Use of geostatistics to determine the spatial distribution and infestation rate of leaf-cutting ant nests (Hymenoptera: Formicidae) in eucalyptus plantations.
One of the fundamental steps in pest sampling is the assessment of the population distribution in the field. Several studies have investigated the distribution and appropriate sampling methods for leaf-cutting ants; however, more reliable methods are still required, such as those that use geostatistics. The objective of this study was to determine the spatial distribution and infestation rate of leaf-cutting ant nests in eucalyptus plantations by using geostatistics. The study was carried out in 2008 in two eucalyptus stands in Paraopeba, Minas Gerais, Brazil. All of the nests in the studied area were located and used for the generation of GIS maps, and the spatial pattern of distribution was determined considering the number and size of nests. Each analysis and map was made using the R statistics program and the geoR package. The nest spatial distribution in a savanna area of Minas Gerais was clustered to a certain extent. The models generated allowed the production of kriging maps of areas infested with leaf-cutting ants, where chemical intervention would be necessary, reducing the control costs, impact on humans, and the environment.


Effects of particulate matter exposure on multiple sclerosis hospital admission in Lombardy region, Italy.
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system, characterized by recurrent relapses of inflammation that cause mild to severe disability. Exposure to airborne particulate matter (PM) has been associated with acute increases in systemic inflammatory responses and neuroinflammation. In the present study, we hypothesize that exposure to PM<10μm in diameter (PM10) might increase the occurrence of MS-related hospitalizations. We obtained daily concentrations of PM10 from 53 monitoring sites covering the study area and we identified 8287 MS-related hospitalization through hospital admission-discharge records of the Lombardy region, Italy, between 2001 and 2009. We used a Poisson regression analysis to investigate the association between exposure to PM10 and risk of hospitalization. A higher RR of hospital admission for MS relapse was associated with exposure to PM10 at different time intervals. The maximum effect of PM10 on MS hospitalization was found for exposure between days 0 and 7: Hospital admission for MS increased 42% (95%CI 1.39-1.45) on the days preceded by one week with PM10 levels in the highest quartile. The p-value for trend across quartiles was<0.001. These data support the hypothesis that air pollution may have a role in determining MS occurrence and relapses. Our findings could open new avenues for determining the pathogenic mechanisms of MS and potentially be applied to other autoimmune diseases.


Targeted Analysis of Protein Phosphorylation by 2D Electrophoresis.
Two-dimensional (2D) gel electrophoresis combines isoelectric focusing in the first and SDS polyacrylamide gel electrophoresis in the second dimension to separate complex mixtures of proteins with unequalled resolution and sensitivity. It is well suited for the analysis of posttranslational protein modifications as most of them affect the isoelectric point and, therefore, the focusing behavior of the protein in the first dimension. It is particularly useful for low-abundance proteins, as it provides a first indication of PTMs, before establishing methods for protein isolation. For targeted proteomics of more abundant proteins, 2D electrophoresis itself may be the method of choice for the isolation of posttranslationally modified isoforms of the protein of interest for mass spectrometric analyses. Protein phosphorylation can be detected by use of phospho-specific stains or antibodies, or by comparing spot patterns of a protein sample before and after phosphatase treatment. Here we describe a simple method, combining 2D gel electrophoresis and western blot analysis with dephosphorylation by λ-phosphatase to analyze the phosphorylation status of oxophytodienoic acid reductase 3 in protein extracts from different organs of tomato and Arabidopsis plants.


Protection of dopaminergic nigrostriatal afferents by GDNF delivered by microspheres in a rodent model of Parkinson's disease.
The use of glial cell line-derived neurotrophic factor (GDNF) appears to be a promising strategy to promote survival and function of the nigrostriatal dopaminergic pathway damaged in Parkinson's disease (PD). However, effective intracerebral administration is required for optimal therapeutic benefit and tools to evaluate such therapies must be developed. A rodent model of PD was therefore developed using striatal injection of 6-hydroxydopamine (6-OHDA) with simultaneous implantation of GDNF-delivering microspheres. The effects of GDNF released from microspheres were assessed by classical methods such as amphetamine-induced rotating behavior and tyrosine hydroxylase (TH) immunoreactivity, as well as by quantitative autoradiography using PE2I, a dopamine transporter (DAT) radiotracer, which is also suitable for SPET imaging in humans. 6-OHDA-lesioned animals that received microspheres without GDNF were used as controls. During the first 3 weeks after simultaneous lesion and implantation, the amphetamine-induced rotating behavior of GDNF-treated rats was improved compared to controls and an increase in TH expression (+26%) was measured in the striatum 6 weeks after lesion. In accordance with these results, an increase in striatal PE2I-labeled DAT density was obtained (+17%) after 3 and 6 weeks of treatment. In conclusion, this study demonstrates the neuroprotective action of GDNF delivered by microspheres and suggests that PE2I may be an appropriate radiotracer for use in SPET scintigraphy to follow up treatment of PD in humans.


Detection of influenza A viruses with a portable real-time PCR instrument.
Timely identification of respiratory pathogens is essential for appropriate patient care and cohorting. In order to do rapid identification-technology near the patient we utilized the field-deployable RAZOR EX-thermocycler with a reverse transcription real-time PCR assay that detects all subtypes of influenza A virus. In addition, we developed a RT PCR assay for specific detection of influenza A(H1N1)pdm09 virus. These assays amplified segments of the matrix (M)- and the hemagglutinin (HA)-gene, respectively. Detection limits of the M-gene and the influenza A(H1N1)pdm09-specific HA-gene assays were 0.15 PFU and 8.8 PFU per reaction, respectively. With 18 influenza A viruses of different subtypes and influenza B, C, and 7 other respiratory viruses the RAZOR EX and standard real-time PCR assay results were in total agreement. From 104 clinical samples identical results were obtained by both PCR methods. Additional 21 clinical samples were tested under field conditions with the RAZOR EX instrument. Results were achieved in 90 min, including 45 min for sample preparation and they were in complete agreement with those obtained by standard real-time PCR under laboratory conditions. These methods enable highly sensitive and rapid on-site diagnostics to reliably identify patients infected with influenza A, including the influenza A(H1N1)pdm09-virus.


Plating of fractures of the middle third of the clavicle.
Twenty mid-clavicular fractures are reported which required plate fixation. This technique gave relief from pain within 12 hours and resulted in bony union in every case. The indications for this operation are described.


[The use of vasopressin during portal bypass (author's transl)].
Vasopressin was infused intra-arterially or intravenously during 12 portal bypass operations. In comparison with a control group (without vasopressin), there was a very significant reduction in blood loss and portal pressure, and a moderate increase in arterial blood pressure.


The plasma membrane-bound phospholipase Ddelta enhances freezing tolerance in Arabidopsis thaliana.
Freezing injury is a major environmental limitation on the productivity and geographical distribution of plants. Here we show that freezing tolerance can be manipulated in Arabidopsis thaliana by genetic alteration of the gene encoding phospholipase Ddelta (PLDdelta), which is involved in membrane lipid hydrolysis and cell signaling. Genetic knockout of the plasma membrane-associated PLDdelta rendered A. thaliana plants more sensitive to freezing, whereas overexpression of PLDdelta increased freezing tolerance. Lipid profiling revealed that PLDdelta contributed approximately 20% of the phosphatidic acid produced in wild-type plants during freezing, and overexpression of PLDdelta increased the production of phosphatidic acid species. The PLDdelta alterations did not affect the expression of the cold-regulated genes COR47 or COR78 or alter cold-induced increases in proline or soluble sugars, suggesting that the PLD pathway is a unique determinant of the response to freezing and may present opportunities for improving plant freezing tolerance.


Nanocoatings: Universal antiviral surface solution against COVID-19.
In the current scenario, there is critical global demand for the protection of daily handling surfaces from the viral contamination to limit the spread of COVID-19 infection. The nanotechnologists and material scientists offer sustainable solutions to develop antiviral surface coatings for various substrates including fabrics, plastics, metal, wood, food stuffs etc. to face current pandemic period. They create or propose antiviral surfaces by coating them with nanomaterials which interact with the spike protein of SARS-CoV-2 to inhibit the viral entry to the host cell. Such nanomaterials involve metal/metal oxide nanoparticles, hierarchical metal/metal oxide nanostructures, electrospun polymer nanofibers, graphene nanosheets, chitosan nanoparticles, curcumin nanoparticles, etched nanostructures etc. The antiviral mechanism involves the repletion (depletion) of the spike glycoprotein that anchors to surfaces by the nanocoating and makes the spike glycoprotein and viral nucleotides inactive. The nature of interaction between the nanomaterial and virus depends on the type nanostructure coating over the surface. It was found that functional coating materials can be developed using nanomaterials as their polymer nanocomposites. The various aspects of antiviral nanocoatings including the mechanism of interaction with the Corona Virus, the different type of nanocoatings developed for various substrates, future research areas, new opportunities and challenges are reviewed in this article.


"On-off" ratiometric fluorescent detection of Hg2+ based on N-doped carbon dots-rhodamine B@TAPT-DHTA-COF.
Covalent-organic frameworks (COFs) are new porous crystalline materials owning outstanding stability, adsorbability and hypotoxicity. The assembly of fluorescence probes into porous COF provides a good method for ratiometric fluorescence detection avoiding the toxic effects of fluorescence probes to the samples. Herein, a two-dimensional COF (TAPT-DHTA-COF) was employed as a host to encapsulate N-doped carbon dots (NCDs) and Rhodamine B (RhB) (NCDs-RhB@COF). NCDs and RhB were uniformly assembled into the pores of TAPT-DHTA- COF based on the hydrogen bond. The as-prepared NCDs-RhB@COF nanocomposites exhibited blue emission of NCDs at 440 nm and red emission of RhB at 570 nm at excitation of 340 nm. After the addition of Hg2+, the blue emission became weaker while the red emission was enhanced due to the strong coordination between NCDs-RhB@COF and Hg2+. This "on-off" fluorescence probe was applied in detection of trace Hg2+ with linear range of 0.048-10 μM and detection limit of 15.9 nM together with appropriate selectivity, acceptable sensitivity and stability. The work shreds some light for COF as platform to construct ratiometric fluorescent sensor for industrial and biological application.


