Long Term Effects of Liraglutide in Japanese Patients with type 2 Diabetes Among the Subgroups with Different Renal Functions: Results of 2-Year Prospective Study.
Aims Very few studies have ever examined the effects of long-term (>1 year) administration of liraglutide in patients with type 2 diabetes mellitus (T2DM) and renal impairment. Therefore, we conducted a 2-year study to prospectively examine the effects of liraglutide in those patients. Methods A total of 148 patients with T2DM were enrolled and treated with liraglutide (0.6 or 0.9 mg/day). 97 patients completed the 2-year study without protocol deviations. These patients were divided into 3 groups according to the baseline estimated glomerular filtration ratio (eGFR) (in mL/min/1.73 m2): group A, ≥60 (n=39); group B, ≥30 to <60 (n=38); and group C, <30 (n=20). The changes in blood and urine variables, and echocardiographic left ventricular mass index (LVMI) from baseline to 2 years were analyzed in each group. Primary outcomes were changes of the renal parameters of eGFR and albuminuria after the treatment of liraglutide. Results Blood glucose and systolic blood pressure decreased significantly after 24 months of liraglutide treatment in all groups compared with baseline (p<0.05). The eGFR increased significantly in group B (p<0.05), and remained unchanged in groups A and C. Albuminuria and LVMI decreased significantly in all 3 groups compared with baseline (p<0.05). Conclusions These findings suggest that 2 years of liraglutide treatment in Japanese patients with T2DM and impaired renal function was effective in terms of suppressing the deterioration of renal function, and reducing albuminuria. Long-term liraglutide treatment also improved glycemic control and blood pressure, and reduced left ventricular hypertrophy in this study.


The chicken hypersensitivity site 4 core insulator blocks promoter interference in lentiviral vectors.
Lentiviral vectors, including double internal promoters, can be used to express two transgenes in a single vector construct; however, transcriptional activities from double internal promoters are often inhibited by promoter interference. To determine whether the chicken hypersensitivity site 4 insulator (cHS4) could block promoter interference, lentiviral vectors including an MSCV-U3 promoter (Mp) and an EF1α promoter (Ep) were generated, and transgene expression was evaluated among transduced cells. In the Ep-Mp configuration, transcriptional activity from Mp was much lower, while Mp-Ep had similar transcription levels from both promoters. The cHS4 core insulator increased expression levels from Mp in HeLa cells, hematopoietic cell lines, and mouse peripheral blood cells following hematopoietic stem cell transplantation transduced with the Mp-Ep configured vector. This blocking function was mainly mediated by barrier activity regions in the insulator but not by CCCTC-binding factor (CTCF) binding sites. Cytosine-phosphate-guanine (CpG) methylation did not contribute to this barrier activity. In summary, combining the cHS4 insulator in double promoter vectors can improve transgene expression levels in various cell lines and mouse hematopoietic repopulating cells. These findings are useful for developing hematopoietic stem cell gene therapy.


Nrf2 responses and the therapeutic selectivity of electrophilic compounds in chronic lymphocytic leukemia.
Recent studies show that redox-active small molecules are selectively cytotoxic to chronic lymphocytic leukemia (CLL). Although elevated levels of reactive oxygen species in CLL cells have been implicated, the molecular mechanism underlying this selectivity is unclear. In other cell types, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway regulates the oxidative stress response. We found elevated Nrf2 signaling in untreated CLL cells compared with normal lymphocytes. Therefore, we tested 27 known electrophilic and antioxidant compounds with drug-like properties and determined their CLL-selective cytotoxicity and effect on Nrf2 signaling. The selected compounds were from five distinct structural classes; alpha-beta unsaturated carbonyls, isothiocyanates, sulfhydryl reactive metals, flavones, and polyphenols. Our results show that compounds containing alpha-beta unsaturated carbonyls, sulfhydryl reactive metals, and isothiocyanates are strong activators of Nrf2 in a reporter assay system and in primary human CLL based on increased expression of the Nrf2 target heme oxygenase-1. alpha-beta Unsaturated carbonyl-containing compounds were selectively cytotoxic to CLL, and loss of the alpha-beta unsaturation abrogated Nrf2 activity and CLL toxicity. The alpha-beta unsaturated carbonyl containing compounds ethacrynic acid and parthenolide activated Nrf2 in normal peripheral blood mononuclear cells, but had a less potent effect in CLL cells. Furthermore, ethacrynic acid bound directly to the Nrf2-negative regulator Kelch-like ECH-associated protein 1 (Keap1) in CLL cells. These experiments document the presence of Nrf2 signaling in human CLL and suggest that altered Nrf2 responses may contribute to the observed selective cytotoxicity of electrophilic compounds in this disease.


Management of oral complications of disease-modifying drugs in rheumatoid arthritis.
Stomatitis is a troublesome adverse effect of disease-modifying anti-rheumatic drug (DMARD) therapy in rheumatoid arthritis (RA) patients. This review presents data to examine the incidence, clinical features and consequences of DMARD-related stomatitis, and suggests an algorithm for its clinical management. The specific objectives of the two studies presented here were to determine the incidence of DMARD-related stomatitis and its effect on DMARD continuation, and secondly to identify the clinical and laboratory risk factors. We investigated two cohorts of patients: (i) a retrospective survey of data collected from drug monitoring clinics run for patients on DMARDs from 1987 to 1994 involving 1539 patients and 2394 drug exposures; (ii) a prospective study of 25 consecutive RA patients presenting with DMARD-related stomatitis compared to 29 RA controls with no history of DMARD stomatitis. The retrospective survey showed that 2% of DMARD patients stopped therapy because of stomatitis, but 55% of these were able to resume the same therapy. In the case control study. 24% of patients discontinued temporarily and 8% permanently. Cases of DMARD-related stomatitis differed from controls in that they had a higher incidence of previous mouth ulcers (40% vs 14%), they smoked less (8% vs 31%) and Schirmer's test was more often abnormal (44% vs 21%). There were no differences in RA severity, disease activity or oral hygiene. Haematinic deficiencies were equally common in cases and controls: 30% for iron, 8% for vitamin B12 and 24% for folic acid. Herpes simplex virus was involved in a minority (8%) of cases. In conclusion, the occurrence of stomatitis in RA patients on DMARD should not lead to cessation of drug therapy, but to a careful evaluation so that patients may be maintained on effective treatment.


Effects of omega-3 fatty acids in hypertriglyceridemic states.
In the experimental studies reported in this review, dietary omega-3 fatty acids from fish and fish oil had profound hypolipidemic effects in normal subjects and in hypertriglyceridemic patients with combined hyperlipidemia (type IIb) and type V hyperlipidemia. In these studies, 68 adults participated in carefully controlled metabolic experiments. In all subjects and patients, there were marked reductions in plasma cholesterol and triglyceride concentrations, with triglyceride lowering being especially great. There were also reductions in VLDL, chylomicrons, remnants, LDL, apo B, and apo E. The HDL changes were inconstant and varied from subject to subject. Whereas the mechanism of the hypolipidemic action of the omega-6-rich vegetable oils containing linoleic acid, such as corn or safflower oil, still remains obscure, the mechanism of action of the omega-3 fatty acids in fish oil has been well documented within a few years of their use as hypolipidemic agents. The synthesis of triglyceride and VLDL in the liver is greatly reduced by omega-3 fatty acids. At the same time, the turnover of VLDL in plasma is greatly shortened. LDL production is decreased. Combined with other dietary manipulations, such as a reduction in saturated fat and dietary cholesterol, the use of omega-3 fatty acids to treat hyperlipidemic and especially hypertriglyceridemic patients would appear to have a well-supported rationale. Further studies are required to delineate exact doses and precise indications for different types of hyperlipidemia and to differentiate the effects of, if any, the two major omega-3 fatty acids in fish oil, EPA and DHA. Coupled with the known antithrombotic actions of omega-3 fatty acids from fish oil because of changes in prostaglandin secretion and platelet function, these hypolipidemic effects would appear to have an important potential role in the control of coronary heart disease and other atherosclerotic disorders.


Comparison of the roles of CD8 alpha alpha and CD8 alpha beta in interaction with MHC class I.
The CD8 molecule is expressed either as an alpha/alpha homodimer or an alpha/beta heterodimer on thymocytes and cytotoxic T cells, and functions as a coreceptor in concert with TCR for binding the MHC class I/peptide complex. Although CD8alpha/beta heterodimers have been shown to be more effective coreceptors, the precise role of the beta-chain in TCR-mediated thymic maturation and T cell activation is not understood. To understand the role of CD8beta in mediating CD8/MHC class I interaction, we examined whether cell surface CD8alpha/beta heterodimer promotes better cell-cell adhesion with MHC class I than the CD8alpha/alpha homodimer. The abilities of different forms of CD8 to adhere to MHC class I were measured with a cell-cell binding assay. Using a wild-type CD8beta and -alpha, we found that CD8alphabeta heterodimers did not mediate greater cell-cell adhesion than CD8alphaalpha homodimers. Furthermore, we found that chimeric CD8beta-alpha homodimers afforded no detectable binding. These results do not support the idea that CD8alphabeta binding to MHC class I is greater than that of CD8alphaalpha. Rather, they point to an alternative explanation in which CD8beta may play an role in promoting CD8/TCR interaction and/or in signaling/regulatory pathways.


Porous Nb4N5/rGO Nanocomposite for Ultrahigh-Energy-Density Lithium-Ion Hybrid Capacitor.
To meet the increasing demands for high-performance energy storage devices, an advanced lithium-ion hybrid capacitor (LIHC) has been designed and fabricated, which delivers an ultrahigh energy density of 295.1 Wh kg-1 and a power density of 41 250 W kg-1 with superior cycling stability. The high-performance LIHC device is based on the uniform porous Nb4N5/rGO nanocomposite, which has an intimate interface between the firmly contacted Nb4N5 and rGO through the Nb(Nb4N5)-O(rGO)-C(rGO) bonds, significantly improving the electron transport kinetics. Moreover, the introduction of rGO nanosheets can prevent the Nb4N5 nanoparticles from agglomeration, not only resulting in a larger specific surface area to provide more active sites but also accommodating the strain during Li ion insertion/deinsertion. Therefore, the Nb4N5/rGO nanocomposite exhibits a higher reversible specific capacity and better rate and cycling performance than the Nb4N5 nanoparticle. In view of the scalable preparation and superior electrochemical characteristics, the Nb4N5/rGO nanocomposite would have great potential practical applications in the future energy storage devices.


