Hybrid and Conventional Endoscopic Submucosal Dissection for Early Gastric Neoplasms: A Multi-Center Randomized Controlled Trial.
Hybrid endoscopic submucosal dissection (H-ESD), which incorporates endoscopic submucosal dissection (ESD) with endoscopic mucosal resection, has been developed to make ESD technically easier. This study aimed to determine if H-ESD is superior to conventional ESD (C-ESD) for small early gastric neoplasms (EGNs). We conducted a multi-center, prospective, open-label, randomized controlled trial to compare the treatment outcomes of H-ESD and C-ESD (Hybrid-G Trial). Patients with differentiated type intramucosal EGN ≤20 mm in diameter and without ulceration were randomly assigned (1:1) to groups that underwent H-ESD or C-ESD. A single multi-functional snare, SOUTEN (ST1850-20, Kaneka, Medix, Tokyo, Japan), was used for H-ESD. The primary outcome was procedure time. Secondary outcomes included mucosal incision time, time and speed of submucosal dissection, curability, and endoscopic procedural adverse events. A total of 39 and 40 patients underwent H-ESD and C-ESD, respectively. The procedure time of H-ESD was significantly shorter than that of C-ESD (33.16 min vs 62.46 min; H-ESD/C-ESD ratio: 0.53; 95% confidence interval, 0.41-0.69; P < .0001). There was no significant difference in mucosal incision time between the 2 groups; the time and speed of submucosal dissection of H-ESD were significantly shorter than those of C-ESD. No difference was observed between the 2 groups in other outcomes. H-ESD has significantly shorter procedure time than C-ESD, with high and comparable curability and safety for both H-ESD and C-ESD. H-ESD can be a good option for the endoscopic treatment of small EGNs. (UMIN Clinical Trials Registry, Numbers: UMIN000041244).


Delayed gastric emptying and reduced postprandial small bowel water content of equicaloric whole meal bread versus rice meals in healthy subjects: novel MRI insights.
Postprandial bloating is a common symptom in patients with functional gastrointestinal (GI) diseases. Whole meal bread (WMB) often aggravates such symptoms though the mechanisms are unclear. We used magnetic resonance imaging (MRI) to monitor the intragastric fate of a WMB meal (11% bran) compared with a rice pudding (RP) meal. Twelve healthy volunteers completed this randomised crossover study. They fasted overnight and after an initial MRI scan consumed a glass of orange juice with a 2267 kJ WMB or an equicaloric RP meal. Subjects underwent serial MRI scans every 45 min up to 270 min to assess gastric volumes and small bowel water content, and completed a GI symptom questionnaire. The MRI intragastric appearance of the two meals was markedly different. The WMB meal formed a homogeneous dark bolus with brighter liquid signal surrounding it. The RP meal separated into an upper liquid layer and a lower particulate layer allowing more rapid emptying of the liquid compared with solid phase (sieving). The WMB meal had longer gastric half-emptying times (132±8 min) compared with the RP meal (104±7 min), P<0.008. The WMB meal was associated with markedly reduced MRI-visible small bowel free mobile water content compared with the RP meal, P<0.0001. WMB bread forms a homogeneous bolus in the stomach, which inhibits gastric sieving and hence empties slower than the equicaloric rice meal. These properties may explain why wheat causes postprandial bloating and could be exploited to design foods that prolong satiation.


Universal surveillance for methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals.
The effect of large-scale expanded surveillance for methicillin-resistant Staphylococcus aureus (MRSA) on health care-associated MRSA disease is not known. To examine the effect of 2 expanded surveillance interventions on MRSA disease. Observational study comparing rates of MRSA clinical disease during and after hospital admission in 3 consecutive periods: baseline (12 months), MRSA surveillance for all admissions to the intensive care unit (ICU) (12 months), and universal MRSA surveillance for all hospital admissions (21 months). A 3-hospital, 850-bed organization with approximately 40,000 annual admissions. Polymerase chain reaction-based nasal surveillance for MRSA followed by topical decolonization therapy and contact isolation of patients who tested positive for MRSA. Poisson and segmented regression models were used to compare prevalence density of hospital-associated clinical MRSA disease (bloodstream, respiratory, urinary tract, and surgical site) in each period. Rates of bloodstream disease with methicillin-susceptible S. aureus were used as a control. The prevalence density of aggregate hospital-associated MRSA disease (all body sites) per 10,000 patient-days at baseline, during ICU surveillance, and during universal surveillance was 8.9 (95% CI, 7.6 to 10.4), 7.4 (CI, 6.1 to 9.0; P = 0.15 compared with baseline), and 3.9 (CI, 3.2 to 4.7; P < 0.001 compared with baseline and ICU surveillance), respectively. During universal surveillance, the prevalence density of MRSA infection at each body site had a statistically significant decrease compared with baseline. The methicillin-susceptible S. aureus bacteremia rate did not statistically significantly change during the 3 periods. In a segmented regression model, the aggregate hospital-associated MRSA disease prevalence density changed by -36.2% (CI, -65.4% to 9.8%; P = 0.17) from baseline to ICU surveillance and by -69.6% (CI, -89.2% to -19.6%]; P = 0.03) from baseline to universal surveillance. During universal surveillance, the MRSA disease rate decreased during hospitalization and in the 30 days after discharge; no further reduction occurred thereafter. Surveillance with clinical cultures would have identified 17.8% of actual MRSA patient-days, and ICU-based surveillance with polymerase chain reaction would have identified 33.3%. The findings rely on observational data. The introduction of universal admission surveillance for MRSA was associated with a large reduction in MRSA disease during admission and 30 days after discharge.


Effects of FoxO1 on podocyte injury in diabetic rats.
This study was designed to investigate the protective effect of forkhead transcription factor O1 (FoxO1) on podocyte injury in rats with diabetic nephropathy. Streptozotocin-induced diabetic rats were served as DM group, while DM rats transfected with blank lentiviral vectors (LV-pSC-GFP) or lentiviral vectors carrying constitutively active FoxO1 (LV-CA-FoxO1) were served as LV-NC group or LV-CA group, respectively. The control group (NG) consisted of uninduced rats that received an injection of diluent buffer. At 2, 4, and 8 weeks after transfection, the levels of urine albumin, blood glucose, blood urea nitrogen, serum creatinine and urine podocalyxin were measured. Real-time PCR and western blotting were performed to measure mRNA and protein levels of FoxO1, podocalyxin, nephrin, and desmin in renal cortex. In addition, light and electron microscopy were used to detect structural changes in the glomerulus and podocytes. Compared with the rats in LV-NC and DM groups, LV-CA rats showed a significant increase in FoxO1 mRNA and protein levels and a distinct decrease in urine albumin, blood urea nitrogen, and serum creatinine (except at the two-week time point) levels (p < 0.05). Podocalyxin and nephrin mRNA and protein levels increased (p < 0.05), whereas desmin mRNA and protein levels decreased (p < 0.05). Pathological changes in glomerulus were also ameliorated in LV-CA group. Upregulating expression of FoxO1 by transduction with recombinant lentivirus ameliorates podocyte injury in diabetic rats.


Operative management of colonic diverticular disease in the setting of immunosuppression: A systematic review and meta-analysis.
Immunosuppressed patients with diverticular disease are at higher risk of postoperative complications, however reported rates have varied. The aim of this study is to compare postoperative outcomes in immunosuppressed and immunocompetent patients undergoing surgery for diverticular disease. Medline, EMBASE, and CENTRAL were searched. Articles were included if they compared immunosuppressed and immunocompetent patients undergoing surgery for diverticular disease. From 204 citations, 11 studies with 2,977 immunosuppressed patients and 780,630 immunocompetent patients were included. Mortality was greater in immunosuppressed patients compared to immunocompetent patients for emergent surgery (RR 1.91, 95%CI 1.24-2.95, p < 0.01), but not elective surgery (RR 1.70, 95%CI 0.14-20.47, p = 0.68). Morbidity was greater in immunosuppressed patients compared to immunocompetent patients for elective surgery (RR 2.18, 95%CI 1.02-4.65, p = 0.04), but not emergent surgery (RR 1.40, 95%CI 0.68-2.90, p = 0.37). Increased consideration for elective operation may preclude the need for emergent surgery and the associated increase in postoperative mortality.


Pilot study of a repeated random sampling method for surveys focusing on date-specific differences in alcohol consumption among university students.
This paper proposes and pilots a repeated random sampling method to promote the likelihood of collecting drinking data equally representative of the behavior of university students at all times through the academic year. From October, 2016, to May, 2017, random samples of 1350 students were selected from the 39,155 undergraduate students enrolled in the fall semester at University of Houston. These students were sent an email inviting them to complete an online survey (entered into a weekly draw for a $50 gift certificate if responded). The response rate was low (6%). Among participants who reported drinking in the last week, there was a variation as expected in the amount of drinking observed depending on the time of year (e.g., during exams). While the sampling methods show promise, procedures would need to be implemented to substantially increase response rates before the proposed methods could be seen as an advantage over existing survey sampling procedures.


Role of flower and pollen aromas in host-plant recognition by solitary bees.
The means by which newly emerged pollen-specific (oligolectic) solitary bees locate their appropriate pollen host plant is not clearly understood. To evaluate the role of flower and pollen odors in this recognition process, preference tests were performed on foraging-inexperienced and, for comparison, field-experienced individuals of the solitary bee Colletes fulgidus longiplumosus. The bees were presented with a choice of four plant species, offered in the form of aromas from flowers, whole pollen, pollenkitt, and internal pollen lipids. Observed feeding-attempt response patterns suggest: 1) that bees can distinguish between plant species on the basis of odors from flowers, whole pollen, and pollenkitt, 2) inexperienced bees show a preference for the pollen on which they were reared as larvae, and 3) chemicals eliciting feeding responses to pollen appear to be contained in the pollenkitt. Feeding responses by experienced bees differ from those of inexperienced bees in ways which indicate that the insects' odor-based search image of the host plant becomes modified by foraging experience.