Transjugular Intrahepatic Portosystemic Shunt Flow Reduction with Adjustable Polytetrafluoroethylene-Covered Balloon-Expandable Stents Using the "Sheath Control" Technique.
A complication of transjugular intrahepatic portosystemic shunts (TIPS) placement is refractory portosystemic encephalopathy (PSE) often requiring TIPS reduction. We report the results of a "sheath control technique" utilizing constraining sheaths during deployment of polytetrafluoroethylene (PTFE)-covered balloon-expandable stents, minimizing stent migration, and providing additional procedural control. TIPS reduction was performed in 10 consecutive patients for PSE using Atrium iCast covered stents (Atrium Maquet Getinge Group, Germany). Within the indwelling TIPS stent, a 9 mm × 59 mm iCast stent was deployed with 2 cm exposed from the sheath's distal end and the majority of the stent within the sheath to create the distal hourglass shape. During balloon retraction, the stent was buttressed by the sheath. The proximal portion of the stent was angioplastied to complete the hourglass configuration, and the central portion of the stent was dilated to 5 mm. Demographics, pre- and post-procedure laboratory values, and outcomes were recorded. Ten patients underwent TIPS reduction with 100 % technical success. There was no stent migration during stent deployment. All patients experienced initial improvement of encephalopathy. One patient ultimately required complete TIPS occlusion for refractory PSE, and another developed TIPS occlusion 36 days post-procedure. There was no significant trend toward change in patients' MELD scores immediately post-procedure or at 30 days (p = 0.46, p = 0.47, respectively). TIPS reduction using Atrium iCast PTFE balloon-expandable stents using the "sheath control technique" is safe and effective, and minimizes the risk of stent migration.


How healthy are Dutch general practitioners? Self-reported (mental) health among Dutch general practitioners.
To investigate the level of burnout and health status of male and female Dutch general practitioners (GPs), and to compare this with former samples of GPs and with the Dutch general population. A postal survey of 350 male and 350 female practising GPs in the Netherlands. Although levels of emotional exhaustion of Dutch GPs were lower than those of national samples of GPs in the 1990s, the prevalence of burnout was still almost twice that of the general population. In contradiction with this, GPs reported better general health and fewer diseases than their fellow countrymen. Another remarkable finding was that female GPs were as healthy as their male colleagues, while in the general population, males report better health than females. The positive self-reported health status of general practitioners might reflect the high standards of the medical profession, which make physicians reluctant to show their own vulnerability. This might result in fewer, but more serious cases of (mental) illness among GPs as compared to the general population.


Effect of amphotericin B on hepatic cytochrome P-450 and glucose-6-phosphatase in the rat.
The effect of amphotericin B on hepatic microsomal cytochrome P-450 (P-450) concentration was measured in vitro, in vivo and ex vivo in the rat. In vitro, both amphotericin B (0-500 micrograms/ml) and its vehicle, sodium deoxycholate (0-410 micrograms/ml), caused similar dose-dependent decreases of P-450 concentrations and glucose-6-phosphatase activity. Intravenous amphotericin B (3 mg/kg) given daily for 3 days decreased antipyrine clearance from control values of 1.24 +/- 0.24 ml/min to 0.67 +/- 0.12 ml/min (p less than 0.001); whereas antipyrine clearance was unchanged by sodium deoxycholate. The P-450 concentration on the third day was reduced from 0.74 +/- 0.14 nmol/mg protein in control rats to 0.33 +/- 0.09 nmol/mg protein in rats treated with amphotericin B (p less than 0.001). Sodium deoxycholate had no effect on P-450 concentration. In contrast, amphotericin B had no effect on either antipyrine clearance or P-450 concentration following enzyme induction by phenobarbital. Amphotericin B had no effect on microsomal glucose-6-phosphatase activity in vivo. Neither amphotericin B nor sodium deoxycholate induced lipid peroxidation, measured as malondialdehyde production. These results show that amphotericin B decreases hepatic cytochrome P-450 content and function in the rat. These effects can not be observed in the enzyme induced state. Amphotericin B has no effect on glucose-6-phosphatase in vivo, the key enzyme of the gluconeogenesis, indicating selective effects on hepatic microsomal function.


Urban-Rural Disparities for COVID-19: Evidence from 10 Countries and Areas in the Western Pacific.
Limited evidence on the effectiveness of various types of social distancing measures, from voluntary physical distancing to a community-wide quarantine, exists for the Western Pacific Region (WPR) which has large urban and rural populations. We estimated the time-varying reproduction number (R t ) in a Bayesian framework using district-level mobility data provided by Facebook (i) to assess how various social distancing policies have contributed to the reduction in transmissibility of SARS-COV-2 and (ii) to examine within-country variations in behavioural responses, quantified by reductions in mobility, for urban and rural areas. Social distancing measures were largely effective in reducing transmissibility, with R t estimates decreased to around the threshold of 1. Within-country analysis showed substantial variation in public compliance across regions. Reductions in mobility were significantly lower in rural and remote areas than in urban areas and metropolitan cities (p < 0.001) which had the same scale of social distancing orders in place. Our findings provide empirical evidence that public compliance and consequent intervention effectiveness differ between urban and rural areas in the WPR. Further work is required to ascertain the factors affecting these differing behavioural responses, which can assist in policy-making efforts and increase public compliance in rural areas where populations are older and have poorer access to healthcare.


Epididymal cystadenomas and epithelial tumourlets: effects of VHL deficiency on the human epididymis.
Although epididymal cystadenomas (ECAs) are among the most frequent VHL disease-associated tumours, fundamental questions about their pathogenesis have remained unanswered. Classification of ECAs is controversial, and the cell of origin is unknown. It is also unknown whether ECAs-like other VHL disease-associated tumours-arise as a result of VHL gene inactivation, and whether ECAs exhibit subsequent activation of hypoxia-inducible factor HIF. Moreover, the morphological spectrum of earliest ECA formation is unknown. In a detailed molecular pathological analysis of a series of epididymides collected from VHL patients at autopsy, we found that ECAs are true neoplasms that arise secondary to inactivation of the wild-type copy of the VHL gene, followed by early and simultaneous activation of HIF1 and HIF2 associated with up-regulation of downstream targets, including CAIX and GLUT-1. The observations also indicate that ECA formation evolves from a variety of microscopic epithelial tumourlets, and that these tumourlets are confined to the efferent ductular system. Although genetic and immunohistochemical analysis of precursor structures consistently revealed VHL gene inactivation and activation of HIF in the precursor lesions, only a small subset appears to progress into frank cystadenoma. Thus, ECA tumorigenesis in VHL disease shares fundamental principles with tumorigenesis in other affected organ systems.


[Clinical phenotypes associated with selective IgA deficiency: a review of 330 cases and a proposed follow-up protocol].
Selective IgA deficiency is the most common Primary Immune Deficiency. Only a small proportion of these patients present during childhood, but this proportion increases over the years, and may be associated with an IgG subclass deficiency with increased susceptibility to respiratory and digestive tract infections. During childhood, IgA deficient patients may also refer to symptoms related to allergic and autoimmune diseases or tumours. To describe the relationship of selective IgA deficiency with infections, allergic diseases, autoimmune disorders and tumours. To investigate the presence of other immune disorders associated with selective IgA deficiency. To suggest a follow-up protocol for these patients. Retrospective study of paediatric patients (<18 years) being followed-up in the Clinical Immunology Department between 1992 and 2007, as well as laboratory records with IgA values below 50mg/L. Clinical records were reviewed (frequency and intensity of diseases associated with selective IgA deficiency) along with immunology tests performed. A total of 330 paediatric patients were identified with a selective IgA deficiency: 39 (11.8%) suffered from recurrent ear infections (2 developed secondary deafness), 58 (17.5%) from recurrent upper respiratory tract infections, and 20 patients (6%) from recurrent pneumonia, 6 of whom developed secondary bronchiectasis and 2 underwent a lobectomy. A relationship with atopic disease was found in 62 (18.78%) of patients. Regarding digestive disorders, chronic diarrhoea was found in 21 (6.5%), coeliac disease in 22 (6.6%), and persistently high plasma transaminases in 3. Autoimmune manifestations were found in 38 (11.5%), juvenile chronic arthritis, type 1 diabetes, vitiligo, cytopenia, and Crohn's disease, amongst others). Tumours were identified in 5 (1.5%). An IgG sub-class deficiency was found in 5 patients (4%), and 6 patients had a confirmed deficiency in antibody production. In our cohort, 56.6% of patients with IgA deficiency showed other comorbidities which were, in decreasing frequency: recurrent infections (respiratory and ear infections), allergic diseases, autoimmunity and tumours. Some patients will develop a more severe humoral defect (IgG subclass deficiency with or without antibody deficiency).


The effect of bilirubin on lipid peroxidation and antioxidant enzymes in cumene hydroperoxide-treated erythrocytes.
Recently, it has been suggested that bilirubin may act as a potent biological chain-breaking antioxidant. To observe the effects of free bilirubin on antioxidant reactions in cumene hydroperoxide-treated erythrocytes (15 g hemoglobin/dl), we added bilirubin at four different concentrations (0.5, 1, 5, and 10 mg/dl). We measured the thiobarbituric acid-reactive substance and reduced glutathione levels, and some antioxidant enzyme activities, namely superoxide dismutase, catalase, and glucose-6-phosphate dehydrogenase. Thiobarbituric acid-reactive substance and chemiluminescent signals decreased during the incubation. Superoxide dismutase activities also decreased but not as much as in the control group. Glucose-6-phosphate dehydrogenase activities and reduced glutathione levels increased, but catalase activities remained the same as the control group. Our results suggest that bilirubin--in the concentrations we have used--partially prevented the oxidant effects of cumene hydroperoxide.