Bariatric surgery in adolescence.
Surgical treatment for morbid obesity is relatively contraindicated in patients less than 18 years of age. However, on some occasions, there is extreme obesity in this age group that does not respond to nonsurgical treatment. The aim of this study was to evaluate the surgical management of severe morbid obesity in adolescents. During a 4-year period, the authors assessed 11 adolescent patients with severe morbid obesity. All patients underwent extensive preoperative evaluation including thorough psychological evaluation together with their families. Laparoscopic adjustable gastric banding (LAGB) was performed in all patients. Patients underwent follow-up for a mean of 23 months. The mean age of the 11 children in this study was 15.7 years (range, 11 to 17 years). Associated conditions included heart failure and pulmonary hypertension in one patient, amenorrhea in 2 patients, and gallstones in 1 patient. Mean preoperative body mass index (BMI) was 46.4 kg/m2 (range, 38 to 56.6). There were no operative complications. Over a mean follow-up period of 23 months (range, 6 to 36 months), the mean BMI dropped from 46.6 to 32.1 kg/m2 with marked improvement in medical conditions and general psychologic well being. No late complications developed in any patient. Children are routinely excluded from bariatric surgery programs because of the difficulties involved in psychologically and cognitively preparing this population for surgery. However, extreme morbid obesity rarely responds to nonsurgical therapy for any extended period. This select population will benefit from bariatric surgery if an effort is made to properly prepare patients, together with their families, for the postoperative change in lifestyle and body image.


Controlled Air-Etching Synthesis of Porous-Carbon Nanotube Aerogels with Ultrafast Charging at 1000 A g-1.
Supercapacitors are energy storage systems capable of fast charging and discharging, thus generating superior power density. Porous carbon with high surface area and tunable pore size represents a promising candidate to construct ultrafast supercapacitors; so far, most porous carbon-based electrodes can only be charged to a moderate current density (100-200 A g-1), also with significant capacitance loss at increasing rate. Here, it is shown that a 3D aerogel consisting of interconnected 1D porous-carbon nanotubes (PCNs) can serve as a freestanding supercapacitor electrode with excellent rate performance. As a result, the PCN aerogel electrodes achieve 1) ultrafast charging at current densities up to 1000 A g-1 (corresponding to a charge period of 16 ms), which is the highest value among other porous carbon-based supercapacitors, 2) superior cycling stability at high charging rates (88% capacitance retention after 105 cycles at 1000 A g-1). Mechanism study reveals favorable kinetics including a centralized pore size distribution at 0.8 nm which is a dominant factor to allow high-rate charging, a low and linear IR drop, and a metallic feature of 1D PCNs by theoretical calculation. The results indicate that 1D PCNs with controlled porous structures have potential applications in ultrafast energy conversion and storage.


Pulmonary fibrosis and its related factors in discharged patients with new corona virus pneumonia: a cohort study.
Thousands of Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals Persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis. This study involves 462 laboratory-confirmed patients with COVID-19 who were admitted to Shenzhen Third People's Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 to 150 days after the onset of the disease, and lung function tests were conducted about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established. Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0-30, 31-60, 61-90, 91-120 and > 120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of the COVID-19 patients revealed abnormal conditions in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups. Persistent pulmonary fibrosis was more likely to develop in patients with older age, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average area under the curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.


Successful Treatment of Corticosteroid with Antiviral Therapy for a Neonatal Liver Failure with Disseminated Herpes Simplex Virus Infection.
Background Herpes simplex virus (HSV) infection carries one of the poorest outcomes of neonatal liver failure (NLF). Neonates with disseminated HSV infection can develop hemophagocytic lymphohistiocytosis (HLH), and occasionally need orthotopic liver transplantation. Early interventions may be critical for the cure of NLF. Case Report We describe herewith a 6-day-old neonate with fulminant hepatic failure due to disseminated HSV-1 infection, who successfully responded to high-dose corticosteroid therapy 72 hours after the onset of disease. Preceding acyclovir, gamma globulin, and exchange blood transfusion therapies failed to control the disease. Methylprednisolone pulse therapy led to a drastic improvement of liver function and cytokine storms, and prevented the disease progression to HLH. Sustained levels of plasma and cerebrospinal fluid HSV DNA declined after prolonged acyclovir therapy. Bilateral lesions of the periventricular white matter areas, assessed by magnetic resonance imaging, disappeared at 3 months of age. The infant showed normal growth and development at 4 years of age. Conclusion Early anti-hypercytokinemia therapy using corticosteroid, and prolonged antiviral therapy might only provide the transplantation-free cure of NLF with HSV dissemination.


Systemic blockade of LPA1/3 lysophosphatidic acid receptors by ki16425 modulates the effects of ethanol on the brain and behavior.
The systemic administration of lysophosphatidic acid (LPA) LPA1/3 receptor antagonists is a promising clinical tool for cancer, sclerosis and fibrosis-related diseases. Since LPA1 receptor-null mice engage in increased ethanol consumption, we evaluated the effects of systemic administration of an LPA1/3 receptor antagonist (intraperitoneal ki16425, 20 mg/kg) on ethanol-related behaviors as well as on brain and plasma correlates. Acute administration of ki16425 reduced motivation for ethanol but not for saccharine in ethanol self-administering Wistar rats. Mouse experiments were conducted in two different strains. In Swiss mice, ki16425 treatment reduced both ethanol-induced sedation (loss of righting reflex, LORR) and ethanol reward (escalation in ethanol consumption and ethanol-induced conditioned place preference, CPP). Furthermore, in the CPP-trained Swiss mice, ki16425 prevented the effects of ethanol on basal c-Fos expression in the medial prefrontal cortex and on adult neurogenesis in the hippocampus. In the c57BL6/J mouse strain, however, no effects of ki16425 on LORR or voluntary drinking were observed. The c57BL6/J mouse strain was then evaluated for ethanol withdrawal symptoms, which were attenuated when ethanol was preceded by ki16425 administration. In these animals, ki16425 modulated the expression of glutamate-related genes in brain limbic regions after ethanol exposure; and peripheral LPA signaling was dysregulated by either ki16425 or ethanol. Overall, these results suggest that LPA1/3 receptor antagonists might be a potential new class of drugs that are suitable for treating or preventing alcohol use disorders. A pharmacokinetic study revealed that systemic ki16425 showed poor brain penetration, suggesting the involvement of peripheral events to explain its effects.


Synthesis of novel N1-substituted bicyclic pyrazole amino acids and evaluation of their interaction with glutamate receptors.
N1-substituted bicyclic pyrazole amino acids (S)-9a-9c and (R)-9a-9c, which are conformationally constrained analogues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested for activity at ionotropic and metabotropic glutamate receptors. Some of them turned out to be selective for the NMDA receptors, where they behaved as weak antagonists. The biological activity is mainly due to the interaction with the glutamate binding site, and not with the glycine co-agonist site.


Biosynthesis of Escherichia coli Braun's lipoprotein precursors in vitro and binding to membrane vesicles.
A cell-free system only programmed by endogenous mRNA present in a 30000 X g supernatant fraction is described in which 15-40% of the material produced was constituted by two lipoprotein precursors. These two polypeptides (a) are immunologically related, (b) contain the signal peptide and (c) apparently differ by the presence in one of them of a substituent on the -SH group of the single cysteine residue. The nature of this substituent could not be determined but no evidence was obtained that it could be a glyceride. No processing of any of these prolipoprotein forms could be demonstrated by addition of either Triton X-100 or membrane vesicles. A similar binding of both precursors to inverted membrane vesicles was observed when they were provided either co-translationally or post-translationally and this reaction occurred without the help of major membrane compounds.


Assessment of Empiric Vancomycin Regimen in the Neonatal Intensive Care Unit.
Vancomycin is used to treat serious gram-positive infections in neonates. Currently, there is no consensus on the preferred empiric dosing regimen or target trough vancomycin levels for neonates. The current Fraser Health empiric dosing regimen, implemented in 2010, was designed to achieve target trough levels of 5 to 15 mg/L. To determine the percentage of neonates receiving vancomycin in whom target trough levels of 5 to 15 mg/L were achieved, to identify the times to negative culture result and clinical resolution, and to determine the incidence of nephrotoxicity. A chart review was completed for patients who had received vancomycin in the neonatal intensive care unit of either Surrey Memorial Hospital or Royal Columbian Hospital from June 2012 to May 2017 and for whom at least 1 interpretable vancomycin level was available. A total of 87 vancomycin encounters (in 78 neonates) were identified in which the drug had been given according to the Fraser Health empiric dosing regimen. Target trough vancomycin level (5 to 15 mg/L) was achieved in 75% of these encounters. The mean times to negative culture result and clinical resolution were 5 and 6 days, respectively. There was no statistically significant correlation between vancomycin level and time to clinical resolution (rs = 0.366, p = 0.072). Among cases in which the trough vancomycin level exceeded 15 mg/L, the incidence of nephrotoxicity was 22% (4/18). The current Fraser Health empiric dosing regimen for vancomycin achieved target trough levels of the drug for most neonates in this study. Targeting trough levels less than 15 mg/L when appropriate to the infection type may limit nephrotoxicity associated with vancomycin in neonates. Further studies are needed to evaluate the clinical significance of various vancomycin levels.


Safety and efficacy studies on trivalent inactivated vaccines against infectious coryza.
The safety and efficacy of an inactivated oil-emulsion infectious coryza vaccine containing three Avibacterium paragallinarum isolates (one each of Page serovars A, B, and C) was evaluated. The safety of six batches of the vaccine was confirmed by testing with chickens vaccinated with a single large dose or vaccinated repeatedly with a normal dose. Efficacy tests were carried out on three batches of vaccine using both specific pathogen free (SPF) chickens and conventional chickens. In SPF chickens given a single vaccination at 42 days of age, the protection rate against all three serovars of Av. paragallinarum was at least 80% at 30 days post vaccination. The conventional chickens, which were immunized at 42 and 110 days of age, were challenged at 9 months post the second vaccination and the protection rate was at least 80% for all three serovars. The effect of storage on the vaccine was evaluated in SPF chickens using three batches of vaccine stored at 4-8°C for 1 year. The protection rate against challenge from all three serovars (single vaccination at 42 days of age and challenge at 30 days post-vaccination) was at least 80%.


