Interactions between Delta(9)-tetrahydrocannabinol and mu opioid receptor agonists in rhesus monkeys: discrimination and antinociception.
Opioid receptor agonists can enhance some effects of cannabinoid receptor agonists, and cannabinoid receptor agonists can enhance some effects of opioid receptor agonists; however, the generality of these interactions is not established. This study examined interactions between the discriminative stimulus and antinociceptive effects of mu opioid receptor agonists and Delta(9)-tetrahydrocannabinol (THC) in rhesus monkeys. Neither heroin nor morphine (intravenous (i.v.) or subcutaneous (s.c.)) altered the discriminative stimulus effects of THC in monkeys (n = 5) discriminating 0.1 mg/kg THC i.v. In contrast, THC (s.c.) markedly attenuated the discriminative stimulus effect of morphine and heroin in nondependent monkeys (n = 4) discriminating 1.78 mg/kg morphine s.c. Doses of THC that attenuated the discriminative stimulus effects of morphine in nondependent monkeys failed to modify the discriminative stimulus effects of morphine in morphine-dependent (5.6 mg/kg/12 h) monkeys (n = 4) discriminating 0.0178 mg/kg naltrexone s.c. THC also failed to modify the discriminative stimulus effects of naltrexone in morphine-dependent monkeys or the effects of midazolam in monkeys (n = 4) discriminating 0.32 mg/kg midazolam s.c. Doses of THC (s.c.) that attenuated the discriminative stimulus effects of morphine in nondependent monkeys enhanced the antinociceptive effects of morphine (s.c.) in nondependent monkeys. While mu receptor agonists did not alter the discriminative stimulus effects of THC, THC altered the effects of mu receptor agonists in a context-dependent manner. That the same doses of THC enhance, attenuate, or do not affect morphine, depending on the condition, suggests that attenuation of morphine by THC can result from perceptual masking rather than common pharmacodynamic mechanisms or pharmacokinetic interactions.


Chronic mild stress induces widespread decreases in thyroid hormone alpha1 receptor mRNA levels in brain--reversal by imipramine.
While considerable clinical evidence implicates thyroid hormones (THs) in depressive illness, the specific nature of this involvement remains unclear. The alpha1 subtype (TR-alpha1) is the most abundant TH receptor in brain. Here we investigated changes in TR-alpha1 mRNA in the chronic mild stress (CMS) model of depression. Rats were exposed to a CMS schedule for 3 weeks, which resulted in a progressive decreases in sucrose preference (an index of anhedonia). They were then treated daily with either imipramine (IMI, 10mg/kg) or vehicle (VEH) for 2 weeks before being sacrificed for quantitative in situ hybridization analyses of TR-alpha1 mRNA throughout the brain. Results indicated that CMS followed by VEH induced widespread decreases in TR-alpha1 mRNA in brain. In contrast, CMS-exposed rats receiving IMI for the last 2 weeks prior to sacrifice showed full recovery of sucrose preference. Furthermore, brain TR-alpha1 mRNA levels in these animals were similar to those of non-stressed controls receiving either SAL or IMI. These results reveal that TR-alpha1 mRNA brain levels are very sensitive to CMS effects. The reversal of both anhedonic and TR-alpha1 effects of CMS by IMI suggests that TR-alpha1 may play a role both in stress-induced depressive symptoms and in their reversal by antidepressant interventions.


Conversion from trabeculectomy to deep sclerectomy. Prospective study of the first 44 cases.
To evaluate the outcomes of conversion from trabeculectomy to deep sclerectomy with placement of a drainage implant. Department of Ophthalmology, Hospital of Buskerud, Drammen, Norway. Deep sclerectomy was performed in 41 patients (44 eyes) from November 1999 to January 2002. An absorbable implant (AquaFlow((R)), Staar Surgical) and a nonabsorbable implant (T.Flux((R)), IOLTech Laboratories) were used in 75% and 25% of eyes, respectively. Patients with open-angle glaucoma who needed filtering surgery were enrolled consecutively in a prospective study. Patients with 2 or more previous filtering surgeries or neovascular glaucoma were excluded, as were children. Of the original 48 eyes, accidental perforation of the trabeculo-Descemet's membrane occurred in 8.3%; these eyes were excluded from the study. The severity of optic nerve damage was considered in the decision to start therapy. An intraocular pressure (IOP) above 22 mm Hg was always treated. After a mean follow-up of 12.9 months +/- 7.1 (SD), 61.4% of eyes were controlled without therapy. When eyes with previous surgery were excluded, the rate increased to 66.7% after a mean follow-up of 13.8 +/- 7.2 months. The mean IOP preoperatively and after 12 months was 27.9 +/- 6.9 mm Hg and 14.6 +/- 3.5 mm Hg, respectively (P<.001). The mean number of medications decreased from 3.4 +/- 1.0 preoperatively to 0.6 +/- 1.1 12 months postoperatively (P<.001). A reoperation was required in 2 cases (4.5%). There were no complications related to hypotony or other significant complications. This study shows that conversion from trabeculectomy to deep sclerectomy with placement of an implant is safe. The postoperative IOP reduction was acceptable, and no significant complications occurred.


[Treatment of ureteric lithioasis with ureteroscope: report of 234 patients].
To sum up the experience in the treatment of ureteric lithioasis with ureteroscope. From January. 1991 to November 1998 234 patients with ureteric lithiasis were treated with lithotripsy of ureteroscopy. 185 of 234 the patients (79%) were successfully treated with lithotripsy of ureteroscopy. Three of the patients (1.3%) had operative complications (ureterperforation 2 patients and ureteral mucosa avulsion in 1). Lithotripsy of ureteroscope is one of the effective methods in the treatment of ureteric lithiasis, especially in the lower part of ureters.


Prevention of cardiovascular ischemic complications with new platelet glycoprotein IIb/IIIa inhibitors.
Agents that block platelet glycoprotein IIb/IIIa integrin, the receptor that mediates the final common pathway of platelet aggregation, represent a promising new approach to preventing cardiovascular ischemic complications and late restenosis after percutaneous coronary revascularization. In the large-scale Evaluation of c7E3 for the Prevention of Ischemic Complications (EPIC) trial that involved high-risk patients undergoing coronary intervention procedures, a monoclonal antibody Fab fragment (c7E3) directed against this receptor, administered as a bolus and and through infusion, significantly reduced the 30-day incidence of major ischemic events relative to placebo. Treatment was associated with higher rates of bleeding complications and transfusion, the risk of which appeared to be inversely related to body weight. The c7E3 bolus and infusion also significantly decreased the need for repeat revascularization during the 6-month blinded follow-up period. Ongoing trials are now exploring strategies for refining the practical aspects of glycoprotein IIb/IIIa therapy and minimizing the risk of bleeding.


Simultaneous determination of methylparaben, propylparaben, hydrocortisone acetate and its degradation products in a topical cream by RP-HPLC.
A novel reversed-phase high-performance liquid chromatographic method with UV spectrophotometric detection was developed and validated for the determination of compounds in topical cream. The method describes determination of active component hydrocortisone acetate (HCA), its degradation products hydrocortisone (HC) and cortisone acetate (occurring in formulation after long-term stability tests) and two preservatives presented in the cream-methylparaben and propylparaben, using dexamethasone as an internal standard. The chromatographic separation was performed on a 5 microm SUPELCO Discovery C18 125 x 4-mm ID column. The optimised mobile phase for separation of all the compounds consists of methanol, acetonitrile and water (15:27:58, v/v/v), with the analysis time less than 13 min. The method was applicable for routine analysis (assays and stability tests) of active compound HCA, preservatives and degradation products in pharmaceutical product--topical cream Hydrocortizone cream 1%.


Plasma vasopressin concentration in the anaesthetized dog before, during and after atrial distension.
Plasma vasopressin (AVP) concentration in dogs anaesthetized with chloralose was measured by radioimmunoassay and was within the range of 2-5 pg/ml. during control periods. Distension of the left atrium led within 2 min to a fall in plasma AVP concentration which reached a steady lower value within 4 min. After cessation of atrial distension the AVP concentration returned to pre-distention values within 4 min. Cooling the cervical vagosympathetic nerves to 8-10 degrees C led to a rise in plasma AVP concentration. Atrial distension during cooling of the vagi resulted in a further increase of plasma AVP concentration.


Clinicopathological study of bilateral developmental cataracts diagnosed in utero.
We report a case of unusual, bilateral developmental cataracts in a fetus with a supernumerary chromosome. A 42-year-old woman presented during her 6th pregnancy for assessment of fetal karyotype. This showed a supernumerary chromosome derived from chromosome 21. Subsequently fetal ultrasound suggested the presence of bilateral cataracts and the pregnancy was terminated at 19 weeks and 3 days' gestation. Both eyes were submitted for histopathological and electron microscopical examination. Histopathological examination revealed unusual bilateral developmental cataracts with abnormal bladder-type cells lining the posterior aspect of the lens vesicle, a poorly formed nuclear bow and a central mass of fibrillar material associated with macrophages lying within an area of liquefaction. Transmission electron microscopy revealed the presence of peg and socket joints in both central and posterior regions and degenerate crystallins in the posterior region. We described an unusual case of developmental cataract diagnosed in utero by ultrasound. The morphological appearances suggest that the defect occurred during or after formation of the secondary lens fibres. Detailed descriptions of cases such as this one may contribute to our understanding of lens development and cataract formation.


Expression of the cloned subunits of bacterial luciferase from separate replicons.
The lux A and lux B genes of Vibrio harveyi, encoding the alpha and beta subunits of bacterial luciferase, were cloned individually into Escherichia coli in two different compatible plasmids. Active luciferase was formed in an amount equal to that produced in cells carrying a plasmid with the cloned genes on a single fragment.


Does hemoperfusion in combination with other treatments reduce the mortality of patients with paraquat poisoning more than hemoperfusion alone: A systematic review with meta-analysis.
Paraquat (PQ) poisoning is a serious public health problem in many countries. In spite of different treatments, the mortality is still high. We performed a meta-analysis to see whether hemoperfusion (HP) in combination with other treatments reduces the mortality more than HP alone in patients with PQ poisoning. We searched EMBASE, PubMed, Google Scholar, ISI Web of Knowledge, Cochrane Central Register of Controlled Trials, Scopus, Springer, TRIP, ProQuest, and references of the included studies from January 2000 to August 2017. Two reviewers independently searched and extracted data. We measured I 2 to determine variance contributed by heterogeneity. To investigate the publication bias, Begg's and Egger's tests were used along with funnel plot analysis. Ultimately 12 articles were included in the meta-analysis. Five articles compared HP with conventional therapy with a total of 1311 patients, and seven articles compared mortality of patients received HP versus those received HP in combination with an additional treatment. HP alone reduced the odds of death (odds ratio [OR] = 0.20; 95% confidence interval [CI]: 0.11-0.40, P < 0.0001) compared to conventional therapy. Furthermore, the odds of death was higher in HP group compared to those received HP in combination of additional treatments (OR = 1.24; 95% CI: 1.05-1.46, P = 0.01). The mortality was less in HP-treated group compared to those received only conventional therapy. Addition of other treatments with HP reduced the mortality more than HP alone.