The surface distribution of low density lipoprotein receptors on cultured fibroblasts and endothelial cells. Ultrastructural evidence for dispersed receptors.
The distribution of low density lipoprotein (LDL) receptors marked with colloidal gold-conjugated low density lipoproteins has been mapped on the surfaces of cultured human skin fibroblasts and bovine aortic endothelial cells viewed whole in the transmission electron microscope. A dispersed or scattered population of LDL receptors, in addition to and clearly distinct from clustered receptors was detected on the surfaces of both fibroblasts and dividing endothelial cells. No LDL receptors could be detected on contact-inhibited endothelial cells. Clustered receptors imaged in whole-mount preparations were often arranged in rings with an approximate diameter of 250 nm. In ultra-thin sections of marked cells, clustered receptors were localised in coated pits while the few dispersed receptors seen were restricted to non-coated membrane regions. Clustered receptors often appeared localised on the rims of coated pits whose central areas were not marked. The dispersed population of receptors was usually distributed diffusely amongst the clusters on dividing endothelial cells and normal fibroblasts. Only the dispersed population appeared on LDL receptor internalisation-defective mutant fibroblasts. The marginal zones of both fibroblasts and dividing endothelial cells were populated by dispersed receptors. Clusters appeared further "inland" and were rarely seen near the cell margins. These results indicate that LDL receptors on dividing endothelial cells and fibroblasts may be dispersed on the cell surface upon or soon after their insertion during recycling.


Spatiotemporal pattern of hand-foot-mouth disease in China: an analysis of empirical orthogonal functions.
Hand-foot-mouth disease (HFMD) is the most common infectious disease in China. Spatial and temporal patterns of HFMD in China provide valuable information on the relationship between HFMD and the geographical environment, and help in the prediction of HFMD transmission. Cross-sectional study. Total HFMD morbidity per 10 days from May 2008 to March 2009 was recorded in 1966 counties in China. Empirical orthogonal function (EOF) analysis was used to obtain spatial and temporal patterns of HFMD. The first five modes of HFMD morbidity explained 84.24% of the total variance. The dominant mode (first mode showing the highest variance) showed high HFMD morbidity in the western counties of Bohai Bay, the mid-south of China, the Yangtze River delta, the Pearl River delta and the areas bordering Vietnam from early May to late July 2008. The second mode showed high HFMD morbidity in the western counties of Bohai Bay, the north-east of China, north of Xinjiang and the Yangtze River delta from late May to the middle of August 2008. The third mode showed high HFMD morbidity in the Yangtze River delta, the Pearl River delta and the middle of the Huaihe River basin in early May 2008. EOF analysis of HFMD morbidity shows the main spatiotemporal patterns and can explain variance in HFMD in China.


Pediatric patient with systemic lupus erythematosus & congenital acquired immunodeficiency syndrome: An unusual case and a review of the literature.
The coexistence of systemic lupus erythematosus (SLE) in patients with congenital human immunodeficiency virus (HIV) infection is rare. This is a case report of a child diagnosed with SLE at nine years of age. She initially did well on non-steroidal anti-inflammatory agents, hydroxychloroquine, and steroids. She then discontinued her anti-lupus medications and was lost to follow-up. At 13 years of age, her lupus symptoms had resolved and she presented with intermittent fevers, cachexia, myalgias, arthralgias, and respiratory symptoms. Through subsequent investigations, the patient was ultimately diagnosed with congenitally acquired immunodeficiency syndrome (AIDS).


[Reduction of 5alpha-dehydrotestosterone in sex steroid target cells--catabolism or directed biotransformation into hormones?].
Based on analysis of the published experimental data, we propose a hypothetical mechanism of action of two androgens, 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol), which are produced when 5 alpha-dihydrotestosterone (DHT) is reduced in sex steroids target cells. The mode of action of these diols as regulatory factors assumes that the androgens possess autocrine, paracrine, and endocrine action that differs from the action of DHT in animals and man and do not merely represent catabolites or metabolites capable of controlling the level of true androgenic hormone DHT. It is proposed that both diols should be classified as parahormones.


Effect of adjuvant paclitaxel and carboplatin for advanced stage epithelial ovarian cancer: a population-based cohort study of all patients in western Sweden with long-term follow-up.
To evaluate long-term survival and prognostic factors for all epithelial ovarian cancer (EOC) patients after adjuvant treatment with paclitaxel and carboplatin. Prospectively collected data from a population-based cohort. Western Sweden Health Care Region. All women diagnosed with EOC between 1998 and 2005. Data related to age, stage, surgery, histopathology, grade, ploidy status, CA-125, follow-up, recurrence and death of EOC patients (n=976) were prospectively collected in a quality register. No patient was lost to follow-up and the median follow-up was 68 months (range: 27-110). Relative survival at 5 and 8 years for all and for those treated with chemotherapy; median progression-free survival (PFS) for stage IIB-IV patients treated with paclitaxel and carboplatin. Relative 5- and 8-year survival rates in the subgroup of patients treated with chemotherapy after surgery (n=853) were 50.4% (95% CI: 46.4-54.3) and 40.5% (95% CI: 35.4-45.6), respectively. The median relative survival time of the entire group of patients was 60 months (95% CI: 52-73). The median PFS for the patients in stage IIB-IV treated with paclitaxel and carboplatin was 18 months (95% CI: 17-20). Well-established prognostic factors of age, stage, residual tumor and post-operative CA-125 were of prognostic significance. Post-surgical adjuvant chemotherapy of paclitaxel and carboplatin for advanced stages of EOC does not seem to increase the relative 5-year survival rate or the median PFS compared to results of earlier studies of a similar patient cohort from the same geographical area.


Fast determination of beef quality parameters with time-domain nuclear magnetic resonance spectroscopy and chemometrics.
The noteworthy of this study is to predict seven quality parameters for beef samples using time-domain nuclear magnetic resonance (TD-NMR) relaxometry data and multivariate models. Samples from 61 Bonsmara heifers were separated into five groups based on genetic (breeding composition) and feed system (grain and grass feed). Seven sample parameters were analyzed by reference methods; among them, three sensorial parameters, flavor, juiciness and tenderness and four physicochemical parameters, cooking loss, fat and moisture content and instrumental tenderness using Warner Bratzler shear force (WBSF). The raw beef samples of the same animals were analyzed by TD-NMR relaxometry using Carr-Purcell-Meiboom-Gill (CPMG) and Continuous Wave-Free Precession (CWFP) sequences. Regression models computed by partial least squares (PLS) chemometric technique using CPMG and CWFP data and the results of the classical analysis were constructed. The results allowed for the prediction of aforementioned seven properties. The predictive ability of the method was evaluated using the root mean square error (RMSE) for the calibration (RMSEC) and validation (RMSEP) data sets. The reference and predicted values showed no significant differences at a 95% confidence level.


Local reaction and migration of injected silicone gel: experimental study.
A study of the local and migratory effects of free silicone gel taken from a mammary prosthesis is reported. Thirty eight Wistar rats were injected in their subcutaneous space with 1 cm3 of silicone gel. The animals were sacrificed on day: 3, 7, 15, 30, 60, 180, 240, 360, 420, 450. The visceral organs (heart, kidneys, lungs, stomach, gonads, liver, pancreas, spleen, intestine), as well as the tissue adjacent to the region of injection, were histologically analyzed. There was no detectable silicone and no damage to the visceral organs based on routine histopathological analysis. The greatest fibrosis was observed at the extremities of the disk formed by the silicone in the subcutaneous space.


Dorsal hypothalamic dopaminergic neurons play an inhibitory role in the hypothalamic-pituitary-adrenal axis via activation of D2R in mice.
The present study investigated the effects of dorsal hypothalamic dopamine (dh-DA) neurons on activation of hypothalamic-pituitary-adrenal (HPA) axis in adult male mice. Tyrosine hydroxylase-labelled DA neurons, DA content, c-Fos immune-positive (c-Fos+) cells and CRH expression in paraventricular nuclei (PVN), serum CORT and ACTH were examined at 4-, 8-, and 12-hour after a signal injection of MPTP (20 mg kg-1 ) respectively. The dh-DA neurons and DA content in PVN at 4-hour post-MPTP were reduced with recovery at 12-hour post-MPTP, while decline of nigrostriatal DA neurons and DA content in striatum started from 12-hour post-MPTP. Number of c-Fos+ cells, and CORT/ACTH levels increased at 4-hour post-MPTP, followed by recovery at 12-hour post-MPTP. The CRH mRNA was elevated at 4-hour post-MPTP, and sustained for over 12 hours. At 2-hour post-MPTP, PVN-injection of D2R agonist quinpirole corrected the increases in c-Fos+ cells, CORT/ACTH and CRH mRNA, but D1R agonist SKF38393 did not. PVN-injection of D2R antagonist L-sulpiride alone caused increases in c-Fos+ cells, CORT/ACTH and CRH mRNA. Similarly, PVN-injection of CB1R agonist WIN552,12 prevented the increases in c-Fos+ cells and CORT/ACTH rather than CRH mRNA, which were blocked by CB1R antagonist AM251. Levels of PKA and CREB phosphorylation in PVN were increased at 4-hour post-MPTP, which were blocked by quinpirole, but not WIN552,12. PKA inhibitor H89 corrected the increase of CRH mRNA at 8-hour post-MPTP. The activation of dh-DA neurons regulates negatively HPA axis through targeting D2Rs of CRH neurons to enhance endocannabinoid release and inhibit PKA-CREB pathway.


The Irish experience of kidney transplantation among recipients with prior non-renal solid organ transplants: A retrospective study on short- and long-term outcomes.
This study aims to evaluate allograft and patient outcomes among recipients of kidney transplants after non-renal solid organ transplants. We also aim to compare our findings with recipients of a repeat kidney transplant. We performed an analysis on kidney transplant recipients who underwent kidney transplantation after a non-renal solid organ transplant. Survival data were stratified into 2 groups: Group A (n = 37) consisted of recipients of a kidney transplant after prior non-renal solid organ transplant, and Group B (n = 330) consisted of recipients of a repeat kidney transplant. The 1-,5-, and 10-year graft survival (death-censored) for recipients of a kidney transplant post-non-renal solid organ transplant (Group A) were 97.3%, 91.5%, and 86.9%, compared with 97.9%, 90.2%, and 83.4% for recipients of a repeat kidney transplant (Group B) (p = .32). The 1-, 5-, and 10-year patient survival rates were 97.3%, 82.7%, and 79.1% in Group A compared to 97.9%, 90.2%, and 83.4% in Group B. Unadjusted overall patient survival was significantly lower for Group A (p = .017). Kidney transplant recipients who have undergone a previous non-renal solid organ transplant have similar allograft survival outcomes, but higher long-term mortality rates compared to repeat kidney transplant recipients.


Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin.
Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis characterized by oculocutaneous albinism and prolonged bleeding. These clinical findings reflect defects in the formation of melanosomes in melanocytes and dense bodies in platelets. HPS type-3 (HPS-3) results from mutations in the HPS3 gene, which encodes a 1004 amino acid protein of unknown function that contains a predicted clathrin-binding motif (LLDFE) at residues 172-176. Clathrin was co-immunoprecipitated by HPS3 antibodies from normal but not HPS3 null melanocytes. Normal melanocytes expressing a GFP-HPS3 fusion protein demonstrated partial co-localization of GFP-HPS3 with clathrin following a 20 degrees C temperature block. GFP-HPS3 in which the predicted clathrin-binding domain of HPS3 was mutated (GFP-HPS3-delCBD) did not co-localize with clathrin under the same conditions. Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region. In contrast, GFP-HPS3-delCBD did not co-localize with clathrin and exhibited a largely cytoplasmic distribution. HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. These results suggest a role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking.


