissions within 1 year, with a hazard ratio (HR) and its 95% CI of 1.134 (1.006-1.279). Three models were used to analyze patients with different blood potassium levels and, after correction, the high potassium group was at high risk relative to the low and normal groups, with significant differences in outcome events, with HRs and their 95% CI of 1.266 (1.03-1.557), 1.245 (1.01-1.534), and 1.439 (1.142-1.812), respectively. The robustness of the model was also demonstrated by competing risk models with subgroup analysis, showing that blood potassium levels had a stable effect on outcome events and were not altered by covariates (age, sex, diabetes, chronic kidney disease, NT-proBNP, high-sensitivity troponin, and glomerular filtration rate). The results show that high blood potassium levels are associated with the outcome event of readmission within 1 year in elderly patients with HF. Blood potassium levels at the time of the first hospitalization may therefore be a valuable predictor.


Unusual features of GABA responses in layers IV-V neurons of neocortex.
Perikaryal application of GABA produced a hyperpolarization and increased the input conductance in neurons of layers IV-V of neocortex (guinea pig). This response faded during brief applications and had a long duration when the application period was increased from 4s to greater than 10 s. The sensitivity of the first response to blockade by the selective antagonist, bicuculline, indicated a mediation by gamma-aminobutyric acid-A (GABAA) receptors. The longer duration response was mimicked to some extent by the GABAB agonist, baclofen. Dendritic application of GABA induced a depolarization and a conductance increase - a response which was not particularly sensitive to antagonism by bicuculline. The depolarizing response also did not have a clearly defined reversal potential and may be a consequence of complex changes in membrane conductance, possibly for Cl and Ca or Na. Fading in both types of responses may result from a concomitant postsynaptic activation of a Cl conductance with Na-dependent GABA uptake.


The interaction of Rhodococcus equi and foal neutrophils in vitro.
Polymorphonuclear neutrophil leukocytes (PMNL) from 8 healthy foals (2-14 weeks of age) and 2 foals with bacterial pneumonia were separated from whole blood using a 2 step Percoll gradient. Purified PMNL were tested for bactericidal function against Rhodococcus equi and Staphylococcus aureus in the presence of normal horse serum. The percentage uptake after a 15-min pre-incubation of PMNL and bacteria was also calculated. Ultrastructural examination of the interaction of R. equi and normal foal PMNL was performed after 15 min incubation. Results indicated that foal PMNL effectively phagocytose and destroy R. equi and S. aureus in the presence of normal horse serum. The mean percent uptake for R. equi was 99.3 +/- 0.4% and for S. aureus 99.9 +/- 0.1%. Further, 97.8 +/- 0.1% ingested R. equi and 98.4 +/- 0.1% ingested S. aureus were destroyed in the 15-min incubation period. Over the 3-h incubation, 91.9% of remaining R. equi were killed, but only 49.2 +/- 31.9% of S. aureus (P less than 0.01). Total bactericidal effect of foal PMNL, however, was 99.3 +/- 0.4% against R. equi and 99.9 +/- 0.1% against S. aureus. The percentage uptake and total bactericidal efficacy of neutrophils from sick foals was greater than 95%. Ultrastructural examination of the PMNL-R. equi interaction after 15 min incubation revealed phagocytosis of the bacteria and morphologic changes consistent with neutrophil degranulation. This study suggests that a defect in PMNL bactericidal capability is not likely to be a contributing factor in the pathogenesis of R. equi pneumonia in foals.


Preparation of substituted quaternized arylfuran chitosan derivatives and their antimicrobial activity.
Heterocyclic modification of chitosan has been achieved through the formation of a Schiff base intermediate by the reaction of chitosan with substituted arylfurfural. The Schiff bases were further reacted with 10% sodium borohydride followed by reaction with methyl iodide to get the quaternized products. The formation of the Schiff bases and quaternized derivatives has been confirmed by elemental analysis, FTIR, (1)H NMR and UV-vis spectroscopy. The compounds are also characterized by thermo-gravimetric analysis. The parent compound and quaternized derivatives were compared for their antibacterial and antifungal activity. The results indicated that quaternized derivatives possess better inhibitory property than chitosan. Further this study confirms that heterocyclic aromatic substituent containing 'Cl' and 'NO2' are effective in enhancing the antimicrobial activity of Chitosan.


Digital hand atlas and web-based bone age assessment: system design and implementation.
Bone age assessment is a procedure frequently performed in pediatric patients to evaluate their growth disorder. A simple method commonly used in bone age assessment is atlas matching by a radiological examination of a left-hand radiograph against a small reference set of Greulich-Pyle atlas patterns of normal standards. The method however can lead to significant deviation in age assessment, due to a variety of observers with different levels of training. The Greulich-Pyle atlas developed in the 1950s based on middle upper class white populations, is also not fully applicable for children of today, especially regarding the standard development in other racial groups. In this paper, we present our system design and initial implementation of a digital hand atlas and computer-aided diagnostic (CAD) system for Web-based bone age assessment. The CAD system is built on top of existing picture archiving and communication system (PACS), as well as recent advances in Internet technology. It consists of a hand atlas database, a CAD module and a Java-based Web user interface. The digital atlas is based on a large new set of clinically normal hand images of diverse ethnic groups. A relational image database system is used to organize hand images, their extracted quantitative features and patient data. The digital atlas removes the disadvantages of the currently out-of-date Greulich-Pyle atlas and allows the bone age assessment to be computerized. The Java-based Web user interface allows users to interact with the hand image database from browsers. Users can use a Web browser to push a clinical hand image to the CAD server for a bone age assessment. Quantitative features on the examined image, which reflect the skeletal maturity, are then extracted and compared with patterns from the atlas database to assess the bone age. The digital atlas method based on open system Internet technology provides an alternative to supplement or replace the traditional one for a quantitative, accurate and cost-effective assessment of bone age.


Visual adaptability and retinal characterization of the Egyptian fruit bat (Rousettus aegyptiacus, Pteropodidae): New insights into photoreceptors spatial distribution and melanosomal activity.
Our study was conducted to characterize the retinal structure of the Egyptian fruit bat, Rousettus aegyptiacus to determine the distribution of photoreceptors and melanosomal populations in various retinal zones. Also, we paid attention to the specific structural and functional adaptations related to their nocturnal habits. We analyzed the retinae of 12 adult male Egyptian fruit bats using morphometrical, histological, ultrastructural, and immunoblotting standard techniques. Histological findings revealed that the retinal cells have variations in geometrical architecture and different retinal thickness together with their corresponding layers bearing specific choroidal papillae projecting towards the inner retina. Immunoblotting and ultrastructure results showed that the microstructure of the retina conforms to that pattern found in mammalian species. The retinal photoreceptors are rod-dominant; alternatively, possess two spectral types of cones: SWS and LW/MWS cones as evidence for the basis for dichromatic vision. In addition, the outer retina showed densely-distributed melanin granules with a significant increase in the number of pigment epithelium cells in the eccentric retina. Furthermore, the asymmetric distribution among the retinal quadrants for the visual pigments of both rods and cones coinciding with neuronal cells such as bipolar and ganglion cells confers instructive information about their visual perception and orientation. In conclusion, our findings indicate that R. aegyptiacus efficiently discriminates colors with complex visual adaptations to mediate increased visual acuity coopted for the nocturnal niches.