Clarification and standardization of substance abuse terminology.
A four-stage Delphi survey of substance abuse experts was conducted to help achieve greater clarity and uniformity in terminology associated with alcohol and other drug-related problems. This multidisciplinary group of experts was asked to reach a consensus on alcohol and other drug-related terms and definitions. Results produced a list of 50 substance abuse terms deemed important, along with the most agreed on definition for each term.


Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene. IV. Effects on gastric lesions in rats induced by cold-restraint stress and thyrotropin-releasing hormone.
Propyl-methylenedioxyindene (pr-MDI; 30 mg/kg, i.p.), an intracellular calcium antagonist, significantly reduced the number and size of erosions per stomach induced by cold-restraint stress by 69% and 86%, respectively. Our previous findings indicate that the antiulcer activity of pr-MDI is highly correlated with its inhibitory effect on gastric motor activity. Since central TRH is suggested as the brain mediator responsible for cold-restraint stress gastric ulcers in rats, the inhibitory action of pr-MDI was evaluated in the TRH-induced gastric lesion model. Pr-MDI (30 mg/kg) did not reduce the gastric erosions induced by intracisternal administration of 100ng RX77368, a stable thyrotropin-releasing hormone (TRH) analogue, even though it abolished the RX77368-induced stimulation of gastric emptying, gastric acidity, and acid output. Since pr-MDI (30 mg/kg, i.p.) significantly inhibited the stimulation of gastric motility by both cold-restraint stress and TRH, but only cold-restraint stress-induced gastric erosions were effectively reduced by the drug, the present findings suggest a possible dissociation between the ulcerogenic mechanisms of cold-restraint stress and intracisternal administration of TRH.


DON-glycosides: Characterisation of synthesis products and screening for their occurrence in DON-treated wheat samples.
DON-3ß-glucopyranoside was synthesized and characterized by LC-MS/MS. The formation of by-products in the chemical synthesis was further evaluated and, according to their different fragmentation behaviours, it was possible to postulate their structures. The occurrence of these substances in nature was investigated by the analysis of wheat ears, which were treated with DON at anthesis. For the first time DON-3-glucoside could be detected in wheat, strongly indicating that it could also occur in naturally contaminated cereals.


Sarcomatoid chromophobe renal cell carcinoma revealed by acute pyelonephritis in a diabetic patient.
Chromophobe renal cell carcinoma (CRCC) is a rare tumor comprising 2 types of cells (eosinophilic and clear cells), coexisting in varying proportions. CRCC has an overall good prognosis. However, the rarely encountered sarcomatoid differentiation is associated with a pejorative outcome and must, therefore, be rigorously ruled out. Acute pyelonephritis and other infectious complications rarely occur. We report a case of CRCC with sarcomatoid differentiation in a woman in her sixties which was revealed by acute pyelonephritis and had a lethal outcome.


Differential sensitivity of head and neck cancers to non-major histocompatibility-restricted killer cell activity.
Cell lines derived from squamous cell carcinoma of the upper aerodigestive tract (head and neck cancer) were phenotypically characterized with regard to differential sensitivity to nonmajor histocompatibility restricted (non-MHCr) killer cell activity. Requirements for detectable lysis of the cell lines in a standard chromium release assay included either isolation of fresh enriched Leu 19+ large granular lymphocytes (both Leu 19+CD3+ and Leu 19+CD3- populations) or interleukin-2 (IL-2) stimulation of peripheral blood lymphocytes (PBL). In neither circumstance could lytic activity be identified among Leu 19- populations. With PBL IL-2 stimulation significant differential sensitivity to lysis expressed by the head and neck cancer cell lines (P less than 0.001 by analysis of variance) was identified and maintained regardless of PBL source, i.e., PBL from healthy controls and three differing populations of head and neck cancer patients categorized by disease status and treatment. One factor associated with a cell line's increased sensitivity was degree of tumor differentiation, poorly differentiated tumors (as defined by intermediate filament cytochemical staining [decreased keratin and increased vimentin]) being more sensitive. Furthermore, as tumor cell lytic sensitivity increased, major histocompatibility complex (MHC)-class I antigen expression diminished concurrently. In 1 of 4 cell lines tested, however, pretreatment of tumor cells with interferon-gamma induced diminished lytic sensitivity independent of changes in MHC-class I expression, indicating factors not related to MHC-class I expression are likewise relevant. In previous studies we defined the in vivo prognostic significance of non-MHCr killer cell cytotoxicity activity against K562 targets, diminished activity being principally predictive of metastatic disease development in persons with poorly differentiated head and neck cancers. This report extends these observations by demonstrating in vitro that poorly differentiated head and neck cancer target cells are highly sensitive to changes in lytic function expressed by Leu 19+ non-MHCr effector cells.


Cellular proliferative activity of mammographic normal dense and fatty tissue determined by DNA S phase percentage.
A prospective study was undertaken to evaluate associations among mammographic normal dense and fatty tissue, benign histologic findings, and cellular proliferative activity determined by DNA S phase percentages. Mammographic and histologic findings of benign, normal dense and fatty tissue contained in 100 excised specimens were cross-tabulated with flow cytometric DNA S phase percentages of needle aspirates obtained under radiographic guidance. Histologic evidence of atypia or hyperplasia was present in 21 (32%) of 66 fatty tissue samples and 11 (32%) of 34 dense tissue samples (p = NS). The median S phase percentages were identical for mammographic fatty and dense tissue (median % S phase = 5.35). The frequency of high S phase percentages (above the median) was not significantly different for tissue containing atypia or hyperplasia, 47% (15 of 32), as compared to tissue containing other benign histology, 52% (35 of 68) (p = NS). These frequencies were similar in women 49 and younger or 50 and older. These data show that mammographic normal dense and fatty tissues contain similar frequencies of histologic atypia or hyperplasia and low and high cellular proliferative activity determined by DNA S phase percentages in women aged 49 and younger and 50 and older.


Comparison of two techniques for diagnosis of cryptosporidiosis in diarrhoeic goat kids and lambs in Cyprus.
This study was conducted in the Larnaca area of Cyprus and included 28 goat and 15 sheep flocks suffering from neonatal diarrhoea (>20%). Faecal samples from diarrhoeic animals revealed that 25 of the 28 goat and 12 of the 15 sheep flocks were positive for Cryptosporidium. The ELISA was more accurate in the diagnosis of cryptosporidiosis compared to the Ziehl-Neelsen staining technique (P < 0.05). Flock size and the period of kidding/lambing were found to be the main risk factors implicated in the occurrence of neonatal goat kid/lamb cryptosporidiosis.


Clinicopathological factors influencing the number of stages of Mohs surgery for basal cell carcinoma.
Mohs Micrographic Surgery (MMS) is commonly used to treat high-risk basal cell carcinoma (BCC). Correlate clinicopathologic preoperative features with the number of MMS stages (primary endpoint) and margins (secondary endpoint) required for BCC complete excision. We retrospectively analyzed BCCs treated by MMS in a 2-year period at the study's institution. Variables studied included the patient gender, age, immune status, lesion size, location, if it was a primary, recurrent, or persistent tumor, histopathologic characteristics, number of surgical stages, and amount of tissue excised. 116 BCCs were included. The majority (61.2%, n = 71) required a single-stage surgery for complete clearance, requiring a final margins of 3.11 ± 2.35 mm. Statistically significant differences between locations in different high-risk areas (periocular, perioral, nose, ear) and the number of MMS stages required for complete excision (p = 0.025) were found, with periocular tumours requiring the highest mean of stages (2.29 ± 0.95). An aggressive histopathology significantly influenced the number of MMS stages (p = 0.012). Any significant relation between clinicopathological features and variation in the final surgical margins was found, just certain tendencies (male patients, persistent tumor, periocular location, and high-risk histopathological tumors required larger margins). Neither patient age or tumor dimension correlated significantly with both number of MMS stages and final surgical margins. Limitations of this study include its single-center nature with a small sample size, which limits the value of conclusions. Main factors related to a greater number of MMS stages were periocular location and high-risk histopathological subtype of the tumor.


Infant heart transplantation with extremely oversized donor heart: is the donor-recipient size matching too conservative?
Heart transplantation (HTx) remains the gold standard treatment for end-stage heart failure in children but is restricted due to the limitation of donors. The donor-recipient weight ratio (DRWR) of 0.8-2.5 was the main selection criterion, and reports were particularly scarce in cases of DRWR > 3.0. We present an infant HTx case with DRWR of 6.5. The recipient was a 66-day-old female infant, weighing 3 kg, diagnosed with complex congenital heart disease and refractory severe heart failure, whereas the donor was a 4-year-old girl weighing 19.5 kg. The phased delayed sternal closure was performed and accomplished on the 23rd day after operation without wound infection. After treating complications with extracorporeal membrane oxygenation, peritoneal dialysis, and mechanical ventilation, the patient was successfully discharged. After 1 year of follow-up, the patient was still in optimal condition. Extending DRWR range may help enlarge the donor pool and shorten recipients' waiting time.


A 10-year study of steady employment and non-vocational outcomes among people with serious mental illness and co-occurring substance use disorders.
Employment promotes recovery for persons with serious mental illness by providing extra income and a valued social role, but the impact of employment on other psychosocial and clinical outcomes remains unclear. This study examined non-vocational outcomes in relation to steady employment over 10 years among people with serious mental illness and co-occurring substance use disorders. Researchers interviewed people with co-occurring disorders at baseline and yearly for 10 years and tracked employment in relation to five non-vocational outcomes: independent living, psychiatric symptoms, substance use disorder, healthy (non-substance-abusing) relationships, and life satisfaction. Latent class trajectory analysis identified steady workers, and mixed-effects regression models compared steady workers with non-workers. Both steady workers (n=51) and non-workers (n=79) improved substantially; for example, a majority of each group achieved independent housing and stable remission of substance use disorders. Steady workers achieved independent housing and higher quality of life during the first 5 years of follow-up, but the two groups achieved similar outcomes by 10 years. People with co-occurring disorders can improve markedly. Those with steady employment may improve faster, but those without employment may achieve similar long-term outcomes at a slower pace.


