Gastrointestinal and retroperitoneal sarcoma--local experience and review of the literature.
Gastrointestinal and retroperitoneal sarcoma are uncommon tumours. Out of 26 cases treated over the last 6 years, there were 16 smooth muscle tumours (SMT) and 10 non Hodgkin Lymphomas (ML). 7 cases of SMT were leiomyosarcoma. The majority of the cases were found in the stomach. 8 cases presented as acute emergencies while the non acute cases had non specific complaints. Despite the use of barium studies, gastroscopy and CT scan, only 5 cases were diagnosed preoperatively. The majority underwent curative resection. ML cases had a combination of radiotherapy and chemotherapy. 2 patients with large and high grade leiomyosarcomas have died. 4 patients with ML have also died, 2 with locally advanced disease and 2 with distant metastases. We conclude that most cases are not diagnosed preoperatively due to their rarity and nonspecific clinical presentation. The important prognostic factors are size and mitotic index for SMT and stage of the disease for ML.


Optimal Fasting Time before Measurement of Serum Triglyceride Levels in Healthy Volunteers.
Coronary heart disease is a major public health problem. Elevated triglyceride levels are a risk factor for atherosclerosis and coronary heart disease. Food intake interferes with the measurement of serum triglyceride levels, and in previous studies, fasting for 12 hours was recommended before blood sampling. In real-world practice, long fasting times cause patient discomfort and poor compliance, and the present study was, therefore, designed to determine the appropriate fasting time prior to measuring serum triglyceride levels. To determine the appropriate fasting time before measuring serum triglyceride levels. This was a pilot study performed using healthy volunteers aged between 20 and 30 years old from November 2013 to December 2013 at Rajavithi Hospital. The first blood sample was measured in the morning after fasting over 12 hours. The subjects then took their regular breakfast, after which they fasted for 8 hours. Blood samples were taken 6 and 8 hours later and sent to the laboratory for measurement of serum triglyceride levels. 40 volunteers, of whom 25 were female, were enrolled. Their mean age was 25.9 ± 2.81 years old, and their mean weight, height, and body mass index were 61.5 ± 12.5 kg, 167.2 ± 8.3 cm and 21.84 ± 3.1 kg/m2, respectively. Mean fasting serum triglyceride level at 12 hours was 80.23 ± 36.33 mg/dl, at 6 hours it was 110.65 ± 73.45 mg/dl, and at 8 hours it was 75.62 ± 46.81 mg/dl. The group fasting for 12 hours had significantly lower serum triglyceride levels than the group fasting for 6 hours (p-value = 0.003), but no significant difference was found between the group fasting for 12 hours and the one fasting for 8 hours (p-value = 0.493). The present study showed no significant difference in triglyceride levels in patients who had fasted or 8 hours and those who had done so for 12 hours. Fasting for only 8 hours before measurement of serum triglyceride may be sufficient.


Comparative analysis of requirements for quality of fish oil for food and medical applications.
Fish oil is reach natural source of vitamins А, Е, D and polyunsaturated fatty acids (PUFA) which are useful for supplementation, prophylaxis and therapy in food industry, medicine and veterinary. The analysis of regulatory documents for the quality of fish oil (based on concentration of main nutrients) leads to conclusion that content of vitamins A and D, and PUFA is controlled in medicinal preparations. With regard to fish oil for food application there is no unified approach. In particularly, content of vitamin D in food supplements with fish oil available on Russian market is not indicated by manufacturer or its concentration varies in 3-10 folds. Because of important biological functions and pharmacological activity, it is very important to have uniform standardization for vitamins and PUFA in fish oil for application in food industry and medicine. Development and unification of analytical methods became special attention for these reasons.


Complete genome sequences of agricultural azole-resistant Penicillium rubens encoding CYP51A and ERG11 paralogues.
Azoles are major antifungals in agriculture and medicine. However, the surge of intrinsic azole resistance is critical for public health. Here, we present the complete long-read sequencing of three azole-resistant Penicillium rubens from food crops. The presence of CYP51A and ERG11 paralogues was confirmed, as in other azole-resistant P. rubens.