Intraoperative local adjuvant cancer chemotherapy for carcinoma of the thoracic esophagus.
Two forms of effective, supplemental, intraoperative chemotherapy for carcinoma of the esophagus have been devised, i.e., Bleomycin (BLM)-Spongel aimed at prevention of a local recurrence and trans-lymph-nodal administration of BLM for prevention of recurrence in the intramediastinal lymph nodes. Fifty-one patients given one or both of these local cancer chemotherapy had a lower incidence of local and/or lymph node recurrence in twelve months after surgery than did the controls. As both procedures are simple and there are few adverse effects, further application of this form of chemotherapy is warranted.


Identification and quantification of lower gastrointestinal flexible endoscopic microflora.
After use in 29 patients undergoing mechanical bowel preparation and cleansing by an acceptable, standardized method, flexible colonoscopes and sigmoidoscopes were cultured for identification and enumeration of bacterial organisms that might be transmitted during subsequent endoscopic procedures. Using a unique, new application, RODAC aerobic and anaerobic cultures of the shaft surface showed no evidence of residual fecal contamination, sparse growth of cutaneous and airborne organisms on some instruments, and no aerobic or anaerobic bacterial growth on others. There were no post-endoscopy infectious complications. Our results would indicate that proper cleaning of the flexible endoscope using an acceptable method does prevent bacterial disease transmission from patient to patient.


Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia.
Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (-/-) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (-/-) mice. Untreated G6pase (-/-) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia.


The binding of FITC-insulin to ANAE-positive cells in rat thymus.
To determine if thymic macrophages have insulin receptors, alternate sections of rat thymus were stained with FITC-insulin and examined for nonspecific esterase (ANAE) activity. Cells showing a diffuse ANAE staining pattern also bound FITC-insulin. These cells were concentrated in the cortico-medullary border and increased in number following administration of cortisol. Thymic macrophages may be insulin-dependent and therefore could be malfunctional in diabetes.


Assessment of Moral Development Among Undergraduate Pharmacy Students and Alumni.
Objective. This study's principal aim was to assess the moral development of undergraduate pharmacy students and alumni at a university in Jordan.Methods. Using the Professional Ethics in Pharmacy (PEP) test, the moral reasoning of 512 pharmacy students and alumni was assessed in a cross-sectional design. The main assessment measure was the Principled Morality Score, which reflects an individual's level of moral judgment development and is given as a percentage, where higher values indicate greater moral development.Results. The response rate was 49%. The median Principled Morality Score was 16.7, with no significant differences observed across all five cohorts. No significant differences in median Principled Morality Scores were found between men and women (16.7 vs 20, respectively). Also, no significant differences in median Principled Morality scores were observed between students who had completed the ethics course versus those who had not completed the ethics course at the time of data collection (median Principled Morality Score 20 vs 16.7, respectively). No trends in median Principled Morality Scores were observed.Conclusion. In this study, the professional moral reasoning of prospective pharmacists was lower than expected. A further longitudinal study of the cohort, which attempts to correlate moral development with age, sex, education level, and moral education strategy, is warranted.


Sequence-Based In-silico Discovery, Characterisation, and Biocatalytic Application of a Set of Imine Reductases.
Imine reductases (IREDs) have recently become a primary focus of research in biocatalysis, complementing other classes of amine-forming enzymes such as transaminases and amine dehydrogenases. Following in the footsteps of other research groups, we have established a set of IRED biocatalysts by sequence-based in silico enzyme discovery. In this study, we present basic characterisation data for these novel IREDs and explore their activity and stereoselectivity using a panel of structurally diverse cyclic imines as substrates. Specific activities of >1 U/mg and excellent stereoselectivities (ee>99 %) were observed in many cases, and the enzymes proved surprisingly tolerant towards elevated substrate loadings. Co-expression of the IREDs with an alcohol dehydrogenase for cofactor regeneration led to whole-cell biocatalysts capable of efficiently reducing imines at 100 mM initial concentration with no need for the addition of extracellular nicotinamide cofactor. Preparative biotransformations on gram scale using these 'designer cells' afforded chiral amines in good yield and excellent optical purity.


Preliminary studies into percorneal penetration and elemental content of the stratum corneum using X-ray microanalysis.
A technique is described which measures the penetration of substances through the stratum corneum (SC) and the distribution of elements in this structure employing scanning electron microscopy and energy dispersive analysis. Preliminary observations show that the normal SC shows a concentration gradient of potassium, high in the surface layers and lowest deeper down whereas the reverse is true for phosphorus. It has been shown that sulphur rapidly tranverses the SC and seems to penetrate through all parts of the horny layer whereas lead and zinc do not easily enter this structure.


Technique for Treatment of Subchondral Compression Fracture of the Lateral Femoral Condyle Associated With ACL Tear.
Excessive knee pivoting that causes a complete anterior cruciate ligament (ACL) tear may result in a subchondral compression fracture on the lateral femoral condyle after impacting the lateral tibial condyle. Because this mechanism is similar to the humeral head that has an impact on the glenoid during an anterior shoulder dislocation, such an osteochondral fracture can be considered equivalent to a "Hill-Sachs lesion of the knee." Restoring the native anatomy of the lateral femoral condyle articular surface is crucial, because its depression alters knee biomechanics, leading to bony knee instability, potentially greatly elevating the risk of ACL reconstruction failure and meniscal tears. In addition, bony knee instability increases the forces acting on the cartilage, which may impair one's quality of life and lead to the development of osteoarthritis. The fact that many patients with complete ACL tears are relatively young emphasizes the key role of osteoarthritis prevention. The aim of this report is to present a minimally invasive procedure to treat the "Hill-Sachs-like" knee lesion, a tricky enemy of knee stability.


Adverse reaction in patients with drug allergy history after simultaneous intravenous fundus fluorescein angiography and indocyanine green angiography.
To examine the safety of outpatient clinic simultaneous intravenous fundus fluorescein angiography (IVFA) and indocyanine green angiography (ICGA) in patients with any/all drug allergy history. In a single-center retrospective study conducted from February 2007 to March 2011, 390 consecutive outpatients with drug allergy history and 3426 patients without allergy history underwent simultaneous intravenous IVFA and ICGA. The detailed drug allergy history, the symptoms and time of the adverse reaction during simultaneous IVFA and ICGA were recorded in all the patients. Of the 390 patients with drug allergy history who received IVFA and ICGA, 28 patients (7.2%) had an adverse reaction. In contrast, 145 of the 3426 patients (4.2%) without allergy history had an adverse reaction during simultaneous IVFA and ICGA. Statistical significance in the incidence (P=0.008) and severity (P=0.001) of the adverse reaction was observed between patients with drug allergy history and those without drug allergy history. In 390 patients with drug allergy history, no statistical significance was indicated in the incidence of the adverse reaction among different types of drug allergy (P>0.05). Simultaneous IFVA and ICGA are generally safe procedures with an acceptable incidence of an adverse reaction. However, patients with drug allergy history may have a higher incidence and greater severity of an adverse reaction.


The effects of neck muscle vibration on postural orientation and spatial perception: A systematic review.
Neck muscle vibration (NMV) is increasingly used for its modulation of body orientation and spatial perception, but its mechanisms of action are still not well known. To describe the effects of NMV on postural orientation and spatial perception, in both healthy people and patients with disturbed balance potentially related to distorted body orientation perception. Following the PRISMA guidelines, a systematic search was performed using the databases MEDLINE, EMBASE, Cochrane library and PEDrO with the key words ((Postural balance) OR (Spatial reference)) AND (Neck muscle vibration) for articles published through to July 2016. A total of 67 articles were assessed; these exhibited wide heterogeneity and generally poor quality methodology. In healthy subjects, under bilateral NMV, the body tilts in the anterior direction (Level of Evidence LoE II). Under unilateral NMV, the visual environment moves towards the side opposite the vibration (LoE II) and the subject's experience of "straight ahead" is shifted towards the side of the vibration (LoE II). NMV also modulates both spatial and postural bias between stroke and vestibular patients. NMV modulates both spatial and postural bias and could thus be proposed as a tool in rehabilitative therapy. However, due to the heterogeneity of published data and the various significant shortfalls highlighted, current research does not allow clear guidelines to be proposed.


Correlation of Nasal Mucosal Temperature and Nasal Patency-A Computational Fluid Dynamics Study.
Recent evidence suggests that detection of nasal mucosal temperature, rather than direct airflow detection, is the primary determinant of subjective nasal patency. This study examines the role of nasal mucosal temperature in the perception of nasal patency using in vivo and computational fluid dynamics (CFD) measurements. Healthy adult participants completed Nasal Obstruction Symptom Evaluation (NOSE) and Visual Analogue Scale (VAS) questionnaires. A temperature probe measured nasal mucosal temperature at the vestibule, inferior turbinate, middle turbinate, and nasopharynx bilaterally. Participants underwent a CT scan, used to create a 3D nasal anatomy model to perform CFD analysis of nasal mucosal and inspired air temperature and heat flux along with mucosal surface area where heat flux >50 W/m2 (SAHF50). Eleven participants with a median age of 27 (IQR 24; 48) were recruited. Probe-measured temperature values correlated strongly with CFD-derived values (r = 0.87, p < 0.05). Correlations were seen anteriorly in the vestibule and inferior turbinate regions between nasal mucosal temperature and unilateral VAS (r = 0.42-0.46; p < 0.05), between SAHF50 and unilateral VAS (r = -0.31 to -0.36; p < 0.05) and between nasal mucosal temperature and SAHF50 (r = -0.37 to -0.41; p < 0.05). Subjects with high patency (VAS ≤10) had increased heat flux anteriorly compared with lower patency subjects (VAS >10; p < 0.05). Lower nasal mucosal temperature and higher heat flux within the anterior nasal cavity correlates with a perception of improved unilateral nasal patency in healthy individuals. 4 Laryngoscope, 133:1328-1335, 2023.