Toluene degradation using plasma-catalytic hybrid system over Mn-TiO2 and Fe-TiO2.
This paper proposed a hybrid system that combined dielectric barrier discharge plasma with catalysis (DPC) for toluene degradation. To improve the performance of DPC, photocatalysts TiO2 were doped by Mn and Fe, respectively. All prepared photocatalysts were characterized using UV-Visual DRS., SEM, XPS, BET, and XRD. The effects of the doping ratio, AC frequency, electric field intensity, gas flow rate, and initial concentration on toluene degradation efficiency, ozone decomposition capacity, and COx selectivity have been investigated. The best doping ratios of Mn and Fe were both 1.0 at%. The increase of electric field intensity in the range of 6.9-10.3 kV/cm could favor the synergism for DPC significantly, but the ascending of AC Frequency failed to do that. Fe-DPC showed slightly better performance than Mn-DPC in degradation efficiency and COx selectivity, while Mn-DPC was ahead of Fe-DPC for the ozone decomposition. Mn-DPC and Fe-DPC both could maintain the high toluene degradation efficiency, when gas flow rate and initial concentration increase from 2.5 to10.1 cm/s and from 700 to 2300 mg/cm3, respectively.


Stabilization and improved in vivo performance of amorphous etoricoxib using Gelucire 50/13.
Amorphous drugs have gained importance because of their advantageous biopharmaceutical properties; however, their stabilization remains a challenge. The purpose of this work was to stabilize the amorphous form of etoricoxib (ET) by using a low excipient/drug ratio to improve drug dissolution and thus bioavailability. The effect of Gelucire and polyvinylpyrrolidone (PVP) on stabilization and bioavailability of amorphous etoricoxib (AET) was studied. X-ray powder diffractometry, differential scanning calorimetry, and scanning electron microscopy were used to study the physical state of the drug. Dissolution studies were performed for melt granules of AET with Gelucire 50/13 (MG-AET) and solid dispersion with PVP (SDP) to differentiate dissolution performance. A stability study on samples was conducted for 3 months to evaluate the physical state of the drug and its dissolution in the formulation. The in vivo performance of the optimized and stable formulation of ET was evaluated in rat. Dissolution of MG-AET was significantly improved as compared to AET and SDP. Both factors, amorphization of drug and melt granulation with lipid, seemed to be important for improving dissolution. Stability data revealed that MG-AET was significantly advantageous for AET stabilization, whereas PVP was not. The amount of Gelucire required for the stabilization of one part of AET was 0.5 part (by weight), whereas even 1.5 part (by weight) of PVP failed to elicit the same result. The superior in vivo performance of MG-AET has been attributed to the altered physiochemical properties of AET and the presence of lipid in the system. Gelucire can stabilize AET and improve its biopharmaceutical performance at a low excipient/drug ratio and may provide a better alternative to conventional stabilizers such as PVP.


The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar cell development.
In the mouse retina, at least ten distinct types of bipolar interneurons are involved in the transmission of visual signals from photoreceptors to ganglion cells. How bipolar interneuron diversity is generated during retinal development is poorly understood. Here, we show that Irx5, a member of the Iroquois homeobox gene family, is expressed in developing bipolar cells starting at postnatal day 5 and is localized to a subset of cone bipolar cells in the mature mouse retina. In Irx5-deficient mice, defects were observed in the expression of some, but not all, immunohistological markers that define mature Type 2 and Type 3 OFF cone bipolar cells, indicating a role for Irx5 in bipolar cell differentiation. The differentiation of these two bipolar cell types has previously been shown to require the homeodomain-CVC transcription factor, Vsx1. However, the defects observed in Irx5-deficient retinas do not coincide with a reduction of Vsx1 expression, and conversely, the expression of Irx5 in cone bipolar cells does not require the presence of a functional Vsx1 allele. These results indicate that there are at least two distinct genetic pathways (Irx5-dependent and Vsx1-dependent) regulating the development of Type 2 and Type 3 cone bipolar cells.


Social networking sites in romantic relationships: attachment, uncertainty, and partner surveillance on facebook.
Social networking sites serve as both a source of information and a source of tension between romantic partners. Previous studies have investigated the use of Facebook for monitoring former and current romantic partners, but why certain individuals engage in this behavior has not been fully explained. College students (N=328) participated in an online survey that examined two potential explanatory variables for interpersonal electronic surveillance (IES) of romantic partners: attachment style and relational uncertainty. Attachment style predicted both uncertainty and IES, with preoccupieds and fearfuls reporting the highest levels. Uncertainty did not predict IES, however. Future directions for research on romantic relationships and online surveillance are explored.


Segregation analysis of the BRCA2 c.9227G>T variant in multiple families suggests a pathogenic role in breast and ovarian cancer predisposition.
Classification of variants in the BRCA1 and BRCA2 genes has a major impact on the clinical management of subjects at high risk for breast and ovarian cancer. The identification of a pathogenic variant allows for early detection/prevention strategies in healthy carriers as well as targeted treatments in patients affected by BRCA-associated tumors. The BRCA2 c.9227G>T p.(Gly3076Val) variant recurs in families from Northeast Italy and is rarely reported in international databases. This variant substitutes the evolutionary invariant glycine 3076 with a valine in the DNA binding domain of the BRCA2 protein, thus suggesting a high probability of pathogenicity. We analysed clinical and genealogic data of carriers from 15 breast/ovarian cancer families in whom no other pathogenic variants were detected. The variant was shown to co-segregate with breast and ovarian cancer in the most informative families. Combined segregation data led to a likelihood ratio of 81,527:1 of pathogenicity vs. neutrality. We conclude that c.9227G>T is a BRCA2 pathogenic variant that recurs in Northeast Italy. It can now be safely used for the predictive testing of healthy family members to guide preventive surgery and/or early tumor detection strategies, as well as for PARP inhibitors treatments in patients with BRCA2-associated tumors.


[Cryosurgery in the treatment of basal cell epithelioma of the eyelids].
Modern cryosurgery, based on impedance measurement, is a valuable addition to excisional surgery and radiation therapy in the management of eyelid malignancies. The advantages of the procedure are the good cosmetic and functional results. For the management of basal cell carcinoma situated near the punctum lacrimale and lacrimal canaliculus, cryosurgery may be preferred to surgery and radiotherapy. We review principles, methods, clinical and histological presentation of cryosurgery and describe our preliminary results.


Synaptic MAGUK multimer formation is mediated by PDZ domains and promoted by ligand binding.
To examine the scaffolding properties of PSD-95, we have taken advantage of established ligand/PDZ domain interactions and developed a cell-based assay for investigating protein complex formation. This assay enables quantitative analysis of PDZ domain-mediated protein clustering using bimolecular fluorescence complementation (BiFC). Two nonfluorescent halves of EYFP were fused to C-terminal PDZ ligand sequences to generate probes that sense for PDZ domain binding grooves of adjacent (interacting) molecules. When these probes are brought into proximity by the PDZ domains of a multiprotein scaffold, a functional fluorescent EYFP molecule can be detected. We have used this system to examine the properties of selected PSD-95 variants and thereby delineated regions of importance for PSD-95 complex formation. Further analysis led to the finding that PSD-95 multimerization is PDZ domain-mediated and promoted by ligand binding.


Neural control of micturition in humans: a working model.
Results from functional brain scanning have shown that neural control of the bladder involves many different regions. Yet, many aspects of this complex system can be simplified to a working model in which a few forebrain circuits, acting mainly on the midbrain periaqueductal grey (PAG), advance or delay the triggering of the voiding reflex and generate bladder sensations according to the volume of urine in the bladder, the safety of voiding and the emotional and social propriety of doing so. Understanding these circuits seems to offer a route to treatment of conditions, such as urgency incontinence or overactive bladder, in patients without overt neurological disease. Two of these circuits include, respectively, the medial prefrontal cortex and the parahippocampal complex, as well as the PAG. These circuits belong to a well-known network that is active at rest and deactivated when attention is required. Another circuit, comprising the insula and the midcingulate or dorsal anterior cingulate cortex, is activated by bladder filling and belongs to a salience network that generates sensations such as the desire to void. Behavioural treatments of urgency incontinence lead to changes in brain function that support the working model and suggest the mechanism of this type of treatment.


Radiotherapy of breast cancer.
Adjuvant radiotherapy is an essential component of the treatment of breast cancer. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. A boost dose over the tumour bed is required if the patient is younger than 50 years-old. Partial breast irradiation could be routinely proposed as an alternative to whole breast irradiation, but only in selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neoadjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra- and infraclavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Hypofractionation regimens (42.5Gy in 16 fractions, or 41,6Gy en 13 or 40Gy en 15) are equivalent to conventional irradiation and must prescribe after tumorectomy in selected patients. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with or after radiotherapy.


Ethyl 2-oxo-3-(3-phthalimidoprop-yl)-2,3-dihydro-1H-1,3-benzimidazole-1-carboxyl-ate.
In the title compound, C21H19N3O5, the phthalimide and benzamidazole ring systems are linked by a propyl chain. The benzamidazole unit also carries an eth-oxy-carbonyl substit-uent. The phthalimido and benzimidazole ring systems are essentially planar, the maximum deviations from their mean planes being 0.008 (2) and 0.020 (2) Å, respectively. The two ring systems are almost orthogonal to one another, making a dihedral angle of 82.37 (8)°. In the crystal, C-H⋯O hydrogen bonds and C-H⋯π contacts stack the mol-ecules along the b axis.