Bromide strongly influences the formation of reaction products during the ozonation of diclofenac, metoprolol and isoproturon.
Bromide as an omnipresent matrix component in wastewater can react with ozone to form hypobromous acid (HOBr). This secondary oxidant can subsequently react with micropollutants but also with formed intermediates. Therefore, bromide and especially HOBr can highly influence the formation of transformation products (TPs). This has already been reported for the ozonation of N,N-dimethylsulfamide leading to the formation of the cancerogenic N-nitrosodimethylamine only in bromide containing waters. In this study, the influence of different bromide and ozone concentrations on the formation of TPs during the ozonation of isoproturon (ISO), metoprolol (METO) and diclofenac (DCF) were investigated. Additionally, TPs were identified, which are formed in the direct reaction of the micropollutants with HOBr with and without subsequent ozonation. The results showed that even if the reactions of ozone with the substances should be favored bromide can highly influence the formation of TPs already at low concentrations. In summary, new TPs after the reaction with HOBr (and subsequent ozonation) could be postulated for ISO, METO and DCF. This underlines that the present water matrix can have a high influence on the formation of TPs and that these mechanisms need to be investigated further.


The neutrophil-to-lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90-day mortality in non-cirrhotic chronic severe hepatitis.
To investigate the relationship between systemic inflammatory response and short-term mortality in patients with non-cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil-to-lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet-to lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). Data were collected from two prospectively enrolled CATCH-LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90-day liver transplant (LT)-free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90-day LT-free mortality. Kaplan-Meier method was used to estimate the 90-year LT-free survival. The prevalence of CSH was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively, for patients with non-cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90-day LT-free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection. NLR may be an independent risk factor for 90-day LT-free mortality in patients with non-cirrhotic chronic liver disease. A NLR of 2.9 as the cut-off value can be used to predict disease aggravation in CSH patients without infection.


Ischemia-reperfusion impairs ascending vasodilation in feed arteries of hamster skeletal muscle.
Vasodilation originating within the microcirculation ascends into proximal feed arteries during muscle contraction to attain peak levels of muscle blood flow. Ascending vasodilation (AVD) requires an intact endothelium, as does conducted vasodilation in response to acetylcholine (ACh). Whereas ischemia-reperfusion (I-R) can affect endothelial cell function, the effect of I-R on AVD is unknown. The authors tested the hypothesis that I-R (1h-1h) would impair AVD. Using the retractor muscle of anesthetized hamsters, contractions were evoked using field stimulation (200 ms at 40 Hz every 2 s for 1 min) and ACh was delivered using microiontophoresis (1 microm tip, 500-4000 ms pulse at 800 nA). Feed artery responses were monitored 500-1500 microm upstream. Neither resting (51 +/- 4 microm) nor maximal diameter (81 +/- 5 microm; 10 microm sodium nitroprusside) following I-R (n = 8) were different from time-matched controls (n = 10). With peak active tension of 23 +/- 4 mN x mm(-2), control AVD was 26 +/- 2 microm. Following I-R, active tension fell by 48% (p < .05) and AVD by 57% (p < .05). Stimulation at 70 Hz restored active tension but AVD remained depressed by nearly half (p < .05), as did local and conducted responses to ACh. Nevertheless, control responses to 500 ms ACh were restored by increasing stimulus duration to 4000 ms. Ischemia-reperfusion impairs the initiation of feed artery dilation with muscle contraction and with ACh while conduction along the vessel wall is preserved. Respective components of endothelial cell signaling events may differ in their susceptibility to I-R.


Left ventricular-coronary sinus fistula after mitral valve replacement.
One of the more rare complications after mitral valve replacement is the development of a left ventricular-coronary sinus fistula, which has been reported only twice before. In the reported cases a common feature has been multiple valve replacements. Our case was one of the late development (8 years) of a fistula in a patient who had only one previous replacement but in whom a murmur was detected 3 months after the operation.


Ig class and IgG subclass responses to Treponema pallidum in patients with syphilis.
The Ig class and IgG subclasses of anti-Treponema pallidum antibodies in human serum were quantified using solid-phase enzyme-linked immunosorbent assays. Development of these assays with monoclonal antibodies, each specific for a human immunoglobulin class or IgG subclass, provided quantitative data concerning the major antibody specificities. In patients with primary syphilis, anti-T. pallidum activity was limited almost exclusively to IgG1 and IgM. Coordinate, restricted expression of IgG1 and IgG3 responses in T. pallidum-specific assays was observed with sera from patients with active secondary syphilis. IgG1 and IgG3 accounted for roughly 53 and 43% of the total anti-treponemal IgG antibody activity, respectively. While IgM antibody levels were elevated in the patients with secondary syphilis, IgG2 and IgG4 levels, if present at all, represented less than 10 and 2% of the total IgG activity, respectively. Ig in sera from patients who had been treated adequately for secondary syphilis were restricted almost entirely to IgG3 and IgG1. Considering the low level of IgG3 in serum, disproportionately high percentages of antitreponemal antibodies were found in this subclass during and after treatment for secondary syphilis. The restricted, coexpression of the IgG1 and IgG3 isotypes may reflect the close genetic linkage of the gamma 1 and gamma 3 genes and possibly the impact of immunoregulatory mechanisms in response to the induction and expression of autoantibodies which arise during the course of secondary syphilis.


Anastomotic stability and wound healing of colorectal anastomoses sealed and sutured with a collagen fleece in a rat peritonitis model.
Anastomotic insufficiency is associated with increased morbidity and mortality. A collagen fleece that supports anastomosis is effective for preventing anastomosis insufficiency. The objective of this study was to compare between the stability of sutured anastomoses and that of anastomoses sealed with a thrombin/fibrinogen-coated collagen fleece in a rat peritonitis model. In 72 male Wistar rats, peritonitis was induced with a specially prepared human fecal solution. Surgery at the rectosigmoid junction was performed 24-36 hours later. The different anastomotic techniques used were circular sutured anastomoses, semicircular sutured anastomosis and closure of the anterior wall with collagen patch, and complete closure with a collagen fleece. Bursting pressure, histology of anastomosis, mRNA expression of collagen types I and III, matrix metalloproteinase-13, and vascular endothelial growth factor (VEGF) were investigated after 24 hours, 72 hours, and 120 hours. All animals developed peritonitis of comparable severity. There were no differences in bursting pressures between the three suture techniques after 24 hours, 72 hours, or 120 hours. Anastomoses sealed with a collagen fleece appeared to be slightly less stable only at 24 hours, whereas they appeared to be more stable than semisutured or fully sutured anastomoses at 72 hours and 120 hours. Sealing with a collagen fleece was associated with an increase in granulation tissue, higher mRNA levels for collagen types I and III, and higher VEGF compared to sutured anastomoses. The use of a thrombin/fibrinogen-coated collagen fleece showed similar efficacy to conventional sutures in colorectal anastomoses in the presence of peritonitis inflammation, and may provide additional benefits due to an increase in mature granulation tissue.


Efficacy and safety of two ramipril and hydrochlorothiazide fixed-dose combination formulations in adults with stage 1 or stage 2 arterial hypertension evaluated by using ABPM.
Fixed-dose combinations of antihypertensive agents demonstrate advantages in terms of efficacy, tolerability, and treatment adherence. This study was designed to compare the efficacy and safety of 2 ramipril and hydrochlorothiazide (HCTZ) fixed-dose combinations in patients with hypertension stage 1 or 2. Patients' blood pressure (BP) profiles were evaluated by using 24-hour ambulatory BP monitoring (ABPM). This was a multicenter, prospective, randomized, open-label, parallel-group, noninferiority trial of adult patients (age ≥18 years) with hypertension stage 1 or 2 and systolic blood pressure (SBP) within 140 to 179 mm Hg or diastolic blood pressure (DBP) 90 to 109 mm Hg. After a 2-week washout period, eligible patients were randomized to receive 1 of 2 ramipril/HCTZ fixed-dose combination formulations (5/25 mg/d) for 8 weeks. The primary end point was the difference in 24-hour ABPM SBP/DBP mean reductions between groups after 8 weeks of treatment. The secondary end points were the changes in daytime and nighttime ABPM and in office BP. Safety profile and tolerability assessments included monitoring of adverse events. A total of 102 patients with hypertension (54 in group A [test formulation] and 48 in group B [reference formulation]), aged 27 to 85 years, completed the 8-week treatment period. The decreases in SBP and DBP according to 24-hour ABPM from baseline to week 8 were significant and similar in both groups. SBP decreased from 149.1 to 133.0 mm Hg (-16.1 mm Hg) in group A and from 146.2 to 130.6 mm Hg in group B (-15.6 mm Hg) (P = 0.8537); DBP was reduced by 8.8 mm Hg in group A and by 8.5 mm Hg in group B (P = 0.8748). Because the lower 95% CI limit for the difference between groups A and B of 3.96 mm Hg in SBP and 3.54 mm Hg in DBP was lower than that preestablished by the trial protocol (4 mm Hg), noninferiority of the test formulation was demonstrated compared with the reference formulation. For the secondary end points, there was no significant difference between groups in SBP and DBP during daytime or nighttime at the end of week 8. Office BP was significantly reduced in both treatment groups, with no significant differences between groups. The incidence of adverse events was 23.7% in group A and 21.7% in group B. Both treatment options were well tolerated and equally reduced BP. The results support the conclusion that group A (new fixed-dose combination of ramipril/HCTZ) was noninferior to group B (reference medication in Brazil). ISRCTN Register: ISRCTN05051235.


Developing and psychometric testing of a short-form problem areas in diabetes scale in chinese patients.
The 20-item Problem Areas in Diabetes (PAID) scale is widely used to measure diabetes-related emotional distress. The short-form PAID scale is helpful for the rapid screening of diabetes-related emotional distress in clinical settings. This study developed and examined the psychometric properties of a short-form Chinese-version PAID (SF-PAID-C) scale. The Chinese-version 20-item PAID (PAID-C) scale was administered to 855 patients with type 2 diabetes mellitus. Item analysis, exploratory factor analysis, and confirmatoryfactoranalysis were then applied to develop the SF-PAID-C and evaluate its construct validity. The correlations between SF-PAID-C and the latest HbA1c close to the measurement of PAID-C (baseline HbA1c) 3 months and 12 months later were used to examine the concurrent and predictive validity of the SF-PAID-C. Receiver operating characteristic curve analysis was used to examine the sensitivity and specificity of the SF-PAID-C. Cronbach's alpha was used to assess internal consistency. Test-retest on 24 patients was used to examine the stability of the SF-PAID-C. An 8-item SF-PAID-C was developed. The SF-PAID-C significantly correlated with the PAID-C (r = .941, p < .001), baseline HbA1c (r = .148, p < .001), 3-month HbA1c (r = .147, p < .001), and 12-month HbA1c (r = .142, p < .001). The sensitivity and specificity of the SF-PAID-C were 93.2% and 94.2%, respectively. The Cronbach's α and test-retest reliability of the SF-PAID-C were .85 and .93, respectively. The SF-PAID-C is a reliable and valid scale that can be used to screen for diabetes-related emotional problem in Chinese patients with type 2 diabetes mellitus in clinical settings.