Testosterone Replacement Therapy Versus Clomiphene Citrate in the Young Hypogonadal Male.
The use of testosterone to treat hypogonadal symptoms has increased during the past decade. Consequently, one clinical challenge that has arisen is how to approach the young and treatment-naïve hypogonadal patient who is still within his reproductive years and may desire children in the future. Testosterone is known to suppress the hypothalamic-pituitary-gonadal axis resulting in suppressed spermatogenesis. There is a concern that, in some men, prolonged testosterone use may result in permanent spermatogenic failure. PATIENT SUMMARY: In this review, we discuss the risks and benefits of available treatment options for the young hypogonadal patient for whom future fertility is an important consideration. Fortunately, alternatives such as clomiphene citrate and human chorionic gonadotropin have been shown to increase endogenous testosterone production. However, their efficacy as treatments for hypogonadal symptoms is still under debate.


Surgical repair of a left main coronary artery aneurysm.
We report the repair of a 6.5 × 5.3-cm left main coronary artery aneurysm by marsupialization of the aneurysm sac and coronary artery bypass grafting.


Clinical Efficacy of Creatine Phosphate Sodium and/or Vitamin C in the Treatment of Children with Viral Myocarditis: A Meta-Analysis.
This study performed a meta-analysis to explore the clinical efficacy of creatine phosphate sodium (CPS) and/or vitamin C for viral myocarditis (VMC) in children, to provide guidance for its clinical treatment. A literature search was performed on PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang databases to obtain published clinical randomized controlled trials (RCTs) on CPS and/or vitamin C for VMC in children, with a time span from 2013 to 2022. Relevant data was extracted and meta-analysis was performed using the statistical software Stata 16.0. A total of 723 studies were retrieved and 19 studies were finally included for meta-analysis, with a total of 1,957 patients. The meta-analysis results showed that the observation group (conventional treatment + CPS and/or vitamin C) was superior to the control group (conventional treatment alone) in treatment effective rate (OR = 3.60, 95% CI (2.55, 5.07), and P < 0.001). Additionally, the observation group had lower levels of cardiac troponin-I (SMD = - 2.63, 95% CI (- 3.51, - 1.76), and P < 0.001), creatine kinase isoenzyme (SMD = -2.78, 95% CI (- 3.53, - 2.03), and P < 0.001), lactate dehydrogenase (SMD = -1.95, 95% CI (- 2.49, - 1.42), and P < 0.001), aspartate aminotransferase (SMD = -0.87, 95% CI (- 1.84, 0.09), and P = 0.076), tumor necrosis factor-α (SMD = -3.90, 95% CI (- 4.47, - 3.06), and P < 0.001), and higher superoxide dismutase levels (SMD = 2.48, 95% CI (1.64, 3.33), and P < 0.001). Except aspartate aminotransferase, there were significant differences between the two groups in the other parameters. CPS and/or vitamin C treatment could greatly improve the treatment, protect myocardial function, and relieve inflammatory response in children with VMC.


High-density lipoprotein revisited: biological functions and clinical relevance.
Previous interest in high-density lipoproteins (HDLs) focused on their possible protective role in atherosclerotic cardiovascular disease (ASCVD). Evidence from genetic studies and randomized trials, however, questioned that the inverse association of HDL-cholesterol (HDL-C) is causal. This review aims to provide an update on the role of HDL in health and disease, also beyond ASCVD. Through evolution from invertebrates, HDLs are the principal lipoproteins, while apolipoprotein B-containing lipoproteins first developed in vertebrates. HDLs transport cholesterol and other lipids between different cells like a reusable ferry, but serve many other functions including communication with cells and the inactivation of biohazards like bacterial lipopolysaccharides. These functions are exerted by entire HDL particles or distinct proteins or lipids carried by HDL rather than by its cholesterol cargo measured as HDL-C. Neither does HDL-C measurement reflect the efficiency of reverse cholesterol transport. Recent studies indicate that functional measures of HDL, notably cholesterol efflux capacity, numbers of HDL particles, or distinct HDL proteins are better predictors of ASCVD events than HDL-C. Low HDL-C levels are related observationally, but also genetically, to increased risks of infectious diseases, death during sepsis, diabetes mellitus, and chronic kidney disease. Additional, but only observational, data indicate associations of low HDL-C with various autoimmune diseases, and cancers, as well as all-cause mortality. Conversely, extremely high HDL-C levels are associated with an increased risk of age-related macular degeneration (also genetically), infectious disease, and all-cause mortality. HDL encompasses dynamic multimolecular and multifunctional lipoproteins that likely emerged during evolution to serve several physiological roles and prevent or heal pathologies beyond ASCVD. For any clinical exploitation of HDL, the indirect marker HDL-C must be replaced by direct biomarkers reflecting the causal role of HDL in the respective disease.


Low-1 level mechanical vibration improves bone microstructure, tissue mechanical properties and porous titanium implant osseointegration by promoting anabolic response in type 1 diabetic rabbits.
Type 1 diabetes mellitus (T1DM) is associated with reduced bone mass, increased fracture risk, and impaired bone defect regeneration potential. These skeletal complications are becoming important clinical challenges due to the rapidly increasing T1DM population, which necessitates developing effective treatment for T1DM-associated osteopenia/osteoporosis and bone trauma. This study aims to investigate the effects of whole-body vibration (WBV), an easy and non-invasive biophysical method, on bone microstructure, tissue-level mechanical properties and porous titanium (pTi) osseointegration in alloxan-diabetic rabbits. Six non-diabetic and twelve alloxan-treated diabetic rabbits were equally assigned to the Control, DM, and DM with WBV stimulation (WBV) groups. A cylindrical drill-hole defect was established on the left femoral lateral condyle of all rabbits and filled with a novel non-toxic Ti2448 pTi. Rabbits in the WBV group were exposed to 1h/day WBV (0.3g, 30Hz) for 8weeks. After sacrifice, the left femoral condyles were harvested for histological, histomorphometric and nanoindentation analyses. The femoral sample with 2-cm height above the defect was used for qRT-PCR analysis. The right distal femora were scanned with μCT. We found that all alloxan-treated rabbits exhibited hyperglycemia throughout the experimental period. WBV inhibited the deterioration of cancellous and cortical bone architecture and tissue-level mechanical properties via μCT, histological and nanoindentation examinations. T1DM-induced reduction of bone formation was inhibited by WBV, as evidenced by elevated serum OCN and increased mineral apposition rate (MAR), whereas no alteration was observed in bone resorption marker TRACP5b. WBV also stimulated more adequate ingrowths of mineralized bone tissue into pTi pore spaces, and improved peri-implant bone tissue-level mechanical properties and MAR in T1DM bone defects. WBV mitigated the reductions in femoral BMP2, OCN, Wnt3a, Lrp6, and β-catenin and inhibited Sost mRNA expression but did not alter RANKL or RANK gene expression in T1DM rabbits. Our findings demonstrated that WBV improved bone architecture, tissue-level mechanical properties, and pTi osseointegration by promoting canonical Wnt signaling-mediated skeletal anabolic response. This study not only advances our understanding of T1DM skeletal sensitivity in response to external mechanical cues but also offers new treatment alternatives for T1DM-associated osteopenia/osteoporosis and osseous defects in an economic and highly efficient manner.


Parahisian radiofrequency catheter ablation in dogs: comparison of the above-valve and below-valve approaches.
In patients with an accessory pathway close to the His bundle, radiofrequency catheter ablation (RFCA) requires additional care to avoid damage to the normal conduction system. To assess differences between approaches from above or below the tricuspid valve (TV), we performed RFCA in 20 dogs (from above, group A, n=10; from below, group B, n=10). RF energy with temperature control at 60 degrees 60 seconds was administered at the site where a small His potential was recorded from the ablation catheter guided by fluoroscopy and transesophageal echocardiography (TEE) (in the latter six dogs). Before and after RFCA, electrophysiological testing was performed and histological findings were compared. An ablated lesion was created in 7 of 10 (2 of 2 guided by TEE) dogs in group A and 5 of 10 (3 of 4 TEE) dogs in group B. In group A, an ablated lesion involved the atrium and ventricle in the anterior site of His bundle, but the lesion was only in the ventricle in group B. An atrioventricular block (AVB) and severe damage to the penetrating bundle was observed in one dog of group A. A large hematoma on the TV was made in 2 dogs and the complete right bundle branch block (CRBBB) occurred in 3 dogs of group B. The approach from below the TV was safer than that from above the TV in parahisian RFCA, because it did not create an AVB, although it has a high incidence of CRBBB and associated technical difficulties.


Considerations of pool size in the manufacture of plasma derivatives.
The pooling of human plasma from many donors for the purpose of manufacturing therapeutic proteins increases the risk of exposing recipients of these proteins to pathogens that may contaminate 1 or a few units included in the pool. This risk is estimated for a range of manufacturing scales that would derive material from a varied number of donors and for a number of hypothetical infectious agents that may exist in the donor population over a wide range of prevalence. Risk is also calculated both for recipients of single doses of a plasma protein and for those who depend on long-term treatment with plasma derivatives. Risk of exposure increases with pool size and the prevalence of the agent in question and accumulates with repeated treatments with material manufactured from different pools. Reducing pool size would at best decrease this risk in proportion to the reduction in manufacturing scale. However, for individuals requiring repeated or continuous treatments, the risk of exposure to all but the rarest infectious agents would be only minimally affected, even by large reductions in manufacturing scale.