MR spectroscopy of cervical spinal cord in patients with multiple sclerosis.
MR spectroscopy (MRS) of the brain in patients with multiple sclerosis has been well studied. However, in vivo MRS of the spinal cord in patients with MR spectroscopy has not been reported to our knowledge. We performed MRS of normal-appearing cervical spinal cords in multiple sclerosis patients and in healthy controls. N-acetyl aspartate was shown to be reduced within the cervical spinal cord of multiple sclerosis patients when compared with healthy controls. This finding supports axonal loss and damage within even normal-appearing spinal cords of multiple sclerosis patients.


Levels of thrombin activatable fibrinolysis inhibitor in gestational diabetes mellitus.
Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase, which is synthesised in liver and activated by thrombin and the thrombin-thrombomodulin complex. TAFI suppresses fibrinolysis by removing carboxy-terminal lysine residues from partially degraded fibrin. In this study we aimed to assess the circulating levels of TAFI antigen, 'a fibrinolytic parameter' in women with gestational diabetes (GDM). Thirty-four pregnant women with GDM and 50 pregnant women with normal glucose tolerance were included in the study. Plasma TAFI antigen levels were significantly higher in pregnant women with GDM when compared with controls. Increased TAFI levels may contribute to the decreased fibrinolytic potency, causing a thrombophilic state. GDM is regarded as a specific form of diabetes, and it could in addition be a predictor of type 2 diabetes mellitus in the future and the risk of complications due to hypercoagulability increases in this disease. Increased TAFI levels may also have a role in increased risk of hypercoagulability.


Efficacy against sheep lice (Bovicola ovis) and fleece wetting of six shower dip preparations.
The relative efficacy of 6 shower dip chemicals most frequently used for the treatment of sheep lice (Bovicola ovis) in Western Australia was examined. Groups of 20 sheep infested with lice were treated with products containing either alphamethrin, cyhalothrin, diazinon or diazinon plus piperonyl butoxide and rotenone, formulated as emulsifiable concentrates, and with products containing either coumaphos or magnesium fluorosilicate, formulated as wettable powders. All treatments were applied through a shower dip (Sunbeam model SSD). Inspections for lice were conducted until 9 months after dipping. No lice were found on sheep treated with the 4 emulsifiable concentrate products. In contrast, treatment with the wettable powders, which contained either coumaphos or magnesium fluorosilicate as the active ingredient, did not eradicate the lice infestations. The degree to which the fleece was wetted was assessed 20 minutes after dipping and showed that the wettable powder dips penetrated the fleece less than the emulsifiable concentrate dips. Less fluid was retained by wool staples in an in-vitro test when dip wash was made with the wettable powders. It was concluded that the degree of wetting attained at dipping was an important factor in achieving eradication of sheep lice.


The efficacy of graduated compression stockings in the prevention of deep vein thrombosis after major gynaecological surgery.
The efficacy of graduated compression stockings in the prevention of deep vein thrombosis (DVT) after major gynaecological surgery was investigated in a controlled randomized prospective trial in 196 patients who were greater than 35 years of age. The stockings were worn by 104 of the 196 patients throughout their stay in hospital, the other 92 patients did not wear the stockings (control group). All the patients were scanned for DVT postoperatively with the 125I-labelled fibrinogen test. None of the 104 patients who wore the stockings developed a thromboembolism, but four of the 92 control patients who did not wear the stockings had DVT. This difference between the two groups was statistically significant.


First Occurrence of Trichogramma bruni Nagaraja (Hymenoptera: Trichogrammatidae) Parasitizing Eggs of Anticarsia gemmatalis Hübner (Lepidoptera: Erebidae) in Brazil.
The occurrence of Trichogramma bruni Nagaraja (Hymenoptera: Trichogrammatidae) is described for the first time parasitizing eggs of the velvetbean caterpillar Anticarsia gemmatalis Hübner (Lepidoptera: Erebidae) in Lapa, Paraná, Brazil. This parasitoid was successfully kept in the laboratory on eggs of the velvetbean caterpillar; previously, this species was mainly associated with forest and fruit trees environments, although snap beans and other annual crops were also recorded as hosting lepidopteran eggs parasitized by T. bruni. This is the sixth Trichogramma species recorded parasitizing eggs of A. gemmatalis on soybeans in Brazil.


Integrating self blood pressure monitoring into the routine management of uncontrolled hypertension: translating evidence to practice.
Improving hypertension control is a public health priority and could reduce health disparities. Self blood pressure monitoring (SBPM) is effective but not widely integrated into clinical care. A pragmatic study distributing blood pressure (BP) monitors was conducted to assess its effectiveness in the management of uncontrolled hypertension under conditions consistent with clinic resources. Patients, predominantly black and Hispanic adults from clinics in low-income, medically underserved communities with uncontrolled BP were enrolled. Follow-up assessments were conducted 9 months after enrollment. Approximately half (53%) of the patients had controlled hypertension at follow-up. Systolic and diastolic BP decreased by 18.7 mm Hg and 8.5 mm Hg, respectively, at follow-up. Although attenuated, decreases persisted after adjustment for regression to the mean. Clinicians were supportive of the program, although collecting follow-up data from enrolled patients was a common challenge. The integration of SBPM into routine management of uncontrolled hypertension demonstrated substantial improvements in control. Systems to identify and track patients who are self-monitoring may increase impact.


Enhancement of the anaphylactoid reaction in rats by salicylates.
Low doses of sodium or copper salicylate, administered at the same time as agents producing the anaphylactoid reaction in rats, significantly enhanced the onset, height and duration of the responses. The enhancement occurred after intraperitoneal or local administration. Enhanced transport of the high molecular weight agents into the bloodstream is suggested. However, the salicylates did not enhance histamine release from isolated peritoneal mast cells of rats induced by dextran and phosphatidyl serine.


A randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc in children with intractable epilepsy.
This study was conducted to assess the efficacy of oral zinc supplementation in children with intractable epilepsy. Forty-five children aged between three and 12 years and diagnosed with idiopathic intractable epilepsy at Assiut University Hospital, Assiut, Egypt were recruited. The patients were randomly allocated to two groups: the intervention group received oral zinc supplementation (1 mg/kg/day) while the placebo group received placebo, each for six months. The parents of each child filled in a detailed questionnaire that covered demographic characteristics, type of seizures, frequency, duration of seizures, previous hospital admissions, postictal phenomena and the occurrence of status epilepticus. The primary outcome (frequency of seizures) was compared between the two groups. Zinc supplementation resulted in a significant reduction of seizure frequency in 31% of the treated children. Zinc is an important trace element. Our results suggest that it has mildly beneficial effects in children with intractable epilepsy. We recommend further investigation of oral zinc supplementation as an adjunctive therapy for managing intractable epilepsy in children. Zinc therapy may be an option in treatment protocols for intractable epilepsy in the near future.


Morphology of plantar interdigital neuroma: a comparative cadaveric study of elderly Finnish and Japanese individuals.
To examine morphological differences in Morton's interdigital neuroma between two elderly human populations, we conducted comparative study using 40 Japanese (27 males, 13 females; mean age, 81.2 years) and 21 Finnish (6 males, 15 females; mean age, 80.5 years) cadavers. We defined the neuroma as a thickening of the nerve of at least two-fold relative to the non-pathological proximal part. The incidence of this neuroma was 25% (10/40) in the Japanese and 33.3% (7/21) in the Finnish cadavers. Moderate or severe hallux valgus (with an angle of more than 20 degrees) was seen in half of the 40 Japanese cadavers (7 males, 13 females), but was absent in the Finnish cadavers. Such hallux valgus was present in 7 (5 males, 2 females) of the 10 Japanese cadavers with neuroma. Moreover, in 2 Japanese cadavers, a paper-like, specialized type of neuroma was associated with the deformity. Pathogenesis of Morton's neuroma might be different between human populations with or without hallux valgus.


Hematopoietic stem cell capture and directional differentiation into vascular endothelial cells for metal stent-coated chitosan/hyaluronic acid loading CD133 antibody.
A series of metal stents coated with chitosan/hyaluronic acid (CS/HA) loading antibodies by electrostatic self-assembled method were prepared, and the types of cells captured by antibodies and their differentiation in vascular endothelial cells (ECs) evaluated by molecular biology and scanning electron microscope. The results showed that CD133 stent can selectively capture hematopoietic stem cells (HSC),which directionally differentiate into vascular ECs in peripheral blood by (CS/HA) induction, and simultaneously inhibit migration and proliferation of immune cells and vascular smooth muscle cells (MCs). CD34 stent can capture HSC, hematopoietic progenitor cells that differentiate into vascular ECs and immune cells, promoting smooth MCs growth, leading to thrombosis, inflammation, and rejection. CD133 stent can be implanted into miniature pig heart coronary and can repair vascular damage by capturing own HSC, thus contributing to the rapid natural vascular repair, avoiding inflammation and rejection, thrombosis and restenosis. These studies demonstrated that CD133 stent of HSC capture will be an ideal coated metal stent providing a new therapeutic approach for cardiovascular and cerebrovascular disease.


Spin Hall drag in electronic bilayers.
We predict a new effect in electronic bilayers: spin Hall drag. The effect consists of the generation of spin accumulation across one layer by an electric current along the other layer. It arises from the combined action of spin-orbit and Coulomb interactions. Our theoretical analysis, based on the Boltzmann equation formalism, identifies two main contributions to the spin Hall drag resistivity: the side-jump contribution, which dominates at low temperature, going as T2, and the skew-scattering contribution, which is proportional to T3. The induced spin accumulation, while generally quite small, should be observable in optical rotation experiments.