Diagnosis and treatment of multifocal motor neuropathy.
Multifocal motor neuropathy (MMN) is a unique disease mimicking motor neuron disease, but it is treatable with intravenous immunoglobulins. Anti-GM1 IgM antibody titers are not sensitive enough to predict the outcome. Electrodiagnosis is essential for the diagnosis of MMN. Conduction block has been suggested as the best diagnostic marker, but it is not found in all treatable cases. Activity-dependent conduction changes, as revealed by comparing conduction before and after maximal voluntary contraction of the muscle, are a convenient and promising tool. Treatment options include various immunosuppressants (including cyclophosphamide), but there has not been ample evidence in favor of any of these agents in randomized controlled trials. Intravenous immunoglobulins remain the mainstay for treating MMN.


Three monthly doses of 150,000 IU of oral cholecalciferol correct vitamin D deficiency in adolescents: A pragmatic study.
To assess the efficacy of an oral high-dose cholecalciferol regimen in correcting vitamin D deficiency (VDD) in adolescents and to explore potential predictive factors on the response to treatment. This is a retrospective chart review conducted in the Adolescent Outpatient Clinic, Geneva University Hospitals, Switzerland. One hundred-three otherwise healthy vitamin D deficient [serum 25-hydroxyvitamin D, 25(OH)D, level <50 nmol/L] adolescents (mean age 16.6) attending the clinic between 1 January 2016 and 31 December 2018 received 150,000 IU of oral cholecalciferol every month for 3 months (cumulative dose of 450,000 IU). We measured the change in serum 25(OH)D levels pre- and post-treatment and the achievement of serum 25(OH)D level post-treatment ≥75 nmol/L. The mean serum 25(OH)D level increased by 320%, from 26 nmol/L at baseline to 83 nmol/L at the end of the study (P < .001). The rise was significantly higher for patients initially tested in the winter/spring (mean 65 nmol/L) compared with those initially tested in the summer/autumn (mean 48 nmol/L) (P < .003). No clear relationship was found between the response to treatment and the vitamin D status at baseline. The effect of age, gender, origin and body mass index was not statistically significant. The present intermittent high-dose regimen is effective in treating VDD in healthy adolescents without significant variations in response between different subgroups.


Sniffing out pharmacology: interactions of drugs with human olfaction.
Advances in the understanding of the sense of smell have increased awareness of the role of olfaction in human life. Odors are perceived via specific G protein-coupled receptors (GPCRs) with cAMP as the second messenger. Drugs that interact with this signaling cascade, such as opioids, cannabinoids and sildenafil, are known to reduce olfactory function. Drugs that are active in the central nervous system (CNS) may also hinder the complex processing of olfactory information to distinguish, via pattern recognition, thousands of odors from the signals of only ∼400 distinct olfactory receptors. Many other interactions with drug targets expressed at the olfactory bulb are also likely to occur. However, olfactory drug effects have rarely been explored in controlled studies. In the current activities of drug development and re-purposing, olfaction could become highly important because it can impact significantly upon the enjoyment of food. With an established molecular basis and using available tools, the assessment of olfaction in drug development and approval is advised.


Multiple reference tissue method for contrast agent arterial input function estimation.
A precise contrast agent (CA) arterial input function (AIF) is important for accurate quantitative analysis of dynamic contrast-enhanced (DCE)-MRI. This paper proposes a method to estimate the AIF using the dynamic data from multiple reference tissues, assuming that their AIFs have the same shape, with a possible difference in bolus arrival time. By minimizing a cost function, one can simultaneously estimate the parameters and underlying AIF of the reference tissues. The method is computationally efficient and the estimated AIF is smooth and can have higher temporal resolution than the original data. Simulations suggest that this method can provide a reliable estimate of the AIF for DCE-MRI data with a moderate signal-to-noise ratio (SNR) and temporal resolution, and its performance increases significantly as the SNR and temporal resolution increase. As demonstrated by its clinical application, sufficient reference tissues can be easily obtained from normal tissues and subregions segmented from a tumor region of interest (ROI), which suggests this method can be generally applied to cancer-based DCE-MRI studies to estimate the AIF. This method is applicable to general kinetic models in DCE-MRI, as well as other CE imaging modalities.


Interaction of thiourea and urea with maleimide: comparative theoretical DFT study.
A gas-phase mechanism reaction of maleimide with urea or thiourea was studied by DFT method. A comparison between atomic charges, Fukui index evaluation and Frontier orbitals theory was carried out. The involvement of pre- and post-reactive complexes was examined as the reaction profiles are modelled. For each mechanism, two approaches have been proposed through nitrogen and sulfur (for thiourea), or oxygen and nitrogen (for urea) attack. The results indicate that the carbon double bonded of maleimide is the electophilic site and chalcogen atom of chalcogenourea is the nucleophilic one. The obtained activation free energies predict suitable specie that could be generated after an opening-cycle and new bonds formation. Consequently, the sulfur attack of thiourea was promoted on oxygen (urea) which is in accordance with the experiments.


Bone marrow toxicity after yellow phosphorus ingestion.
Suicidal ingestions of fireworks containing yellow phosphorus occur often during holidays. A case is reported of a 17 year old woman who intentionally ingested an estimated amount of 5.5 mg of yellow phosphorus, presenting with upper abdominal pain as the only complaint, a physical examination was normal. Blood tests showed a considerable decrease in the granulocyte count; the bone marrow biopsy revealed a decreased cellular mass with degenerative changes. Spontaneous remission was observed during the next 48 hours, with no further complaints.


Silencing UHRF1 enhances cell autophagy to prevent articular chondrocytes from apoptosis in osteoarthritis through PI3K/AKT/mTOR signaling pathway.
Osteoarthritis (OA) is a common chronic degenerative joint disease, and chondrocyte apoptosis is one of most important pathological changes of OA pathogenesis. Growing studies have shown that Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important epigenetic regulatory factor that regulates cell proliferation and apoptosis of various tumors, but its role in OA remains ill-defined. In the present study, we found that UHRF1 expression was increased in human OA cartilage tissues, compared with normal cartilage tissues. Interleukin-1β (IL-1β), a major inflammatory cytokine that promotes cartilage degradation in OA, was used to stimulate primary human chondrocytes in vitro. The expression of UHRF1 was also enhanced in IL-1β-induced chondrocytes. Moreover, down-regulation of UHRF1 induced an increase on cell proliferation and autophagy, and a decrease on apoptosis of chondrocytes after IL-1β treatment. Further data indicated that silencing UHRF1 attenuated the up-regulation of IL-1β on phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in chondrocytes. Then, an activator of PI3K weakened the effect of UHRF1 silencing on cell proliferation, autophagy, apoptosis of IL-1β-induced chondrocytes, and the cell autophagy special inhibitor 3-methyladenine (3-MA) also showed a same impact on UHRF1, hence suggesting that knockdown of UHRF1 enhances cell autophagy to protect chondrocytes from apoptosis in OA through PI3K/AKT/mTOR signaling pathway. In conclusion, our study suggests that UHRF1 may be a potential regulator of chondrocyte apoptosis in the pathogenesis of OA.


Astral microtubule asymmetry provides directional cues for spindle positioning in budding yeast.
Cortical force generators play a central role in the orientation and positioning of the mitotic spindle. In higher eukaryotes, asymmetrically localized cortical polarity determinants recruit or activate such force generators, which, through interactions with astral microtubules, position the mitotic spindle at the future site of cytokinesis. Recent studies in budding yeast have shown that, rather than the cell cortex, the astral microtubules themselves may provide polarity cues that are needed for asymmetric pulling on the mitotic spindle. Such asymmetry has been shown to be required for proper spindle positioning, and consequently faithful and accurate chromosome segregation. In this review, we highlight results that have shed light on spindle orientation in this classical model of asymmetric cell division, and review findings that may shed light on similar processes in higher eukaryotes.


In vivo crushing of an aortic stent enables endovascular repair of a large infrarenal aortic pseudoaneurysm.
To report an unusual approach to endovascular exclusion of a large aortic pseudoaneurysm. A 63-year-old male had an unsuccessful endovascular repair of an aortic anastomotic pseudoaneurysm that left an expanded, uncovered Palmaz stent lying obliquely within the aorta. After nearly 3 years, the pseudoaneurysm enlarged to 7 cm, and the patient became symptomatic. Repair of the pseudoaneurysm was accomplished by crushing the indwelling stent to allow placement of a stent-graft. Malpositioned stents that are hindering an endoluminal procedure may be crushed against the arterial wall in vivo to facilitate passage of endovascular instruments or devices.


Tree water-use efficiency and growth dynamics in response to climatic and environmental changes in a temperate forest in Beijing, China.
Understanding the responses of local forests to the gradually rising atmospheric CO2 concentrations (ca) and changing environment is critical for appropriate management activities. This work used tree ring width measures (i.e. basal areal increment, BAI) and carbon (C) and nitrogen (N) signals to explore the intrinsic water use efficiency (iWUE) and tree growth dynamics of three major tree species (Pinus massoniana, P.tabuliformis and Larix gmelinii) in the Miyun Reservae Basin (MRB) of Beijing. The results indicate that ca was a primary contributor to tree growths, especially at the remote site where rising ca accounted for 92% and 74% of BAI changes for P. tabuliformis and L. gmelinii, respectively. N deposition was found to have a positive effect on BAI at this site. The controlling effect of ca on tree growth at the close-to-city site was smaller (52% and 44% of the contributions for P. tabuliformis and P. massoniana, respectively), while the negative influences of N deposition on BAI tends to be intensified. iWUE showed consistent increase during the entire growth period at all sites. Quadratic relationships between iWUE and BAI were observed, which indicated that the rising ca stimulated photosynthesis, contributing to the initial BAI and iWUE increase. However, the intensified water stress resulting from reduced precipitation and increased temperature led to a reduction in tree stomatal conductance causing the subsequent increase in iWUE but decrease in BAI. Of the site- and species-related responses of tree growth to ca, climatic and environmental changes in the MRB, the site-related variation dominated. The non-linear relationship between BAI and ca combined with the quadratic relationship between BAI and iWUE indicate a decreased ability of forests to capture atmospheric CO2 once the CO2 tipping point has passed.