Elevated neutrophil extracellular traps by HBV-mediated S100A9-TLR4/RAGE-ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma.
Neutrophil extracellular traps (NETs) are considered significant contributors to cancer progression, especially metastasis. However, it is still unclear whether NETs are involved in hepatitis B virus (HBV)-related hepatocarcinogenesis and have potential clinical significance during evaluation and management for hepatocellular carcinoma (HCC). In this study, we aimed to investigate the functional mechanism of NETs in HBV-related hepatocarcinogenesis and their clinical significance. A total of 175 HCC patients with and without HBV infection and 58 healthy controls were enrolled in this study. NETs were measured in tissue specimens, freshly isolated neutrophils and blood serum from these patients, and the correlation of circulating serum NETs levels with malignancy was evaluated. The mechanism by which HBV modulates NETs formation was explored using cell-based studies. In addition, in vitro and in vivo experiments were further performed to clarify the functional mechanism of NETs on the growth and metastasis of HCC. We observed an elevated level of NETs in blood serum and tissue specimens from HCC patients, especially those infected with HBV. NETs facilitated the growth and metastasis of HCC both in vitro and in vivo, which were mainly dominated by increased angiogenesis, epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinases (MMPs)-induced extracellular matrix (ECM) degradation and NETs-mediated cell trapping. Inhibition of NETs generation by DNase 1 effectively abrogated the NETs-aroused HCC growth and metastasis. In addition, HBV-induced S100A9 accelerated the generation of NETs, which was mediated by activation of toll-like receptor (TLR4)/receptor for advanced glycation end products (RAGE)-reactive oxygen species (ROS) signaling. Further, circulatory NETs were found to correlate with viral load, TNM stage and metastasis status in HBV-related HCC, and the identified NETs could predict extrahepatic metastasis, with an area under the ROC curve (AUC) of 0.83 and 90.3% sensitivity and 62.8% specificity at a cutoff value of 0.32. Our findings indicated that activation of RAGE/TLR4-ROS signaling by HBV-induced S100A9 resulted in abundant NETs formation, which subsequently facilitated the growth and metastasis of HCC cells. More importantly, the identified circulatory NETs exhibited potential as an alternative biomarker for predicting extrahepatic metastasis in HBV-related HCC.


Analysis of the coupled transport, reaction, and deactivation phenomena in the immobilized glucose oxidase and catalase system.
In a previous paper, the overall or macrokinetics of the immobilized glucose oxidase--catalase system has been presented. In this paper a detailed analysis of the interaction of diffusion and reaction in this system will be presented. The mathematical treatment includes two consecutive reactions with two-substrate kinetics. Furthermore, the deactivation of both enzymes due to the intermediate product peroxide is taken into account. The predicted results suggest that the efficiency of the glucose oxidase reaction depends on the concentration ranges of the two substrates. Furthermore, the external mass-transfer rate may cause a shift from glucose limitation to oxygen limitation. The efficiency of the coupled system is always higher than that predicted for the uncoupled reaction path. The calculations show that the economics of the coupled system depend a great deal on the deactivation of the enzymes.


Pretreatment with ondansetron blunts plasma vasopressin increases associated with morphine administration in ferrets.
Postoperative nausea and vomiting are significant problems. A method for measuring vomiting thresholds for anesthetics using plasma markers, such as arginine vasopressin (AVP), would be useful. We measured the change in AVP concentrations associated with morphine alone or in combination with ondansetron pretreatment. Data were collected from ferrets implanted with IV catheters. After recovery, the ferrets were administered IV morphine alone or with ondansetron pretreatment. Baseline blood samples were taken before morphine injection, and at 5, 10, 15, 30, 45, 60, and 90 min after morphine injection. Plasma AVP levels were measured using radioimmunoassay. Morphine alone was associated with a significant increase in plasma AVP concentrations from baseline at 45, 60, and 90 min (P < 0.05). Ondansetron alone did not change the plasma AVP concentration after 20 min (P > 0.46). There was no significant increase (P > 0.46) in AVP concentration in animals that were pretreated with ondansetron before administration of morphine. Two-way analysis of variance confirmed that ondansetron significantly decreased the increase in AVP by morphine at 60 and 90 min (P < 0.05). These data suggest that plasma AVP concentration may be an accurate marker for nausea, and may be useful to guide treatment for this condition. The antiemetic, ondansetron, has an effect not only on clinically perceived vomiting, but also on plasma vasopressin level.


The Ninth Plenary of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES-9): sustainable use, values, and business (as usual).
The Intergovernmental Science-Policy Platform for Biodiversity and Ecosystem Services (IPBES) held its ninth plenary session in hybrid form at Bonn, Germany in July 2022. The plenary had a packed agenda with assessments on the Sustainable Use of Wild Species and Values of Biodiversity to consider, as well as discuss a "Nature Future Framework" and a scoping document for business and biodiversity. Here, we present key issues that emerged from the plenary and suggest some matters Platform members need to consider for the future.


Meta-analysis update of association between dopamine transporter SLC6A3 gene polymorphism and smoking cessation.
The SLC6A3 gene is involved in the dopamine pathway, which influences smoking behavior. This study was conducted to present updated results of a meta-analysis to evaluate the association between SLC6A3 polymorphism and smoking cessation. In total, eight studies were assessed, and 9-repeat alleles and no 9-repeat alleles were compared by smoking cessation outcomes. No significant association between SLC6A3 genotype and smoking cessation was observed for the main analysis (odds ratio = 1.128; 95% confidence interval = 0.981-1.298). In conclusion, the genetic variations in SLC6A3 are not associated with smoking cessation, which is not consistent with the results of the previous meta-analysis.


Interstitial cells of Cajal are diminished in critically ill patients: Autopsy cases.
Gastrointestinal dysmotility in critically ill patients is important as enteral nutrition is crucial. However, normal gut motility is impaired under conditions of critical illness subsequent to severe insult. Interstitial cells of Cajal (ICC) form an extensive network associated with the myenteric plexus in the enteric nervous system. There are few reports about ICC distribution in critically ill patients. The aim of this study was to evaluate ICC in critically ill patients. Postmortem colon harvest was obtained from critically ill patients. Control specimens were obtained from patients without bowel movement problems who underwent hemicolectomy. The tissues were stained with c-Kit for ICC. The number of ICC was identified by counting from 10 high-power fields (HPFs). Specimens from six patients were analyzed and compared with those from six control patients. All patients had abnormalities of crypt architecture and inflammatory cell infiltrations. Mucosal thickness tended to be lower in the critically ill patients than in the controls (147 ± 47 versus 231 ± 127 μm; P = 0.15). Muscle layer thickness tended to be higher in the critically ill patients than in the controls (494 ± 163 versus 394 ± 258 μm; P = 0.44). ICC in the critically ill patients were almost depleted in the colon compared with those in the controls. Significantly fewer ICC were present in the critically ill patients than in the controls (0.45 versus 7.25 cells/HPF; P < 0.05). Critical illness is associated with diminished numbers of ICC in the colon. This finding could have implications for dysmotility in critically ill patients.


The Use of Proximal Femur Replacement for the Management of Oncologic Lesions in the Proximal Femur: A Review.
With improved chemotherapeutic treatment, patients with primary or metastatic bone tumor have improved prognoses and longer life expectancies; therefore, durable limb-salvage constructs are critical. For tumors of the proximal femur, endoprosthetic replacement is an option for treatment in primary and metastatic disease, with the goals being tumor and pain control, earlier mobilization, shorter recovery period, and, in primary tumors, cure. This study provides a summary of current concepts in the treatment of oncologic lesions in the proximal femur with endoprostheses. Discussion of the inherent complications of these constructs is presented as well as the risks and treatment of reconstruction failure.


Association between visit-to-visit fasting glycemic variability and depression: a retrospective cohort study in a representative Korean population without diabetes.
Glycemic variability (GV) is a risk factor for depression in patients with diabetes. However, whether it is also a predictor of incident depression in people without diabetes remains unclear. We aimed to investigate the association between visit-to-visit variability in fasting serum glucose (FSG) levels and the incidence of depression among Koreans without diabetes. This retrospective cohort study included data of people without diabetes who did not have depression at baseline and had at least three FSG measurements (n = 264,480) extracted from the 2002-2007 Korean National Health Insurance Service-National Health Screening Cohort. GV was calculated as the average successive variability of FSG. Among 264,480 participants, 198,267 were observed during 2008-2013 and their hazard ratios (HR) of incident depression were calculated. Participants with the highest GV showed a higher risk of depression in fully adjusted models than those with the lowest GV (HR, 1.09; 95% CI, 1.02-1.16). The risk of incident depression heightened with increasing GV (p for trend < 0.001). Greater visit-to-visit GV may be associated with the risk of developing depression in people without diabetes. Conversely, maintaining steady FSG levels may reduce the risk of incident depression in people without diabetes.


Inverse association of hospital volume with in-hospital mortality rate of patients receiving EUS-guided interventions for pancreatic fluid collections.
EUS-guided interventions currently serve as first-line treatment for symptomatic pancreatic fluid collections (PFCs) but require high-level expertise and multidisciplinary care. Hospital caseload has not been fully examined in relation to clinical outcomes of patients with endoscopically managed PFCs. Using the Diagnosis Procedure Combination database (a Japanese nationwide inpatient database), we identified 4053 patients receiving EUS-guided treatment of PFCs at 486 hospitals between 2010 and 2020 and examined an association of hospital volume (average annual number of cases at a hospital) with in-hospital mortality. Associations with bleeding, length of stay, and total costs were examined as secondary analyses. Multivariable logistic regression analysis was conducted with adjustment for potential confounders. The hospital volume was inversely associated with the risk of in-hospital mortality (Ptrend < .001). The adjusted odds ratio for in-hospital mortality comparing the extreme quintiles of hospital volume was .17 (95% confidence interval, .09-.33). A restricted cubic spline analysis yielded no statistically significant evidence on the nonlinear relationship (Pnonlinearity = .19). The types of stents (plastic vs lumen-apposing metal stent) seemed to have no effect modification on the volume-mortality relationship (Pinteraction = .58). Higher hospital volume was also associated with lower risk of bleeding, shorter length of stay, and lower medical costs of inpatient care. Higher hospital volume was associated with a lower risk of in-hospital mortality of patients receiving EUS-guided treatment of PFCs. A further investigation is warranted to justify the volume-based selective referral of the patients.


Long-term clinical and molecular follow-up of large animals receiving retrovirally transduced stem and progenitor cells: no progression to clonal hematopoiesis or leukemia.
There has been significant progress toward clinically relevant levels of retroviral gene transfer into hematopoietic stem cells (HSC), and the therapeutic potential of HSC-based gene transfer has been convincingly demonstrated in children with severe combined immunodeficiency syndrome (SCID). However, the subsequent development of leukemia in two children with X-linked SCID who were apparently cured after transplantation of retrovirally corrected CD34+ cells has raised concerns regarding the safety of gene therapy approaches utilizing integrating vectors. Nonhuman primates and dogs represent the best available models for gene transfer safety and efficacy and are particularly valuable for evaluation of long-term effects. We have followed 42 rhesus macaques, 23 baboons, and 17 dogs with significant levels of gene transfer for a median of 3.5 years (range 1-7) after infusion of CD34+ cells transduced with retroviral vectors expressing marker or drug-resistance genes. None developed abnormal hematopoiesis or leukemia. Integration site analysis confirmed stable, polyclonal retrovirally marked hematopoiesis, without progression toward mono- or oligoclonality over time. These results suggest that retroviral integrations using replication-incompetent vectors, at copy numbers achieved using standard protocols, are unlikely to result in leukemogenesis and that patient- or transgene-specific factors most likely contributed to the occurrence of leukemia in the X-SCID gene therapy trial.