A New Water-Soluble Nanomicelle Formed through Self-Assembly of Pectin-Curcumin Conjugates: Preparation, Characterization, and Anticancer Activity Evaluation.
Curcumin is a dominating active component of Curcuma longa and has been studied widely because of its prominent biological activities. The extremely low aqueous solubility, stability, and bioavailability of curcumin limit its application in the field of medicine. In this study, we developed pectin-curcumin (PEC-CCM) conjugates that could self-assemble water-soluble nanomicelles in aqueous solution. The structure of PEC-CCM conjugates was characterized by ultraviolet-visible spectra, fluorescence spectra, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance spectroscopy. The thermal property of PEC-CCM conjugates was investigated by thermogravimetric analysis. It was found that PEC-CCM conjugates had formed nanomicelles in aqueous medium via self-assembly. These nanomicelles were observed as small spheres or ellipsoids and aggregated with a size range of 70-190 nm by transmission electron microscopy analysis. In a solution of nanomicelles, the stability of curcumin was improved, and its antioxidant property was preserved. The anticancer activity of PEC-CCM conjugates was quantified by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay using a hepatic cancer cell line (HepG2), a breast cancer cell line (MCF-7), a cervical cancer cell line (HeLa), and a human normal kidney cell line (293A). It was found that the curcumin of PEC-CCM conjugates had a more significant inhibitory effect on cancer cells and was less cytotoxic to normal cells than free curcumin was. PEC-CCM conjugates have great potential for some food and pharmaceutical applications.


Multilocus sequence typing of methicillin-resistant Staphylococcus aureus from an area of low endemicity by real-time PCR.
A protocol for multilocus sequence typing (MLST) of methicillin-resistant Staphylococcus aureus (MRSA) was adapted to real-time LightCycler System PCR for efficient and rapid amplification of seven housekeeping genes in the same PCR run and real-time detection of the products. The method was evaluated on a representative and well-characterized collection of clinical MRSA isolates (n = 57) obtained from an area of low endemicity. Twenty sequence types (STs) and nine clonal complexes were identified. Combining STs and the staphylococcal cassette chromosome mec (SCCmec) type identified 27 different genotypes, and type IV SCCmec was present in 11 different STs. The presence of the Panton Valentine leukocidin (PVL) genes was found in isolates of four different STs. Eleven different STs were found among the community-acquired as well as among the hospital-acquired MRSA. The genetic heterogeneity was also denoted by pulsed-field gel electrophoresis analysis that showed 24 different pulsotypes among the 57 MRSA isolates. The presence of more than one different type of SCCmec in the same ST indicates that the MRSA clones have arisen at several occasions in the same genetic background by independent acquisition of SCCmec into methicillin-sensitive strains. This circumstance shows the importance of combining MLST data with SCCmec-typing results when investigating the origins of MRSA.


Renal insufficiency without albuminuria is associated with peripheral artery atherosclerosis and lipid metabolism disorders in patients with type 2 diabetes.
A high prevalence of a low glomerular filtration rate (GFR) has recently been reported in patients with diabetes without albuminuria. We aimed to clarify the clinical characteristics of such patients, including the associations between these characteristics and atherosclerosis. We investigated the correlations between the estimated GFR (eGFR) and lipid profiles, the ankle-brachial index (ABI) and the intima-media thickness (IMT) in 450 patients with type 2 diabetes without macroalbuminuria. The prevalence of renal insufficiency (RI) (GFR <60 mL/min/1.73 m(2)) in the patients without albuminuria was 19.1%. The ABI values of the patients with RI were significantly lower than those of the patients without RI, regardless of the presence of microalbuminuria, while there were no significant differences in IMT between the patients with and without RI. In a multivariate analysis, a low ABI was found to be significantly associated with a low eGFR, independent of age, sex, smoking, history of hypertension and/or dyslipidemia and duration of diabetes (β=0.134, p=0.013), whereas no significant associations were observed between the ABI and the urinary albumin excretion rate (UAER). The ApoB/LDL-C ratios and levels of ApoC3 were significantly higher in the patients with RI than those observed in the patients without RI, regardless of the presence of albuminuria. RI without albuminuria is closely associated with atherosclerosis of the peripheral arteries in diabetic patients. Furthermore, alterations in lipid metabolism may underlie this association.