The Use Of Anterolateral Thigh Flap (ALTF) For Functional Tongue Reconstruction With Postoperative Quality Of Live Evaluation.
The use of microsurgery for oral reconstruction of cancer patients, has become standard treatment in restoring oral function. The free anterolateral thigh flap is one of the most preferred options in reconstruction after total, subtotal or hemiresection of the tonque due to squamous cell cancer. The aim of the study was to present the reconstructive method using anterolateral thigh free flap with evaluation of quality of live. Clinical material includes 46 consecutive patients with tongue cancer, who underwent complex surgical treatment between 2009 and 2011. There were 36 males and 10 females and the M: F ratio was 3.6: 1. All of them were reconstructed using the anterolateral thigh free flap. The quality of life was evaluated 6 months after completing the treatment, based on postoperative functional and aesthetic status. The overall flap survival rate was 96%. Surgical complications were observed in 8 patients (17%). Donor site was closed primarly in 42 cases and in remaining 4 skin graft was required. In all 46 cases understandable speech and return to unrestricted diet mastication and swallowing were achieved. The mean follow-up period after treatment was 32 months. Analysis of aesthetic effects evaluated in 23 cases and shows generally very good results. According to average transformed scores the QOL can be characterized as excellent for >90, very good for 76-90, good for 51-75, moderate for 25-50 and bad for <25 points. Anterolateral thigh flap, with its versatility in design, long pedicle with a suitable vessel diameter, low donor site morbidity, and very good aesthetic effects, could be the ideal flap for functional tongue reconstruction.


Feminism's healing effect.
Helen Bequaert Holmes and Laura M. Purdy have done medical ethicists and clinical practitioners an enormous favor by publishing in book form their edited collection of 21 essays, Feminist Perspectives in Medical Ethics. This is an anthology of articles applying feminist methods and theories to problems in medical ethics. It is a fitting initiation for healthcare professionals and theorists who have yet to introduce themselves to the methods, analyses, and diverse contributions of feminism. In one simple volume, readers can sample feminist contributions to medical ethics that otherwise would be scattered in books or journals unavailable in most medical libraries.


Xpert(®) MTB/RIF for improved case detection of extra-pulmonary TB in a tertiary care setting in urban India.
Department of microbiology at a tertiary care hospital, Mumbai, India. To determine 1) the sensitivity and specificity of the Xpert(®) MTB/RIF assay in comparison with microscopy and culture in extra-pulmonary tuberculosis (EPTB), and 2) the number of additional cases of EPTB and rifampicin (RMP) resistance detected using this assay. The study was conducted from July 2013 to April 2015. All consecutive patients with clinically suspected EPTB referred for microscopic examination to the Department of Microbiology that were sufficient in specimen volume were included in the study. Of the 728 specimens included in the study, respectively 5.5%, 23.5% and 20.9% were positive on smear, culture and Xpert. Compared to culture, Xpert had a sensitivity of 84.2% (95%CI 81.4-86.6) and specificity of 98.2% (95%CI 90-104). All specimens with high and medium load on assay were positive on culture; 28 (18.4%) specimens were RMP-resistant and 124 (81.6%) were Xpert-susceptible. No additional RMP-resistant cases were detected using Xpert as compared to phenotypic drug susceptibility testing. The ability of the Xpert assay to rapidly detect a significantly greater number of bacteriologically confirmed EPTB cases, including RMP-resistant cases, makes it an important diagnostic tool in a TB-endemic country.


Factors affecting multiresidue determination of priority herbicides when using solid-phase microextraction.
A solid-phase microextraction (SPME) procedure was developed for the determination of 10 selected organonitrogen herbicides (s-ethyl dibropylthiocarbamate [EPTC], molinate, propachlor, trifluralin, simazine, atrazine, propazine, terbuthylazine, alachlor, and prometryn) and was tested with various natural waters. Gas chromatography coupled with flame thermionic and mass spectrometric detection was used for quantitation. For this purpose, polydimethylsiloxane and polyacrylate fibers were used and the factors affecting the SPME process such as pH, ionic strength, methanol content, memory effect, stirring rate, and adsorption-time profile were investigated and optimized. By using spiked liquid chromatography water, optimal factors were determined to be 25% salt, <0.5% methanol, stirring rate of 960 rpm, pH 4, and an equilibrium time of 30 min. These conditions were used in further studies of the fibers and in analysis of natural water samples. The method was applied to spiked natural waters such as ground water, sea water, lake water, and river water at a concentration range of 0.5-10 microg/L. Limits of detection ranged from 5 to 90 ng/L, and precision ranged from 5 to 15% (as relative standard deviation), depending on the pesticide, fiber, and detector used. The recoveries of herbicides were 70.2-118.4%, and the average r2 values of the calibration curves were >0.99 for all analytes. The results demonstrate the suitability of the SPME method to determine these organonitrogen herbicides in various natural waters. River water samples originating from the Epirus region (Northwestern Greece) were analyzed to verify the performance of the optimized method by comparing the results obtained by SPME with those obtained by using conventional solid-phase extraction of the selected herbicides.


[Use of memantine for elderly patients in the mild stage of Alzheimer's and vascular dementia].
To evaluate the efficiency menantine (antagonist of NMDA-type glutamate receptor) for treatment of the mild stage of Alzheimer and vascular dementia, we conducted a comprehensive neurological, experimental psychological, neurophysiological examination of 33 patients. It was found that the treatment course with memantine, 5-10 mg daily during 3 months resulted in reducing the severity of cognitive impairment, improved bioelectric activity of the brain in patients with dementia, and also helped to improve the patients' behavior, which resulted in stress loads on the surrounding people. It is shown that the treatment was well tolerated, and memantine may be recommended as one of the drugs for treatment of cognitive impairment accompanying aging in the mild stage of dementia of different genesis.


Reproductive and contraceptive characteristics of premenopausal kidney transplant recipients.
To obtain information on menstrual patterns before and after transplantation, desire for future pregnancy, and use of contraception among premenopausal kidney transplant recipients. This observational study collected information using self-administered anonymous questionnaires during a routine outpatient clinic visit. Of the 107 women who completed the questionnaire, 41 identified themselves as being premenopausal. Among the 41 premenopausal women, approximately half of the women reported their current menstrual patterns as normal and 26% were not using any form of contraception. Overall, 10 women (24%) reported a desire to become pregnant and 4 women (10%) had a successful pregnancy after transplantation. Most of the women who desired a future pregnancy (8/10) were receiving an immunosuppressive regimen that included mycophenolate mofetil. Kidney transplantation in the current era is associated with a return of normal menstrual function in the majority of female transplant recipients. A substantial fraction of women desire pregnancy after transplantation and many are using an immunosuppressive drug with limited safety data on use during pregnancy. More caution should be used with the use of newer immunosuppressive agents in sexually active premenopausal transplant recipients until more safety data are available.


Immunocytochemical demonstration of LH-RH, somatostatin, and ACTH-like peptide in osmium-postfixed, resin-embedded median eminence.
In guinea pig median eminences that were fixed with a glutaraldehyde paraformaldehyde mixtures, postfixed with osmium tetroxide, and embedded in araldite, immunocytochemical stainings for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and alpha 17-39 ACTH have been obtained on semithin sections. These positive reactions were obtained after araldite was removed with sodium methoxide and after treatment with hydrogen peroxide. These data suggest that osmium tetraoxide postfixation can be used for the detection of low molecular weight peptides such as LH-RH, somatostatin, and ACTH-like-peptides not only in the median eminence but also in the hypothalamus.


Hospice outcomes: meeting requirements and developing a national consensus.
This article describes the rationale for outcome measurement in hospice care and the requirements related to such measurement as stipulated by regulatory bodies, third party payers, and accreditation organizations. Also discussed are the end-result outcomes of hospice care and efforts by the National Hospice and Palliative Care Organization to develop consensus related to definition and measurement of these outcomes.


In vivo quantitative evaluation of vascular parameters for angiogenesis based on sparse principal component analysis and aggregated boosted trees.
To solve the multicollinearity issue and unequal contribution of vascular parameters for the quantification of angiogenesis, we developed a quantification evaluation method of vascular parameters for angiogenesis based on in vivo micro-CT imaging of hindlimb ischemic model mice. Taking vascular volume as the ground truth parameter, nine vascular parameters were first assembled into sparse principal components (PCs) to reduce the multicolinearity issue. Aggregated boosted trees (ABTs) were then employed to analyze the importance of vascular parameters for the quantification of angiogenesis via the loadings of sparse PCs. The results demonstrated that vascular volume was mainly characterized by vascular area, vascular junction, connectivity density, segment number and vascular length, which indicated they were the key vascular parameters for the quantification of angiogenesis. The proposed quantitative evaluation method was compared with both the ABTs directly using the nine vascular parameters and Pearson correlation, which were consistent. In contrast to the ABTs directly using the vascular parameters, the proposed method can select all the key vascular parameters simultaneously, because all the key vascular parameters were assembled into the sparse PCs with the highest relative importance.


Method for the Identification of Taxon-Specific k-mers from Chloroplast Genome: A Case Study on Tomato Plant (Solanum lycopersicum).
Polymerase chain reaction and different barcoding methods commonly used for plant identification from metagenomics samples are based on the amplification of a limited number of pre-selected barcoding regions. These methods are often inapplicable due to DNA degradation, low amplification success or low species discriminative power of selected genomic regions. Here we introduce a method for the rapid identification of plant taxon-specific k-mers, that is applicable for the fast detection of plant taxa directly from raw sequencing reads without aligning, mapping or assembling the reads. We identified more than 800 Solanum lycopersicum specific k-mers (32 nucleotides in length) from 42 different chloroplast genome regions using the developed method. We demonstrated that identified k-mers are also detectable in whole genome sequencing raw reads from S. lycopersicum. Also, we demonstrated the usability of taxon-specific k-mers in artificial mixtures of sequences from closely related species. Developed method offers a novel strategy for fast identification of taxon-specific genome regions and offers new perspectives for detection of plant taxa directly from sequencing raw reads.


The effect of feeding a semipurified diet to chickens infected with coccidia.
Four experiments were conducted using broiler chicks to study the effects of feeding a semipurified diet on coccidial infection. Chickens fed a semipurified diet and inoculated with E. tenella had a very mild infection with little or no mortality and no effect on body weight gain, feed intake, feed conversion ratio, and blood cell loss as judged by hematocrit. At necropsy the infected chickens had light cecal lesions. However, no difference in response was observed between chickens fed either the corn-soybean meal or the semipurified diet and inoculated with a mixture of E. acervulina, E. maxima, and E. brunetti. Chickens fed a diet composed of 25% of the corn-soybean meal diet plus 75% of the semipurified diet and inoculated with E. tenella had the same mortality as chickens fed the corn-soybean meal diet. Feeding chickens the semipurified diet as early as 6 days before inoculation did not affect the severity of E. tenella infection. No difference was observed in the intestinal or cecal pH or food passage time of noninfected chickens fed either the corn-soybean meal or the semipurified diet. No differences were found in the number of oocysts discharged between 2 and 9 hr after inoculation expressed as a percentage of the infective dose. The results of these studies show that a semipurified diet ameliorates infection of chickens with the cecal parasite E. tenella but not coccidial infections of the small intestine.