Massachusetts Health Reform's Effect on Hospitals' Racial Mix of Patients and on Patients' Use of Safety-net Hospitals.
Because of residential segregation and a lack of health insurance, minorities often receive care in different facilities than whites. Massachusetts (MA) health reform provided insurance to previously uninsured patients, which enabled them to potentially shift inpatient care to nonminority-serving or nonsafety-net hospitals. Examine whether MA health reform affected hospitals' racial mix of patients, and individual patients' use of safety-net hospitals. Difference-in-differences analysis of 2004-2009 inpatient discharge data from MA, compared with New York (NY), and New Jersey (NJ), to identify postreform changes, adjusting for secular changes. (1) Hospital-level analysis (discharges): 345 MA, NY, and NJ hospitals; (2) patient-level analysis (patients): 39,921 patients with ≥2 hospitalizations at a safety-net hospital in the prereform period. Prereform to postreform changes in percentage of discharges that are minority (black and Hispanic) at minority-serving hospitals; adjusted odds of patient movement from safety-net hospitals (prereform) to nonsafety-net hospitals (postreform) by age group and state. Treating NJ as the comparison state, MA reform was associated with an increase of 5.8% (95% CI, 1.4%-10.3%) in the percentage of minority discharges at MA minority-serving hospitals; with NY as the comparison state, the change was 2.1% (95% CI, -0.04% to 4.3%). Patient movement from safety-net to nonsafety-net hospitals was greater in MA than comparison states (difference-in-differences adjusted OR=1.3; 95% CI, 1.0-1.7; P=0.04). Following MA health reform, the safety-net remains an important component of the health care system.


Protein kinase C zeta. A novel regulator of both phosphorylation and de-phosphorylation of cardiac sarcomeric proteins.
Our experiments investigated associations of specific isoforms of protein kinase C (PKC) with individual proteins in the cardiac troponin complex. Troponin I (cTnI) associated with PKCepsilon and zeta and troponin T (cTnT) associated with PKC alpha, delta, and epsilon. Based on its association with cTnI, we hypothesized that PKCzeta is a major regulator of myofilament protein phosphorylation. To test this, we infected adult cardiac myocytes with adenoviral constructs containing DsRed monomer-tagged wild type (WT) and the following constitutively active forms of PKCzeta: the pseudo-substrate region (A119E), 3'-phospho-inositide-dependent kinase-1 (T410E), and auto-phosphorylation (T560E). The A119E and T410E mutants displayed increased localization to the Z-discs compared with WT and T560E. Immunoprecipitations were performed in myocytes expressing PKCzeta using PKC phospho-motif antibodies to determine the phosphorylation of cTnI, cTnT, tropomyosin, myosin-binding protein C, and desmin. We did not find serine (Ser) phosphorylation of cTnI or cTnT. However, we observed a significant decrease in threonine (Thr) phosphorylation of cTnI and cTnT notably by PKCzeta T560E. Ser phosphorylation of tropomyosin was increased by all three active mutants of PKCzeta. Ser/Thr phosphorylation of myosin-binding protein C increased primarily by PKCzeta A119E. Both PKCzeta A119E and T410E mutants increased desmin Ser/Thr phosphorylation. To explain the apparent Thr dephosphorylation of cTnI and cTnT, we hypothesized that PKCzeta exists as a complex with p21-activated kinase-1 (Pak1) and protein phosphatase 2A (PP2A), and this was confirmed by immunoprecipitation Western blot. Our data demonstrate that PKCzeta is a novel regulator of myofilament protein phosphorylation.


Quality of synthetic hexaploid wheat containing null alleles at Glu-A1 and Glu-B1 loci.
Triticum turgidum ssp. dicoccon PI94668 and PI349045 were identified as containing null alleles at Glu-A1 and Glu-B1 loci in previous investigation. Sequencing of the respective HMW-GS genes Ax, Bx, Ay and By in both accessions indicated equal DNA lengths with gene silencing caused by 1 to 4 in-frame stop codon(s) in the open reading frames. Six synthetic hexaploid wheat lines were produced by crossing PI94668 or PI349045 with six Aegilops tauschii by spontaneous chromosome doubling of unreduced gametes. As expected, these amphiploids had three different HMW-GS: Dx 3.1(t) + Dy11(*t), Dx2.1(t) +10(t) and Dx2(t) +Dy12(t) in Glu-D1 but double nulls in Glu-A1 and Glu-B1. Quality tests showed that most quality parameters in two T. turgidum ssp. dicoccon parents were very low due to the lack of HMW-GSs. However, incorporation of HMW-GS from Ae. tauschii in six synthetic hexaploid wheat lines significantly increased most quality related parameters. The potential values of these wheat lines in improving the quality of wheat are discussed.


Structure prediction and docking-based molecular insights of human YB-1 and nucleic acid interaction.
Y-box-binding protein 1 (YB-1), a cold shock domain protein, is one of the most conserved nucleic acid-binding proteins. The multifunctional human YB-1 is a member of a large family of proteins with an evolutionary ancient cold shock domain. The presence of a cold shock domain is a specific feature of Y-box-binding proteins and allows attributing them to a wider group of proteins containing a cold shock domain. This protein is involved in a number of cellular processes including proliferation, differentiation and stress response. The YB-1 performs its function both in the cytoplasm and in the cell nucleus. In this study, we present the structure of full-length human YB-1 protein along with investigation of their nucleic acid-binding preferential. The study also focuses on biases for particular purine and pyrimidine bases. The overall goal of this study was to model and validate full-length YB-1 protein and to compare its nucleic acid-binding studies with previous reports.


Probiotic supplementation for management of cardiovascular risk factors in adults with type II diabetes: A systematic review and meta-analysis.
The effectiveness of probiotics in control of hypertension and dyslipidemia in diabetic patients remains unclear. Therefore, we systematically reviewed relevant data to elucidate the effects of probiotics on blood pressure and lipid profile of type 2 diabetic patients. We searched PubMed, ISI Web of Knowledge, Scopus, The Cochrane Library, ClinicalTrials.gov, ProQuest Dissertations and Theses databases until May 2016. The primary outcomes were systolic blood pressure (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Other biochemical response and adverse effects were considered as secondary outcomes. Data was extracted from included studies and pooled in meta-analysis whenever possible (both standardized mean difference (SMD) analysis and weighted mean difference (WMD) analysis were performed). Eleven eligible randomized controlled trial (n = 641) were identified. Pooling data from these trials demonstrated probiotic consumption significantly decreased SBP (WMD, -3.28 mmHg; 95% confidence interval [CI], -5.38 to -1.18), DBP (WMD, -2.13 mmHg; 95% CI, -4.5 to 0.24), LDL-C (WMD, 8.32 mg/dl; 95% CI, -15.24 to -1.4), TC (WMD, -12.19 mg/dl; 955 CI -17.62 to -6.75) and TG (WMD, -24.48 mg/dl; 95% CI, -33.77 to -11.18) in type 2 diabetic patients compared with placebo. The methodological quality varied across trials included in this study. This systematic review suggests probiotics supplementation may be helpful for control of dyslipidemia and hypertension in type 2 diabetic patients. Conducting more trails with large sample size and long follow-up time still is necessary to develop clinical practice guidelines for management of cardiovascular risk factors in patient with type 2 diabetes.


[Is there an alternative to traditional stress tests? (One more time about transesophageal cardiac pacing)].
To assess diagnostic potential of transesophageal cardiac pacing in patients with ischemic heart disease. One hundred patients with overt or suspected ischemic heart disease (IHD) unable to perform or complete standard exercise test. In addition to clinical investigation and transesophageal cardiac pacing stress Doppler echocardiography was carried out in 60 and coronary angiography in 30 patients. Transesophageal pacing was completed in 95% of patients. Sensitivity of the test for diagnosis of IHD was 85%, specificity--77%, predictive value of positive and negative results--95 and 73%, respectively. Combined use of transesophageal pacing and Doppler echocardiography increased sensitivity of diagnosis of IHD up to 92%. Blood pressure increment during transesophageal pacing did not exceed 10 mm Hg. Transesophageal cardiac pacing is a highly informative, simple, safe and widely available selective stress test. Results of this test does not depend on concomitant pathology and physical fitness of a patient. Therefore it presents an alternative to standard stress tests and is a method of choice in many diagnostic situations.


Protein kinase C-and ras-dependent activation of c-jun gene by human papillomavirus type 11 E5a oncoprotein.
E5a of HPV-11 is a transforming oncogene. Previously, we have shown that E5a constitutively activates the expression of protooncogene c-jun by transcriptional regulation through the AP-1 binding site in the c-jun promoter. In the present study, we used two different types of cells: the E5a transfected NIH 3T3 cells and human epidermal keratinocytes, and selectively inhibited different signal transduction pathways to investigate effects of E5a on c-jun expression. We find that protein kinase C and ras-dependent pathways are important for the c-jun induction by E5a, but not the cAMP-dependent pathway.


The developing crisis in the national general surgery workforce.
The number of surgeons willing to practice general surgery in its traditional form is in decline. One becomes acutely aware of this shortage, as a residency program director, given the many requests for new general surgeons (GS). From the 7th of February 2007 through the 30th of April 2007, and from May 23, 2007 through August 10, 2007, one program director collected all solicitations and advertised openings sent to him for a new GS. These communications varied from email submissions to formal letters. To assess the economic impact of a GS on a hospital, data were collected from existing recruiting industry surveys, the chief financial officer of a large inner-city teaching hospital, and an individual rural surgeon. There were 140 openings nationally for GSs during the initial study period. During the second study period, there were 149 positions in 40 states. The annual economic worth of a GS was estimated to be between $1.05 million and $2.4 million. Currently, there is an imbalance in supply and demand for the field of general surgery. If GSs retire or leave small hospitals and cannot be replaced, those hospitals will be threatened with closing. This will strain the large, safety-net hospitals even more. Solutions should include a national workforce survey, allowing hospitals to supplement a surgeon's income, the Residency Review Committee for Surgery should consider an immediate 20% increase in the number of categorical spots in general surgery, and focused recruitment of medical graduates from other countries.