Lymphocyte subsets in the lymph nodes of rats with autoimmune orchitis.
We determined temporal variations of cell subpopulations in the immunization draining lymph nodes during the development of an experimental autoimmune orchitis (EAO) induced in Wistar rats. A phenotypic characterization of T cells and their subsets (CD4+ and CD8+), B, and Ia+ cells was performed by immunofluorescent technique. At the end of the immunization period (30 days), rats injected with testicular homogenate plus adjuvants presented a considerable increase in absolute cell number but normal lymphocyte subset percentages. Testicular damage became evident at 50 days after the first immunization and increased its severity at 80 days: animals that developed EAO presented a lower number of CD8+ cells as compared with undamaged rats. This latter group showed a low CD4/CD8 ratio due to the high proportion of CD8+ cells, which could probably have a suppressor function. At 80 days massive testicular infiltration and decreased absolute cell number in lymph nodes suggest the possible migration of specific lymphocytes to the target organ.


Relationship of maternal weight status to selected pregnancy events.
The relationship of maternal weight status to the probability of appearance of one or a combination of three or more undesirable pregnancy events ( UPE ) was analyzed. A total of 711 women presenting for prenatal care before 16 weeks estimated gestational age were categorized according to early pregnancy body mass ( EPBM ) and subsequent weight gain. Statistical analysis revealed weight gain related to the appearance of one UPE only in women with an EPBM less than 120 pounds. In gestations complicated by three or more UPEs , a relationship to weight gain was shown only in women with an EPBM of 120-199 pounds.


Individual and Collective Competence.
Concepts of competence and competency management continue to challenge and stress nursing professional development practitioners. A shift from focusing on individual competence to building the competence of a team is one strategy to meet the increasing needs of the current health care environment. J Contin Educ Nurs. 2017;48(4):148-150.


Benzalkonium chloride induces subconjunctival fibrosis through the COX-2-modulated activation of a TGF-β1/Smad3 signaling pathway.
The purpose is to investigate the mechanism of subconjunctival fibrosis caused by benzalkonium chloride (BAC), which is the most common preservative in ophthalmic preparations. The left eyes of male Sprague-Dawley rats were topically treated with 0.01% BAC or PBS twice daily for 1 month. Primary conjunctival fibroblasts (CFs) were exposed for 24 hours to 0.00005% BAC, 0.000075% BAC, 0.000075% BAC + LY2157299 (a selective transforming growth factor β receptor type I inhibitor); 0.000075% BAC + NS-398 (a selective cyclooxygenase-2 inhibitor) and PBS, respectively. The pathological changes of the bulbar conjunctival tissue of rats were examined using hematoxylin-eosin (HE), Van Gieson's (vG), periodic acid-Schiff (PAS) stains, or immunohistochemisty (IHC). The expression of the extracellular matrix (ECM), the transforming growth factor β (TGF-β) signaling pathway-related molecules, and cyclooxygenase-2 (COX-2) in bulbar conjunctival tissues and CFs were detected using Western blot (WB) and quantitative real-time RT-PCR (qRT-PCR). Rats treated with 0.01% BAC exhibited a slight increase of the fibroblast density and a more compact collagen deposition in the bulbar subepithelial connective tissues in comparison with rats treated with PBS. Western blot and qRT-PCR analyses showed that the expression of ECM, TGF-β signaling pathway-related molecules, and COX-2 were markedly increased in the bulbar conjunctival tissues of rats exposed to 0.01% BAC and in CFs exposed to 0.00005% and 0.000075% BAC. In conjunctival fibroblasts, BAC-induced ECM expression was clearly decreased by LY2157299, while the BAC-induced activation of the TGF-β1/Smad3 signaling pathway was greatly attenuated by NS-398. Subconjunctival fibrosis BAC-induced is a consequence of excessive ECM production of CFs through the COX-2-modulated activation of a TGF-β1/Smad3 signaling pathway.