Theophylline affects the inotropic status of guinea-pig left atria by actions on the sarcolemma and sarcoplasmic reticulum.
Theophylline (0.1, 0.3 mM) produced a positive inotropism which was maximum by 15 min but was partially or completely absent by 45 min. The mechanism for this response was investigated using post-rest potentiation and positive staircase, phenomenon associated with the sarcoplasmic reticulum and sarcolemma, respectively. Staircase was enhanced at 15 min, but not after 45 min. Post-rest potentiation was attenuated by theophylline. The data suggest that theophylline's effect on cardiac contractility results from opposing actions on the sarcolemma and sarcoplasmic reticulum.


Structural characterization of a polysaccharide from bamboo (Phyllostachys edulis) shoot and its prevention effect on colitis mouse.
A water-soluble dietary fiber named BSDF-1 (polysaccharide) was isolated from the bamboo (Phyllostachys edulis) shoot. BSDF-1was characterized as a backbone consisting predominately of 1,4-linked Glcp, and the protective effects and mechanisms of the anti-inflammatory activity were investigated using a dextran sulfate sodium (DSS)-induced colitis mouse model. BSDF-1 administration significantly reduced colonic pathological damage, inhibited the activation of inflammatory signaling pathways, including nuclear factor-kappa B and NLR family pyrin domain containing 3 inflammasomes pathways. It restored the mRNA expression of tight junction proteins, including zonula occludens-1, claudin-1, and occludin. Furthermore, BSDF-1 treatment reduced Parabacteroides, Mucispirillum, Helicobacter, Bacteroides, and Streptococcus levels, whereas high-dose BSDF-1 treatment increased Prevotella, Alitipes, Anaerostipes, Odoribacter, Bifidobacterium, Butyricimonas, and Lactobacillus levels. In conclusion, BSDF-1 can inhibit the activation of inflammatory signaling pathways and restore the intestinal barrier function. Thus, BSDF-1 may be a valuable food supplement or nutraceutical to manage and prevent ulcerative colitis.


[Molecular mechanisms for proliferation of the earliest human hemopoietic cells].
The advance in research concerning the biology of human haematopoietic stem cells are reviewed. All these data are discussed regarding practical application of hemopoietic cells enriched in stem cells in clinical medicine and especially haematological transplantation.


Trait sensitivity to social disconnection enhances pro-inflammatory responses to a randomized controlled trial of endotoxin.
One proposed mechanism for the association between social isolation and poor health outcomes is inflammation. Lonely or socially disconnected individuals show greater inflammatory responses, including up-regulation of pro-inflammatory gene expression, and people who are sensitive to cues of social disconnection (e.g., high levels of anxious attachment) exhibit greater inflammation in response to psychological stress. However, no studies have examined how sensitivity to social disconnection may influence pro-inflammatory responses to an inflammatory challenge. In the present study, we investigated the impact of sensitivity to social disconnection (a composite score comprised of loneliness, anxious attachment, fear of negative evaluation, and rejection sensitivity) on pro-inflammatory cytokines and gene expression in response to endotoxin, an inflammatory challenge, vs. placebo in a sample of one hundred and fifteen (n=115) healthy participants. Results showed that those who are more sensitive to social disconnection show increased pro-inflammatory responses (i.e., increased levels of tumor necrosis factor-alpha and interleukin-6) to endotoxin, as well as up-regulation of multiple genes related to inflammation. Furthermore, bioinformatics analyses revealed that those in the endotoxin group who are more sensitive to social disconnection exhibited a conserved transcriptional response to adversity (CTRA) regulatory profile, involving up-regulation of beta-adrenergic and pro-inflammatory transcription control pathways and down-regulation of antiviral transcription factors in response to endotoxin. These results may ultimately have implications for understanding the links between social isolation, inflammation, and health. ClinicalTrials.gov NCT01671150.


Endocranial volume of Australopithecus africanus: new CT-based estimates and the effects of missing data and small sample size.
Estimation of endocranial volume in Australopithecus africanus is important in interpreting early hominin brain evolution. However, the number of individuals available for investigation is limited and most of these fossils are, to some degree, incomplete and/or distorted. Uncertainties of the required reconstruction ('missing data uncertainty') and the small sample size ('small sample uncertainty') both potentially bias estimates of the average and within-group variation of endocranial volume in A. africanus. We used CT scans, electronic preparation (segmentation), mirror-imaging and semilandmark-based geometric morphometrics to generate and reconstruct complete endocasts for Sts 5, Sts 60, Sts 71, StW 505, MLD 37/38, and Taung, and measured their endocranial volumes (EV). To get a sense of the reliability of these new EV estimates, we then used simulations based on samples of chimpanzees and humans to: (a) test the accuracy of our approach, (b) assess missing data uncertainty, and (c) appraise small sample uncertainty. Incorporating missing data uncertainty of the five adult individuals, A. africanus was found to have an average adult endocranial volume of 454-461 ml with a standard deviation of 66-75 ml. EV estimates for the juvenile Taung individual range from 402 to 407 ml. Our simulations show that missing data uncertainty is small given the missing portions of the investigated fossils, but that small sample sizes are problematic for estimating species average EV. It is important to take these uncertainties into account when different fossil groups are being compared.


Comparative electrophysiologic profiles of calcium antagonists with particular reference to bepridil.
The calcium antagonist bepridil hydrochloride differs pharmacologically from the conventional agents that block the myocardial slow channel. Its clinical electrophysiologic effects are poorly defined. The effects of 2 mg/kg + 1 mg/kg of intravenously administered bepridil in 10 patients were compared with those of 3 mg/kg + 1 mg/kg in 9 patients undergoing electrophysiologic evaluation of clinical symptoms. The overall effects of the 2 regimens did not differ significantly. The drug reduced the heart rate slightly; it had no effect on the PR interval but significantly lengthened the AH interval by 2 to 10%, HV by 2 to 12% and QTc by 5 to 8%. The most striking effect was the prolongation of the functional (up to 17%, p less than 0.001) and the effective (up to 13%, p less than 0.001) refractory periods of the atrioventricular node with a lengthening of the Wenckebach cycle (up to 17%, p less than 0.001). In contrast to the action of verapamil, bepridil significantly prolonged the ventricular (4 to 7%, p less than 0.01 to p less than 0.001) and the atrial (12 to 19%, p less than 0.05 to p less than 0.001) effective refractory periods. The data indicate that bepridil hydrochloride has a wide spectrum of electrophysiologic activity in man consistent with inhibitory actions on myocardial slow and fast channels and a significant lengthening of cardiac repolarization. These overall effects suggest that the antiarrhythmic profile of the drug is likely to be wider than those of conventional calcium antagonists.


Strategy for highly selective ion-exchange capture using a charge-polarizing fusion partner.
To achieve efficient recovery of recombinantly produced target proteins using cation-exchange chromatography, a novel basic protein domain is used as a purification handle. The proteolytic instability usually encountered for basic peptide tags is avoided by the use of a highly constrained alpha-helical domain based on staphylococcal protein A into which positively charged amino acids have been introduced. Here we show that this domain, consisting of 58 amino acids with a calculated isoelectric point (pI) of 10.5, can be used to efficiently capture different fused target proteins, such as a bacterial DNA polymerase (Klenow fragment), a viral protease (3C) and a fungal lipase (Cutinase). In contrast to standard cation-exchange chromatography, efficient capture can be achieved also at a pH value higher than the pI of the fusion protein, demonstrated here by Zbasic-Klenow polymerase (pI approximately/= 5.8) and ZZ-Cutinase-Zbasic (pI approximately/= 7.2) both purified at a pH of 7.5. These results show that the Zbasic domain is able to confer a regional concentration of positive charge on the fusion protein even at a relatively high pH. Hence, the data suggest that this domain could be used for highly efficient and selective capture of target proteins at conditions where most host-cell proteins do not bind to the chromatographic resin. The obtained purity after this one-step procedure suggests that the strategy could be an alternative to standard affinity chromatography. Methods for site-specific proteolysis of the fusion proteins to release native target proteins are also discussed.


The clinical usefulness of peritoneal dialysis fluids with neutral pH and low glucose degradation product concentration: an open randomized prospective trial.
Long-term peritoneal dialysis (PD) is associated with the development of various structural and functional changes to the peritoneal membrane when bioincompatible conventional peritoneal dialysis fluids (PDFs) are used. In this study, we looked at patients that were treated with conventional PDFs and then changed to novel biocompatible PDFs with a neutral pH and a low concentration of glucose degradation products (GDPs) to investigate whether this change could result in the arrest or reversal of peritoneal membrane deterioration. In an open label, randomized prospective trial, the clinical effects of conventional PDFs and biocompatible PDFs with neutral pH and very low concentration of GDPs were compared in 104 patients equally divided between both study PDFs. Blood and effluent dialysate samples, peritoneal equilibration tests, and adequacy evaluation were undertaken at baseline, 4, 8, and 12 months. The target variables were the ratio of dialysate-to-plasma (D/P) creatinine, peritoneal ultrafiltration, residual renal function, dialysis adequacy indices, and effluent cancer antigen 125 (CA125). D/P creatinine values were not different in the two groups. Peritoneal ultrafiltration was significantly higher in the low-GDP PDF group than in the conventional PDF group at all follow-up times (4 months: 9.1 +/- 4.3 vs 6.0 +/- 3.0; 8 months: 8.3 +/- 3.4 vs 6.0 +/- 3.0; 12 months: 8.9 +/- 3.3 vs 6.1 +/- 3.3 mL/g dextrose/day; p < 0.05). Peritoneal Kt/V urea values and total weekly Kt/V urea values at 4 months were significantly higher in the low-GDP PDF group than in the conventional PDF group. Residual renal function was not statistically significant. Effluent CA125 levels were significantly higher in the low-GDP PDF group at all follow-up visits (4 months: 37.8 +/- 20.8 vs 22.0 +/- 9.5; 8 months: 41.2 +/- 20.3 vs 25.9 +/- 11.3; 12 months: 40.4 +/- 21.4 vs 28.6 +/- 13.0 U/mL; p < 0.05). Among anuric patients, peritoneal ultrafiltration at 4, 8, and 12 months, total weekly Kt/V at 4 and 8 months, and CA125 levels at all follow-up visits were significantly higher in patients treated with low-GDP PDF than those treated with conventional PDF. However, among anuric patients, D/P creatinine showed no significant differences between the low-GDP PDF group and the conventional PDF group. The use of biocompatible PDFs with neutral pH and low GDP concentration can contribute to improvement of peritoneal ultrafiltration and peritoneal effluent CA125 level, an indicator of peritoneal membrane integrity in PD patients.