UiO-66-NH2 MOF-based ratiometric fluorescent probe for the detection of dopamine and reduced glutathione.
Metal-organic framework materials (MOFs) are highly promising materials for biomedical applications owing to high porosity, adjustable pore structure and high loading capacity. In this paper, we herein reported a novel UiO-66-NH2 MOF-based ratiometric fluorescent probe for the high sensitive detection of dopamine and reduced glutathione. Light-emitting metal-organic framework materials UiO-66-NH2 MOF with a fluorescence emission wavelength of 450 nm was synthesized by a simple hydrothermal synthesis. Dopamine could self-oxidize in polyethyleneimine (PEI) solution to form copolymer (PDA-PEI), which can emit yellow-green fluorescence at 530 nm. PDA-PEI can quench the fluorescence of UiO-66-NH2 MOF via FRET and the fluorescence intensity of PDA-PEI at 530 nm is increasing. Due to the reductive properties of glutathione, the formation of PDA-PEI could be blocked and the fluorescence of the UiO-66-NH2 MOF could be restored. Therefore, dopamine and reduced glutathione could be detected simultaneously via monitoring the ratiometric fluorescence intensity (I530/I450). The ratiometric fluorescent method showed good linearity curve with the concentration of dopamine in the range of 4-50 μM and with the concentration of reduced glutathione in the range of 1-70 μM. Furthermore, the ratiometric fluorescent method had a low detection limit for DA (0.68 μM) and GSH (0.57 μM), and was successfully applied for DA and GSH determination in human serum.


Conduction disturbances after correction of tetralogy of Fallot: are electrophysiologic studies of prognostic value?
Late complete heart block may occur after correction of tetralogy of Fallot. Whether postoperative electrophysiologic studies can identify patients at risk of developing this conduction disturbance is unknown. In this study, 57 children who underwent electrophysiologic investigation after correction of tetralogy of Fallot were followed up for 1 to 13 (mean 6.5) years after the investigation. One late death and two cases of late complete heart block occurred. The late death was due to ventricular arrhythmia and not to a conduction disturbance. The cases of late heart block occurred 2 and 5 years, respectively, after electrophysiologic study, and in both cases the patient had a prolonged HV interval; in one patient progressive lengthening of the HV interval could be demonstrated at two subsequent studies 1 year apart. Another five patients with a prolonged HV interval had normally conducted sinus rhythm up to 11 years after study. Atrial pacing at increasing rates (up to the occurrence of second degree atrioventricular block) during electrophysiologic study was the best means of predicting late heart block: of three patients with block below the bundle of His occurring at pacing rates less than 180/min, two developed late complete heart block. Thus, electrophysiologic testing of the conduction system after correction of tetralogy of Fallot is useful in predicting late complete heart block and should be performed in patients with a history of transient heart block after surgery and in those with a prolonged PR interval.


[Ecological industry chain designing of making paper industry: turning pollution industry into ecological industry].
This paper gave a definition of ecological industry chain of renewal resources, and according to this definition designed the ecological industry chain of paper making industry of China; presented a basic principle of designing and ecological industry chain of renewal resources and five necessary conditions to establish an ecological industry chain of renewal resources, i.e. imitating the ecological closed-circuit system, increasing stock of renewal resources, getting benefits from resource productivity, developing long-run social demand and engaging in systematic innovation. It was found that the ecological industry chain of paper making industry was a representative example of ecological industry chain of renewal resources. The ecological industry chain of paper making industry solved three difficult constrain problems and offered an effective way to change the paper making industry of China from pollution industry into ecological industry.


Evidence of cis-acting factors in replication-mediated trinucleotide repeat instability in primate cells.
The mechanism of disease-associated trinucleotide repeat instability involves cis-acting factors (cis-elements) in the vicinity of the repeat, but the nature of these elements is unknown. One cis-element may be the location of the replication origin relative to the repeat. We have used an SV40 DNA replication system to investigate the effect of the location of replication initiation on (CTG)(n)*(CAG)(n) stability in primate cells. Depending on the distance between the SV40 replication origin and the repeat tract, templates with 79 repeats yield predominantly expansions or predominantly deletions or remain intact. All templates with 17 repeats are stable. Thus, cis-elements that affect the sites of Okazaki fragment initiation relative to the repeat are crucial determinants of instability. This model system recapitulates the bias for expansions observed in many of the diseases associated with trinucleotide repeats. Our results might explain the variable amounts of CTG/CAG instability that are observed in different chromosomal contexts.


Unloading results in rapid loss of TGFβ signaling in articular cartilage: role of loading-induced TGFβ signaling in maintenance of articular chondrocyte phenotype?
Recently it was shown that loading of articular cartilage explants activates TGFβ signaling. Here we investigated if in vivo chondrocytes express permanently high TGFβ signaling, and the consequence of the loss of compressive loading-mediated TGFβ signaling on chondrocyte function and phenotype. Bovine articular cartilage explants were collected within 10 min post mortem and stained immediately and after 30, 60 and 360 min for phosphorylated-Smad2, indicating active TGFβ signaling. Explants were unloaded for 48 h and subsequently repeatedly loaded with a compressive load of 3 MPa. In addition, explants were cultured unloaded for 2 weeks and the effect of loading or exogenous TGFβ on proteoglycan level and chondrocyte phenotype (Col10a1 mRNA expression) was analyzed. Unloading of articular cartilage results in rapid loss of TGFβ signaling while subsequent compressive loading swiftly restored this. Loading and exogenous TGFβ enhanced expression of TGFβ1 and ALK5. Unloading of explants for 2 weeks resulted in proteoglycan loss and increased Col10a1 expression. Both loading and exogenous TGFβ inhibited elevated Col10a1 expression but not proteoglycan loss. Our data might imply that in vivo regular physiological loading of articular cartilage leads to enduring TGFβ signaling and TGFβ-induced gene expression. We propose a hypothetical model in which loading activates a self-perpetuating system that prevents hypertrophic differentiation of chondrocytes and is crucial for cartilage homeostasis.


Reverse left ventricular remodeling by intermittent dobutamine infusions and amiodarone in end-stage heart failure due to idiopathic dilated cardiomyopathy.
The aim of this study was to evaluate the long-term effect of combined intermittent dobutamine infusions (IDI) and oral amiodarone on reverse left ventricular (LV) remodeling and hemodynamics of patients with idiopathic dilated cardiomyopathy (IDC) and end-stage congestive heart failure (CHF). This non-randomized, prospective, clinical trial included sixteen consecutive patients suffering from dyspnea for a mean of 76+/-43 months, who presented with acute cardiac decompensation and were weaned from dobutamine therapy after an initial 72-h infusion. They were then placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. The long-term clinical outcomes and the effects of treatment on reverse LV remodeling (echocardiographic parameters) and hemodynamics were evaluated at 3, 6, and 12 months of follow up. A significant degree of reverse LV remodeling, hemodynamic improvements, and survivals >1.5 years were observed in 9 of the 16 patients (56%). In addition, 5 patients (31% of entire cohort) were weaned from IDI after a mean of 61+/-41 weeks, and 4 remained clinically stable for 116+/-66 weeks thereafter. At 12 months of follow-up, LV end-diastolic and end-systolic volume indices had decreased from 231+/-91 to 206+/-80 ml/m2 (P=0.002) and from 137+/-65 to 110+/-50 ml/m2 (P=0.003), respectively, right atrial pressure from 16+/-6 to 5.6+/-4 mm Hg, (P=0.031), and pulmonary capillary wedge pressure from 29+/-4 to 16+/-5.4 mm Hg, P=0.000, while LV ejection fraction had increased from 22+/-6% to 27.3+/-8% (P=0.006). In end-stage CHF due to IDC, long-term treatment with IDI and oral amiodarone caused reverse LV remodeling, and allowed permanent and successful weaning from IDI in 1/4 of patients.