Design and evaluation of buccal films as paediatric dosage form for transmucosal delivery of ondansetron.
In the process of implementation and innovation of paediatric dosage forms, buccal films for transmucosal administration of drug represent one of the most interesting approach. In fact, films are able to provide an extended duration of activity allowing minimal dosage and frequency and offer an exact and flexible dose, associated with ease of handling. The objective of the present study was to develop polymeric films for the sustained release of ondansetron hydrochloride, a selective inhibitor of 5-HT3 receptors indicated in paediatrics for the prevention and treatment of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy and postoperatively. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of hydroxypropylmethylcellulose (HPMC) with chitosan (CH) or sodium hyaluronate (HA) or gelatin (GEL) and characterized for their physico-chemical and functional properties. The presence of HA, GEL and CH did not improve the mucoadhesive properties of HPMC film. The inclusion of GEL and CH in HPMC film increased in vitro drug release with respect to the inclusion of HA, although films containing HA showed the highest water uptake. Moreover in agreement with the release behaviour, the inclusion of CH and GEL provided higher drug permeation through porcine buccal mucosa with respect to HPMC film and ensured linear permeation profiles of drug.


Divergent and Modular Synthesis of Terpenoid Scaffolds via a AuI Catalyzed One-Pot Cascade.
A one-pot cascade sequence to generate synthetically challenging polycyclic scaffolds is reported utilizing a novel Lewis acid gold catalyst for the key cyclization step, enabling the divergent synthesis of both 6,6,5-tricyclic and 6,6,6,5-tetracyclic cores through both ligand and reaction condition control. We have combined the intrinsic complexity and stereoselectivity of cycloadditions with the electronic and steric properties of gold complexes to selectively generate complex polycyclic scaffolds in a single operation.


Cdc48 cofactor Shp1 regulates signal-induced SCFMet30 disassembly.
Organisms can adapt to a broad spectrum of sudden and dramatic changes in their environment. These abrupt changes are often perceived as stress and trigger responses that facilitate survival and eventual adaptation. The ubiquitin-proteasome system (UPS) is involved in most cellular processes. Unsurprisingly, components of the UPS also play crucial roles during various stress response programs. The budding yeast SCFMet30 complex is an essential cullin-RING ubiquitin ligase that connects metabolic and heavy metal stress to cell cycle regulation. Cadmium exposure results in the active dissociation of the F-box protein Met30 from the core ligase, leading to SCFMet30 inactivation. Consequently, SCFMet30 substrate ubiquitylation is blocked and triggers a downstream cascade to activate a specific transcriptional stress response program. Signal-induced dissociation is initiated by autoubiquitylation of Met30 and serves as a recruitment signal for the AAA-ATPase Cdc48/p97, which actively disassembles the complex. Here we show that the UBX cofactor Shp1/p47 is an additional key element for SCFMet30 disassembly during heavy metal stress. Although the cofactor can directly interact with the ATPase, Cdc48 and Shp1 are recruited independently to SCFMet30 during cadmium stress. An intact UBX domain is crucial for effective SCFMet30 disassembly, and a concentration threshold of Shp1 recruited to SCFMet30 needs to be exceeded to initiate Met30 dissociation. The latter is likely related to Shp1-mediated control of Cdc48 ATPase activity. This study identifies Shp1 as the crucial Cdc48 cofactor for signal-induced selective disassembly of a multisubunit protein complex to modulate activity.


Potential antitumor agents. I. Synthesis of pyrroloindazole derivatives related to the pyrroloindole moieties of the antitumor antibiotic CC-1065.
The synthesis of some derivatives of the unknown 1(2),8-dihydropyrrolo[3,2-g]indazole is reported starting from 7-oxo-4,5,6,7-tetrahydroindole. The new pyrroloindazole derivatives resemble the B and C subunit structure of the antitumor antibiotic CC-1065.


Rates of evolutionary change of resident Escherichia coli O157:H7 differ within the same ecological niche.
Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a pathogen known to reside in cattle feedlots. This retrospective study examined 181 STEC O157:H7 strains collected over 23 years from a closed-system feedlot. All strains were subjected to short-read sequencing, with a subset of 36 also subjected to long-read sequencing. Over 96% of the strains fell into four phylogenetically distinct clades. Clade membership was associated with multiple factors including stx composition and the alleles of a well-characterized polymorphism (tir 255 T > A). Small plasmids (2.7 to 40 kb) were found to be primarily clade specific. Within each clade, chromosomal rearrangements were observed along with a core phageome and clade specific phages. Across both core and mobile elements of the genome, multiple SNP alleles were in complete linkage disequilibrium across all strains within specific clades. Clade evolutionary rates varied between 0.9 and 2.8 SNP/genome/year with two tir A allele clades having the lowest evolutionary rates. Investigation into possible causes of the differing rates was not conclusive but revealed a synonymous based mutation in the DNA polymerase III of the fastest evolving clade. Phylogenetic trees generated through our bioinformatic pipeline versus the NCBI's pathogen detection project were similar, with the two tir A allele clades matching individual NCBI SNP clusters, and the two tir T allele clades assigned to multiple closely-related SNP clusters. In one ecological niche, a diverse STEC O157:H7 population exhibited different rates of evolution that associated with SNP alleles in linkage disequilibrium in the core genome and mobile elements, including tir 255 T > A.


Hypertension knowledge among patients from an urban clinic.
To determine levels and correlates of hypertension knowledge. Cross-sectional telephone survey. Urban, public hospital clinic. 296 adults with hypertension. Hypertension knowledge was assessed through a 10-item test; respondents received one point for each correct answer. Eighty-nine percent of respondents were Black, 79% were female, 75% had a monthly income < $1000, and 62% had completed high school. Items with the lowest percentage of correct responses included knowing that hypertension does not cause cancer (41.9% correct), a blood pressure of 130/80 mm Hg is normal (59.8% correct), hypertension lasts a lifetime (60.5% correct), and renal failure is a complication of hypertension (76.4% correct). Overall, 39% answered 9 or 10 questions correctly. Low hypertension knowledge (< or = 7 questions correct) was associated with age > or = 60 years, having less than a high school education, and reporting a first hypertension diagnosis within 9 years before being surveyed. Hypertension knowledge deficits in specific content areas and among certain subgroups were present in this urban population. Educational programs focusing on newly diagnosed hypertensive patients and aimed at filling targeted knowledge deficits may be a cost-effective approach to increase hypertension knowledge in similar populations.


Urinary excretion of metabolites of norepinephrine in Tourette's syndrome.
Urinary excretion of the norepinephrine metabolites 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NMR) was measured in Tourette's Syndrome (TS) patients and in control subjects matched for age and education. The 24-h excretion (expressed per gram of creatinine) of total MHPG and of free and total (free + conjugated) NME was significantly lower in TS patients than in the normal subjects.


Purkinje cell axon collateral distributions reflect the chemical compartmentation of the rat cerebellar cortex.
Monoclonal antibody mabQ113 has been used to study the distribution of Purkinje cell axon collaterals in the rat cerebellar cortex. MabQ113 recognizes a polypeptide antigen, zebrin I, that is confined to a subset of Purkinje cells. Antigenic Purkinje cells are arranged in parasagittal compartments running throughout the cortex. No other cerebellar cells are immunoreactive. Immunoreactive axon collaterals are confined principally to the infraganglionic plexus with only a few extending into the molecular layer. Three probable target cells for the axon collaterals have been identified: Golgi cells, Lugaro cells, and other Purkinje cells. About 90% of immunoreactive axon collaterals in the anterior lobe are located beneath the mabQ113+ Purkinje cell compartment in which they originate but some do invade the neighboring mabQ113- territory. In the anterior lobe vermis, the distribution of invading mabQ113+ collaterals is not symmetrical, such that the probability of an invading collateral from the P2+ compartment is greater at the medial boundary into P1- than at the lateral into P2-. The distribution of immunoreactive collaterals is consistent with their playing a role in synchronizing the firing of Purkinje cells within the same compartment.


Methods for microstimulation and recording of single neurons and evoked potentials in the human central nervous system.
An apparatus and technique are described for microstimulation and recording of both slow wave and single neuron (single unit) activities during functional stereotaxic procedures. This method facilitates microstimulation and evoked potential and single unit analysis which, in combination, provide optimum definition of stereotaxic targets in the treatment of functional disorders of the human central nervous system.


Empowering the Research Community to Investigate Misconduct and Promote Research Integrity and Ethics: New Regulation in Scandinavia.
Researchers sometimes engage in various forms of dishonesty and unethical behavior, which has led to regulatory efforts to ensure that they work according to acceptable standards. Such regulation is a difficult task, as research is a diverse and dynamic endeavor. Researchers can disagree about what counts as good and acceptable standards, and these standards are constantly developing. This paper presents and discusses recent changes in research integrity and ethics regulation in Norway, Denmark, and Sweden. Recognizing that research norms are developed through practice and are therefore unsuited for comprehensive national regulation, the Scandinavian countries focus on empowering the research community to regulate itself instead, except for the most severe cases of misconduct. This empowerment takes the form of giving research institutions tools and investigatory powers while also holding them responsible for ensuring that both the institution and individual researchers are up to date on relevant norms. In this way, the Scandinavian governments seek to avoid some of the challenges found in more legalistic approaches, which risk lagging behind the continuous development of research norms and can be insensitive to the fact that different disciplines have different norms. While the new approach in Scandinavian has several potential benefits, it also involves potential trade-offs and limitations. The new laws can create confusion about what researchers are allowed to do. Another issue is that it only addresses the fundamental drivers of misconduct to a limited extent.


Tetanus in a case of lepromatous leprosy.
A patient of Lepromatous Leprosy had neuropathic plantar ulcer of 6 months duration. He developed "Tetanus". We are reporting this case with review of literature, as there is dearth of published literature on this association of Leprosy and Tetanus.


On the requirement of nitric oxide signaling in the amygdala for consolidation of inhibitory avoidance memory.
Evidence suggests that the NO/sGC/PKG pathway plays a key role in memory processing but the actual participation of this signaling cascade in the amygdala during memory consolidation remains unknown. Here, we show that when infused in the amygdala immediately after inhibitory avoidance training, but not later, the NO synthase inhibitor L-NNA hindered long-term memory retention without affecting locomotion, exploratory behavior, anxiety state or retrieval of the avoidance response. The amnesic effect of L-NNA was not state-dependent and was mimicked by the soluble guanylyl cyclase inhibitor LY83583 and the PKG inhibitor KT-5823. On the contrary, post-training intra-amygdala infusion of the NOS substrate L-Arg, the NO-releasing compound SNAP or the non-hydrolysable analog of cGMP 8Br-cGMP increased memory retention in a dose-dependent manner. Co-infusion of 8Br-cGMP reversed the amnesic effect of L-NNA and LY83583 but not that of KT-5823. Our data indicate that the NO-induced activation of PKG in the amygdala is a necessary step for consolidation of inhibitory avoidance memory.