Laparoscopic Removal of Angelchik Prosthesis Followed by Interval Sleeve Gastrectomy.
The Angelchik prosthesis (AP) is a historic antireflux device which consists of a C-shaped silicone ring placed around the gastroesophageal junction (GEJ) and secured by Dacron tape. We present a rare experience with an AP and its impact on bariatric surgical outcomes. Our patient is a 66-year-old woman who had an open antireflux procedure with an AP in 1987. She presented to a bariatric clinic for consideration of bariatric surgery for the treatment of morbid obesity and associated comorbidities. She also reported significant problems with reflux and dysphagia. After an appropriate work-up, an AP was identified at her GEJ. She was taken to the operating room for laparoscopic removal with planned interval laparoscopic sleeve gastrectomy. Intraoperatively, the AP was identified around the GEJ; after extensive adhesiolysis, the prosthesis was removed. Postoperatively, in order to determine if the AP had caused any lasting esophageal motility problems, the patient underwent a high-resolution esophageal manometry which demonstrated normal esophageal motility. Interval laparoscopic sleeve gastrectomy was performed safely 9 weeks later. Although rarely used, it is still possible to encounter an Angelchik prosthesis in practice. General and bariatric surgeons need to be aware of this rare device and understand how to manage its related complications.


[Treatment of hepatitis C with peginterferon and ribavirin in Iceland from 2002-2012].
Hepatitis C is a major cause of chronic liver disease and cirrhosis in Western countries. Its treatment aims at eradicating the virus and patients are considered cured if the virus is undetectable by PCR in blood 12-24 weeks after end of treatment (sustained virological response, SVR). The aim of this study is to investigate the results of treating hepatitis C in Iceland during the period 2002-2012. Retrospective study including all patients with hepatitis C receiving treatment with peginterferone and ribavirin at Landspitali University hospital during the period 2002-2012. Patients who had been treated previously were excluded. Information was obtained from medical records and the hospital pharmacy. A total of 207 patients were included, 136 (66%) males and 71 (34%) females. Mean age was 38 years (range 17-66). Genotyping revealed that 71 (34%) patients had genotype 1, 135 (65%) genotype 3 and one genotype 2. A total of 147 (71%) patients achieved SVR. The rate of SVR was 77.8% for genotype 3 and 57.7% for genotype 1. 9 patients (4%) had cirrhosis and 3 of them had SVR. Of 161 patients who finished treatment per protocol, 87.5% and 77.1% with genotypes 3 and 1 respectively had SVR. The study demonstrates higher rates of SVR in clinical practice in Iceland compared to controlled clinical trials. The improved effectiveness may be explained by younger patient population, low rate of cirrhosis and close follow-up of patients. Key words: Hepatitis C, peg-interferon, sustained virological response. Correspondence: Sigurdur Olafsson, email@example.com.


Intracellular transport blockade caused by disruption of the disulfide bridge in the third external domain of major histocompatibility complex class I antigen.
The third external domain of major histocompatibility class I antigens has a highly conserved disulfide bridge between cysteine-203 and cysteine-259. To elucidate the functional significance of this disulfide bridge, we have produced a mutant H-2Ld gene by site-directed mutagenesis in which the codon for cysteine-203 is changed to a codon for serine, which is unable to form a disulfide bridge. The mutant H-2Ld gene was introduced into mouse L cells and its expression has been studied. No measurable expression of the H-2Ld antigen was detected on the cell surface of the transformants by antibody-binding assays. However, a large quantity of the mutant H-2Ld antigen was found in the cytoplasm of the transformants as observed by immunoprecipitation of metabolically labeled lysate and by immunocytochemistry of membrane-permeabilized cells, using an antibody specific for the first external domain of the H-2Ld antigen. The mutant antigen was glycosylated and associated, at least in part, with beta 2-microglobulin. Subcellular fractionation experiments indicated that the transport of the antigen was blocked between the endoplasmic reticulum and the plasma membrane. It is concluded that structural integrity of the third external domain is a prerequisite for intracellular transport of class I antigens. On the basis of these findings we suggest that the domain structure containing the disulfide bridge serves as a signal structure necessary for receptor-mediated intracellular transport and that this requirement is the evolutionary basis for high conservation of similar structures present throughout the immunoglobulin supergene family.