Autophagic and lysosomal defects in human tauopathies: analysis of post-mortem brain from patients with familial Alzheimer disease, corticobasal degeneration and progressive supranuclear palsy.
The accumulation of insoluble proteins within neurons and glia cells is a pathological hallmark of several neurodegenerative diseases. Abnormal aggregation of the microtubule-associated protein tau characterizes the neuropathology of tauopathies, such as Alzheimer disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). An impairment of the lysosomal degradation pathway called macroautophagy, hereafter referred to as autophagy, could contribute to the accumulation of aggregated proteins. The role of autophagy in neurodegeneration has been intensively studied in the context of AD but there are few studies in other tauopathies and it is not known if defects in autophagy is a general feature of tauopathies. In the present study, we analysed autophagic and lysosomal markers in human post-mortem brain samples from patients with early-onset familial AD (FAD) with the APP Swedish mutation (APPswe), CBD and PSP and control individuals. FAD, CBD and PSP patients displayed an increase in LC3-positive vesicles in frontal cortex, indicating an accumulation of autophagic vesicles. Moreover, using double-immunohistochemistry and in situ proximity ligation assay, we observed colocalization of hyperphosphorylated tau with the autophagy marker LC3 in FAD, CBD and PSP patients but not in control individuals. Increased levels of the lysosomal marker LAMP1 was detected in FAD and CBD, and in addition Cathepsin D was diffusely spread in the cytoplasm in all tauopathies suggesting an impaired lysosomal integrity. Taken together, our results indicate an accumulation of autophagic and lysosomal markers in human brain tissue from patients with primary tauopathies (CBD and PSP) as well as FAD, suggesting a defect of the autophagosome-lysosome pathway that may contribute to the development of tau pathology.


Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR.
Transitioning from pluripotency to differentiated cell fates is fundamental to both embryonic development and adult tissue homeostasis. Improving our understanding of this transition would facilitate our ability to manipulate pluripotent cells into tissues for therapeutic use. Here, we show that membrane voltage (Vm) regulates the exit from pluripotency and the onset of germ layer differentiation in the embryo, a process that affects both gastrulation and left-right patterning. By examining candidate genes of congenital heart disease and heterotaxy, we identify KCNH6, a member of the ether-a-go-go class of potassium channels that hyperpolarizes the Vm and thus limits the activation of voltage gated calcium channels, lowering intracellular calcium. In pluripotent embryonic cells, depletion of kcnh6 leads to membrane depolarization, elevation of intracellular calcium levels, and the maintenance of a pluripotent state at the expense of differentiation into ectodermal and myogenic lineages. Using high-resolution temporal transcriptome analysis, we identify the gene regulatory networks downstream of membrane depolarization and calcium signaling and discover that inhibition of the mTOR pathway transitions the pluripotent cell to a differentiated fate. By manipulating Vm using a suite of tools, we establish a bioelectric pathway that regulates pluripotency in vertebrates, including human embryonic stem cells.


The value of genetic and pharmacological approaches to understanding the complexities of GABA(A) receptor subtype functions: the anxiolytic effects of benzodiazepines.
The identification of gamma-aminobutyric acid A (GABA(A)) receptor subunit genes over the last twenty years has shown that GABA(A) receptors are made up of many different subtypes. As such the dissection of which receptor subtypes mediate which functions of clinically useful GABAergic drugs, such as benzodiazepines, has been extremely complicated. Two complimentary approaches have been taken: the development of subtype-selective drugs and the genetic manipulation of different receptor subunits. Both have yielded exciting results, but sometimes with contradictory findings. This review highlights the strengths and weaknesses of both approaches, illustrating with specific discussion of the work, to uncover which receptor subtype(s) mediates the anxiolytic effects of benzodiazepines.


Cytogenetic toxicity of gentian violet and crystal violet on mammalian cells in vitro.
The cytogenetic toxicity of gentian violet in Chinese hamster CHO cells in vitro has been studied by analyzing (1) squash preparations from direct fixation for recording mitotic anomalies and (2) air-dried preparations (with colcemid--hypotonic pretreatments) for recording metaphase chromosome aberrations. It was concluded that this compound is a mitotic poison as well as a clastogen in vitro. Its clastogenic property was confirmed in 5 other different mammalian cel types. 10 samples of different gentian violet and crystal violet were surveyed and all were shown to be clastogenic. Unless in vivo studies prove otherwise, gentian violet and crystal violet should be regarded as biohazardous substances.


Apicoectomy with retrograde gutta-percha root filling.
Sixty-four teeth were treated by means of apicoectomy with retrograde gutta-percha filling with the use of new instruments that we devised. The new instruments consisted of a biangle explorer, angle reamers, and angle files. Operations with this technique showed a success rate of 95.3% (61/64 teeth). We conclude that our technique for apicoectomy with retrograde gutta-percha filling is not only simple in procedure, but also shows excellent results.


The effect of donor age on human fibroblast beta-adrenergic receptor response and agonist-induced desensitization.
Aging has been associated with changes in beta-adrenergic receptor (beta-receptor) function in several tissues. The relative contribution of cellular aging and age-related changes in homeostatic regulation of receptor function is unknown. We have examined beta-receptor function in fibroblasts of young and old donors (young: mean age 31.2 +/- 0.8 years +/- S.E., n = 6; old: mean age 81.8 +/- 0.6 years +/- S.E., n = 6). Beta-receptor responses to isoproterenol (ISO), (1 microM) were similar in the two groups. The concentration of ISO required for 50% maximal beta-receptor-mediated cyclic AMP production (EC50) was similar in both groups. Fibroblast beta-receptor density was also similar in young and old groups. ISO-induced beta-receptor desensitization was both dose- and time-dependent. Submaximal desensitization by acute exposure (30 min) to ISO (1 mM) caused similar levels of beta-receptor desensitization in young (42.5 +/- 2.5%) and old (42.8 +/- 2.8%) groups and a similar increase in ISO EC50. These findings demonstrate that aging in vivo does not cause changes in fibroblast beta-receptor regulation that are retained in culture.


Transforming Surgical Education through a Resident Robotic Curriculum.
Here, we describe a systematic approach to design, implement, and assess a robotic surgery curriculum for surgical residents. By describing our process, including identifying and addressing institutional challenges, we illustrate successful development of a robust curriculum. As robotic-assisted surgeries increase, educational challenges have emerged and illustrate an alarming impact on medical training. Robotic curricula are frequently grounded in the industry's educational materials resulting in a variety of existing resident curricula that lack cognitive components and critical evaluation. As such, surgical educators struggle to identify the curricular restructuring needs that likely accompany emerging technologies. It is essential to develop a curricular framework for the surgical education community to approach the ongoing and inevitable integration of new technologies. Our process parallels the widely accepted approach to curricular development in medical education described by Kern et al. Using this 6-step model, we describe derivation of a curriculum that was data driven, features multimodal educational strategies, and provides documentation methods that allow for continued evaluation and assessment at the individual and departmental level. This study highlights the systematic process of design, implementation and assessment of a robotic surgery curriculum for surgical residents. Built on a robust national and local needs assessment, and further strengthened by preemptive identification of institutional challenges, this curricular model includes a structured documentation system that allows for ongoing evaluation, assessment, and monitoring of curricular progress. We illustrate a robustly built curricular structure that can be adopted, adapted, and successfully implemented at other training institutions around the world.