Improvement of Astaxanthin Production in Aurantiochytrium limacinum by Overexpression of the Beta-Carotene Hydroxylase Gene.
Aurantiochytrium limacinum is a heterotrophic eukaryotic microorganism that can accumulate high levels of commercial products such as astaxanthin and docosahexaenoic acid. Due to its rapid growth and relatively simple extraction method, A. limacinum is considered a promising astaxanthin resource to replace the conventional microalgal production. However, the astaxanthin biosynthetic process in A. limacinum remains incompletely understood, especially in those catalysed by β-carotene hydroxylase (CrtZ) and ketolase. In this study, we overexpressed a crtZ candidate gene to increase astaxanthin production and expand our understanding of the conversion from beta-carotene to astaxanthin. The resultant transformant AlcrtZ#10 cultivated for 5 days showed a significant increase in astaxanthin production per culture (2.8-fold) and per cell (4.5-fold) compared with that of the wild-type strain. Strikingly, longer light exposure increased astaxanthin production and decreased the beta-carotene content in the wild-type strain, suggesting that light exposure duration is important for astaxanthin production in A. limacinum. Among several predicted intermediates, furthermore, the cantaxanthin produced from β-carotene by ketolase activity were enhanced in the transformant AlcrtZ#10. Although the further investigation is needed, this result suggested that the main route of astaxanthin was via cantaxanthin. Thus, our findings will be valuable not only for its application, but also for understanding the astaxanthin biosynthetic process in A. limacinum.


Immunohistochemical demonstration of tissue kallikrein in the neurons of rat brain.
The distribution of tissue kallikrein (EC.126.96.36.199) in the rat brain was investigated by an enzyme-linked immunosorbent assay (ELISA) and immunohistochemical technique using antiserum against rat urinary kallikrein. More than 75% of the total amount of kallikrein in the extracts of the cerebral cortex and brain stem was determined by the ELISA to be in the form of prokallikrein, suggesting that the greater part of the enzyme exists in the form of pro-enzyme in the central nervous system. Furthermore, immunohistochemical examination revealed that, although the kallikrein-positive cells were widespread and scattered in the brain, the immunoreactive substances preferentially locate in the neuronal cell bodies and their processes in both the cerebral cortex and brainstem.


Anatomical Society core regional anatomy syllabus for undergraduate medicine: the Delphi process.
A modified Delphi method was employed to seek consensus when revising the UK and Ireland's core syllabus for regional anatomy in undergraduate medicine. A Delphi panel was constructed involving 'expert' (individuals with at least 5 years' experience in teaching medical students anatomy at the level required for graduation). The panel (n = 39) was selected and nominated by members of Council and/or the Education Committee of the Anatomical Society and included a range of specialists including surgeons, radiologists and anatomists. The experts were asked in two stages to 'accept', 'reject' or 'modify' (first stage only) each learning outcome. A third stage, which was not part of the Delphi method, then allowed the original authors of the syllabus to make changes either to correct any anatomical errors or to make minor syntax changes. From the original syllabus of 182 learning outcomes, removing the neuroanatomy component (163), 23 learning outcomes (15%) remained unchanged, seven learning outcomes were removed and two new learning outcomes added. The remaining 133 learning outcomes were modified. All learning outcomes on the new core syllabus achieved over 90% acceptance by the panel.


Nephrogenic systemic fibrosis: A survey of the use of gadolinium-based contrast agents in Ghana.
The aim of this study is to identify current practice of administration of gadolinium-based contrast agents (GBCAs) in Ghana. A total of 13 MRI (magnetic resonance imaging) facilities were sent a survey questionnaire to request information on their current practice with the use of GBCAs. Gadodiamide, a high risk GBCA accounted for 67% of first line agents. 5 (42%) had a departmental protocol on the administration of GBCAs with regards to its association with nephrogenic systemic fibrosis (NSF). Of the 8 that use gadodiamide, 3 check kidney function in all patients, 2 check in selected patients, and 3 do not check at all. All 3 that screen all patients do not use contrast if the patient has an eGFR (estimated glomerular filtration rate) of 30-59 ml/min, 1 considers other modality; and if the patient has an eGFR of <30 ml/min, 2 do not use contrast but consider other modality, however 1 continues with the high risk agent. Gadodiamide is widely used, with varied practice in screening for renal function, and risk factors associated with NSF. Current evidence shows that it is advisable to administer macrocyclic agents in patients with compromised renal function. It is also imperative to establish local guidelines in line with international guidelines in order to minimize the incidence of NSF.


A nationwide survey on bariatric surgery in Germany--results 2005-2007.
Most studies on bariatric surgery outcomes are performed as clinical trials or reflect the clinical experience in single centers. The status of bariatric surgery in Germany has been examined since January 1st, 2005 with the cooperation of clinics and hospitals at the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University of Magdeburg (Germany). In this prospective multicenter observational study, the data obtained for all primary bariatric procedures, including all repeated operations, performed on consecutive patients with morbid obesity at participating hospitals from 2005 to 2007 were prospectively collected using an Internet online data registry. In particular, perioperative characteristics, such as the spectrum of diagnostic measurements, type of surgical procedures, and short- and long-term outcomes, were investigated. During the study period, 629 surgical procedures were performed at 21 hospitals in 2005, 828 procedures at 32 hospitals in 2006, and 1,666 procedures at 35 hospitals in 2007. In 2005 and 2006, gastric banding was the most frequently performed operation, followed by the Roux-en-Y gastric bypass (RYGBP). In 2007, a RYGBP was carried out in 42.1% of all bariatric procedures. Among all patients, 74.4% were female. The mean body mass index (BMI) was 48.5 kg/m(2) in 2005, 48.4 kg/m(2) in 2006, and 48.0 kg/m(2) in 2007. Follow-up data after 12 months were available for 63.8% of the patients in 2005 and 2006; these data showed greater reduction of BMI after malabsorptive rather than restrictive bariatric procedures. The mortality was 0.1% (30 days) and 0.16% (overall). As indicated by the worldwide trend, there is an ongoing change from restrictive bariatric procedures to malabsorptive procedures and sleeve gastrectomy. Although the BMIs of German patients undergoing bariatric surgery appear to be substantially higher than those of patients from most other countries, there were no differences in intraoperative and short-term complications or in overall outcomes during follow-up when compared with published studies.


A theoretical study on the exciton circular dichroism of propeller-like metal complexes of bipyridine and tripodal tris(2-pyridylmethyl)amine derivatives.
Time-dependent density functional theory (TD-DFT) has been employed to simulate the circular dichroism (CD) spectra of bipyridyl ruthenium(II) complexes as well as zinc(II) and copper(II) complexes containing tris(2-pyridylmethyl)amine (TPA) derivatives. A qualitative model is used to account for the mechanism by which the bis- and tris-bipyridine complexes (or analogous systems) exhibit exciton CD. The model is further used to predict the sign of the exciton CD bands. The predictions are in agreement with experiment and DFT calculations. A comprehensive analysis is presented of the subtle differences in the CD spectra of this series of related complexes.


The promise of nuclear medicine technology: status and future perspective of high-resolution whole-body PET.
Positron emission tomography has rapidly emerged over the past 50+ years resulting in highly sophisticated tools for medical diagnosis. However, spatial resolution is still one of the drawbacks of PET. Modern whole-body PET devices provide a spatial resolution in the range of 4-6mm FWHM. Physical constraints are equally responsible for limited spatial resolution as factors caused by geometrical effects or by detector crystal properties. This paper focuses on the question why it is still a major challenge--despite the invention of new crystals and readout electronics--to build a high-resolution whole-body PET system for humans. Physical constraints are discussed and possible solutions for high-resolution PET are presented.


Time From Infection to Disease and Infectiousness for Ebola Virus Disease, a Systematic Review.
We systematically reviewed the literature to estimate the incubation and latent periods of Ebola virus disease. We found limited epidemiological data from individuals with discrete 1-day exposures. Available data suggest that the incubation and latent periods may differ, and mathematical models may be improved by distinguishing between the two periods.


Chronic Exposure to Excess Nutrients Left-shifts the Concentration Dependence of Glucose-stimulated Insulin Secretion in Pancreatic β-Cells.
Hyperinsulinemia (HI) is elevated plasma insulin at basal glucose. Impaired glucose tolerance is associated with HI, although the exact cause and effect relationship remains poorly defined. We tested the hypothesis that HI can result from an intrinsic response of the β-cell to chronic exposure to excess nutrients, involving a shift in the concentration dependence of glucose-stimulated insulin secretion. INS-1 (832/13) cells were cultured in either a physiological (4 mm) or high (11 mm) glucose concentration with or without concomitant exposure to oleate. Isolated rat islets were also cultured with or without oleate. A clear hypersensitivity to submaximal glucose concentrations was evident in INS-1 cells cultured in excess nutrients such that the 25% of maximal (S0.25) glucose-stimulated insulin secretion was significantly reduced in cells cultured in 11 mm glucose (S0.25 = 3.5 mm) and 4 mm glucose with oleate (S0.25 = 4.5 mm) compared with 4 mm glucose alone (S0.25 = 5.7 mm). The magnitude of the left shift was linearly correlated with intracellular lipid stores in INS-1 cells (r(2) = 0.97). We observed no significant differences in the dose responses for glucose stimulation of respiration, NAD(P)H autofluorescence, or Ca(2+) responses between left- and right-shifted β-cells. However, a left shift in the sensitivity of exocytosis to Ca(2+) was documented in permeabilized INS-1 cells cultured in 11 versus 4 mm glucose (S0.25 = 1.1 and 1.7 μm, respectively). Our results suggest that the sensitivity of exocytosis to triggering is modulated by a lipid component, the levels of which are influenced by the culture nutrient environment.