Clinical and Molecular Aspects of C2orf71/PCARE in Retinal Diseases.
Mutations in the photoreceptor-specific C2orf71 gene (also known as photoreceptor cilium actin regulator protein PCARE) cause autosomal recessive retinitis pigmentosa type 54 and cone-rod dystrophy. No treatments are available for patients with C2orf71 retinal ciliopathies exhibiting a severe clinical phenotype. Our understanding of the disease process and the role of PCARE in the healthy retina significantly limits our capacity to transfer recent technical developments into viable therapy choices. This study summarizes the current understanding of C2orf71-related retinal diseases, including their clinical manifestations and an unclear genotype-phenotype correlation. It discusses molecular and functional studies on the photoreceptor-specific ciliary PCARE, focusing on the photoreceptor cell and its ciliary axoneme. It is proposed that PCARE is an actin-associated protein that interacts with WASF3 to regulate the actin-driven expansion of the ciliary membrane during the development of a new outer segment disk in photoreceptor cells. This review also introduces various cellular and animal models used to model these diseases and provides an overview of potential treatments.


Sequence specific DNA cross-linking triggered by visible light.
A new biocompatible strategy for photoinduced DNA interstrand cross-linking is presented. Methylene blue induced (1)O(2) formation triggers furan oxidation; the resulting aldehyde then rapidly reacts with complementary A or C with formation of stable adducts. Easily accessible furan modified nucleosides, a commercially available photosensitizer, and visible light irradiation constitute the necessary tools to achieve selective duplex interstrand cross-linking.


Successful Daptomycin Use in a Pediatric Patient With Acute, Bilateral Osteomyelitis Caused by Methicillin-Resistant Staphylococcus aureus.
Staphylococcus aureus is the most common bacteria associated with the development of osteomyelitis in pediatric patients. Osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) can be difficult to safely and effectively treat. Vancomycin, linezolid, and clindamycin are commonly used to treat osteomyelitis caused by MRSA. While adult studies suggest intravenous (IV) daptomycin may by beneficial for the treatment of MRSA osteomyelitis, it is not Food and Drug Administration approved for use in pediatrics, and minimal data are available related to its use in this population. This case report describes the successful use of daptomycin (8 mg/kg/dose IV daily) combined with rifampin for 5 weeks, followed by 5 weeks of oral sulfamethoxazole/trimethoprim, for treatment of acute bilateral osteomyelitis caused by MRSA in an 8-year-old male. The patient did not initially respond to the combination of vancomycin plus rifampin and gentamicin, nor did he respond to ceftaroline treatment. After initiation of daptomycin, his fevers quickly subsided, his pain rapidly improved, and his inflammatory markers significantly decreased. While daptomycin was effective in this patient, additional research is needed to determine the true safety and efficacy of this drug for treatment of osteomyelitis caused by MRSA in pediatric patients.


Diagnostic significance of adenosine deaminase in pleural tuberculosis.
Tuberculosis (TB) is a major cause of pleural effusion, which in TB usually has lymphocytic and exudative characteristics. Analysis of adenosine deaminase (ADA) activity is a very useful diagnostic approach to achieve a more rapid and precise diagnosis in cases of Pleural TB (pTB). Fifty male and fifty female patients presenting with tuberculous pleural effusion was included in the study. The patients were taken from the medical ward of Sir Ganga Ram Hospital between September 2001 and September 2002. Activity of Adenosine Deaminase (ADA) was estimated by the technique of Sodium dodecyl sulphate electrophoresis (SDS-EF) using 10% polyacrylamide gel. Mean age of males was 45.72 +/- 19.22 years and of female was 43.74 +/- 16.09 years. Mean protein level was 3.39 +/- 0.24 g/dl in males, and it was 3.02 +/- 0.26 g/dl in females. Mean specific gravity both in males and females was 1.020 +/- 0.01. The results show an increased level of enzyme ADA in patients as compared to normal subjects. Estimation of ADA activity may provide basis for rapid and efficient diagnosis of pleural TB in different clinical settings. However study should be extended to larger number of patients to reach a better conclusion.