Comparison of Postoperative Outcomes Between Donation After Circulatory Death and Donation After Brain Death Liver Transplantation Using the Comprehensive Complication Index.
To test the total burden of complications in the early postoperative period after liver transplantation (LT) between donation after circulatory death (DCD) and donation after brain death (DBD) grafts with the novel Comprehensive Complication Index (CCI). LT is complex surgery and the increasing use of high-risk grafts is pressuring current postoperative outcomes. DCD grafts in particular are associated with ischemic-type biliary lesions (ITBL) with subsequent impaired graft survival rates. Retrospective single-center study of all LT since the start of DCD program (2001-2015). CCI (at hospital discharge and after 6 months) was the result of all complications weighted by their Clavien-Dindo grade. A multiple logistic regression model was used to identify factors associated with a complex postoperative course (CCI at 6 months >60). In total, 441 cases were included: 115 DCD and 326 DBD grafts. Median in-hospital CCI was comparable for both groups (DCD 38.2; DBD 36.7; P = 0.429). Six-month postoperative median CCI was significantly higher for DCD grafts (53.4 vs 47.2; P = 0.041). Moreover, more DCD recipients underwent retransplantation for ITBL in this period (4% vs 1%; P = 0.031). Logistic regression identified recipient BMI (P = 0.046), recipient warm ischemia time (odds ratio, OR, 1.032; 95% CI, 1.008-1.056; P = 0.008), and DCD graft (OR 3.913; 95% CI 1.200-12.767; P = 0.024) as risk factors for a CCI >60. This analysis shows a comparable complication rate during the index hospital stay for DCD and DBD LT, but the CCI increases significantly for DCD recipients in 6 months after transplantation. Reduction of biliary complications, especially ITBL, is needed to improve the outcomes for DCD grafts.


Anaerobic metazoans: no longer an oxymoron.
The sediments of a deep-sea hypersaline and sulfidic Mediterranean basin have yielded an unexpected discovery, the first multicellular animals living entirely without oxygen. Reported by Danovaro et al. in BMC Biology, these three new species of Loricifera add a new and remarkable dimension to anoxic ecosystems previously thought to support only unicellular life.


Reinfection and relapse in early Lyme disease.
To determine whether recurrent episodes of appropriately treated Lyme disease are caused by reinfection or relapse, we monitored pertinent clinical manifestations and serology of residents of an endemic site each year for 14 years. Of 253 episodes of early Lyme disease recorded among 213 residents, we observed 40 recurrent episodes. Virtually all included an erythema migrans (EM) rash that appeared at body sites that differed from those of the initial rash, no subjects produced detectable levels of specific antibody between sequential episodes, all episodes occurred a year or more after the initial EM episode, and all occurred during late spring and early summer. People experiencing recurrent episodes tended to have frequent contact with vector ticks. Prompt administration of standard antibiotic therapy for early Lyme disease reliably eliminates persistent infection and prevents relapse.


Alteration of Monoamine Receptor Activity and Glucose Metabolism in Pediatric Patients with Anticonvulsant-Induced Cognitive Impairment.
A landmark study from the Institute of Medicine reported that the assessment of cognitive difficulties in children with epilepsy is timely and imperative. Anticonvulsant-induced cognitive impairment could influence the quality of life more than seizure itself in patients. Although the monoaminergic system is involved in the regulation of cognitive process, its role in anticonvulsant-induced cognitive impairment remains unclear. Methods: To explore in vivo monoamine receptor binding activity in patients with anticonvulsant-induced cognitive impairment, each patient underwent PET imaging with both monoamine receptor binding agent 11C-N-methylspiperone and glucose metabolic agent 18F-FDG. Tests of intelligence quotient (IQ), including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ), were performed in each patient. Results: Compared with the patients with monotherapy, patients with polytherapy had significantly lower VIQ, PIQ, and FSIQ (P < 0.01 in each comparison), as well as significantly lower monoamine receptor activities detected in the caudate nucleus, prefrontal cortex, dorsal anterior cingulate cortex, and amygdale (P < 0.05 in each comparison). However, regarding the glucose metabolism, there was no significant difference found in patients with monotherapy or polytherapy (P > 0.05). Conclusion: Monoamine receptor PET imaging could be a promising in vivo imaging biomarker for mapping anticonvulsant-induced cognitive impairment.


Extracellular vesicles: Novel promising delivery systems for therapy of brain diseases.
Extracellular vesicles (EVs) are cell-derived membrane vesicles virtually secreted by all cells, including brain cells. EVs are a major term that includes apoptotic bodies, microvesicles and exosomes. The release of EVs has been recognized as an important modulator in cross-talking between neurons, astrocytes, microglia and oligodendrocytes, not only in central nervous system (CNS) physiology but also in neurodegenerative and neuroinflammatory disease states as well as in brain tumors, such as glioma. EVs are able to cross the blood brain barrier (BBB), spread to body fluids and reach distant tissues. This prominent spreading ability has suggested that EVs can be exploited into several different clinical applications ranging from biomarkers to therapeutic carriers. Exosomes, the well-studied group of EVs, have been emerging as a promising tool for therapeutic delivery strategies due to their intrinsic features, such as the stability, biocompatibility and stealth capacity when circulating in bloodstream, the ability to overcome natural barriers and inherent targeting properties. Over the last years, it became apparent that EVs can be loaded with specific cargoes directly in isolated EVs or by modulation of producer cells. In addition, the engineering of its membrane for targeting purposes is expected to allow generating carriers with unprecedented abilities for delivery in specific organs or tissues. Nevertheless, some challenges remain regarding the loading and targeting of EVs for which more research is necessary, and will be discussed in this review. Recently-emerged promising derivations are also discussed, such as exosome associated with adeno-associated virus (AAV) vectors (vexosomes), enveloped protein nanocages (EPNs) and exosome-mimetic nanovesicles. This article provides an updated review of this fast-progressing field of EVs and their role in brain diseases, particularly focusing in their therapeutic applications.


Mitochondria-Targetable Ratiometric Time-Gated Luminescence Probe for Carbon Monoxide Based on Lanthanide Complexes.
As a critical gasotransmitter, carbon monoxide (CO) has been demonstrated to be related with mitochondrial respiration, but the monitoring of CO in mitochondria remains a great challenge. In this work, a unique ratiometric time-gated luminescence (TGL) probe, Mito-NBTTA-Tb3+/Eu3+, that can specifically respond to mitochondrial CO has been developed. The probe was designed by incorporating a mitochondria-targeting moiety, triphenylphosphonium, into a CO-activatable terpyridine polyacid derivative, 4'-(4-nitrobenzyloxy-2,2':6',2''-terpyridine-6,6''-diyl) bis(methylenenitrilo) tetrakis(acetic acid), for coordinating to Eu3+ and Tb3+ ions to construct lanthanide complex-based probe for ratiometric TGL detection of CO. Upon reaction with CO, accompanied by the conversion of nitro group to amino group, a 1,6-rearrangement-elimination reaction occurs, which leads to the cleavage of 4-nitrobenzyl group from Mito-NBTTA-Tb3+/Eu3+, resulting in the significant increase of Tb3+ emission at 540 nm and moderate decrease of Eu3+ emission at 610 nm. After the reaction, the I540/ I610 ratio was found to be 48-fold enhanced. This feature allowed Mito-NBTTA-Tb3+/Eu3+ to be employed as a ratiometric TGL probe for CO detection with the I540/ I610 ratio as a signal. In addition, the probe showed outstanding mitochondria-localization characteristic, which enabled the probe to be successfully applied to imaging CO within mitochondria of living cells under TGL and ratiometric modes. The application of Mito-NBTTA-Tb3+/Eu3+ was demonstrated by the visualization and quantitative detection of exogenous and endogenous CO in living cells and mouse liver tissue slices, as well as in living Daphnia magna and mice. All of the results suggested the potential of Mito-NBTTA-Tb3+/Eu3+ for the quantitative monitoring of CO in vitro and in vivo.


Site-Specific Fat-1 Knock-In Enables Significant Decrease of n-6PUFAs/n-3PUFAs Ratio in Pigs.
The fat-1 gene from Caenorhabditis elegans encodes a fatty acid desaturase which was widely studied due to its beneficial function of converting n-6 polyunsaturated fatty acids (n-6PUFAs) to n-3 polyunsaturated fatty acids (n-3PUFAs). To date, many fat-1 transgenic animals have been generated to study disease pathogenesis or improve meat quality. However, all of them were generated using a random integration method with variable transgene expression levels and the introduction of selectable marker genes often raise biosafety concern. To this end, we aimed to generate marker-free fat-1 transgenic pigs in a site-specific manner. The Rosa26 locus, first found in mouse embryonic stem cells, has become one of the most common sites for inserting transgenes due to its safe and ubiquitous expression. In our study, the fat-1 gene was inserted into porcine Rosa 26 (pRosa26) locus via Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. The Southern blot analysis of our knock-in pigs indicated a single copy of the fat-1 gene at the pRosa26 locus. Furthermore, this single-copy fat-1 gene supported satisfactory expression in a variety of tissues in F1 generation pigs. Importantly, the gas chromatography analysis indicated that these fat-1 knock-in pigs exhibited a significant increase in the level of n-3PUFAs, leading to an obvious decrease in the n-6PUFAs/n-3PUFAs ratio from 9.36 to 2.12 (***P < 0.0001). Altogether, our fat-1 knock-in pigs hold great promise for improving the nutritional value of pork and serving as an animal model to investigate therapeutic effects of n-3PUFAs on various diseases.