Comprehensive analysis of maté (Ilex paraguariensis) compounds: development of chemical strategies for matesaponin analysis by mass spectrometry.
Ilex paraguariensis (maté) is an important plant from southern Brazil, Paraguay, Uruguay and Argentina, where its leaves are widely used in hot or cold beverages. We now present a comprehensive ULPC-PDA-MS analysis of the compounds found in its leaves. The analysis was rapid, less than 13 min and many compounds were identified, among these, the chlorogenic acid series, and other quinic acid derivatives, xanthines, and several saponins, many of which have not been previously described, including many isomers. The isomerism could occur in the aglycone moiety, namely ursolic or oleanolic acid, or in the carbohydrate moiety. Additionally, many acetylated saponins were detected. The structure of known and novel saponins was determined using per-O-methylation with ESI-MS analysis, as well as with GC-MS of their partially O-methylated alditol acetate (PMAA) derivatives, along with ESI-MS analysis of the O-isopropylidene (IPP) derivatives provided fundamental information on interglycosidic linkages, avoiding the purification steps.


The Piragua Gene Is not Essential for Drosophila Development.
Proteins with clusters of C2H2 zinc finger domains (C2H2-proteins) constitute the most abundant class of transcription factors in higher eukaryotes. N-terminal ZAD (zinc finger-associated domain) dimerization domain has been identified in a large group of C2H2-proteins mostly in insects. The piragua gene encodes one of these proteins, Fu2. We have generated CRISPR/Cas9-mediated deletion of the piragua gene that has no phenotype. We have used φC31-mediated attP/attB recombination to generate a transgenic line expressing Fu2 protein fused with HA epitope. This line will be useful for analysis of DNA binding profile and functions of Fu2 protein.


Burkitt lymphoma in Iraqi children: A distinctive form of sporadic disease with high incidence of EBV+ cases and more frequent expression of MUM1/IRF4 protein in cases with head and neck presentation.
Epstein-Barr virus (EBV)-related lymphoproliferative disorders are relatively common in Iraqi children. Burkitt lymphoma (BL) accounted for 40% of lymphoma cases. The mean age of 125 BL cases was 5.9 ± 3.1 years, and the male-to-female ratio was 3.6:1. Clinical presentation was abdominal in 66% and head and neck in 34%. Bone marrow involvement was higher (P < 0.001) in children with head and neck disease. Tumor cells had MYC translocation (96%) and were CD20+ /CD10+ /MYC+ /BCL2- . MUM1/IRF4 staining was expressed by a fraction of tumor cells in 19 of 125 cases (15%) and was more frequent (P < 0.007) in head and neck disease (12/42; 29%). EBV-encoded RNA was positive in 100 of 125 (80%) BL cases.


Electrophoresis in the presence of Coomassie brilliant blue R-250 stains polyacrylamide gels during protein fractionation.
A method of staining polyacrylamide gels in which the dye is electrophoresed together with the sample is proposed. The method cuts short and simplifies the conventional electrophoresis procedure by eliminating the separate poststaining step. In the gels run in the presence of sodium dodecyl sulfate, the method produces protein staining patterns which are quantitatively identical to the ones obtained by conventional staining procedure. Additional advantages of the method are easy control over the degree of staining and homogenous staining independent of the gel thickness and concentration of the dye.


DRAQ5-based DNA content analysis of hematolymphoid cell subpopulations discriminated by surface antigens and light scatter properties.
Analysis of cell cycle kinetics offers important information regarding the behavior of normal and neoplastic cells. Most often, cell cycle determinations by flow cytometry (FCM) have been performed using whole-sample analysis with intercalating dyes like propidium iodide (PI). The cell cycle phase assessment in individual cell subsets in heterogeneous samples is best performed using combined antigen/scatter and DNA analysis. DRAQ5, a novel DNA binding dye that excites at 488 nm and emits in the far red spectra, rapidly penetrates intact live cells while preserving their light scatter properties and expression of surface antigens. We evaluated the ability of this dye to measure cell cycle phases in a variety of clinical hematolymphoid samples. We first compared whole sample DRAQ5 and PI cell cycle analyses in 26 clinical hematolymphoid samples. Next, we analyzed cell subpopulations in 39 samples of nonpathologic bone marrow by performing simultaneous CD45/CD34 and DRAQ5 staining. We assessed cell cycle characteristics specific to each population identified by CD45/CD34/side light scatter: lymphocytes, monocytes, immature and mature granulocytes, nucleated erythroid cells, and early precursors. Whole sample DNA cell cycle analyses by DRAQ5 and PI showed no significant differences in S-phase. DRAQ5, however, produced slightly larger coefficients of variation. DRAQ5-based DNA content analysis was easily performed on the distinct marrow cell subpopulations, since light scatter and antigen expression were completely preserved. Significant differences in S-phase were noted between subpopulations of cells exhibiting different degrees of maturation. Because of its simplicity of use, excitability with 488 nm lasers, and the ability to stain viable cells, DRAQ5 should prove most useful in the kinetic evaluation of normal and neoplastic hematolymphoid cell subsets identified by light scatter and antigenic expression.


The effects of local and regional treatment on the metastatic outcome in prostatic carcinoma with pelvic lymph node involvement.
The effect of local and regional treatment on the development of distant metastases in patients with localized node negative and node positive carcinoma of the prostate is examined. Distant metastases-free survival was evaluated in 1078 patients with Stage B-C node negative (733 patients) or node positive (345 patients) carcinoma of the prostate, staged with pelvic lymph node dissection and treated with retropublic 125I implantation at the Memorial Sloan-Kettering Cancer Center between 1970 and 1985. The 15-year actuarial distant metastases-free survival rate for the entire group of patients was 27%. Lymph node involvement was the most significant covariate affecting distant metastases-free survival, although local failure, stage, and grade were also independent variables. Distant metastases-free survival varied with the extent of lymph node involvement (N0 vs. N1, p < 0.0001; N1 vs. N2, p < 0.0001). However, the difference between N1 and N2 patients was due to a faster rate of development of distant metastases in N2 patients. The ultimate 10-year distant metastases-free survival rate was similar for the two patient groups (11% for N1 and 9% for N2). Local failure correlated with the metastatic outcome in patients with B-C/N0 disease (p < 0.00001), but not in N1 or N2 patients. Although distant metastases-free survival in locally controlled N1 patients was improved compared to N2 patients (p = 0.004), when stratified by primary tumor stage and grade, the differences were no longer significant. Essentially all node positive patients with carcinoma of the prostate will develop distant metastatic disease if followed for sufficiently long periods of time. This is consistent with the hypothesis that in such patients distant micrometastatic dissemination already exists at the time of initial diagnosis. The data suggest that clinical trials designed to test whether improvements in local therapy impact on survival should be restricted to node negative patients. The data also raise concerns regarding the therapeutic value of elective whole pelvic irradiation.


Chitosan nanoparticles containing the insecticide dimethoate: A new approach in the reduction of harmful ecotoxicological effects.
Organophosphate insecticides such as dimethoate (DMT) are widely used in agriculture. As a side effect, however, these insecticides contaminate bodies of water, resulting in damage to aquatic organisms. The development of nanopesticides may be an innovative alternative in the control of agricultural pests, increasing effectiveness and reducing their toxicological effects. Based upon this, the present study has investigated encapsulated DMT in alginate chitosan nanoparticles (nanoDMT) and evaluated its toxicological effects on non-target organisms. The nanoparticles were characterized by DLS, NTA and AFM, as well as being evaluated by the release profile. Nanoparticle toxicity was also evaluated in comparison with DMT, empty nanoparticles and DMT (NP + DMT), and commercial formulations (cDMT), in the embryos and larvae of Danio rerio (zebrafish) according to lethality, morphology, and behavior. The nanoparticle control (NP) showed hydrodynamic size values of 283 ± 4 nm, a PDI of 0.5 ± 0.05 and a zeta potential of -31 ± 0.4 mV. For nanoparticles containing dimethoate, the nanoparticles showed 301 ± 7 nm size values, a PDI of 0.45 ± 0.02, a zeta potential of -27.9 ± 0.2 mV, and an encapsulation of 75 ± 0.32%, with slow-release overtime (52% after 48 h). The AFM images showed that both types of nanoparticles showed spherical morphology. Major toxic effects on embryo larval development were observed in commercial dimethoate exposure followed by the technical pesticide, predominantly in the highest tested concentrations. With regard to the toxic effects of sodium alginate/chitosan, although there was an increase for LC50-96 h concerning the technical dimethoate, the behavior of the larvae was not affected. The data obtained demonstrate that nanoencapsulated dimethoate reduces the toxicity of insecticides on zebrafish larvae, suggesting that nanoencapsulation may be safer for non-target species, by eliminating collateral effects and thus promoting sustainable agriculture.


RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans.
Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963(∗)] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration.


Ectopic thyroids have lower computed tomography attenuation values than orthotopic thyroids.
To determine whether ectopic thyroid had the same computed tomography (CT) value as orthotopic thyroid. Twenty-one patients with 23 ectopic thyroids and 23 controls with orthotopic thyroids underwent CT scans and were included in this retrospective study. The CT images were reviewed in a blinded fashion by two radiologists. Independent-Samples T-test was used for comparison of CT attenuation values between two groups. Ectopic thyroids had significantly lower non-enhanced attenuation (91.04 ± 5.97 Hounsfield Units vs. 106.56 ± 4.06 Hounsfield Units, P = 0.038) and contrast-enhanced attenuation (141.32 ± 6.42 Hounsfield Units vs. 169.82 ± 4.30 Hounsfield Units, P = 0.001) values than orthotopic thyroids. Ectopic thyroids have lower CT attenuation values than orthotopic thyroids probably due to the structural or functional abnormalities. The dysgenesis and pathological changes of the ectopic thyroids may contribute to functional deficiency which finally leads to decrease of the CT attenuation values.