Absence of chromosome damage in human lymphocytes exposed to allopurinol and oxipurinol.
The biochemical evidence against incorporation of the purine analogues, allopurinol and oxipurinol, into nucleic acids is reviewed. Cytological experiments have been carried out to investigate the possibility that chromosomal damage might result from exposure of human lymphocytes to these drugs. Lymphocytes from 19 patients receiving allopurinol and one receiving oxipurinol were examined for the presence of chromatid aberrations during metaphase, and lymphocytes from untreated subjects were similarly studied during in vitro exposure to the drugs. The low frequency of aberrations observed was well within normal limits, and it is concluded that allopurinol and oxipurinol have no deleterious effects on chromosome structure.


Transcatheter closure of postinfarction ventricular septal defects.
Postinfarction ventricular septal defect (VSD) is a rare but fatal complication after myocardial infarction. Surgery for postinfarction VSD is considered the gold standard. However, it is associated with high morbidity and mortality, patient discomfort, need of cardiopulmonary bypass, sternotomy, and skin scarring. As a consequence, less invasive interventional techniques have been developed for postinfarction VSD closure. The current review focuses on patient selection, techniques, results, potential complications and outcome of percutaneous postinfarction closure.


Oxygen saturation before and after mechanical thrombectomy and functional outcome in patients with acute ischemic stroke.
Currently, there is a lack of effective neuroprotective strategies to break the ceiling effect of mechanical thrombectomy (MT), and one of the most promising is normobaric oxygen treatment. However, the impact of pre- and post-MT oxygen saturation on clinical outcomes in patients with acute ischemic stroke (AIS) remains unclear. We aimed to determine the influence of preoperative and postoperative oxygen saturation on 3-month poor outcome in patients with AIS. A total of 239 consecutive stroke patients with successful recanalization by MT between May 2017 and March 2021 were analyzed. Oxygen saturation was measured non-invasively by pulse oximetry at baseline and continually after MT. Regression analysis was used to assess the association of preoperative and postoperative oxygen saturation with a 3-month poor outcome (modified Rankin Scale score: 3-6). Decreased preoperative oxygen saturation level was associated with an increased risk of poor outcome (odds ratio, 0.85; 95% CI, 0.73-0.98; P = 0.0293). Postoperative oxygen saturation had the opposite effect on poor outcome (odds ratio, 1.60; 95% CI, 1.13-2.27; P = 0.0088). Preoperative and postoperative oxygen saturation have different impacts on 3-month poor outcome in patients with AIS with successful recanalization by MT.


[Analysis of heart rate variability during parallel swinging].
To study the pilots' heart rate variability (HRV) characteristic before, during and after parallel swing and the possibility of evaluating vestibule-vegetative nervous reaction under linear acceleration. 37 healthy male pilots participated in parallel swing test. Dynamic ECG was recorded for 15 min before, during and after swing, using model MR-4500 Holter recorder. All spectra were estimated from 15 min HRV by autoregressive (AR) modeling method, the model order (8-15) was chosen using automatic program. The ratio of lower-frequency (LF) to high-frequency (HF) power of HRV spectrum (LF/HF) was computed. The relation between change of those ratios in different swing stage and swing time was analysed. Ratio of LF to HF during swing was markedly lower than those of before and after swing (P<0.01). The vagal nervous activity was markedly increased during swing. There were complexity and versatility in the heart automatic nervous regulation before, during and after swing.