The benefits of the multi-target approach in drug design and discovery.
Promiscuous binding has been considered to be a problem in the design and development of new drugs against a given disease. However, promiscuity in molecular recognition is not all bad news, and scientists are currently taking advantage of the emerging 'promiscuous binding' or 'multi-target approach' in medicinal chemistry.


Psychological status on informal carers for stroke survivors at various phases: a cohort study in China.
In China, the risk of stroke is higher than that in developed countries such as Europe and North America. Informal caregivers play a major role in providing support to stroke survivors. Currently, only limited studies on changes in psychological state of the caregivers at different stages of stroke have been published. To investigate the stress and psychological state of informal caregivers of stroke patients in different periods and to explore the factors that affect their states. 202 informal caregivers of stroke patients were selected in a 3a-grade hospital in Chengdu, Sichuan. Follow-up was conducted by face-to-face interviews, telephone calls, or home visits on days 3, 2 months, and 1 year after onset. We investigated the basic information about the caregivers, including their anxiety, depression and social support conditions. We analyzed the pressure and psychological conditions of informal caregivers at different stages of stroke and analyzed its influencing factors. The data were displayed by the number and percentage of the cases; the continuous variables were described by means and standard deviation. In addition, the data were compared by Pearson correlation analysis and logistic regression analysis. (1) Within 3 days after the onset of stroke, the informal caregivers had the highest stress, the most severe anxiety and depression, the heaviest burden, and the lowest score of medical-social support. Over time, the pressure and burden of the caregivers are gradually decreasing, anxiety and depression are increasing, and social support is also increasing. (2) The stress and psychological status of informal stroke caregivers are affected by multiple factors, including the caregiver's age, relationship with the patient, patient's age, and patient's physical conditions. The stress and psychological status of informal caregivers varied in the different stages of stroke, and they were affected by several factors. Medical staff should pay attention to informal caregivers while providing care for patients. Relevant interventions may be developed based on the results to improve the health of informal caregivers and thus to promote the health of patients.


Porous inorganic capsules in action: modelling transmembrane cation-transport parameter-dependence based on water as vehicle.
Insight into basic principles of cation transport through "molecular channels", and especially details of the related fundamental H2O vehicle function, could be obtained via7Li NMR studies of the Li+ uptake/release processes by the unique porous nanocapsule [{(MoVI)MoVI5O21(H2O)6}12{MoV2O4(SO4)}30]72- which behaves as a semi-permeable inorganic membrane open for H2O and small cations; channel traffic as well as internal cavity distribution processes show a strong dependence on "environmental" effects such as exerted by solvent properties, the amount of water present, and competing complexing ligands, and end up in a complex equilibrium situation as in biological leak channels.


Ultrastructure of Sporothrix schenckii treated with iodine-potassium iodide solution.
The ultrastructural changes produced by iodine-potassium iodide solution on yeast cells of Sporothrix schenckii were investigated by transmission electron microscopy in order to clarify the mechanism of oral potassium iodide therapy for sporotrichosis. Yeast cells were dipped with solutions containing various concentrations of iodine. The rate of germination decreased markedly between the range of iodine concentrations from 0.63 microgram/ml to 5.0 micrograms/ml. No significant ultrastructural changes were seen at the concentration of the iodine of 1.25 microgram/ml (80% germination) or less. In the concentration of 2.5 micrograms/ml (50% germination), normal cells and degenerated cells coexisted. When the cells were treated with 5.0 micrograms of iodine per ml (0% germination) or more, their interior structures were completely destroyed. It is assumed that iodine treatment of the organism causes rapid destruction in the whole cell.


A method for quantitative histological evaluation of neural cell populations.
In an attempt to facilitate quantitative analysis of neural perikarya, an inexpensive system of gridded coverslips has been developed to permanently map sections of tissue on microscopic slides. Utilizing common photographic copying techniques with Kodalith film, a mylar coverslip is produced which is imprinted with a grid of known dimensions. The exact scale of the grid can be varied precisely for compatibility with a particular field of magnification. The versatility and economy of this technique make it useful in many microscopic studies requiring superimposition of discrete landmarks.


A case of tumour simulating pulp space infection.
General practitioners and accident and emergency departments are often involved in the management of hand or finger sepsis. Such cases are usually easily diagnosed and treated. We report a more serious disorder which may mimic the condition and cause diagnostic confusion.


Glucocorticoids regulate innate immunity in a model of multiple sclerosis: reciprocal interactions between the A1 adenosine receptor and beta-arrestin-1 in monocytoid cells.
Desensitization of seven transmembrane receptors (7TMRs), which are modulated by the beta-arrestins, leads to altered G protein activation. The A1 adenosine receptor (A1AR) is an antiinflammatory 7TMR exhibiting reduced expression and activity in both multiple sclerosis (MS) and the murine MS model, experimental autoimmune encephalomyelitis (EAE) in monocytoid cells. Herein, we report that beta-arrestin-1 expression was increased in brains of MS patients relative to non-MS brains, whereas A1AR expression was concomitantly reduced. This inverse relationship between beta-arrestin-1 and A1AR was confirmed in cultured monocytoid cells as beta-arrestin-1 overexpression resulted in a down-regulation of A1AR together with the internalization of the surface receptor. Moreover, a physical interaction between beta-arrestin-1 and A1AR was demonstrated in monocytoid cells. Proinflammatory cytokines regulated the A1AR/beta-arrestin-1 interactions, while A1AR activation also modulated proinflammatory cytokines expression. During EAE, beta-arrestin-1 and A1AR expression in the spinal cord displayed a similar pattern compared to that observed in MS brains. EAE-induced neuroinflammation and neurobehavioral deficits were suppressed by glucocorticoid treatments, accompanied by concurrent reduced beta-arrestin-1 and enhanced A1AR expression. Thus, the interplay between beta-arrestin-1 and A1AR in the central nervous system during neuroinflammation represents a reciprocal regulatory mechanism through which neuroprotective therapeutic strategies for neuroinflammatory diseases might be further developed.


Embryology of the Absent Vas Supported by 2 Cases of Congenital Unilateral Absence of Vas With Varied Associations.
Congenital absence of the vas occurs in up to 1% of men. Congenital unilateral absence of the vas deferens can be related to cystic fibrosis transmembrane conductance regulator mutations or in 79% of cases, renal agenesis. We present a case of each, diagnosed in children at operation for elective inguinal hernia repairs. One patient had associated ipsilateral renal agenesis with a normal cystic fibrosis screen. The other patient had an ipsilateral pelvic kidney and a mutation detected on cystic fibrosis screening. Current understanding of the embryology of the relationship between these defects would seem to be supported by our cases.


ADAM8 expression in breast cancer derived brain metastases: Functional implications on MMP-9 expression and transendothelial migration in breast cancer cells.
Metastatic breast cancer affects long-term survival and is a major cause of cancer death for women worldwide. The Metalloprotease-Disintegrin ADAM8 promotes breast cancer development and brain metastasis in a mouse breast cancer model. Here, abundant ADAM8 expression was detected in primary human breast tumors and associated brain metastases. To investigate the function of ADAM8 in metastasis, MB-231 breast cancer cells with ADAM8 knockdown (MB-231_shA8) and scramble control cells (MB-231_shCtrl) were analyzed for their capability to develop metastases. In vitro, formation of metastatic complexes in hanging drops is dependent on ADAM8 and blocked by ADAM8 inhibition. MB-231_shA8 in contrast to MB-231_shCtrl cells were impaired in transmigration through an endothelial and a reconstituted blood-brain barrier. Out of 23 MMP and 22 ADAM genes, only the MMP-9 gene was affected by ADAM8 knockdown in MB-231_shA8 cells. Following re-expression of wild-type ADAM8 in contrast to ADAM8 lacking the cytoplasmic domain in MB-231_shA8 cells caused increased levels of activated pERK1/2 and pCREB (S133) that were associated with elevated MMP-9 transcription. Application of ADAM8 and MMP-9 antibodies reduced transmigration of MB-231 cells suggesting that ADAM8 affects transmigration of breast cancer cells by MMP-9 regulation. ADAM8-dependent transmigration was confirmed in Hs578t cells overexpressing ADAM8. Moreover, transmigration of MB-231 and Hs578t cells was significantly reduced for cells treated with an antibody directed against P-selectin glycoprotein ligand (PSGL-1), a substrate of ADAM8. From these data we conclude that ADAM8 promotes early metastatic processes such as transendothelial migration by upregulation of MMP-9 and shedding of PSGL-1 from breast cancer cells.


Characteristics of users of cigars, bidis, and kreteks and the relationship to cigarette use.
In the 1990s, youth use of alternative tobacco products including cigars, bidis, and kreteks increased. This article discusses the prevalence of youth use of cigars, bidis, and kreteks, and characteristics of users. The Cigar Use Reasons Evaluation (CURE)-a questionnaire assessing alternative tobacco use and associated attitudes and behaviors-was administered to middle and high school students from 12 school districts across Massachusetts. Males were more likely to use all forms of alternative tobacco and females more likely to smoke cigarettes. Hispanics were less likely to smoke kreteks or use smokeless tobacco. Urban students were more likely to smoke bidis or use smokeless tobacco than suburban or rural youth. Most smokeless and alternative tobacco users were lifetime cigarette smokers. There was, however, a significant group of cigar smokers, associated with higher parental education, who were not current cigarette smokers. Use of alternative tobacco poses a risk to the success of tobacco control efforts. While many alternative tobacco users smoke cigarettes, some alternative tobacco users are current cigarette smokers. Cigar use thus constitutes a potential serious risk for youth who otherwise might not be exposed to tobacco.


Clinician Perspectives on Barriers and Facilitators to Implementing e-Health Technology in Substance Use Disorder (SUD) Treatment Facilities.
Substance use disorders (SUDs) in the United States cause many preventable deaths each year. Finding effective ways to manage SUDs is vital to improving outcomes for individuals seeking treatment. This has increased interest in using e-health technologies in behavioral healthcare settings. This research is part of a larger study evaluating the efficacy of the NIATx coaching intervention for implementing RISE Iowa, an e-health patient recovery app, in SUD treatment organizations and seeks to examine clinician perspectives of the barriers and facilitators to its implementation. Semi-structured qualitative interviews were conducted with 13 clinicians from 9 different intervention sites involved in the study. Major barriers to implementing e-health technology include inability to access the technology, lack of time for both patients and clinicians, and a perceived lack of patient motivation to make changes. Facilitators to implementation include collaboration with other staff using e-health technology and integrating technology use into typical workflows. Implementation of e-health technology in SUD treatment will require integrating the technology into clinical workflows and improving patient access to the technology.