Rod bipolar cell dysfunction in POLG retinopathy.
To report the clinical and novel electrophysiological features in a child with POLG-related sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO). The proband, a male child of Indian descent, underwent serial systemic and ophthalmological evaluations from birth until 14 years of age. Eye examinations included visual acuity and extraocular movement assessments, fundus photography, spectral domain optical coherence tomography and full-field electroretinography (ERG). Detailed genetic testing was also performed. The child carried a homozygous mutation in POLG (c.911T > G/p.Leu304Arg) and manifested systemic features such as seizures, headaches, areflexia, hypotonia, myopathy and vomiting. The child's distance visual acuity was 0.50 and 0.40 LogMAR in the right and left eyes, respectively. Bilateral ophthalmoplegia and ptosis were observed at 5 years of age. The dark-adapted (DA) ERG responses to 2.29 cd s m-2 and 7.6 cd s m-2 stimuli showed a markedly reduced b/a ratio; an electronegative configuration was noted to a DA 7.6 ERG. This is the first documented case of an electronegative ERG in a POLG-related disorder consistent with generalized rod ON-bipolar dysfunction. The rest of the proband's systemic and ophthalmological features were consistent with SANDO but some features overlapped with other POLG-related disorders such as Alpers-Huttenlocher syndrome and autosomal dominant progressive external ophthalmoplegia demonstrating the wide phenotypic overlap expected due to POLG mutations.


In vivo stimulation of nerve cells by phytohemagglutinin. II. Alterations in the rate of total and mRNA synthesis in the brain cortex of old rats.
Bacto-phytohemagglutinin-P (PHA-P) was administered in form of a single intralumbar injection of 2 mg/100 g body weight dose to 24- to 28-mth-old female CGY rats. The accuracy of the injection technique was checked by adding 2% lidocaine to the injection mixture, which resulted in a transient and symmetric paralysis of the posterior limbs when reaching the cerebrospinal fluid. The total RNA content of the liver and brain cortex were measured, and phenolic extraction of RNA was performed the brain cortex. Poly(A) +RNA (mRNA) was separated from the total RNA of the brain cortex by oligo(dT)-cellulose chromatography. Pulse labeling with tritiated uridine was performed 45 min before killing the animals and the incorporation of the radiolabel was measured in the respective RNA classes and corrected for the nucleotide pool size. The rates of total and mRNA synthesis are expressed in percentages of the young untreated rats and compared to old untreated animals. The effects of PHA-P was studied at 4, 10, 20 and 44 h after its injection. A considerable increase of the total RNA content of the brain cortex was measured during the first 10 h of the experiment followed by a slow decrease. However, the RNA content of the brain cortex was still significantly higher at the end of experiment compared to untreated old rats. The rate of total RNA synthesis increased significantly during the first 10 h and remained constantly high until 44 h. The rate of mRNA synthesis increased to a higher extent than that of the total RNA, and also remained high until 44 h.


Familial Alzheimer's disease-linked presenilin-1 mutation M146V affects store-operated calcium entry: does gain look like loss?
Alzheimer's disease (AD) is a neurodegenerative disorder that leads to neuron death and synapse loss in the hippocampus and cortex, with consequent cognitive disability and dementia. Mutations in the presenilin-1 (PS1) gene lead to familial Alzheimer's disease (FAD). Here, we report that the expression of FAD-linked PS1 M146V mutant affects store-operated calcium channel activity (Isoc) in human neuroblastoma SK-N-SH cells. Electrophysiological measurements and calcium imaging experiments have revealed the emergent role of calcium sensor STIM2 in the inhibition of calcium release-activated calcium channel activity (Icrac) and enhancement of intracellular Ca(2+) stores content due to PS1 M146V mutant expression. In general, the results of this study suggest that the pathological inhibition of one type of store-operated calcium channels caused by FAD PS1 mutant expression may be accounted for by preceding gain of spontaneous activity of store-operated calcium channels driven by STIM2.


[The correlation of serum parathyroid hormones among patients with dementia of vascular type, hemodialysis, and bone-joint disorders].
PTH levels were analysed in sera of patients receiving maintenance hemodialysis, with the vascular type of dementia and orthopedic patients with bone-joint disorders, using PTH assay kits. There were significant interrelationship among all kinds of PTH levels in the hemodialysis patients, but not in patients with the vascular type of dementia and the bone-joint disorders. Renal functions might be responsible for fragmentation of PTH in blood stream. These results suggested that the measurement of PTH levels is needed to examine various kinds of amino-sequence of PTH levels in keeping normal function of kidney.


Factors associated with acute care service use after epilepsy hospitalisation in people with intellectual disability.
This study aimed to identify factors associated with unplanned acute hospital readmission and emergency department (ED) presentation after hospitalisation for epilepsy in people with intellectual disability (ID). This study is a retrospective cohort study using linked administrative datasets. We identified 3293 people with ID aged 5-64 years with a hospitalisation for epilepsy between 2005 and 2014 in New South Wales, Australia. We examined unplanned readmission and ED presentation within 30 or 365 days and associations with demographic, socio-economic and health status variables. Modified Poisson regression with robust estimation was used to model outcomes within 30 days. Negative binomial regression was used to account for the overdispersion of the data and to model 365-day outcome rates. Around half of the cohort had an unplanned readmission and ED presentation within 365 days of the index hospitalisation. In fully adjusted models, being female, being a young adult and having a longer or acute care index admission, mental and physical comorbidities and a history of incarceration were associated with an elevated risk of readmission or ED presentation. The strongest association was observed between history of self-harm and 365-day readmission (incidence rate ratio 2.15, 95% confidence interval 1.41-3.29). Socio-demographic, justice and health factors are associated with unplanned readmission and ED presentation risk after hospitalisation for epilepsy in people with ID. Interventions targeting improving continuity of care should be tailored for individuals and their support workers. The findings also emphasise the importance of person-centred multidisciplinary care across different health sectors.


Spontaneous angular dichorionic diamniotic twin pregnancy: a case report.
To report a peculiar case of ultrasound diagnosis of spontaneous angular twin pregnancy. In literature, the terms "angular," "interstitial," and "cornual" pregnancies are often used inappropriately. Confusion in terminology may have contributed to difficulties in developing diagnostic ultrasound criteria to differentiate these ectopic pregnancies. Case report. Obstetrics and Gynecology, Community Hospital "S. Maria delle Croci." A 28-year-old patient with a previous cesarean delivery was admitted to our hospital for management of a presumed angular ectopic pregnancy. Transvaginal ultrasound confirmed an ectopic dichorionic diamniotic twin pregnancy eccentrically located in the right superior angle of the uterine cavity: the first gestational sac appeared to have right angular implantation, whereas the second gestational sac seemed to deepen inside the myometrium, with a thin myometrial margin of only 3 mm. After discussing the risks, the patient requested to proceed with termination. A single intramuscular injection of 75 mg of methotrexate was administered, followed by ultrasound-guided hysterosuction after 19 days due to severe vaginal bleeding. An early and accurate ultrasound diagnosis of a high-risk condition allowed for conservative medical treatment. The serum beta-human chorionic gonadotropin levels progressively decreased. After 1 month, a clinical and ultrasound examination showed a regular endometrial line with a regular reappearance of menstrual bleeding. Although there are remarkable advances in ultrasound techniques, angular pregnancy remains a condition of difficult diagnosis and management; it is potentially dangerous and may lead to severe complications. An early and accurate diagnosis of this condition is necessary to avoid complications and individualize the subsequent management.


High-fat, low-carbohydrate diet alters myocardial oxidative stress and impairs recovery of cardiac function after ischemia and reperfusion in obese rats.
Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats. These findings may have important implications for diet selection in obese patients with ischemic heart disease.


Role of morphine, miR-212/132 and mu opioid receptor in the regulation of Bdnf in zebrafish embryos.
Morphine is one of the first-line therapies for the treatment of pain despite its secondary effects. It modifies the expression of epigenetic factors like miRNAs. In the present study, we analyzed miR-212 and miR-132 and their implication in morphine effects in the zebrafish Central Nervous System (CNS) through the regulation of Bdnf expression. We used control and knock-down zebrafish embryos to assess the effects of morphine in miRNAs 212/132 and mitotic or apoptotic cells by qPCR, immunohistochemistry and TUNEL assay, respectively. Bdnf and TrkB were studied by western blot and through a primary neuron culture. A luciferase assay was performed to confirm the binding of miRNAs 212/132 to mecp2. Morphine exposure decreases miR-212 but upregulates miR-132, as wells as Bdnf and TrkB, and changes the localization of proliferative cells. However, Bdnf expression was downregulated when miRNAs 212/132 and oprm1 were knocked-down. Furthermore, we proved that these miRNAs inhibit mecp2 expression by binding to its mRNA sequence. The described effects were corroborated in a primary neuron culture from zebrafish embryos. We propose a mechanism in which morphine alters the levels of miRNAs 212/132 increasing Bdnf expression through mecp2 inhibition. oprm1 is also directly involved in this regulation. The present work confirms a relationship between the opioid system and neurotrophins and shows a key role of miR-212 and miR-132 on morphine effects through the regulation of Bdnf pathway. miRNAs 212/132 are novel regulators of morphine effects on CNS. Oprm1 controls the normal expression of Bdnf.


The contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore.
Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia.


Multiplexed interactions: viruses of endophytic fungi.
Mycoviruses have been detected from all four classes of fungal endophytes. The virus species richness is probably extremely high in endophytes. The incidence and diversity of mycoviruses may be affected by transmission modes, virus-fungus-plant interactions, and endophyte population structures. Endophyte viruses are unlikely to be strong antagonists to their fungal hosts and can clearly play mutualistic roles in the multiplex symbioses with endophytes and plants under some environmental conditions. A better understanding of fungal endophyte viruses will help prospects of future applications for sustainable agriculture.