Conservation implications of limited genetic diversity and population structure in Tasmanian devils (Sarcophilus harrisii).
Tasmanian devils face a combination of threats to persistence, including Devil Facial Tumor Disease (DFTD), an epidemic transmissible cancer. We used RAD sequencing to investigate genome-wide patterns of genetic diversity and geographic population structure. Consistent with previous results, we found very low genetic diversity in the species as a whole, and we detected two broad genetic clusters occupying the northwestern portion of the range, and the central and eastern portions. However, these two groups overlap across a broad geographic area, and differentiation between them is modest (FST = 0.1081). Our results refine the geographic extent of the zone of mixed ancestry and substructure within it, potentially informing management of genetic variation that existed in pre-diseased populations of the species. DFTD has spread across both genetic clusters, but recent evidence points to a genomic response to selection imposed by DFTD. Any allelic variation for resistance to DFTD may be able to spread across the devil population under selection by DFTD, and/or be present as standing variation in both genetic regions.


Domains of professional fulfillment for pediatric hospital medicine: A concept mapping study.
We know little about how pediatric hospital medicine (PHM) physicians conceptualize their professional fulfillment (PF). The objective of this study was to determine how PHM physicians conceptualize PF. The objective of this study was to determine how PHM physicians conceptualize PF. We performed a single-site group concept mapping (GCM) study to create a stakeholder-informed model of PHM PF. We followed established GCM steps. For brainstorming, PHM physicians responded to a prompt to generate ideas describing the concept of PHM PF. Next, PHM physicians sorted the ideas based on conceptual relatedness and ranked them on importance. Responses were analyzed to create point cluster maps where each idea represented one point, and point proximity illustrated how often ideas were sorted together. Using an iterative and consensus-driven approach, we selected a cluster map best representing the ideas. Mean rating scores for all the items in each cluster were calculated. Sixteen PHM physicians identified 90 unique ideas related to PHM PF. The final cluster map described nine domains for PHM PF: (1) work personal-fit, (2) people-centered climate, (3) divisional cohesion and collaboration, (4) supportive and growth-oriented environment, (5) feeling valued and respected, (6) confidence, contribution, and credibility, (7) meaningful teaching and mentoring, (8) meaningful clinical work, and (9) structures to facilitate effective patient care. The domains with the highest and lowest importance ratings were divisional cohesion and collaboration and meaningful teaching and mentoring. Domains of PF for PHM physicians extend beyond existing PF models, particularly the importance of teaching and mentoring.


Aromatase expression in the ovary: hormonal and molecular regulation.
Estrogens are synthesized by the aromatase enzyme encoded by the Cyp19a1 gene, which contains an unusually large regulatory region. In most mammals, aromatase expression is under the control of two distinct promoters a gonad- and a brain-specific promoter. In humans, this gene contains 10 tissue-specific promoters that are alternatively used in various cell types and tumors. Each promoter is regulated by a distinct set of regulatory sequences and transcription factors that bind to these specific sequences. The cAMP/PKA/CREB pathway is considered to be the primary signaling cascade through which the gonad Cyp19 promoter is regulated. Very interestingly, in rat luteal cells, the proximal promoter is not controlled in a cAMP dependent manner. Strikingly, these cells express aromatase at high levels similar to those found in preovulatory follicles, suggesting that alternative and powerful mechanisms control aromatase expression in luteal cells and that the rat corpus luteum represents an important paradigm for understanding alternative controls of the aromatase gene. Here, the molecular and cellular mechanisms controlling the expression of the aromatase gene in granulosa and luteal cells are discussed.


Controlled intra- or extracellular production of staphylococcal nuclease and ovine omega interferon in Lactococcus lactis.
A system for controlled targeting of heterologous protein was developed in the food-grade bacterium Lactococcus lactis. It is composed of the L. lactis strain NZ9000 and of two broad host range expression vectors pCYT:Nuc and pSEC:Nuc for, respectively, cytoplasmic and secreted staphylococcal nuclease (Nuc) nisin-inducible production. The level of intracellular production of Nuc measured with pCYT:Nuc (3 mg x l(-1)) is significantly lower than the one obtained with pSEC:Nuc ( approximately 20 mg x l(-1)). The secretion efficiency (SE) of Nuc is estimated to be approximately 70%, corresponding to approximately 15 mg of secreted Nuc x l(-1). Furthermore, we established that Nuc production continued in L. lactis 10 h after a 1-h nisin-pulse induction. This system was then used for intra- and extracellular production of a protein of therapeutical interest in L. lactis, the ovine interferon-omega (IFN-omega). The SE and the quantity of secreted active IFN-omega were evaluated respectively to be approximately 70% and approximately 1 mg x l(-1) ( approximately two-fold higher than the cytoplasmic form).


Chronic immobilization stress: evidence for decreases of 5-hydroxy-tryptamine immunoreactivity and for increases of glucocorticoid receptor immunoreactivity in various brain regions of the male rat.
Male rats were exposed to severe 14 day immobilization stress. Body weight, body temperature, food and water intake, behavioral parameters, and serum corticosterone levels were measured during and after the stress period. On the 7th day after cessation of stress the experimental animals together with the control rats were taken to immunocytochemical analysis involving morphometry and microdensitometry of tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), various neuropeptide, and glucocorticoid receptor (GR) immunoreactivities (IRs) in a large number of regions of the central nervous system. In addition, adrenocorticotropic hormone (ACTH) IR was analyzed in the pituitary gland. Seven days following cessation of the chronic stress food intake, total locomotion and forward locomotion had been restored to normal. Serum corticosterone levels appeared to remain increased even 6 days following cessation of the chronic immobilization stress, probably caused by increased release of ACTH. Paraventricular corticotropin releasing hormone (CRF) IR was negatively correlated with the pituitary ACTH IR, indicating that the increase in ACTH release was produced by an increased release of CRF from the hypothalamus. The major immunocytochemical change observed 7 days after cessation of stress was a disappearance of 5-HT IR in the 5-HT cell groups B1, B2, B3, and B7. 5-HT IR in nerve terminals was only affected in the dorsal horn, where 5-HT IR was increased in the substantia gelatinosa. GR IR was found to be significantly increased in monoaminergic cell groups: serotoninergic B7, dopaminergic A12, and noradrenergic A1, A2, and A6. A trend for a reduction of TH IR was observed in nigral DA cells associated with significant reductions in TH IR in striatal DA nerve terminals. Finally, increases in 5-HT and substance P (SP) IR were found in the nerve terminals of the substantia gelatinosa of the cervical spinal cord in the stress group. In the present experimental model evidence has been obtained for a maintained activation of the hypothalamic-pituitary-adrenal axis as evaluated 7 days after cessation of severe chronic immobilization stress. The reduction of 5-HT IR in various 5-HT cell groups indicates a reduction of 5-HT synthesis, which may also be associated with reduced 5-HT release from the nerve terminals, since no depletion was observed in terminal regions and in one case an increase in 5-HT IR was noted (substantia gelatinosa).(ABSTRACT TRUNCATED AT 400 WORDS)