A pituitary metastasis, an adenoma and potential hypophysitis: A case report of tumour to tumour metastasis in the pituitary.
Tumour to tumour metastasis is a rare event, especially in the pituitary. Metastases to pituitary adenomas most commonly occurs in late stage disease, commonly presenting with visual field defects and adenohypophyseal dysfunction. The most frequent primary cancers are lung, breast and renal carcinoma which deposit most commonly in prolactinomas, somatotropinomas, gonadotropinomas. In nearly 40% of cases, sellar symptoms are the harbinger to the diagnosis of primary malignancy. The abnormal vascularity and growth promoting microenvironment of pituitary adenomas may encourage metastatic seeding and proliferation of these "collision tumours". Here, we present a case of a breast carcinoma metastasis to a pituitary null-cell adenoma in the setting of immunotherapy. Infundibular thickening in the setting of immunotherapy is often ascribed to hypophysitis, but our case highlights that metastatic spread should be part of the differential diagnosis.


Antinociceptive and antiplasmodial activities of cassane furanoditerpenes from Caesalpinia volkensii H. root bark.
The chloroform and ethyl acetate extract (100mg/kg) of Caesalpinia volkensii H. exhibited significant (P ≤ 0.05) antinociceptive activities using hot plate and writhing tests in mice while the later showed antiplasmodial activity (IC(50) 0.23 ± 0.07 and 4.39 ± 2.49 μg/ml) against chloroquine sensitive (D6) and chloroquine-resistant (W2), respectively. Two new furanoditerpenes [rel. 1β,5α-dihydroxyvoucapane (1) and rel. 1β,6β-dihydroxyvoucapane; 19β-methyl ester (2)] together with seven known compounds [voucapane (3), voucapan-5-ol (4), deoxycaesaldekarin C (5), caesaldekarin C (6), 5-hydroxyvinhaticoic acid (7), triacontanyl-(E)-ferulate (8), triacontanyl-(E)-caffaete (9) and 30'-hydroxytriacontanyl-(E)-ferulate (10)] were isolated from the two extracts. The administration of 3, 4, 5 and 6 (100mg/kg i.p) caused a significant (P ≤ 0.05) reduction in the number of writhing episodes induced by acetic acid and (P ≤ 0.01) increased pain latency threshold in hot-plate test compared to control. However, the pure compounds indicated relatively (P ≤ 0.05) low antiplasmodial activity. The phytochemical constituents from the root bark of C. volkensii had better analgesic properties than antimalarial properties, justifying the use of the plant root bark as a remedy for pain.


Food allergies and other adverse reactions to foods.
Adverse reactions to foods do occur. Their true degree of prevalence remains unknown. Many mechanisms are involved, including events at the gut mucosa surface, immunologic pathways, and nonimmunologic and possibly genetic influences, not all of which have yet been well studied. The major manifestations of food allergy have been cutaneous, gastrointestinal, and pulmonary. Others are less convincingly established. Of particular interest is the likelihood that certain rheumatic symptoms may be related to food sensitivity. Establishing a diagnosis of adverse food reaction requires thoughtful clinical evaluation and laboratory testing, confirmatory immunologic studies, and double-blind food challenge. Skin testing is a valuable screening tool and can help direct the physician to those patients for whom double-blind food challenge may be indicated. The simplest therapy is avoidance of foods to which an individual is sensitive. Sodium cromoglycate, antihistamines, prostaglandin synthetase inhibitors, and steroids have been used, but their efficacy has not yet been carefully evaluated.


[Rehabilitation for gait and activity of daily livings at home: an informed form for Parkinson's disease patients].
Rehabilitation aims to provide patients and their supporters with the knowledge, skills and support necessary to maintain their autonomy, minimize disability and maximize the level of participation of individual. This may be the case in Parkinson's disease (PD) patients. However, to our knowledge, previous papers concerning rehabilitation for PD patients have been not easily to understand and not suit for usage in clinical activities. In this review, we provide comprehensive explanations for daily rehabilitation in their habitation for PD patients and doctors.


Vertebrobasilar junction aneurysms associated with fenestration: experience of five cases treated with Guglielmi detachable coils.
Fenestration of vertebrobasilar junction is a rare congenital anomaly and often associated with aneurysm formation. We describe five cases of vertebrobasilar junction aneurysms in four patients associated with fenestration, which were treated with endovascular coil occlusion using Guglielmi detachable coils (GDCs). The importance of preoperative computed tomography (CT) angiography to understand the complex anatomy of fenestration and aneurysm is emphasized. Three patients presented with subarachnoid hemorrhage and one patient presented with headache only. Among 3 patients with subarachnoid hemorrhage, 1 patient was referred for endovascular coil occlusion after clipping of ruptured distal ACA aneurysm. A six-French guiding catheter was placed in the left vertebral artery via right femoral artery, except for 1 patient who had two vertebrobasilar junction aneurysms with complex anatomic relationship, accessed bilaterally. Five vertebrobasilar junction aneurysms with fenestration were treated with endovascular coil occlusion using GDCs. Postoperative angiography demonstrated successful occlusion of aneurysmal sac with preservation of basilar artery. Vertebrobasilar junction aneurysms are frequently associated with fenestrations. In addition to vertebral angiography on both sides, CT angiography may be a valuable tool for better understanding of complex anatomy of aneurysms associated with fenestration. The surgically difficult aneurysms such as vertebrobasilar junction aneurysm with fenestration can be successfully treated with GDCs.


Normalizing attributions may contribute to non-help-seeking behavior in people with fibromyalgia syndrome.
Causal attributions of bodily perceptions indicate the possibility of some degree of control over events. Therefore, attributions are important to support the social significance of experience and confer meaning. The aim of this study is to investigate whether non-patients with fibromyalgia (FMS) use more normalizing attributions than healthy control subjects and help-seeking patients. Thirty-seven FMS patients attending tertiary care were compared with 38 non-patients and 34 healthy controls on mean anxiety, depression, attribution style, and alexithymia scores. Mean normalizing scores were greatest in the non-patient group, followed by the healthy-control group, and smallest in the tertiary-care attending group. Non-patients are using more normalizing explanations than the FMS patients and the healthy-control subjects. Thus, normalization may negatively influence help-seeking behavior and contribute to non-help-seeking behavior.


A formula to improve the reliability of optical axial length measurement in IOL power calculation.
To verify the influence of axial length (AL) variations after cataract surgery in IOL power calculation. Patients underwent ophthalmic evaluation before surgery, including optical biometry with IOLMaster 500. Same exams were repeated 2 months after surgery: AL of operated eye was evaluated using two modes (pseudophakic/aphakic options). Mean Keratometry and AL changes were analyzed. Furthermore, refractive prediction error (PE) was back-calculated with Barrett Universal-II, Hoffer-Q, Holladay-1 and SRK/T formulas. To eliminate any systematic error, the mean error (ME) was zeroed-out for each formula. MEs and median absolute errors (MedAEs) of PEs were analyzed. Two-hundred-one operated eyes of 201 patients and 201 opposite eyes were evaluated. In operated eyes, mean AL difference was - 0.11 ± 0.07 mm (p < 0.001) with pseudophakic option and 0.00 ± 0.07 mm (p = 0.922) with aphakic option. There were not-statistically significant differences between MedAE of PEs calculated after zeroing-out the ME with different ALs (p > 0.05). Instead, only MEs of PEs obtained with postoperative ALs-pseudophakic option were not-statistically different from zero (p > 0.05). AL measurement change after cataract surgery is probably due to a systematic error in optical biometer in case of phakic eyes. A correction factor applied to preoperative AL could eliminate any systematic error in IOL power calculation without modifying the lens constant.


Endoscopic versus open saphenous vein harvest: a comparison of postoperative wound complications.
Wound complications associated with long incisions used to harvest the greater saphenous vein are well documented. Recent reports suggest that techniques of endoscopic vein harvest may result in decreased wound complications. A prospective, nonrandomized study was developed to compare outcomes of open versus endoscopic vein harvest procedures. There were 106 patients in the open vein harvest group, and 154 patients in the endoscopic vein harvest group. Patient characteristics and demographics were similar in both groups. Wound complications identified were dehiscence, drainage for greater than 2 weeks postoperatively, cellulitis, hematoma, and seroma/lymphocele. Wound complications were significantly less in the endoscopic vein harvest group (9 of 133, 6.8%) versus the open vein harvest group (26 of 92, 28.3%), p less than 0.001. By multivariable analysis with logistic regression, the open vein harvest technique was the only risk factor for postoperative leg wound complication (relative risk 4.0). Endoscopic vein harvest offered improved patient outcomes in terms of wound healing compared with the open vein harvest technique.


Y chromosome haplogroups in autistic subjects.
The male to female ratio in autism is 4:1 in the global autistic population, but increases to 23:1 in autistic subjects without physical or brain abnormalities.(1) Despite this well-recognised gender difference, male predisposition to autistic disorder remains unexplained and the role of sex chromosomes is still debated. Numerical and structural abnormalities of the sex chromosomes are among the most frequently reported chromosomal disorders associated with autism. However, genome scans have failed to detect linkage on the X chromosome(2,3,4) and this approach cannot study the non-recombining region of the Y chromosome. In this study, we searched for a specific Y chromosome effect in autistic subjects. Using informative Y-polymorphic markers, the Y chromosome haplotypes of 111 autistic subjects from France, Sweden and Norway were defined and compared with relevant control populations. No significant difference in Y-haplotype distribution between the affected and control groups was observed. Although this study cannot exclude the presence of a Y susceptibility gene, our results are not suggestive of a Y chromosome effect in autism.


Resident education in robotic-assisted vertical sleeve gastrectomy: outcomes and cost-analysis of 411 consecutive cases.
Robotic technology is increasingly prevalent in bariatric surgery, yet there are national deficiencies in exposure of surgical residents to robotic techniques. The purpose of this study is to accurately characterize the perioperative outcomes of a resident teaching model using the robotic-assisted sleeve gastrectomy. University Hospital. We identified 411 consecutive patients who underwent robotic sleeve gastrectomy at our institution from a prospectively maintained administrative database. Perioperative morbidity, operative time, and supply cost of the procedure were analyzed. Mean operative time was 96.4±24.9 minutes; mean robot usage time was 63.9 minutes (range 30.0-122.0 min). Ninety-day morbidities included reoperation (0.72%), major bleeding complications (0.48%), staple line leak (0.24%), stricture (0.97%), need for blood transfusion (3.86%), surgical site infection (1.69%), deep vein thrombosis (0.48%), and pulmonary embolism (0.48%). Mortality was nil. The resident cohort achieved operative time plateaus after five consecutive cases. Subset analysis for fiscal year 2014 demonstrated significantly increased supply cost for robotic sleeve gastrectomy compared with its laparoscopic equivalent. Robotic-assisted sleeve gastrectomy can be instituted as a model for resident robotic education with rates of morbidity and operative times equivalent to historical laparoscopic controls. The robot's enhanced ergonomics and its opportunity for resident education must be weighed against its increased supply cost.