Cyclodeviation in acquired vertical strabismus.
The prevalence and pattern of cyclodeviation can differentiate among superior oblique palsy, dysthyroid ophthalmopathy, myasthenia gravis, and skew deviation. Excyclodeviation was detected in 30 of 33 patients with superior oblique palsy, eight of 15 patients with dysthyroid ophthalmopathy, three of six patients with nondysthyroid restrictive ophthalmopathy, and one of 13 patients with myasthenia. No cyclodeviation was found in cases of skew. Incyclodeviation was found in two patients with dysthyroid ophthalmopathy, two with nondysthyroid restrictive ophthalmopathy, and three with myasthenia. The amount of cyclodeviation did not vary between head-tilt positions, but did vary between primary and eccentric gaze positions, usually in the same direction as the amount of hyperdeviation. The patient's awareness of the presence of cyclodeviation varied with the degree of cyclodeviation, being 100% (4/4) for 15 degrees, 86% (12/14) for 10 degrees, and only 55% (11/21) for 5 degrees.


EDTITRATE (Emergency Department Telemedicine Initiative to Rapidly Accommodate in Times of Emergency).
Objective Emergency Department (ED) patient volumes are unpredictable, which can result in service delays and patients leaving without care. We initiated a programme of emergency physician (EP) telepresence in the ED with the objectives of assessing feasibility, safety, patient and provider acceptance, and throughput time. Methods This was a prospective convenience study. Patients presenting to the ED during operation of the study who were planned for placement in the waiting room were considered for enrolment. A faculty EP conducted patient evaluations via telepresence with confirmatory evaluation by the onsite faculty EP prior to disposition. Patient care was either taken to completion by the telemedicine EP or initiated and handed off to the onsite team. Measures included patient demographics, triage class (ESI 1-5), throughput time and a single question satisfaction survey (rating 1-5, 5 most favourable) completed by patients, registered nurses and EPs. Patients were called within 3 days and the electronic health record reviewed at 7 days looking for unscheduled visits and adverse events. Results In total, 130 patients were enrolled. Mean triage class was 3.9 with a median throughput of 150 minutes (IQR = 116.5, 206). Non-telemedicine patients during the same time period with similar triage classes had a median throughput of 287 minutes (IQR = 199, 408). Mean satisfaction scores were: patient 4.91, nurse 4.75, onsite EP 4.47 and telemedicine EP 4.79. There was one potential misdiagnosis and no adverse events. Conclusion Patient evaluation by EP via telepresence is feasible, safe, readily accepted by patients and providers and associated with reduced throughput time.


Reconstruction of ancestral gene orders using probabilistic and gene encoding approaches.
Current tools used in the reconstruction of ancestral gene orders often fall into event-based and adjacency-based methods according to the principles they follow. Event-based methods such as GRAPPA are very accurate but with extremely high complexity, while more recent methods based on gene adjacencies such as InferCARsPro is relatively faster, but often produces an excessive number of chromosomes. This issue is mitigated by newer methods such as GapAdj, however it sacrifices a considerable portion of accuracy. We recently developed an adjacency-based method in the probabilistic framework called PMAG to infer ancestral gene orders. PMAG relies on calculating the conditional probabilities of gene adjacencies that are found in the leaf genomes using the Bayes' theorem. It uses a novel transition model which accounts for adjacency changes along the tree branches as well as a re-rooting procedure to prevent any information loss. In this paper, we improved PMAG with a new method to assemble gene adjacencies into valid gene orders, using an exact solver for traveling salesman problem (TSP) to maximize the overall conditional probabilities. We conducted a series of simulation experiments using a wide range of configurations. The first set of experiments was to verify the effectiveness of our strategy of using the better transition model and re-rooting the tree under the targeted ancestral genome. PMAG was then thoroughly compared in terms of three measurements with its four major competitors including InferCARsPro, GapAdj, GASTS and SCJ in order to assess their performances. According to the results, PMAG demonstrates superior performance in terms of adjacency, distance and assembly accuracies, and yet achieves comparable running time, even all TSP instances were solved exactly. PMAG is available for free at http://phylo.cse.sc.edu.


Static and Dynamic Water Motion-Induced Instability in Oxide Thin-Film Transistors and Its Suppression by Using Low-k Fluoropolymer Passivation.
Here, we report static and dynamic water motion-induced instability in indium-gallium-zinc-oxide (IGZO) thin-film transistors (TFTs) and its effective suppression with the use of a simple, solution-processed low-k (ε ∼ 1.9) fluoroplastic resin (FPR) passivation layer. The liquid-contact electrification effect, in which an undesirable drain current modulation is induced by a dynamic motion of a charged liquid such as water, can cause a significant instability in IGZO TFTs. It was found that by adopting a thin (∼44 nm) FPR passivation layer for IGZO TFTs, the current modulation induced by the water-contact electrification was greatly reduced in both off- and on-states of the device. In addition, the FPR-passivated IGZO TFTs exhibited an excellent stability to static water exposure (a threshold voltage shift of +0.8 V upon 3600 s of water soaking), which is attributed to the hydrophobicity of the FPR passivation layer. Here, we discuss the origin of the current instability caused by the liquid-contact electrification as well as various static and dynamic stability tests for IGZO TFTs. On the basis of our findings, we believe that the use of a thin, solution-processed FPR passivation layer is effective in suppressing the static and dynamic water motion-induced instabilities, which may enable the realization of high-performance and environment-stable oxide TFTs for emerging wearable and skin-like electronics.


The alga Bryothamnion seaforthii contains carbohydrates with antinociceptive activity.
Bryothamnion seaforthii, a red alga common to the Northeastern coast of Brazil, was used to prepare the protein fraction F0/60 by ammonium sulfate precipitation. The chromatography of F0/60 on DEAE-Sephadel column resulted in two lectin fractions, PI and PII, which have antinociceptive properties in rodents. We determined the antinociceptive activity of the PII fraction and of a carbohydrate-containing fraction (CF) in mice. The CF was prepared from the dried algae, after digestion with 100 mM sodium acetate, pH 6.0, containing 5 mM cysteine, EDTA and 0.4% papain, at 60 masculine C. A 10% cetylpyridinium chloride was added to the filtrate, and the precipitate was dissolved with 2 M NaCl:ethanol (100:15, v/v) followed by the carbohydrate precipitation with ethanol. The final precipitate, in acetone, was dried at 25 masculine C. The PII fraction markedly inhibited acetic acid-induced abdominal writhing after ip administration (control: 27.1 +/- 2.20; PII 0.1 mg/kg: 5.5 +/- 1.85; 1 mg/kg: 1.6 +/- 0.72 writhes/20 min) and after oral administration (control: 32.0 +/- 3.32; PII 0.1 mg/kg: 13.1 +/- 2.50; 1 mg/kg: 9.4 +/- 3.96 writhes/20 min). PII was also effective against both phases of pain induced by 1% formalin (control, ip: 48.2 +/- 2.40 and 27.7 +/- 2.56 s; PII: 1 mg/kg, ip: 34.3 +/- 5.13 and 5.6 +/- 2.14 s; control, po: 44.5 +/- 3.52 and 25.6 +/- 2.39 s; PII 5 mg/kg, po: 26.5 +/- 4.67 and 15.3 +/- 3.54 s for the 1st and 2nd phases, respectively) and in the hot-plate test. The CF (ip) also displayed significant antinociceptive properties in all tests but at higher doses (1 and 5 mg/kg, ip and po). Thus, CF at the dose of 5 mg/kg significantly inhibited writhes (ip: 7.1 +/- 2.47 and po: 14.5 +/- 2.40 writhes/20 min) as well as the 1st (po: 19.6 +/- 1.74 s) and 2nd (po: 7.1 +/- 2.24 s) phases of the formalin test compared to controls ip and po. The antinociceptive effects of both the PII and CF in the formalin and hot-plate tests were prevented at least partially by pretreatment with the opioid receptor antagonist naloxone (2 mg/kg, sc). Moreover, both fractions retained antinociceptive activity in the acetic acid-induced writhing test following heating, a procedure which abolished the hemagglutinating activity of the fraction, presumably due to lectins also present. Finally, both fractions also prolonged the barbiturate-induced sleeping time. These results indicate that carbohydrate molecules present in the PII (26.8% carbohydrate) and CF (21% of the alga dried weight) obtained from B. seaforthii display pronounced antinociceptive activity which is resistant to heat denaturation and is mediated by an opioid mechanism, as indicated by naloxone inhibition.


Visibility Equalizer Cutaway Visualization of Mesoscopic Biological Models.
In scientific illustrations and visualization, cutaway views are often employed as an effective technique for occlusion management in densely packed scenes. We propose a novel method for authoring cutaway illustrations of mesoscopic biological models. In contrast to the existing cutaway algorithms, we take advantage of the specific nature of the biological models. These models consist of thousands of instances with a comparably smaller number of different types. Our method constitutes a two stage process. In the first step, clipping objects are placed in the scene, creating a cutaway visualization of the model. During this process, a hierarchical list of stacked bars inform the user about the instance visibility distribution of each individual molecular type in the scene. In the second step, the visibility of each molecular type is fine-tuned through these bars, which at this point act as interactive visibility equalizers. An evaluation of our technique with domain experts confirmed that our equalizer-based approach for visibility specification was valuable and effective for both, scientific and educational purposes.


Fast Liquid Transfer between Surfaces: Breakup of Stretched Liquid Bridges.
In this work, a systematic experimental study was performed to understand the fast liquid transfer process between two surfaces. According to the value of the Reynolds number (Re), the fast transfer is divided into two different scenarios, one with negligible inertia effects (Re ≪ 1) and the other with significant inertia effects (Re > 1). For Re ≪ 1, the influences of the capillary number (Ca) and the dimensionless minimum separation (H(min)* = H(min)/V(1/3), where H(min) is the minimum separation between two surfaces and V is the volume of liquid) on the transfer ratio (α, the volume of liquid transferred to the acceptor surface over the total liquid volume) are discussed. On the basis of the roles of each physical parameter, an empirical equation is presented to predict the transfer ratio, α = f(Ca). This equation involves two coefficients which are affected only by the surface contact angles and H(min)* but not by the liquid viscosity or surface tension. When Re > 1, it is shown for the first time that the transfer ratio does not converge to 0.5 with the increase in the stretching speed.