Characterisation and evaluation of paramagnetic fluorine labelled glycol chitosan conjugates for (19)F and (1)H magnetic resonance imaging.
Medium molecular weight glycol chitosan conjugates have been prepared, linked by an amide bond to paramagnetic Gd(III), Ho(III) and Dy(III) macrocyclic complexes in which a trifluoromethyl reporter group is located 6.5 Å from the paramagnetic centre. The faster relaxation of the observed nucleus allows modified pulse sequences to be used with shorter acquisition times. The polydisperse materials have been characterised by gel permeation chromatography, revealing an average molecular weight on the order of 13,800 (Gd), 14,600 (Dy) and 16,200 (Ho), consistent with the presence of 8.5, 9.5 and 13 complexes, respectively. The gadolinium conjugate was prepared for both a q = 1 monoamide tricarboxylate conjugate (r1p 11.2 mM(-1) s(-1), 310 K, 1.4 T) and a q = 0 triphosphinate system, and conventional contrast-enhanced proton MRI studies at 7 T were undertaken in mice bearing an HT-29 or an HCT-116 colorectal tumour xenograft (17 μmol/kg). Enhanced contrast was observed following injection in the tail vein in tumour tissue, with uptake also evident in the liver and kidney with a tumour-to-liver ratio of 2:1 at 13 min, and large amounts in the kidney and bladder consistent with predominant renal clearance. Parallel experiments observing the (19)F resonance in the holmium conjugate complex using a surface coil did not succeed owing to its high R2 value (750 Hz, 7 T). However, the fluorine signal in the dysprosium triphosphinate chitosan conjugate [R1/R2 = 0.6 and R1 = 145 Hz (7 T)] was sharper and could be observed in vivo at -65.7 ppm, following intravenous tail vein injection of a dose of 34 μmol/kg.


Technology and educational choices: Evidence from a one-laptop-per-child program.
This paper provides the first causal estimates of the effect of children's access to computers and the internet on educational outcomes in early adulthood, such as schooling and choice of major. I exploit cross-cohort variation in access to technology among primary and middle school students in Uruguay, the first country to implement a nationwide one-laptop-per-child program. Despite a notable increase in computer access, educational attainment has not increased; the schooling gap between private and public school students has persisted, despite closing the technology gap. Among college students, those who had been exposed to the program as children were less likely to enroll in science and technology.


Clinicopathological characteristics, practical treatments, prognosis, and clinical issues of older breast cancer patients in Japan.
Minimal data are available to support the clinical management of older breast cancer patients. Consequently, the standard of care remains unclear. Our aim was to clarify the clinicopathological characteristics, practical treatments, and prognosis of older Japanese breast cancer patients and discuss clinical issues. We reviewed 132,240 cases, diagnosed between 2004 and 2011, from the Japanese Breast Cancer Registry. Focusing on older patients, we compared data among three age groups: 75 years and over (n = 27,385), 65-74 years (n = 43,839), and 55-64 years (n = 61,016). Data revealed the proportions of mucinous and apocrine carcinoma were higher in older patients, and they more frequently had clinical stage II and III cancer. Their ER-positive rates were higher, in contrast to the lower HER2-positive, breast-conserving surgery (BCS), post-BCS irradiation, and adjuvant chemotherapy rates. Almost half of the older patients who underwent chemotherapy received CMF or oral 5FU, during hormone therapy, Tamoxifen was administered more frequently. The overall survival rate decreased with age, but the breast cancer-specific survival (BCSS) at 5 years remained similar. The rate of other cause of death in the oldest group was about a half, and more than double that in those aged 55-64 years. We showed clinical data of older breast cancer patients in Japan. Their disease was more advanced at the time of diagnosis, post-BCS irradiation and primary systemic chemotherapy were omitted more frequently, and overall, BCSS was similar among age categories, although the rate of other causes of death was higher.


Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1.
Genetic deficiencies in transcription factors can lead to the loss of certain types of cells and tissue. The steroidogenic tissue-specific nuclear receptor Ad4BP/SF-1 (NR5A1) is one such gene, because mice in which this gene is disrupted fail to develop the adrenal gland and gonads. However, the specific role of Ad4BP/SF-1 in these biological events remains unclear. Here we use chromatin immunoprecipitation sequencing to show that nearly all genes in the glycolytic pathway are regulated by Ad4BP/SF-1. Suppression of Ad4BP/SF-1 by small interfering RNA reduces production of the energy carriers ATP and nicotinamide adenine dinucleotide phosphate, as well as lowers expression of genes involved in glucose metabolism. Together, these observations may explain tissue dysgenesis as a result of Ad4BP/SF-1 gene disruption in vivo. Considering the function of estrogen-related receptor α, the present study raises the possibility that certain types of nuclear receptors regulate sets of genes involved in metabolic pathways to generate energy carriers.


Radiomic analysis to predict local response in locally advanced pancreatic cancer treated with stereotactic body radiation therapy.
Aim of this study is to assess the ability of contrast-enhanced CT image-based radiomic analysis to predict local response (LR) in a retrospective cohort of patients affected by pancreatic cancer and treated with stereotactic body radiation therapy (SBRT). Secondary aim is to evaluate progression free survival (PFS) and overall survival (OS) at long-term follow-up. Contrast-enhanced-CT images of 37 patients who underwent SBRT were analyzed. Two clinical variables (BED, CTV volume), 27 radiomic features were included. LR was used as the outcome variable to build the predictive model. The Kaplan-Meier method was used to evaluate PFS and OS. Three variables were statistically correlated with the LR in the univariate analysis: Intensity Histogram (StdValue feature), Gray Level Cooccurrence Matrix (GLCM25_Correlation feature) and Neighbor Intensity Difference (NID25_Busyness feature). Multivariate model showed GLCM25_Correlation (P = 0.007) and NID25_Busyness (P = 0.03) as 2 independent predictive variables for LR. The odds ratio values of GLCM25_Correlation and NID25_Busyness were 0.07 (95%CI 0.01-0.49) and 8.10 (95%CI 1.20-54.40), respectively. The area under the curve for the multivariate logistic regressive model was 0.851 (95%CI 0.724-0.978). At a median follow-up of 30 months, median PFS was 7 months (95%CI 6-NA); median OS was 11 months (95%CI 10-22 months). This analysis identified a radiomic signature that correlates with LR. To confirm these results, prospective studies could identify patient sub-groups with different rates of radiation dose-response to define a more personalized SBRT approach.


Sonographic assessment of minor extrathyroidal extension of papillary thyroid microcarcinoma involving the posterior thyroid capsule.
This study aimed to determine sonographic features and clinical significance of minor extrathyroidal extension (ETE) to the posterior thyroid capsule in papillary thyroid microcarcinoma (PTMC) patients. We retrospectively reviewed the records of 506 PTMC patients consisting of 151 patients with minor ETE and 355 patients without ETE. Significant clinicoradiologic features associated with ETE were identified by logistic regression analyses. The diagnostic performance of sonographic features, including the presence of capsular abutment, capsular abutment degree (< 25%, 25-50%, ≥ 50%), and protrusion, were assessed for the diagnosis of posterior minor ETE. Interobserver agreement was calculated. PTMC patients with posterior minor ETE were more likely to have lymphovascular invasion and lateral neck lymph node metastasis (OR = 2.636, 95%CI: 1.754, 3.963 and OR = 2.897, 95%CI: 1.069, 7.848). Regarding the diagnostic performance, the capsular abutment yielded the highest sensitivity (81.5%), followed by ≥ 25% abutment, protrusion, and ≥ 50% abutment (57.0%, 21.9%, and 4.6%, respectively), with similar levels of diagnostic accuracy (71.3-75.1%). The specificity was highest for the sonographic feature of ≥ 50% abutment (99.7%), followed by protrusion, ≥ 25% abutment, and capsular abutment (97.8%, 82.0%, and 68.7%, respectively). Abutment assessment had a moderate interobserver agreement (K = 0.705), and abutment degree and protrusion assessment had a fair and slight interobserver agreement (K = 0.553 and 0.287). Sonographic features of posterior capsular abutment are sensitive and reliable for diagnosis of posterior minor ETE and are associated with lymphovascular invasion and lateral neck lymph node metastasis in PTMC patients. The assessment of posterior minor ETE is important for considering candidates for active surveillance among PTMC patients. • PTMC patients with posterior minor ETE were more likely to have lymphovascular invasion and lateral neck lymph node metastasis. • Sonographic features of posterior capsular abutment are sensitive and reliable for the diagnosis of posterior minor ETE. • The assessment of posterior minor ETE is important for considering candidates for active surveillance among PTMC patients.