Efficacy of surgical navigation in zygomaticomaxillary complex fractures: randomized controlled trial.
Accurate reduction is of vital importance in the treatment of zygomaticomaxillary complex (ZMC) fractures. Computer-assisted navigation systems (CANS) have been employed in ZMC fractures to improve the accuracy of surgical reduction. However, randomized controlled trials on this subject are rare and the benefits of CANS remain controversial. The aim of this study was to compare reduction errors between navigation-aided and conventional surgical treatment for ZMC fractures. Thirty-eight patients with unilateral type B ZMC fractures were enrolled. Preoperative computed tomography data were imported into ProPlan software for virtual surgical planning. Open reduction and internal fixation was performed with CANS (experimental group) or without CANS (control group). Postoperative computed tomography scans were obtained to examine the difference between surgical planning and the actual postoperative outcome, namely reduction errors. The median translational reduction errors in the X, Y, and Z axes were 0.80 mm, 0.40 mm, and 0.80 mm, respectively, in the experimental group and 0.53 mm, 0.86 mm, and 0.83 mm, respectively, in the control group (P > 0.05). The median rotational reduction errors in pitch, roll, and yaw were 0.92°, 2.47°, and 1.54°, respectively, in the experimental group and 1.45°, 3.68°, and 0.76°, respectively, in the control group (P > 0.05). In conclusion, compared with conventional reduction surgery, navigation-aided surgery showed no significant improvement in reduction accuracy in the treatment of type B ZMC fractures (Chinese Clinical Trial Registry, registration number ChiCTR1800015559).


Visual working memory is impaired when the medial temporal lobe is damaged.
The canonical description of the role of the medial temporal lobes (MTLs) in memory is that short-term forms of memory (e.g., working memory [WM]) are spared when the MTL is damaged, but longer term forms of memory are impaired. Tests used to assess this have typically had a heavy verbal component, potentially allowing explicit rehearsal strategies to maintain the WM trace over the memory delay period. Here we test the hypothesis that the MTL is necessary for visual WM when verbal rehearsal strategies are difficult to implement. In three patients with MTL damage we found impairments in spatial, face, and color WM, at delays as short as 4 sec. Impaired memory could not be attributed to memory load or perceptual problems. These findings suggest that the MTLs are critical for accurate visual WM.


MicroRNA expression profiling of the developing murine molar tooth germ and the developing murine submandibular salivary gland.
Using microarrays, miRNA expression profiles have been established at selected times during development (E15.5, P0 and P5) of the murine first molar mandibular tooth germ and the right submandibular salivary gland (E15.5, P0, P5 and P25). Microarray data was validated using real-time PCR, also facilitating RT-PCR profiling of nine selected miRNAs. In general, good agreement between microarray data and real-time PCR data was found. Further, miRNA expression profiles of foetal and adult liver were also investigated, and found to agree with published data. In tooth germ and salivary gland up to 88 different miRNAs were detected. In all tissues examined miRNA expression was highly dynamic; miRNA profiles changing extensively with time of development. Additionally, the expression of some miRNAs was tissue-specific. Bioinformatic analysis of clusters of miRNAs was attempted using the miRGate software, the results suggesting miRNAs to be involved in the regulation of essential developmental processes, e.g., epithelical cell proliferation, mesodermal cell fate determination and salivary gland morphogenesis.


Congenital jejunal and ileal atresia: natural prenatal sonographic history and association with neonatal outcome.
The purpose of this study was to describe the prenatal sonographic features and natural course of congenital jejunal and ileal atresia and correlate the findings with neonatal outcomes. We identified all neonates with surgically confirmed jejunal or ileal atresia that had prenatal sonography and neonatal surgery in our center from January 1, 1995, to April 1, 2005. Sonography reports and images were reviewed, without knowledge of neonatal outcomes, for features of intestinal obstruction. Obstetric and neonatal outcomes were evaluated. Fifteen (60%) of 25 offspring with atresias (10 jejunal, 4 ileal, and 1 jejunoileal) had sonography, of which 13 (86.6%) had features of atresia. Findings, number of affected fetuses, and gestational age at recognition included fetal echogenic bowel (n = 8), mean +/- SD, 21.3 +/- 3.8 weeks (range, 17.7-28.4 weeks); enlarged stomach (n = 5), 27.5 +/- 5.0 weeks (range, 22.0-34.3 weeks); dilated bowel (n = 13), 27.8 +/- 5.8 weeks (range, 18.3-35.9 weeks); and polyhydramnios (n = 6), 33.3 +/- 1.7 weeks (range, 31.0-35.6 weeks). No fetus with ileal atresia had an enlarged stomach or polyhydramnios. Delivery occurred at a mean of 34.7 +/- 3.6 weeks, with 9 (60%) cesarean deliveries. Neonatal outcomes of age at surgery, neonatal intensive care unit days, hospital days, total parenteral nutrition days, and death were similar whether or not fetal echogenic bowel, enlarged stomach, dilated bowel, or polyhydramnios was present. Likewise, these outcomes did not vary by type of atresia or time of diagnosis (prenatal or neonatal). Jejunal and ileal atresia have specific sonographic patterns allowing specific prenatal diagnoses in most affected fetuses. Prenatal sonographic findings and time of diagnosis did not affect neonatal outcome.


Stellate cells differentiate successively in the cat sensorimotor cortex during early postnatal ontogeny.
Golgi and Golgi-Kopsch techniques were used to investigate maturation of stellate and pyramidal cells and development of stellate-pyramidal connections in kittens of the following ages: 2, 7, 14, 21, 28 and 34 days. By two weeks, stellate cells in layer V have become mature. Layer III stellate cells with vertical axon ramifications are differentiated by 2-3 weeks of life and in 3-week-olds the horizontal spread of axon collaterals amounts to 1300 micrometer. Layer II stellate cells which are poorly developed n newborns acquire the greatest number of collaterals and a complex axon branching pattern by 4 weeks of age.


The association of goal-striving stress with sleep duration and sleep quality among African Americans in the Jackson Heart Study.
African Americans (AAs) report a higher frequency of certain stressors over their lifetime which may impact biological processes that can impair sleep. For this reason, goal-striving stress (GSS), the difference between aspiration and achievement, weighted by disappointment, may contribute to poor sleep quality and suboptimal sleep duration among AAs. We completed a cross-sectional analysis using exam 1 data (2000-2004) from the Jackson Heart Study (JHS) (n=4943). GSS was self-reported and categorized in tertiles of low, moderate, and high. Participants self-reported the number of hours they slept each night and rated their sleep quality as (1) very poor to (5) excellent. Sleep duration categories included the following: short sleep (≤6 hours), normal sleep (7-8 hours) and long sleep (≥ 9 hours). Sleep quality was categorized as high (good/very good/excellent) and low (fair/poor). Relative risk ratios (RRRs 95% confidence intervals-CI) were estimated for sleep duration and sleep quality categories by GSS using logistic regression. After full adjustment, there were no significant associations between GSS and sleep duration categories. However, participants who reported high (versus low) GSS had a 20% greater risk (1.20 95% CI: 1.01, 1.43) of low (versus high) sleep quality in the fully adjusted model. The stress due to the deficit between goal aspiration and achievement was associated with poor sleep quality. Future investigations should examine the association of changes in GSS with changes in sleep duration and sleep quality.


Do specific modules of cognitive behavioral therapy for depression have measurable effects on youth internalizing symptoms? An idiographic analysis.
Understanding the efficacy of each module of cognitive behavioral therapy (CBT) may inform efforts to improve outcomes for youth depression, but effects of specific modules have been difficult to examine. Idiographic interrupted time series models offer a robust way to estimate module effects on an individual's symptoms. This study examined the association of specific CBT modules for depression on internalizing symptoms among depressed youths who received modular CBT in a randomized trial. Individual models were created for three youths who met study criteria. Youths completed weekly symptom reports, and clinicians completed records of modules delivered. First order auto-regressive models quantified the change in average internalizing symptom severity between pre- and post-module delivery. All youths had 1-3 modules that were significantly associated with symptom reduction and 1-3 modules associated with deterioration. The 5 modules associated with improvement in at least one youth also lacked association (engagement, relaxation, cognitive reframing), or were associated with worsening (activity selection, parent psychoeducation) in others. Seven modules showed no measurable benefit, or detriment to any youth. This study demonstrated that specific modules have measurable effects, but more work is needed to build an evidence base of specific module effects to inform treatment personalization for youth depression.


Selenium and Polysaccharides of Atractylodes macrocephala Koidz Play Different Roles in Improving the Immune Response Induced by Heat Stress in Chickens.
The aim of the present study was to investigate the effect of acute heat stress (HS) on the chicken immune response and to examine the role of selenium (Se) and the polysaccharides of Atractylodes macrocephala Koidz (PAMK) in immune regulation in the chicken immune system. Two hundred chickens were randomly divided into two groups: the HS group and the control (Con) group. These chickens were treated with Se (0.3 mg/kg), PAMK (200 mg/kg) alone, and a combination of Se (0.3 mg/kg) and PAMK (200 mg/kg). The cytokines; antioxidative enzymes; and HSP60, HSP70, and HSP90 levels were examined in chicken immune organs. The results indicated that HS-induced immune dysfunction included increased levels of TNF-α, IFN-γ, IL-2, IL-4, HSP60, HSP70, HSP90, and malondialdehyde (MDA) as well as decreased levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in immune organs (P < 0.05). Among the affected organs, the bursa of Fabricius was one primary target of HS. The immune dysfunction induced by HS was alleviated (P < 0.05 or not) by treatment with Se and PAMK in different immune organs. However, Se only regulated the expression of TNF-α and IFN-γ, and PAMK influenced more cytokines in immune organs. The results showed that Se specifically regulated the TNF-α and IFN-γ pathways. Therefore, Se and PAMK played different roles in improving the immune response in HS chicken.


D-dimer screening for deep venous thrombosis in traumatic cervical spinal injuries.
Deep venous thrombosis (DVT) in spinal cord injury (SCI) patients is a life-threatening comorbidity. Despite its seriousness, prophylaxis and screening for DVT in SCI patients are still not sophisticated. This study aimed to define the epidemiology and incidence of DVT in acute traumatic cervical SCI in a Japanese population, determine the best timing for DVT screening, and determine the optimal D-dimer threshold level for use as an easy and minimally invasive screening tool. This is a prospective clinical study. The patient sample included acute traumatic cervical SCI patients who were admitted to our facility within 2 weeks after injury. Multivariate logistic regression was performed for outcome measure. We enrolled 268 patients (223 men and 45 women), from April 2007 to December 2012. After excluding early drop-out patients, 211 patients remained. Assessment for neurological status and blood chemistry, especially blood coagulation levels (prothrombin time, prothrombin time-international normalized ratio, activated partial thromboplastin time, and serum D-dimer), was performed every week until 1 month after injury. Ultrasonography was performed for DVT detection every 2 weeks. Deep venous thromboses were detected in 22 patients (10.4% of patients studied). All DVT-positive patients demonstrated severe paralysis classified as C or greater on the American Spinal Injury Association (ASIA) Impairment Scale. Multivariate logistic regression of clinical and laboratory parameters revealed that only the D-dimer level at 2 weeks after injury was an accurate predictor of DVT formation. The optimal threshold of D-dimer for prediction was determined to be 16 μg/dL. The sensitivity and specificity for detecting DVT were 77.3% and 69.2%, respectively. D-dimer levels may be used to predict the likelihood of DVT development in patients with acute cervical SCI. Furthermore, the optimal timing for screening test by D-dimer is 2 weeks after injury, and optimal threshold level for D-dimer for diagnosing DVT is 16 μg/dL. Such a screening test would be cost-efficient and simple to administer and could then be followed with additional investigations, such as ultrasonography or venography.