Review, discussion, and summary of epidemiological studies.
This paper reviews and summarizes the epidemiological studies presented at the Symposium on the Health Effects of Acid Aerosols. Two studies of acute episodes examined different indicators of respiratory morbidity before, during, and after the January 1985 air pollution event in western Europe. In the U.K. no increase in respiratory morbidity, as reported by a group of general practitioners, was observed, but measured concentrations of air pollutants failed to substantiate the existence of an identifiable episode. In the Federal Republic of Germany, the air pollution episode was documented and was associated with a 10 to 25% increase in several indicators of respiratory and cardiovascular morbidity, but could not be attributed to acidic aerosols as such. In two further studies, investigators related day-to-day variations in air pollution with admissions to acute care hospitals in southern Ontario for respiratory disease over a 9-year period, and with daily mortality in London from 1963 to 1972. In the study of hospital admissions, significant correlations were observed with sulfate, ozone, and SO2 pollution, but the data were insufficient to isolate the separate or combined effects of these pollutants. In the London mortality analysis, the strongest correlations were observed for sulfuric acid levels of the prior day, but prefiltering of the mortality data may have dampened the true relationship, and age- and cause-specific analyses would have been desirable. Finally two reports on chronic effects of residence in high air pollution areas have thus far made little contribution to the evidence for an adverse effect of specific pollutants.


Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions.
Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.


Effect of pretreatment with hydrocortisone on insulin secretory response to catecholamines in isolated islets from rats fed with a high fat diet.
Islets isolated from rats fed with a high fat diet for 7 days were pretreated with hydrocortisone, and in the treated-islets the effect of glucose, epinephrine and dopamine on insulin secretion was examined. Glucose-stimulated insulin secretion in the untreated islets was not changed by the fat diet. Insulin secretion stimulated by hydrocortisone (10(-6)M) in the presence of 2.8 mM glucose was twice higher in the control diet group than in the fat diet group. Pretreatment of the islets with hydrocortisone did not affect glucose-stimulated insulin secretion in the control diet group but remarkably reduced that in the fat diet group. Although the fat diet attenuated the inhibitory effect of catecholamines on insulin secretory response to glucose, pretreatment of the islets with hydrocortisone caused to restore the effect of catecholamines, especially at a low concentration. These results indicate that the combined action of a high fat diet and glucocorticoids may induce modification of alpha-adrenergic receptors in the B-cell.


Proximal interphalangeal joint sprains.
We report the first series of proximal interphalangeal joint sprains and reviewed 50 sprains in 48 patients. The majority of patients were males injured at work. The radial collateral ligament was injured about twice as often as the ulnar ligaments. The little finger was injured significantly less than the others. Proximal interphalangeal joint sprains can be diagnosed by the following: pain localized to the injured ligament, swelling greatest at the site of the injured ligament, tenderness greatest at the site of the injured ligament, pain at the site of the injured ligament during lateral stress, and/or mild lateral instability on radiographs or physical examination during stress testing. All patients required several different splints for treatment; in decreasing frequency, we used immobilizing, coupling, dynamic proximal interphalangeal flexion, dynamic proximal interphalangeal and distal interphalangeal flexion, and dynamic proximal interphalangeal extension splints. The mean active range of motion before treatment was 70 degrees and after treatment was 95 degrees. Significantly more patients had loss of full extension than had loss of full flexion. Forty-six percent of the patients had no pain after treatment, 46 percent had mild pain, 8 percent had moderate pain, and none had severe pain. Patients treated within 4 weeks of their injury (group 1) gained significantly greater range of motion (35 degrees) than those treated between 5 and 14 weeks after their injury (10 degrees) (group 2).(ABSTRACT TRUNCATED AT 250 WORDS)


[Benzodiazepines to people with substance abuse problems?].
Benzodiazepines are probably prescribed too often to people with substance abuse problems. The drugs often alleviate symptoms effectively on a short term, but pharmacodynamic interactions and development of dependence cause problems. Indistinct, but important side effects might be overlooked or misunderstood. Evidence-based practice should replace prescriptions based on unclear indications.


Predominant subcortical accumulation of 18F-flortaucipir binding in behavioral variant frontotemporal dementia.
Behavioral variant frontotemporal dementia (bvFTD) is the most common form of frontotemporal dementia, and tau pathology can be found in 40%-50% of bvFTD patients. In this study, we sought to investigate 18F-flortaucipir-binding patterns and their correlates in clinically diagnosed bvFTD patients by comparing with results for Alzheimer's disease (AD) patients. We enrolled 20 bvFTD, 20 AD, and 20 age-matched healthy subjects who underwent neuropsychological tests, magnetic resonance imaging, and tau positron emission tomography scans with 18F-flortaucipir. Regional standardized uptake value ratios for the cerebral cortex and underlying white matter were compared between the 2 groups. The bvFTD patients showed increased 18F-flortaucipir binding in the putamen and globus pallidus when compared to the healthy controls. In addition, bvFTD was associated with increased binding in the white matter regions underlying the frontal, anterior cingulate, and insula cortices. The bvFTD patients may exhibit predominantly subcortical 18F-flortaucipir-binding pattern that is distinct from the patterns seen in AD patients. We hypothesize that the clinical characteristics of bvFTD patients may be attributable to the dysfunctional frontal-subcortical networks. However, concerns remain regarding unknown "off-target" binding in the white matter and the basal ganglia.


Ultrasonic cavitation erosion of 316L steel weld joint in liquid Pb-Bi eutectic alloy at 550°C.
Liquid lead-bismuth eutectic alloy (LBE) is applied in the Accelerator Driven transmutation System (ADS) as the high-power spallation neutron targets and coolant. A 19.2kHz ultrasonic device was deployed in liquid LBE at 550°C to induce short and long period cavitation erosion damage on the surface of weld joint, SEM and Atomic force microscopy (AFM) were used to map out the surface properties, and Energy Dispersive Spectrometer (EDS) was applied to the qualitative and quantitative analysis of elements in the micro region of the surface. The erosion mechanism for how the cavitation erosion evolved by studying the element changes, their morphology evolution, the surface hardness and the roughness evolution, was proposed. The results showed that the pits, caters and cracks appeared gradually on the erode surface after a period of cavitation. The surface roughness increased along with exposure time. Work hardening by the bubbles impact in the incubation stage strengthened the cavitation resistance efficiently. The dissolution and oxidation corrosion and cavitation erosion that simultaneously happened in liquid LBE accelerated corrosion-erosion process, and these two processes combined to cause more serious damage on the material surface. Contrast to the performance of weld metal, base metal exhibited a much better cavitation resistance.


Role of Glucagon-Like Peptide-1 Receptor Agonists on the Weight Loss of Individuals With Type 2 Diabetes: A Systematic Review.
Obesity is highly associated with type 2 diabetes mellitus (T2DM), both of which can be simultaneously treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). There are many antidiabetic drugs that can be used for the treatment of T2DM. These drugs have vast modes of action and therapeutic uses. However, they also have different side effects. Some of these side effects, such as weight changes, are sometimes desirable while others are not. This review examines the literature on how GLP-1RA affects both blood glucose and body weight in patients with T2DM and obesity. In this context, GLP-1RA plays a critical part by controlling not only the blood glucose level but also weight. We followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and searched for articles from PubMed and Google Scholar databases that reported on T2DM, obesity, and GLP-1RA functions. We selected 13 articles that showed the benefits of GLP-1RA in managing both T2DM and obesity. Our review suggests that GLP-1RA is an innovative therapy that can address both conditions simultaneously.


Development of stereotactic radiosurgery using carbon beams (carbon-knife).
The aim of this research is to develop a stereotactic-radiosurgery (SRS) technique using carbon beams to treat small intracranial lesions; we call this device the carbon knife. A 2D-scanning method is adapted to broaden a pencil beam to an appropriate size for an irradiation field. A Mitsubishi slow extraction using third order resonance through a rf acceleration system stabilized by a feed-forward scanning beam using steering magnets with a 290 MeV/u initial beam energy was used for this purpose. Ridge filters for spread-out Bragg peaks (SOBPs) with widths of 5 mm, 7.5 mm, and 10 mm were designed to include fluence-attenuation effects. The collimator, which defines field shape, was used to reduce the lateral penumbra. The lateral-penumbra width at the SOBP region was less than 2 mm for the carbon knife. The penumbras behaved almost the same when changing the air gap, but on the other hand, increasing the range-shifter thickness mostly broadened the lateral penumbra. The physical-dose rates were approximate 6 Gy s-1 and 4.5 Gy s-1 for the 10 × 10 mm2 and 5 × 5 mm2 collimators, respectively.


Congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media. Further evidence that interruption of early embryonic blood supply may result in Adams-Oliver (plus) syndrome.
In this report we describe a male patient with the interesting combination of a large congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media. Follow-up data from birth up to the age of 18 years revealed positive evolution with low to normal intelligence. The findings in the present patient, i.e. an Adams-Oliver syndrome associated with a severe neurological deficit, are best explained as resulting from interruption of the early embryonic blood supply.


Magnetic nanoparticles-based therapy for malignant mesothelioma.
This work was aimed to analyze the versatility of the chick embryo chorioallantoic membrane (CAM) as in vivo model for the study of the malignant pleural mesothelioma (MPM) and the therapeutic potential of Fe3O4÷salicylic acid magnetic nanoparticles (SaMNPs) on MPM cells. The antitumor effects of SaMNPs were studied by in vitro and in vivo tests on CARM-L12 TG3 rat malignant mesothelioma cells and human MPM xenografts implanted on CAMs. In order to assess the human MPM xenograft growth characteristics, calretinin, HBME-1 (Hector Battifora mesothelial epitope-1), and cytokeratins immunohistochemical stainings were performed. The human MPM xenografts continue to develop on the CAMs and xenograft MPM cells showed highly metastatic features and a particular pattern of metastasis. The SaMNPs had a specific uptake by the MPM cells and an antiproliferative effect at therapeutic doses greater than 100 μg÷mL. The results confirmed the possibility to use the CAM as in vivo model to study the biology of MPM and to evaluate the antitumor potential of new therapeutic agents. They highlighted a strong antitumor effect of the SaMNPs on the rat and human MPM cells and open new perspectives in the treatment of MPM.