[Training and providing assistance: images of Curitiba's Senai school in the 1940s and 1950s].
A branch of the Serviço Nacional de Aprendizagem Industrial (Senai) was set up in Paraná in 1943 to train industrial labor. Images and written records held by the Paraná State Federation of Industries depict aspects of technical training at the Senai school in Curitiba, both from an institutional perspective and from the students', through their discourse. A comparison of these images and discourses serves to highlight the vicissitudes of this private institution's vocational training project, which received government support for the instruction of industrial workers, especially apprentices.


Comparison of Bivalirudin versus Bivalirudin plus glycoprotein IIb/IIIa inhibitor versus heparin plus glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes having percutaneous intervention for narrowed saphenous vein aorto-coronary grafts (the ACUITY trial investigators).
Clinical outcomes in patients with acute coronary syndromes randomized in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial who underwent percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) were examined. The ACUITY trial assessed the safety and efficacy of bivalirudin alone versus bivalirudin plus a glycoprotein (GP) IIb/IIIa inhibitor versus heparin plus a GP IIb/IIIa inhibitor in 13,819 patients with moderate- and high-risk acute coronary syndromes, 7,789 of whom underwent PCI. A total of 329 patients (4.2%) underwent PCI of SVGs in ACUITY. The primary end points at 30 days were composite ischemia or major adverse cardiac events (death, myocardial infarction, or unplanned target vessel revascularization), major bleeding (unrelated to coronary artery bypass grafting), and net adverse clinical events (composite ischemia or major bleeding). The rates of ischemic, bleeding, and net clinical end points were similar with bivalirudin monotherapy, bivalirudin plus a GP IIb/IIIa inhibitor, and heparin plus a GP IIb/IIIa inhibitor. Net adverse clinical outcome rates at 30 days were 22%, 26%, and 22% (p = 0.67), respectively, for the 3 groups. Major adverse cardiac event rates at 1 year were 37%, 37%, and 43% (p = 0.95), respectively. Minor bleeding unrelated to coronary artery bypass grafting at 30 days was significantly lower with bivalirudin alone compared with heparin plus a GP IIb/IIIa inhibitor (26% vs 38%, p = 0.05). In conclusion, bivalirudin is an effective anticoagulant in PCI of SVGs in acute coronary syndromes, with similar rates of major adverse cardiac events and net adverse cardiac events and lower minor bleeding complications in comparison with heparin plus a GP IIb/IIIa inhibitor or bivalirudin plus a GP IIb/IIIa inhibitor.


The strange history of phage therapy.
Since the enlightenment, scientists have enjoyed a self-image as rational actors, guided only by reason, evidence and logic. When the Royal Society of London was founded in 1660 it chose as its motto "nullius in verba" (often translated as "on the word of no one") a reference to Horace's Epistles "Nullius addictus iurare in verba magistri…" (being not obliged swear allegiance to any master). Similar to our 21st century contemporaries who embrace the "new evidenced-based medicine," the "virtuosi" of the Royal Society proclaimed a new era in science based only on observation and direct experience.


Implications of applying methodological shortcuts to expedite systematic reviews: three case studies using systematic reviews from agri-food public health.
The rapid review is an approach to synthesizing research evidence when a shorter timeframe is required. The implications of what is lost in terms of rigour, increased bias and accuracy when conducting a rapid review have not yet been elucidated. We assessed the potential implications of methodological shortcuts on the outcomes of three completed systematic reviews addressing agri-food public health topics. For each review, shortcuts were applied individually to assess the impact on the number of relevant studies included and whether omitted studies affected the direction, magnitude or precision of summary estimates from meta-analyses. In most instances, the shortcuts resulted in at least one relevant study being omitted from the review. The omission of studies affected 39 of 143 possible meta-analyses, of which 14 were no longer possible because of insufficient studies (<2). When meta-analysis was possible, the omission of studies generally resulted in less precise pooled estimates (i.e. wider confidence intervals) that did not differ in direction from the original estimate. The three case studies demonstrated the risk of missing relevant literature and its impact on summary estimates when methodological shortcuts are applied in rapid reviews. © 2016 The Authors. Research Synthesis Methods Published by John Wiley & Sons Ltd.


Spatial distribution of antibiotic and heavy metal resistance genes in the Black Sea.
Antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB) are worldwide considered as emerging contaminants of large interest, and a primary threat to human health. It is becoming clear that the environment plays a central role in the transmission, spread, and evolution of antibiotic resistance. Although marine systems have been largely investigated, only a few studies have considered the presence of ARGs in meso- and bathypelagic waters. To date, no molecular based studies have yet been made to investigate the occurrence of ARGs in the Black Sea, the largest meromictic basin in the world, receiving water from a number of important European rivers and their residues of anthropogenic activities in permanently stratified mesopelagic water masses. In this study, we determined the presence and the abundance of five ARGs (blaCTXM, ermB, qnrS, sul2, tetA) and of the heavy metal resistance gene (HMRG) czcA, in different sampling sites in the eastern and western Black Sea, at several depths (up to 1000 m) and various distances from the shoreline. Three ARGs (blaCTXM, sul2, and tetA) and czcA were present in at least 43% of the analysed samples, whereas ermB and qnrS were never detected. In particular, sul2 abundances increased significantly in coastal location, whereas tetA increased with sampling depth. These findings point out the Black Sea as a source of ARGs and HMRGs distributed along the whole water column.


Anticancer Evaluation of Methoxy Poly(Ethylene Glycol)-b-Poly(Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer.
We aimed to inhibit ovarian cancer (OC) development by interfering with microtubule polymerization and inhibiting mTOR signaling. To achieve this, previously developed micelles containing fenbendazole and rapamycin were applied. Herein, we prepared micelles for drug delivery using fenbendazole and rapamycin at a 1:2 molar ratio and methoxy poly(ethylene glycol)-b-poly(caprolactone)(mPEG-b-PCL) via freeze-drying. We revealed their long-term storage capacity of up to 120 days. Furthermore, a cytotoxicity test was performed on the OC cell line HeyA8, and an orthotopic model was established for evaluating in vivo antitumor efficacy. Fenbendazole/rapamycin-loaded mPEG-b-PCL micelle (M-FR) had an average particle size of 37.2 ± 1.10 nm, a zeta potential of -0.07 ± 0.09 mV, and a polydispersity index of 0.20 ± 0.02. Additionally, the average encapsulation efficiency of fenbendazole was 75.7 ± 4.61% and that of rapamycin was 98.0 ± 1.97%. In the clonogenic assay, M-FR was 6.9 times more effective than that free fenbendazole/rapamycin. The in vitro drug release profile showed slower release in the combination formulation than in the single formulation. There was no toxicity, and tumor growth was suppressed substantially by our formulation compared with that seen with the control. The findings of our study lay a foundation for using fenbendazole and rapamycin for OC treatment.