Comprehensive Outpatient Rehabilitation Program: Hospital-Based Stroke Outpatient Rehabilitation.
Few studies have considered the effectiveness of outpatient rehabilitation programs for stroke patients. The objective of this study was to assess the effectiveness of a hospital-based interdisciplinary outpatient stroke rehabilitation program with respect to physical functioning, mobility, and balance. The Comprehensive Outpatient Rehabilitation Program provides a hospital-based interdisciplinary approach to stroke rehabilitation in Southwestern Ontario. Outcome measures from physiotherapy and occupational therapy sessions were available at intake and discharge from the program. A series of paired sample t-tests were performed to assess patient changes between time points for each outcome measure. A total of 271 patients met the inclusion criteria for analysis (56.1% male; mean age = 62.9 ± 13.9 years). Significant improvements were found between admission and discharge for the Functional Independence Measure, grip strength, Chedoke-McMaster Stroke Assessment, two-minute walk test, maximum walk test, Timed Up and Go, Berg Balance Scale, and one-legged stance (P < .003 for all). The findings indicate that an interdisciplinary rehabilitation program was effective at improving the physical functioning, mobility, and balance of individuals after a stroke. A hospital-based, stroke-specific rehabilitation program should be considered when patients continue to experience deficits after inpatient rehabilitation.


Intraoperative internal spermatic vein phlebography in the subfertile male with varicocele.
Intraoperative internal spermatic vein phlebography was performed in 20 subfertile patients with a varicocele; 10 patients with varicoceles and left-sided indirect inguinal hernias without fertility problems served as controls. Phlebography was carried out during surgery with the patient supine and in a 45 degree anti-Trendelenburg position to stimulate an "erect" posture. In all 25 patients with a varicocele, valvular insufficiency was demonstrated at the renal-spermatic vein junction. When visualized, the position of the left adrenal vein in all instances was medial to or opposite the renal-internal spermatic vein confluence. This observation, reinforced by simultaneous determinations of cortisol levels in the internal spermatic and antecubital veins, practically excluded the validity of the theory of adrenal hormonal suppression of testicular tissues. In 40% of subfertile patients with a varicocele, double internal spermatic veins and reflux to the distended external spermatic (cremasteric) venous plexus were demonstrated. In no instance were such phenomena observed in the control groups. The not-infrequent failure of operative correction of varicocele seems to relate directly to such overlooked pathology. Broad clinical application of operative phlebography, especially in recurrent, persistent, or clinically advanced cases, will detect such anomalies and should reduce significantly the operative failures in the surgical correction of varicocele.


Effects of cadmium on the immune system of mice.
Chronic oral exposure of mice to Cd++ inhibits cell-mediated immunity of delayed type hypersensitivity induced by sheep red blood cells (SRBC). No effect was detected on humoral immune response to SRBC. Spleen cells derived from mice exposed to Cd++ showed in vitro enhanced response to T and B cell mitogens. These results demonstrate that Cd++ exposure alters the immune system of mice.


Assessing self-reported empathy and altruism in patients suffering from enduring borderline personality disorder.
Self-report studies on empathy in adults with borderline personality disorder (BPD) have based upon the Interpersonal Reactivity Index (IRI) and generally identified deficits in perspective taking abilities in this group, but indicated less coherent results regarding empathic concern. These two constructs are considered subcomponents of cognitive (CE) and affective empathy (AE), respectively. However, the IRI does not enable for valid investigation of overall levels of these empathy types. Surprisingly, although some findings from the general population suggest that empathy types may be positively related to altruism, neither this link nor general altruism have been examined in BPD. Additionally, these constructs have not been sufficiently studied in this group in the context of alexithymia or potential clinical confounders. Hence, women with BPD (N = 30) and healthy women (N = 38) completed, i.a., the Questionnaire of Cognitive and Affective Empathy, Self-Report Altruism Scale, TAS-20, STAI, and CESD-R. Patients with BPD reported significantly decreased overall CE (including worse online simulation abilities - conceptually similar to perspective taking from the IRI), but a similar level of overall AE. They also demonstrated lower altruism. Taken together, these results suggest that BPD patients have difficulties with imagining what emotions others are feeling and with altruistic responding to their needs.


Synthesis, cytotoxicity and liposome preparation of 28-acetylenic betulin derivatives.
Several novel betulin derivatives were prepared and evaluated for their antitumor activity. 3-O-acetylbetulinic aldehyde served as an ideal starting material for the synthesis of 28-acetylenic derivatives. These compounds were further transformed into pyrazoles and 1,2,3-triazoles. Also, the synthesis of 3-amino substituted butenolides was carried out. The compounds were screened for their antitumor activity in a panel of 15 human cancer cell lines in a sulforhodamine B (SRB) assay. Several compounds showed a noteworthy antitumor activity. In addition, the possibility of encapsulation into liposomes was examined, thereby resulting in an increased cytotoxicity. The results from a trypan-blue test and from DNA laddering provided evidence for an apoptotic cell death.


Tirucallane triterpenes from the leaf extract of Entandrophragma angolense.
From the leaves of Entandrophragma angolense, three triterpenoidal compounds were isolated and structurally elucidated by mass and NMR spectroscopy. They belong to the tirucallane group but two of them possess the rare seco-ring-A feature. The phytochemical data are discussed from a chemotaxonomic and biogenetic points of view.


Lung cancer and incidence of stroke: a population-based cohort study.
Stroke is a known cerebrovascular complication in lung cancer patients; however, whether lung cancer patients are at elevated risk of developing stroke relative to the noncancer population remains unclear. The present study used population-based claims data from the Taiwan National Health Insurance, which identified 52,089 patients with an initial diagnosis of lung cancer between 1999 and 2007, and 104,178 matched noncancer subjects from all insured subjects age 20 years and older. Subsequent occurrence of stroke was measured until 2008, and the association between lung cancer and the hazard of developing stroke was estimated using Cox proportional hazard models. The incidence of stroke was 1.5 times higher (25.9 versus 17.4 per 1000 person-years) in the lung cancer group compared with the comparison group. The multivariate-adjusted hazard ratio (HR) comparing lung cancer patients with the noncancer group was 1.47 (95% CI, 1.39-1.56) for stroke, 1.78 (95% CI, 1.54-2.05) for hemorrhagic stroke, and 1.43 (95% CI, 1.34-1.51) for ischemic stroke. The risk of stroke fell over time, decreasing after 1 year of follow-up for men and after 2 years of follow-up for women. Within the first year of follow-up, the risk of stroke peaked during the first 3 months for men and within 4 to 6 months for women. Lung cancer is associated with increased risk of subsequent stroke within 1 year after diagnosis for men and 2 years after diagnosis for women.


Correction to: The cellular machineries responsible for the division of endosymbiotic organelles.
The article The cellular machineries responsible for the division of endosymbiotic organelles, written by Yamato Yoshida was originally published electronically on the publisher's internet portal (currently SpringerLink) on 12 June 2018 without open access.


Efficacy and safety of an over-the-counter 1% colloidal oatmeal cream in the management of mild to moderate atopic dermatitis in children: a double-blind, randomized, active-controlled study.
The purpose of this study is to evaluate the efficacy and safety of an over-the-counter (OTC) 1% colloidal oatmeal cream versus a prescription barrier cream in children with mild-to-moderate atopic dermatitis (AD). Eligible patients (6 months-18 years) were randomized to OTC or prescription cream. Eczema Area and Severity Index (EASI) scores, Investigator's Global Atopic Dermatitis Assessment (IGADA) scores, patients' and/or caregivers' assessment of itch using 10-cm visual analog scale (VAS) on day 0, weeks 1, 2, and 3 were assessed. The intention to treat (ITT) and per protocol (PP) populations were analyzed. Ninety patients (mean [SD] age, 8.1 [4] years; boys, 45.6%; African American, 54.4%) were randomized (OTC cream, 45; prescription cream, 45). At week 3, EASI scores showed that the OTC cream was non-inferior (non-inferiority margin = 1.5) to the prescription cream (adjusted mean change [95% CI] from baseline: ITT, 0.18 [-0.35, 0.70]; PP, 0.14 [-0.42, 0.70]). IGADA (adjusted mean between group difference, 0.106 [-0.130, 0.341]) and VAS itch (0.103 [-0.831, 1.038]) scores improved in both groups. No safety issues were identified. OTC 1% oatmeal cream was equally effective and safe as the prescription barrier cream for the symptomatic treatment of mild-to-moderate AD in children. NCT01326910.


Metabolic Activation of PCBs to Carcinogens in Vivo - A Review.
Many higher-chlorinated biphenyls, persistent and predominant in foods, are active as promoters in hepatocarcinogenesis. Lower-chlorinated biphenyls, predominating in indoor and outdoor air, are more readily metabolized and therefore shorter lived, 'episodic' contaminants. Thus inhalation of such lower chlorinated biphenyls may expose humans to reactive, possibly genotoxic/carcinogenic intermediates. Lower chlorinated biphenyls may be metabolized via arene-oxides to mono- and dihydroxylated intermediates and further to (semi)quinones, highly reactive intermediates. Covalently bound lower chlorinated biphenyls have been detected in rodent tissues in vivo. We recently showed using the modified Solt-Farber foci assay that several mono- to tetrachlorinated biphenyls have initiating activity in the livers of rats. In a follow-up study of PCB3 (4-chlorobiphenyl) metabolites only one monohydroxy- and one quinoid- metabolite showed initiating activity, indicating that the metabolic activation of PCB3 proceeds via hydroxylation and oxidation to the 3,4-quinone, the ultimate carcinogen. Since cancer initiation is based on genotoxic event(s), we hypothesized that PCB3 and/or its metabolite(s) are mutagenic in rat liver in vivo. To investigate this, BigBlue® rats, transgenic for the lacI reporter gene, were exposed to PCB3 and 4-hydroxy-PCB3 (4-HO-PCB3). In male rats the mutant frequency (MF) of lac I in the liver was significantly elevated and the mutation spectrum differed significantly from the control. 4-HO-PCB3 caused a non-significant (p = 0.115) doubling of the MF compared to the control. These studies prove that lower halogenated biphenyls may be metabolically activated in vivo to genotoxic and initiating intermediates.