Idiopathic lingual artery aneurysm: CT findings and endovascular therapy. A case report.
We describe a 65-year-old woman with an asymptomatic idiopathic lingual artery aneurysm which is suspected to be congenital. We review the literature on external carotid artery branch aneurysms, diagnostic evaluation and discuss treatment options for the various types and the specific chosen in the case presented.


Controlled redox conversion of new X-ray-Characterized Mono- and dinuclear heptacoordinated Mn(II) complexes into di-micro-oxo-dimanganese core complexes.
Two heptacoordinated Mn(II) complexes are isolated and X-ray characterized using the well-known tpen ligand (tpen = N,N,N',N'-tetrakis(2-pyridylmethyl)-1,2-ethanediamine): [(tpen)Mn(OH(2))](ClO(4))(2) (1(ClO(4))(2)) and [(tpen)Mn(micro-OAc)Mn(tpen)](ClO(4))(3).2H(2)O (2(ClO(4))(3).2H(2)O). Crystallographic data for 1(ClO(4))(2) at 110(2) K (respectively at 293(2) K): monoclinic, space group C2/c, a = 15.049(3) A (15.096(3) A), b = 9.932(2) A (10.105(2) A), c = 19.246(4) A (19.443(4) A), beta = 94.21(3) degrees (94.50(3) degrees ), Z = 4. Crystallographic data for 2(ClO(4))(3).0.5(C(2)H(5))(2)O at 123(2) K: triclinic, space group P, a = 12.707(3) A, b = 12.824(3) A, c = 19.052(4) A, alpha = 102.71(3) degrees, beta = 97.83(3) degrees, gamma = 98.15(3) degrees, Z = 2. Investigation of the variation upon temperature of the molar magnetic susceptibility of compound 2(ClO(4))(3).2H(2)O reveals a weak antiferromagnetic exchange interaction between the two high-spin Mn(II) ions (J = -0.65 +/- 0.05 cm(-)(1), H = -JS(1).S(2)). EPR spectra are recorded on powder samples and on frozen acetonitrile solutions, demonstrating the maintenance upon dissolution of the heptacoordination of Mn in complex 1 while complex 2 partially dissociates. Electrochemical responses of complexes 1 and 2 are investigated in acetonitrile, and bulk electrolyses are performed at oxidative potential in the presence of various amounts of 2,6-lutidine (0-2.65 equiv per Mn ion). The formation from either 1 or 2 of the mixed-valent complex [(tpen)Mn(III)(micro-O)(2)Mn(IV)(tpen)](3+) (3) is established from mass spectrometry and EPR and IR spectroscopy measurements. When reaction is started from 2, formation of [(tpen)Mn(IV)(micro-O)(2)(micro-OAc)Mn(IV)](3+) (4) is evidenced from cyclic voltammetry, EPR, and UV-vis data. The Mn vs tpen ratio in the electrogenerated complexes is accurately controlled by the quantity of additional 2,6-lutidine. The role of tpen as a base is discussed.


Social stress, performance after-effects and extra-role behaviour.
The article is concerned with the after-effects of social stress on work performance. In a lab-based experiment, seventy participants were assigned to either a stress condition or a no-stress condition. In the stress condition, participants received fake negative performance feedback and they were ostracised by two confederates of the experimenter. Participants carried out the following tasks: attention and divergent creativity. The effects of social stress were examined at three levels: performance after-effects on unscheduled probe tasks, extra-role behaviour and subjective operator state. The manipulation check confirmed that participants experienced social stress. The results showed after-effects of social stress for some forms of extra-role behaviour (i.e. spontaneous reactions) and for the accuracy component of attention. Furthermore, social stress was found to increase negative affect and to reduce self-esteem. The findings point to the importance of assessing different types of after-effects rather than limiting the methodological approach to instant effects on performance.Practitioner summary: The study aimed to examine the multiple effects of social stress. Social stress resulted in increased negative affect and lower self-esteem. Furthermore, social stress was found to reduce the propensity of humans to show extra-role behaviour (i.e. providing spontaneous help to others).