Mutations in CFTR gene and clinical correlation in Argentine patients with congenital bilateral absence of the vas deferens.
Congenital bilateral absence of the vas deferens (CBAVD) is a form of male infertility in which mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been identified. Here we identify different mutations of CFTR and the poly-T variant of intron 8 (IVS8) in Argentine patients and analyze sweat test values and clinical characteristic related to Cystic Fibrosis (CF). For counseling purposes the two most frequent mutations in Argentine CF population: deltaF508 and G542X were screened in wives. In all cases, it was possible to reduce the risk of CF/CBAVD descendants in these couples because none of the mutation were found in the 36 samples. Eight patients (23%) showed abnormal chloride values (> 60 mmol/l). A second group of 6 patients (18%) had borderline values of sweat chloride (40-59 mmol/l). We defined another group with 6 patients (18%), with normal sweat chloride levels (30-39 mmo/l) and a fourth group of 14 (41%) patients with sweat chloride below 30 mmol/l. deltaF508, the most frequent CF mutation in the Argentine population, was found on 15 of the 72 chromosomes (21%), R117H mutation was detected on 2 of 62 chromosomes (3%). Only one R347P allele was found on 28 chromosomes analyzed (2%). On a sample of 27 patients, IVS8 analysis showed a frequency of 6/56 chromosomes (11%) of 5T allele. Even though these findings present an improvement in the detection of mutations related to clinical correlations in Argentine CBAVD population, the search for other common and uncommon mutations should be continued.


(-)-Deprenyl alters the time course of death of axotomized facial motoneurons and the hypertrophy of neighboring astrocytes in immature rats.
(-)-Deprenyl previously was shown to increase the survival of rat facial motoneurons (FMns) after a loss of muscle-derived trophic support caused by axotomy at Postnatal Day 14 (P14) and to increase reactive astrogliosis after traumatic damage to the adult rat striatum. We estimated reactive astrogliosis in facial nuclei at 1, 3, 7, 14, and 21 days after transection of the facial nerve at P14 by two methods: first, by measuring the relative optical density (OD) of GFAP immunoreaction (GFAP-OD) in the facial nuclei and second by determining the relative area of GFAP immunoreactivity (GFAP-AREA) in the same nuclei. Both measures were taken for multiple immunoreacted sections through the length of each facial nuclei by using a control half section at the same brain stem level taken from an unlesioned, age-matched animal. The experimental and control facial nuclear half sections were coimmunoreacted using the "glued" half brain stem method. The facial nerve transections served to axotomize all of the FMns in the ipsilateral facial nuclei. The numbers of surviving FMns were examined at the same time points as above using counts of Nissl-stained somata from serial sections taken through each facial nucleus. We found that FMn loss occurred rapidly after axotomy in saline-treated animals and could be best fitted with a decaying exponential relationship (time constant 2.7 days). In the saline-treated animals, the FMn loss plateaued between 7 and 14 days at 74.8%, and 47% of the FMns were found to be lost within 3 days. Increases in the facial nuclear GFAP-OD values and GFAP-AREA values were evident as early as 1 day following axotomy (2.5 and 3.3 times normal, respectively) and reached maximal levels by 7 days (5.7 and 37.6 times normal, respectively). The administration of (-)-deprenyl slowed the loss of the FMns by 24-48 h (time constant 3.9 days) and increased the number of surviving FMns at 21 days by 2.1 times. Treatment with (-)-deprenyl was found to significantly increase GFAP-OD and GFAP-AREA at Day 1 by 71 and 32%, respectively, and at Day 3 by 22 and 27%, respectively. In contrast, it decreased GFAP-OD and GFAP-AREA by 42 and 19%, respectively, at Day 7, and by 20 and 12%, respectively at Day 21. Accordingly, as estimated by both measures, the drug increases reactive astrogliosis in the facial nucleus during the first 3 days after facial nerve transection and decreases the gliosis thereafter.(ABSTRACT TRUNCATED AT 400 WORDS)


Encephalocraniocutaneous lipomatosis: A case report with review of literature.
Encephalocraniocutaneous lipomatosis (ECCL) or Haberland syndrome is an uncommon sporadic neurocutaneous syndrome of unknown origin. The rarity and common ignorance of the condition often makes diagnosis difficult. The hallmark of this syndrome is the triad of skin, ocular and central nervous system (CNS) involvement and includes a long list of combination of conditions. Herein we report a case of a 5-month-old male child who presented to our centre with complaint of seizure. The patient had various cutaneous and ocular stigmatas of the disease in the form of patchy alopecia of the scalp, right-sided limbal dermoid and a nodular skin tag near the lateral canthus of the right eye. MRI of the brain was conducted which revealed intracranial lipoma and arachnoid cyst. The constellation of signs and symptoms along with the skin, ocular and CNS findings led to the diagnosis of ECCL.


Release of snRNP and RNA from transcription sites in adenovirus-infected cells.
Small nuclear ribonucleoprotein (snRNP) splicing factors colocalize with nascent RNA in the nucleus of adenovirus-infected cells in a pattern that appears as a series of rings surrounding viral replication centers. We have studied the release of snRNP and RNA from transcription sites following transcription inhibition by actinomycin D. SnRNP, poly(A) RNA, and viral RNA were no longer detected in the ring pattern following transcription inhibition and were instead detected in nuclear clusters. Release of snRNP from transcription sites was blocked when transcription was inhibited at 4 degrees C, suggesting that release requires temperature-dependent processes. Release of snRNP was also inhibited when transcription was blocked in the presence of 9-beta-D-arabinofuranosyladenine, to inhibit 3'-end cleavage and polyadenylation, or staurosporine, to inhibit kinases. By contrast, release of snRNP was not inhibited when transcription was blocked in the presence of cordycepin, to inhibit RNA polyadenylation without affecting 3'-end cleavage, or okadaic acid, to inhibit phosphatase activity. Our results suggest that temperature-dependent processes involved in the release of splicing factors from transcription sites could include 3'-end cleavage of pre-mRNA and phosphorylation events inhibited by stauropsorine.


Influence of overstimulation on temporary threshold shift and the onset of aural overload.
This investigation sought to examine the sensitivity of pure tone thresholds and the onset of aural overload to the fatiguing effects of broad band noise. Noise levels ranging from 35 to 110 dB SPL were presented to 8 normal hearers. Post-exposure pure tone thresholds were determined for octave frequencies 500-4000 Hz while aural overload thresholds were obtained for the fundamental frequencies of 500 and 2000 Hz. Aural overload thresholds were found to decline following exposure levels insufficient to produce measurable TTS. This was particularly evident for low-frequency stimuli (below 2000 Hz). Results suggested that the aural overload test may be a more effective indication of cochlear damage than is the traditional temporary threshold shift procedure. These findings are discussed in terms of the "injured hair cell" hypothesis proffered by Wever & Lawrence (1955).


Endolymphatic sac tumors in von Hippel-Lindau disease: report of three cases.
To illustrate the diagnostic and pathophysiologic issues of endolymphatic sac tumors (ELSTs) and its clinical association with von Hippel-Lindau (VHL) disease and to demonstrate the interest of genetic testing in such cases. Retrospective analysis of 3 cases of ELST with VHL in 3 different clinical and prognostic situations. The first case was diagnosed on the concomitant finding of a central nervous system lesion. The familial genetic testing revealed the presence of the VHL mutation in an asymptomatic daughter, which justified regular follow-up. In the second case of known VHL syndromic disease, the pathophysiologic role of the endolymphatic sac was questioned, with vertigo as the initial, unique symptom of ELST. In the third case, a giant hypervascularized ELST, initially diagnosed as jugular paraganglioma, was the unique manifestation of VHL disease. The young age of the patient could explain the absence of other tumors. Diagnosis of ELSTs may be difficult especially when the original site of the lesion cannot be clearly identified. Such tumors may be revealed or may develop with VHL disease. On presentation of a lytic, vascularized tumor of the posterior face of the petrous bone, clinicians should systematically search for other manifestations of VHL disease and propose a VHL genetic testing for patients, and relatives in case of a positive test, to detect early asymptomatic other tumors. The type of VHL mutation might predict the aggressiveness.


Draft Genome Sequence of the blaOXA-436- and blaNDM-1-Harboring Shewanella putrefaciens SA70 Isolate.
We sequenced a carbapenem-resistant Shewanella putrefaciens isolate cultured from the sink handle of a Pakistan hospital room. Assembly annotation indicates that the isolate has a chromosomal blaOXA-436 carbapenemase and a plasmid-borne blaNDM-1 gene. To our knowledge, this is the first report of a Shewanella species harboring blaNDM.


Parallels in Structural Chemistry between the Molecular and Metallic Realms Revealed by Complex Intermetallic Phases.
The structural diversity of intermetallic phases poses a great challenge to chemical theory and materials design. In this Account, two examples are used to illustrate how a focus on the most complex of these structures (and their relationships to simpler ones) can reveal how chemical principles underlie structure for broad families of compounds. First, we show how experimental investigations into the Fe-Al-Si system, inspired by host-guest like features in the structure of Fe25Al78Si20, led to a theoretical approach to deriving isolobal analogies between molecular and intermetallic compounds and a more general electron counting rule. Specifically, the Fe8Al17.6Si7.4 compound obtained in these syntheses was traced to a fragmentation of the fluorite-type structure (as adopted by NiSi2), driven by the maintenance of 18-electron configurations on the transition metal centers. The desire to quickly generalize these conclusions to a broader range of phases motivated the formulation of the reversed approximation Molecular Orbital (raMO) approach. The application of raMO to a diverse series of compounds allowed us recognize the prevalence of electron pair sharing in multicenter functions isolobal to classical covalent bonds and to propose the 18 - n electron rule for transition metal-main group (T-E) intermetallic compounds. These approaches provided a framework for understanding the 14-electron rule of the Nowotny Chimney Ladder phases, a temperature-driven phase transition in GdCoSi2, and the bcc-structure of group VI transition metals. In the second story, we recount the development of the chemical pressure approach to analyzing atomic size and packing effects in intermetallic structures. We begin with how the stability of the Yb2Ag7-type structure of Ca2Ag7 over the more common CaCu5 type highlights the pressing need for approaches to assessing the role of atomic size in crystal structures, and inspired the development of the DFT-Chemical Pressure (CP) method. Examples of structural phenomena elucidated by this approach are then given, including the Y/Co2 dumbbell substitution in the Th2Zn17-type phase Y2Co17, and local icosahedral order in the Tsai-type quasicrystal approximant CaCd6. We next discuss how deriving relationships between the CP features of a structure and its phonon modes provided a way of both validating the method and visualizing how local arrangements can give rise to soft vibrational modes. The themes of structural mechanisms for CP relief and soft atomic motions merge in the discovery and elucidation of the incommensurately modulated phase CaPd5. In the conclusion of this Account, we propose combining raMO and CP methods for focused predictions of structural phenomena.