A critical examination of the amenorrhea and weight criteria for diagnosing anorexia nervosa.
Amenorrhea and weight loss to below 15% of 'healthy' weight are current diagnostic criteria for anorexia nervosa (AN). This study compares females who meet current International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for AN with females who meet the essential psychopathology and significant self-starvation, but lack either amenorrhea or weight loss below 85%. This study retrospectively examined the medical charts of 588 consecutive admissions to an in-patient treatment program. All diagnoses conformed to ICD-10 and DSM-IV. Of 588 admissions, 297 females had some form of AN with 77.4% (230 of 297) meeting current criteria, while 22.6% (67 of 297) with core psychopathology and self-starvation were classified as eating disorders not otherwise specified or 'atypical' because of some menstrual function or final weight above 85%. The groups showed few statistically significant differences on demographics, illness history, and treatment response, psychopathology, or bone density. Amenorrhea may not be a useful diagnostic criterion. Also, requiring below 85% of healthy weight may need generalization.


A blunted anxiolytic like effect of curcumin against acute lead induced anxiety in rat: involvement of serotonin.
Anxiety is one of the most common mental disorders sharing extreme or pathological anxiety states as the primary disturbance in mood or emotional tone, with increased fear and exaggerated acute stress responses. Medicinal plants are very variable, but some of them are used as a spice such as curcumin (Curcuma longa). Curcumin shows a wide range of pharmacological potentialities, however, little is known about its anxiolytic properties. The aim of our study was to assess the anti-anxiety potential of curcumin extract against experimental lead induced-anxiety in rats. Experiments were carried out on male Wistar rats intoxicated acutely with an intraperitoneal injection of Pb (25mg/kg B.W.) and/or concomitantly with administration of curcumin (30 mg/kg B.W.) for 3 days. Using immunohistochemistry and anxiety assessment tests (dark light box and elevated plus maze), we evaluated, respectively, the expression of serotonin (5HT) in the dorsal raphe nucleus (DRN) and the anxiety state in our animals. Our results showed, for the first time, a noticeable anxiolytic effect of curcumin against lead induced anxiety in rats and this may possibly result from modulation of central neuronal monoaminergic neurotransmission, especially serotonin, which has shown a significant reduction of the immunoreactivity within the DRN.


An alternative treatment approach to mitral regurgitation.
This article aims to increase knowledge and understanding of mitral valve regurgitation to assist nurses in providing effective patient care and support the treatment options available. It focuses on the MitraClip, a procedure to repair the mitral valve using a percutaneous approach.


Fluid shift is moderate and short-lived during acute crystalloid hemodilution and normothermic cardiopulmonary bypass in piglets.
Crystalloids are commonly used as priming solutions during cardiopulmonary bypass (CPB). Consequently, hemodilution is a regular occurrence at the start of a CPB. This study describes the time-course variations of hemodynamic parameters, plasma volume (PV) and fluid exchange following crystalloid hemodilution at start of normothermic CPB. Forty-five anesthetized piglets were given 60-min normothermic CPB. Ringer's solution was used as priming solution and maintenance fluid. Fluid input/losses, PV, colloid osmotic pressures (plasma/interstitium), hematocrit, and s-proteins were measured, and fluid extravasation rates (FER) and intravascular protein-masses calculated. Start of CPB resulted in a 25-30% hemodilution. To keep the fluid level of the CPB-reservoir constant after start of bypass, fluid addition [2.08 +/- 0.36 (mean +/- SEM) ml kg(-1) min(-1)] was necessary during the first 5 min. Thereafter the fluid needs to be leveled off [0.17 +/- 0.03 ml kg(-1) min(-1) (10-60 min), P < 0.001]. Fluid extravasation rate increased immediately following hemodilution from a baseline value of 0.08 +/- 0.01 to 1.75 +/- 0.34 ml kg(-1) min(-1) with a delayed decrease compared to fluid additions, to reach a 'steady-state' level of 0.22 +/- 0.03 ml kg(-1) min(-1) after 30 min (P < 0.001). Differences in time-course variations between fluid added and fluid extravasated were accompanied by changes in PV and mean arterial pressure. The colloid osmotic gradient decreased about 50% throughout the study and could partly explain the increased FER. Acute crystalloid hemodilution contributes to fluid overload during normothermic CPB. The resulting increase in fluid extravasation is, however, moderate, short-lived and levels off to baseline values within 30 min.


Contribution to the knowledge of home range in common shrew Sorex araneus L.
Population density of shrews in a clearing in the submountain spruce forest was established per 1 hectare 17.5 individuals of common shrew, 4.6 of pygmy shrew and 1.1 of alpin shrew. The mean radius of activity in common shrew amounts to 13 m. The ratio of shrew to rodents was 1:3 or 1:2 in summer and autum respectively. Theoretical home range reached 532 m2. The importance of home range studies for synecological studies and theory of natural focality was demonstrated.


Influence of epidermal growth factor on growth of bovine mammary tissue in athymic nude mice.
Bovine mammary tissue obtained from midpregnant Holstein heifers by surgical biopsy was transplanted subcutaneously to ovariectomized athymic nude mice (n = 5 heifers). After 3 weeks recovery, mice were either sham operated or sialoadenectomized (submandibular salivary glands removed). After an additional week, mice were injected with saline or 17 beta-estradiol + progesterone (1 microgram + 1 mg/day) for 2 days. In addition, half of the sialoadenectomized mice were injected with epidermal growth factor (5 micrograms/day). Grafted tissue was removed and rate of deoxyribonucleic acid (DNA) synthesis estimated by incorporation of 3H thymidine. Estradiol + progesterone increased the incorporation of 3H thymidine from 77 +/- 20 dpm/micrograms DNA to 472 +/- 53 dpm/micrograms DNA. In sialoadenectomized mice, DNA synthesis was increased from 88 +/- 16 dpm/micrograms DNA (saline treated) to 360 +/- 29 dpm/micrograms DNA (estradiol + progesterone treated). In sialoadenectomized mice treated with epidermal growth factor, DNA synthesis in estradiol + progesterone treated mice was 529 +/- 36 dpm/micrograms DNA, compared to 112 +/- 30 dpm/micrograms DNA in sialoadenectomized mice treated with epidermal growth factor. These data indicate that sialoadenectomy of athymic nude mice decreased the ability of transplanted bovine mammary tissue to increase DNA synthesis in response to estradiol and progesterone. This inhibition was removed by epidermal growth factor treatment. These data suggest a physiological role of epidermal growth factor in regulating development and hormone responsiveness of bovine mammary tissue.


Iron absorption and oxidant stress during erythropoietin therapy in very low birth weight premature infants: a cohort study.
Iron supplementation may be associated with oxidative stress particularly in premature infants. Our purpose was to examine 1) early supplemental iron during treatment with erythropoietin (EPO) and oxidative stress; 2) enhanced iron absorption during EPO in those infants receiving human milk. Therefore, we determined the effect of erythropoietin plus supplemental iron intakes (4 mg/kg/d) on antioxidant status and iron incorporation. Ten very-low-birth-weight infants who were enterally fed and receiving either human milk or formula were followed for 4 weeks during erythropoietin therapy; blood and urine were collected at 3 times; baseline, 2 and 4 weeks later. Once oral feeds commenced the study protocol was initiated. After baseline blood collection, a dose of Fe57 was administered. Two weeks later, a dose of Fe58 was administered as ferrous chloride to determine the effect of human-milk or formula on iron incorporation into RBCs. Infants started the study at 35 +/- 13 days. Incorporation of isotope into RBCs did not differ between formula fed for Fe57 (mean incorporation 8 +/- 2.9 n = 3) compared to human-milk fed infants (8.7 +/- 5 n = 7) nor for Fe58 (6 +/- 2.7 n = 3 vs. 8.6 +/- 5 n = 7). Tissue damage measured by malondialdehyde in plasma and F-2--isoprostanes in urine, did not differ by feed or over time. Neither ability to resist oxidative stress/nor RBC superoxide dismutase differed according to feed or over time. Data suggest that during erythropoietin therapy antioxidant defence in VLBW infants are capable of dealing with early supplemental iron during treatment with EPO.


A new subtraction technique for molecular cloning of rare antiviral antibody specificities from phage display libraries.
The preparation of random combinatorial libraries exposed on the surface of phage provides a route for the selection of diverse high affinity human monoclonal antibodies. However, in particular settings, the isolation of genes coding for a rare antibody can be elusive because some epitopes are predominant and because, in the case of impure antigens, the protein or any compound of interest can be present in relatively minimal amount. In this paper, we describe the successful utilization of a new strategy of "preadsorption" panning that allowed us to clone a rare human monoclonal antibody fragment and to access a different antibody repertoire. The procedure is easy, fast, inexpensive, can be used together with other panning techniques and can be particularly useful in cloning antibodies against rare or unknown determinants.


Study of the interaction of glutamatergic and nitrergic signalling in conditions of the experimental airways hyperreactivity.
Glutamatergic and nitrergic system participate in the control of respiratory system functions. It is only little information regarding a possible interaction of both systems in the airways hyperractivity. We investigated the effect of agents modulating the activity of these systems on the experimental ovalbumin-induced airways hyperreactivity as well as on the changes of exhaled nitric oxide (eNO) levels. We used the agonists of NMDA receptors - N-methyl-D-aspartic acid (NMDA) and monosodium glutamate (MSG), selective competitive antagonist (DL-2-amino-5-phosphonovaleric acid - AP-5) and selective non-competitive antagonist (dizocilpine - MK-801) of these receptors. We used also non-specific inhibitor of NO synthases N(ω)-nitro-L-arginine methyl ester (L-NAME). The airways responsiveness to histamine or acetylcholine was evaluated under in vitro conditions. NMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. The effect of MSG was less pronounced. MK-801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle. We recorded the changes in eNO levels. The activation of NMDA receptor with NMDA or MSG increased eNO levels. The inhibition of NO synthase with L-NAME caused the fall of eNO levels. MK-801 shows (within the group) the more expressive effect in the eNO levels during sensitization than AP-5 group. The results confirm the possibility of NMDA receptors participation in the experimental airways hyperreactivity.