Meldola blue: a new electron carrier for the histochemical demonstration of dehydrogenases (SDH, LDH, G-6-PDH).
A new electron carrier, Meldolar Blue (8-dimethylamino-2,3-benzophenoxazine; Boehringer Mannheim GmbH, Deutsche Patentschrift P 1959410) was tested for its usefulness in the histochemical demonstration of dehydrogenase activity in adrenal cortex, liver, heart muscle of guinea pig and human oviduct and compared with PMS. For demonstrating SDH activity Meldola Blue (MB) is as efficient as PMS. A decisive advantage of MB as compared with PMS is its low sensitivity to light exposure, facilitating direct visualisation of histochemical reaction processes. Generally, a high diffusion rate of reduced electron carriers (PMS and MB) from the section into the incubation medium (PVA) leads to a loss of reduction equivalents, particularly in the demonstration of NAD- or NADP-dependent dehydrogenases (LDH, G-6-PDH) with lower TNBT concentrations. However, no inhibition of SDH-, LDH- and G-6-PDH activities was observed with incubation media containing the tested concentrations of PMS and MB.


Health risk characterization for exposure to benzene in service stations and petroleum refineries environments using human adverse response data.
Health risk characterization of exposure to benzene in service stations and petroleum refineries has been carried out in previous studies using guideline values set by various agencies. In this work, health risk was characterized with the exposure data as cumulative probability distribution (CPD) plots but using human epidemiological data. This was achieved by using lowest observable adverse effects levels (LOAEL) data plotted as cumulative probability lowest effects distribution (CPLED). The health risk due to benzene was characterized by using probabilistic methods of hazard quotient (HQ50/50 and HQ95/5), Monte-Carlo simulation (MCS) and overall risk probability (ORP). CPD relationships of adverse health effects relationships and exposure data were in terms of average daily dose (ADD) and lifetime average daily dose (LADD) for benzene. For service station environments HQ50/50 and HQ95/5 were in a range of 0.000071-0.055 and 0.0049-21, respectively. On the other hand, the risk estimated for petroleum refinery environments suggests higher risk with HQ50/50 and HQ95/5 values ranging from 0.0012 to 77 and 0.17 to 560, respectively. The results of Monte-Carlo risk probability (MRP) and ORP indicated that workers in petroleum refineries (MRP of 2.9-56% and ORP of 4.6-52% of the affected population) were at a higher risk of adverse health effects from exposure to benzene as compared to exposure to benzene in service station environments (MRP of 0.051 -3.4% and ORP of 0.35-2.7% affected population). The adverse effect risk probabilities estimated by using the Monte-Carlo simulation technique and the ORP method were found to be generally consistent.


Retinal Image Simulation of Subjective Refraction Techniques.
Refraction techniques make it possible to determine the most appropriate sphero-cylindrical lens prescription to achieve the best possible visual quality. Among these techniques, subjective refraction (i.e., patient's response-guided refraction) is the most commonly used approach. In this context, this paper's main goal is to present a simulation software that implements in a virtual manner various subjective-refraction techniques--including Jackson's Cross-Cylinder test (JCC)--relying all on the observation of computer-generated retinal images. This software has also been used to evaluate visual quality when the JCC test is performed in multifocal-contact-lens wearers. The results reveal this software's usefulness to simulate the retinal image quality that a particular visual compensation provides. Moreover, it can help to gain a deeper insight and to improve existing refraction techniques and it can be used for simulated training.


Impacts of nonpoint inputs from potato farming on populations of slimy sculpin (Cottus cognatus).
The potential influence of agricultural activity, particularly potato cultivation, on slimy sculpin populations (Cottus cognatus) was examined at 19 rivers of New Brunswick, Canada. Comparisons with forested streams resulted in differences in fish density, size, and reproductive performance. Young-of-the-year (YOY) sculpin were present only at two of 11 agricultural sites, though they were present at all nine forested sites. Sediment deposition was greatest at agricultural sites, with increased fine sediments deposited. Larger, coarse sands were deposited at two sites with active forest operations. Temperature had a stronger correlation than sedimentation with sculpin size and density in the agricultural region. Agricultural catchments were warmer than in forested catchments (median = 16.0 and 13.3 degrees C, respectively). Body size of slimy sculpin was correlated positively and YOY densities correlated negatively with temperature, and sites with temperatures > or = 25 degrees C were devoid of YOY sculpin. Our data indicate there is a significant effect of temperature on slimy sculpin populations in rivers of potato farming areas, highlighting the importance of examining indirect factors when investigating possible impacts of nonpoint source agricultural inputs. Indirect factors such as sediment deposition and temperature need to be considered in order to discriminate accurately the chronic impacts of agricultural chemicals on fish populations.


[Contribution of imaging in the diagnosis of epiploic appendagitis].
Primary epiploic appendagitis is known to be a rare finding among causes of acute abdomen. Depending on location, it may mimic several disorders such as colonic diverticulitis and acute appendicitis. Diagnosis is sometimes performed during surgery. This is a retrospective descriptive study. The authors report the contribution of imaging for the diagnosis of appendagitis in seven patients investigated between July 2010 and April 2013 by abdominal and pelvic ultrasound or computed tomography (CT). CT scan confirmed the diagnosis in six patients avoiding unnecessary surgery and hospitalization. The seventh patient was a pregnant woman in whom the diagnosis of appendagitis was made during surgery for appendicitis. Appendagitis is a rare cause of acute abdominal pain. Outcome is favorable with medical treatment only. Abdominal ultrasound and CT are helpful diagnostic tests avoiding useless surgical procedure.


Benign fibrous histiocytoma of the small intestine in a cow.
A well circumscribed, firm nodule was found protruding from the duodenal wall of an adult cow at routine meat inspection. On the basis of morphological and immunophenotypic features, a diagnosis of benign fibrous histiocytoma (BFH) was established. Malignant fibrous histiocytoma has been reported previously in the cow, albeit rarely, but to the best of our knowledge this is the first recorded case of bovine intestinal BFH.


Distress of mice induces approach behavior but has an aversive property for conspecifics.
In the first experiment, approach/avoidance behavior of mice to a restrained cage mate was examined. The mice explored the restrained mates but they did not stay longer at the restrained mates in comparison to free moving mates. Conditioned Place Preference (CPP) training in the presence of a restrained mate did not result in preference or aversion to the compartment associated with the restrained mates. A second experiment used formalin injection to a hind paw of a cage mate, instead of restraint. Mice stayed longer at the cage mate injected with the formalin in comparison to intact mates. However, CPP with formalin-injected mates caused conditioned aversion to the compartment associated with the formalin-injected mate. Thus, distress in mice induced short-term approach behavior in conspecifics but also had an aversive property.