Inhibition of spontaneous and evoked unit activity in the rat medial prefrontal cortex by mesencephalic raphe nuclei.
The rat medial prefrontal cortex (PFC) receives a serotoninergic (5-HT) innervation which originates from the mesencephalic raphe nuclei. In the present study we determined the influence of the 5-HT ascending systems on the spontaneous and evoked activity of PFC neurons in anesthetized rats. Stimulation of the dorsal (DRN) and of the median raphe (MRN) nuclei inhibited the spontaneous activity of 35.0% and 52.8% of the PFC cells tested (mean duration of the inhibition: 75.5 and 82.2 ms, respectively). These inhibitory responses are likely mediated by the 5-HT-containing neurons since they were decreased markedly following selective destruction of ascending 5-HT pathways induced by local injections of 5,7-dihydroxytryptamine. Moreover, the inhibitory effect of MRN stimulation could be blocked by systemic administration of the 5-HT2 receptor antagonists: ketanserin and ritanserin. The effects of MRN stimulation on two types of evoked responses were studied. The excitatory responses of PFC neurons induced by the stimulation of the mediodorsal nucleus of the thalamus (MD) were inhibited by MRN stimulation applied before that of MD. Similarly, the activation of PFC cells induced by a noxious tail pinch was suppressed by a concomitant stimulation of the MRN. These results indicate that 5-HT neurons exert an inhibitory control on spontaneous or evoked activity in the rat PFC.


Surges in proteinuria are associated with plasma GL-3 elevations in a young patient with classic Fabry disease.
Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in accumulations of globotriaosylceramide (GL-3) in systemic tissues. Nephropathy is a dominant feature of Fabry disease. It still remains unclear how the nephropathy progresses. Recombinant agalsidase replacement therapy is currently the only approved, specific therapy for Fabry disease. The optimal dose of replacement enzyme also still remains unclear. The worldwide shortage of agalsidase-β in 2009 forced dose reduction of administration. It showed that the proteinuria emerged like surges, followed by temporary plasma GL-3 elevations in the early stages of classic Fabry disease. Additionally, it also showed that 1 mg/kg of agalsidase-β every other week could clear the GL-3 accumulations from podocytes and was required to maintain negative proteinuria and normal plasma GL-3 levels. This observation of a young patient with classic Fabry disease about 5 years reveals that the long-term, low-dose agalsidase-β caused proteinuria surges, but not persistent proteinuria, followed by temporary plasma GL-3 elevations, and agalsidase-β at 1 mg/kg every other week could clear accumulated GL-3 from podocytes and was required to maintain normal urinalysis and plasma GL-3 levels.


Dopamine 2 Receptor Genes Are Associated with Raised Blood Glucose in Schizophrenia.
Type 2 diabetes is commonly found in schizophrenia and is an important contributor to mortality and morbidity in this condition. Dopamine has been implicated in the aetiology of both diabetes and schizophrenia. It is possible that both disorders share a common genetic susceptibility. In a cross-sectional study, we examined 2 dopamine D2 receptor (DRD2) single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia (C939 T, rs6275 and C957 T, rs6277) along with fasting blood glucose and body mass index (BMI) in 207 antipsychotic-treated patients with schizophrenia. All participants met DSM-IV criteria for schizophrenia, and those with other psychiatric disorders were excluded. Analysis of covariance was used to compare fasting glucose results by DRD2 genotypes, after controlling for known confounds. For significant associations, follow-up Bonferroni post hoc tests examined differences in fasting glucose levels between genotypes. Specific comparisons were also made using analysis of variance and chi-square (Fisher's exact test). The 2 DRD2 risk genotypes were associated with significant increases in blood glucose, after controlling for BMI, age, sex, dosage and type of antipsychotic medication, number of hospitalisations, and negative symptoms (rs6275, F(2, 182) = 5.901, P = 0.003; rs6277 SNP, F(2, 178) = 3.483, P = 0.033). These findings support the involvement of DRD2 not only in schizophrenia but also in elevated levels of blood glucose commonly found in antipsychotic-treated patients with schizophrenia. Our data support the notion that diabetes may not merely be a comorbid condition but could be fundamentally associated with the pathogenesis of schizophrenia itself.


Analysis of cytological changes in hepatocytes from rats dosed with 3'-methyl-4-dimethylaminoazobenzene: initial response appears to involve cytokinesis of binucleated cells.
The reduction in the ratio of tetraploid (4N + 2 X 2N) to diploid (2N) hepatocytes in the adult rat after treatment with the hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene (3'M) has been investigated. Analysis of isolated hepatocytes 18-28 days after treatment has confirmed that initially some of the 2 X 2N hepatocytes are converted into 2N cells by cytokinesis, and that there is no DNA synthesis during this process. Shortly afterwards nonpolyploidizing growth commences by proliferation of some 2N cells.


An immunoproteomics approach to screen the antigenicity of the influenza virus.
The structure and antigenicity of protein antigens of the influenza virus are screened in a single step employing an immunoproteomics approach. Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) coupled to gel electrophoresis is used both to identify viral antigens and screen their antigenicity. Earlier evidence that antigen-antibody complexes can survive on MALDI targets has allowed both the primary structure and antigenicity of viral strains to be rapidly screened with the specific localization of protein epitopes. The approach is anticipated to have a greater role in the future surveillance of the virus and should also aid in the development of immunogenic peptide constructs as alternatives to whole virus for vaccination.


Surveillance of suspected adverse reactions to herbal products used as laxatives.
To describe and evaluate spontaneous reports of suspected adverse reactions (ARs) associated with herbal laxatives received by the Italian Medicines Agency and the Italian National Institute of Health between April 2002 and January 2011. Spontaneous reports of suspected ARs were individually analyzed by a multidisciplinary group of experts, and a causality assessment was performed. Twenty-six reactions were reported during the study period. Of these, eight were associated with herbal medicinal products and 18 were related to herbal food supplements. Almost 80% of the reports on ARs involved women. The ARs, classified by System Organ Class, were associated with gastrointestinal, skin and subcutaneous tissue, and hepatobiliary disorders. Fifty percent of the reactions were serious, with the patients requiring hospitalization; of these, one was life-threatening. Most of the herbal remedies associated with the reported ARs contained liquorice, dandelion, and/or plants containing anthraquinones. Possible causes of the ARs were long-term use, idiosyncratic reactions or hypersensitivity, and interaction with other treatments. All of these factors and the presence of a large number of components in the same product increased the unpredictability of the final effect. The total number of 26 ARs recorded in 8 years is limited; however, the an under-reporting effect cannot be excluded. Moreover, taking into account the seriousness of the reported ARs, the low number of reports does not represent a guarantee of safety. To reduce the risk of an adverse outcome, herbal laxatives should be used only over the short term.


Application of homograft for intraoperative severe atherosclerotictic iliac vessel finding in renal transplantation: A case report.
Severe atherosclerosis is a complicated condition in chronic kidney disease (CKD) and could lead to the operation's failure, when it was not detectable by pre-operative diagnostic imaging. Several methods including two-stage approach, synthetic graft, stent… have been reported, but complications (i.e. infection, graft rejection) are a matter of concern. The aim of this case is to provide the one-stage approach, in which renal transplantation and vascular reconstruction using fresh homografts from one brain-dead donor were used. We reported a case of a 33-year-old male, who was diagnosed with CKD caused by chronic glomerulonephritis since the age of 28 and had been on hemodialysis. Not until did the transplantation take place that the operation team spotted the atherosclerotic external iliac artery, and vessel graft from the same donor was used and the renal was transplanted. The patient was discharged 14 days after the surgery without any complications. Kidney transplantation has revolutionized the life of patients with end-stage renal disease (ESRD). Around 6% of patients have severe atherosclerosis and the figure is increasing. Vascular degradation in ESRD might lead to unsuccessful operation. One-stage approach (including renal transplantation and external iliac artery replacement) using homograft from one doner is feasible to handle the situation. Severe atherosclerosis often accompanies with CKD. The difficulties of doing arterial anastomosis increases, which requires advanced techniques to deal with. Surgeons should be prepared about this circumstance. One-stage approach using one donor's homografts, is a possible and safe procedure.


Descending aortic strain quantification by intra-operative transesophageal echocardiography: Multimodality validation via cardiovascular magnetic resonance.
Whereas cardiac magnetic resonance (CMR) imaging provides high temporal resolution imaging of aortic distensibility (strain), transesophageal echocardiography (TEE) is widely used for intra-operative aortic imaging and provides a clinical alternative for aortic assessment. We tested intra-operative global circumferential aortic strain (GCS) measured on TEE in relation to the reference of CMR-derived strain among patients undergoing surgical graft repair of ascending aortic aneurysms. CMR (3T) was prospectively performed in patients scheduled for aortic repair. TEE was performed intra-operatively; images were co-localized with MRI. GCS on CMR and TEE was quantified independently, blinded to results of the other modality. 25 patients (54 ± 10 year-old, 88% male) were studied, inclusive of 13 genetically mediated and 12 degenerative aneurysms: CMR and TEE were performed within 12 ± 9 days. Pulse pressure (PP)-adjusted descending aortic TEE-derived GCS strongly correlated with cine-CMR-derived GCS (r = .75, P = .002) though absolute GCS and PP-adjusted values were slightly lower (5.40 ± 1.11 vs 6.49 ± 1.43% and 11.55 ± 3.04 vs 13.99 ± 4.53%, respectively). Similarly, TEE yielded slightly lower end-diastolic area (EDA [5.1 ± 1.7 cm2 vs 5.8 ± 1.3 cm2 , P = .004]) and end-systolic area (ESA [6.1 ± 1.9 cm2 vs 6.5 ± 1.7 cm2 , P = .10]), with significant correlations between the two modalities (r = .73, .76, P < .05 for all). This exploratory study supports feasibility of TEE for assessing aortic GCS in a surgical at-risk population, as well as magnitude of agreement between intra-operative TEE and preoperative CMR. We found that there is a significant correlation between GCS and EDA and ESA aortic areas, but that TEE-derived parameters underestimated CMR values by a small but significant amount.


Influence of CO2-laser linewidth on the measured absorption coefficients of atmospheric water vapor and ammonia.
We describe the results of analysis of the experimental and calculated data on the water vapor and ammonia absorption coefficients of CO2-laser radiation. We believe that the different halfwidths of CO2-laser lines, caused by different pressures of the working mixtures in specific experiments, are probably the reason for discrepancies between data presented in various papers.