Autologous saphenous vein popliteal-tibial artery bypass for limb-threatening ischemia: a reassessment.
The purpose of this review was to ascertain the cumulative primary and secondary graft patency rates, the cumulative limb salvage rate, and the frequency of atherosclerotic disease progression proximal to the graft origin, in patients with autologous saphenous vein popliteal-tibial artery bypass grafts whose operative indication was limb-threatening ischemia. Forty-three short autologous saphenous vein grafts originating from the popliteal artery were retrospectively reviewed. The life-table method was used to determine primary and secondary graft patency and limb salvage rates. Atherosclerotic disease progression proximal to the graft origin was assessed via follow-up arteriography, segmental limb pressures, or pulse-volume recordings. All other data were compared by chi-square analysis. The cumulative primary graft patency rate at 1, 3, and 5 years (86%, 66%, 58%) was similar to the cumulative secondary patency rate (90%, 70%, 62%) and the cumulative limb salvage rate (80%, 55%, 55%). No patient developed hemo-dynamically significant atherosclerotic disease proximal to the graft origin during the follow-up period. The similarity of the life-table data suggests graft-dependent, poorly collateralized limbs; it is therefore not uncommon for these patients to require major amputations shortly after bypass failure. There was no evidence of critical proximal disease progression that might warrant a more proximal graft origin. Poplitealtibial artery bypass grafts are durable, with acceptable graft patency and limb salvage rates.


Comparison Perioperative Factors During Minimally Invasive Pre-Psoas Lateral Interbody Fusion of the Lumbar Spine Using Either Navigation or Conventional Fluoroscopy.
Retrospective clinical study. The aim of this study was to compare intraoperative conditions and clinical results of patients undergoing pre-psoas oblique lateral interbody fusion (OLIF) using navigation or conventional fluoroscopy (C-ARM) techniques. Forty-two patients (22 patients by navigation and 20 by fluoroscopy) underwent the OLIF procedure at 2 medical centers, and records were reviewed. Clinical data was collected and compared between the 2 groups. Patients were followed-up with a range of 6 to 24 months. There were no significant differences on demographic data between groups. The navigation group had zero radiation exposure (RE) to the surgeon and radiation time compared to the C-ARM group, with total RE of 44.59 ± 26.65 mGy and radiation time of 88.30 ± 58.28 seconds (P < .05). The RE to the patient was significantly lower in the O-ARM group (9.38 mGy) compared to the C-ARM group (44.59 ± 26.65 mGy). Operating room time was slightly longer in the navigation group (2.49 ± 1.35 hours) compared to the C-ARM group (2.30 ± 1.17 hours; P > .05), although not statistically significant. No differences were found in estimated blood loss, length of hospitalization, surgery-related complications, and outcome scores with an average of 8-month follow-up. Compared with C-ARM techniques, using navigation can eliminate RE to surgeon and decrease RE to the patient, and it had no significant effect on operating time, estimated blood loss, length of hospitalization, or perioperative complications in the patients with OLIF procedure. This study shows that navigation is a safe alternative to fluoroscopy during the OLIF procedure in the treatment of degenerative lumbar conditions.


Measurement of mechanical withdrawal thresholds and gait analysis using the CatWalk method in a nucleus pulposus-applied rodent model.
There are some previous reports of gait analysis using a rodent pain model. Applying the CatWalk method, objective measurements of pain-related behavior could be evaluated, but this method has not been investigated using the nucleus pulposus (NP) applied model, which was developed as a model of lumber disc herniation. We aimed to measure mechanical withdrawal thresholds and analyze gait patterns using the CatWalk method for the evaluation of the pain-related behavior caused by NP application. Twenty-four nine-week-old female Sprague-Dawley rats were randomly divided into two experimental groups, the NP group (n = 12), in which autologous NP from the tail was applied to the left L5 dorsal root ganglion, and the sham-operated group (n = 12). Measurements of mechanical withdrawal thresholds were performed using von Frey filaments touching the left footpads, and gait analysis was performed using the CatWalk method. These experiments were conducted 1 day before surgery and 7, 14, 21, and 28 days after surgery. Data were statistically analyzed using the Wilcoxon rank-sum test. The NP group showed significantly lower withdrawal thresholds than the sham group at days 14 and 21. Stand (duration of contact of a paw with the glass plate) was significantly higher in the NP group at days 7 and 14, whereas step cycle (duration between two consecutive initial contacts of the same paw) and duty cycle (stand as a percentage of step cycle) were the same at day 7. Long initial dual stance (duration of ground contact for both hind paws simultaneously, but the first one in a step cycle of a target hind paw) of the right hind paw was measured at days 7 and 14. The left hind paw per right hind paw ratio of the stand index (speed at which the paw loses contact with the glass plate) and mean intensity (mean intensity of the complete paw) changed at day 7 or 14. Phase dispersion (parameter describing the temporal relationship between placement of two paws) of the hind paws decreased at day 7. Rats with applied NP showed a decreased withdrawal threshold and abnormal gait. The differences in gait parameters between the NP and sham groups were observed at an earlier time point than the withdrawal thresholds. Gait analysis could be an effective method for understanding pain caused by applied NP.


Recent micturition does not affect the detection of urethral gonorrhoea.
In 202 men with urethral gonorrhoea (176 symptomatic and 26 asymptomatic) who had modified Thayer-Martin cultures taken before and within five minutes after micturition there was complete agreement between results of the two cultures. Micturition did, however, temporarily eliminate the discharge in 100 (56.8%) and make interpretation of Gram-stained smears more laborious.


Progesterone decreases ovarian cancer cells migration and invasion.
The progression of cancer depends on the interaction between the cells and their microenvironment. Progesterone is a steroid and progestogen sex hormone produced by the corpus luteum, which is a transitory endocrine gland in female mammals and prepares the endometrium for implantation. Also, progesterone is involved in antitumorigenic process in different types of cancer. Our goal is to investigate the role of progesterone in cell invasion and migration. Ovarian cells were treated with different concentrations of progesterone. 500 nM or 1 μM progesterone decreased the migration of the cells in 24 h or less without affecting the viability. Immunoblot showed that treatment with 1 μM progesterone decreased the phosphorylated forms of Src and FAK, and the cells were less polarized. Our results suggest that progesterone interferes with migration and invasion of ovarian cells. Inhibitory experiments inferred the progesterone receptor playing a role in migration and invasion. Decreased phosphorylation of molecules involved in these processes was also found.


Context-dependent roles of the Entamoeba histolytica core promoter element GAAC in transcriptional activation and protein complex assembly.
Transcriptional control of the hgl5 gene of Entamoeba histolytica is mediated through an unusual core promoter composed of TATA, GAAC and Initiator elements. In the hgl5 promoter the GAAC element (AATGAACT) determines the site and rate of transcription initiation. Here we tested the role of the GAAC element in transcription activation from upstream regulatory elements (UREs) in the hgl5 promoter. We also examined the function of the GAAC element in the ferredoxin (fdx) promoter and characterized the protein binding to the GAAC element. Electrophoretic mobility shift assays (EMSA) demonstrated that the GAAC region is necessary for higher-order nuclear protein complex assembly. The function of the GAAC element in transcription activation mediated by UREs revealed that mutation of the GAAC element did not affect transcription activation mediated by the hgl5 URE4 but abrogated activation by the hgl5 URE3. We compared the role of the GAAC elements in the hgl5 and fdx promoters. Competitive gel shift assays were consistent with the same nuclear protein binding to the GAAC elements in both genes. Mutation of the GAAC element in the fdx gene decreased reporter gene expression, however, in contrast to hgl5 gene, had no effect on the site of transcription initiation. These results support a role for the GAAC element in assembly of nuclear proteins at the core promoter and in transcription activation mediated by URE3. The differing effect on transcription initiation in the hgl5 and fdx genes upon mutation of the GAAC element suggests a context-dependence of the GAAC-binding protein in gene expression.