The hyperacute form of allergic encephalomyelitis produced in rats without the aid of pertussis vaccine.
The hyperacute form of experimental allergic encephalomyelitis (EAE), characterized by a short incubation period, severe paralysis, high mortality, and abundant polymorphonuclear leukocytes and fibrin in the lesions, was produced in rats without the use of pertussis vaccine (previously considered an essential requirement) or Freund's adjuvant. Carbonyl iron or mineral oil without mycobacteria were effective adjuvants and whole rat spinal cord was the best antigen. Hyperacute EAE was produced in this manner in some Lewis rats, most dark agouti (DA) rats and most F1 hybrids of these two strains. Clinical signs were earlier in onset and more severe in the DA strain than in the Lewis strain in all adjuvant-antigen combinations that were tested. Dark agouti rats developed clinical signs in six days, histological lesions in five days, and localized EAE lesions could be induced in four days. The data support the hypothesis that hyperacute type lesions (neutrophils and fibrin) can be caused by an exceptionally strong immune response to neural antigen, whether that response is engendered by a particular adjuvant (pertussis vaccine) or by an unusual degree of genetic susceptibility (DA rats).


TAT-NEP1-40 as a novel therapeutic candidate for axonal regeneration and functional recovery after stroke.
Currently available therapeutics has been less effective in promoting functional recovery from stroke or other injuries in the central nervous system (CNS). Axonal damage is a characteristic pathology seen in CNS injuries. Previously, it was reported that Nogo-A extracellular peptide residues 1-40 (NEP1-40), a competitive antagonist of Nogo-66 receptor (NgR1), has the ability to promote axonal regrowth and functional recovery after CNS injury. However, delivery of the therapeutic proteins into the brain parenchyma is limited due to its inability to cross the blood-brain barrier (BBB). We first generated a biologically active NEP1-40 fusion protein containing the protein transduction domain (PTD) of the transactivator of transcription (TAT), TAT-NEP1-40, which crosses the BBB in vivo after systemic delivery. The TAT-NEP1-40 can protect PC12 cells against oxygen and glucose deprivation (OGD) and promote neurite outgrowth when added exogenously to culture medium. The TAT-NEP1-40 protein transduced into the brain continued to sustain biological activities and protected the brain against ischemia/reperfusion injury through inhibition of neuronal apoptosis. Collectively, our data suggest that TAT-NEP1-40 may be a novel therapeutic candidate for axonal regeneration and functional recovery from CNS injuries such as cerebral hypoxia-ischemia, cerebral hemorrhage, brain trauma, and also for spinal cord injury.


[Synthetic studies of imidazole C-nucleosides toward biofunctional molecules].
Synthetic studies of C4-linked imidazole C-nucleosides toward biofunctional molecules are described, in which the following items are covered. 1) Stereoselective synthesis of imidazole C- and pyrazole C-nucleosides via diazafulvene intermediates. 2) Synthesis of tetrahydrofuranylimidazoles using a PhSe group efficiently and its application to the new human histamine H(3) receptor (hH(3)R) agonist, imifuramine, and the first selective human histamine H(4) receptor (hH(4)R) agonist, OUP-16. 3) Synthesis of imidazole ribonucleoside phosphoramidite (Imz-PA) with pivaloyloxymethyl (POM) group for probing the catalytic mechanism of ribozymes. 4) Synthesis of a two-carbon-elongated homologue (Imz-C(2)-PA) with a combination of POM and 2-cyanoethyl groups. 5) Incorporation of C(2)-imidazole nucleoside into position 638 of VS ribozyme using Imz-C(2)-PA and catalytic activities of the thereby generated modified VS ribozyme (G638C(2)Imz).


[A case report of Weber's syndrome associated with supranuclear vertical gaze palsy caused by the ipsilateral thalamomesencephalic lesion].
We report a rare case showing Weber's syndrome associated with supranuclear vertical gaze palsy caused by the ipsilateral lesion of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), which is regarded as the supranuclear control center of vertical gaze. To date, no literature concerning Weber's syndrome associated with the ipsilateral riMLF lesion was documented. The patient was a 53-year-old female, who suddenly developed unconsciousness and left-sided weakness. Neurological findings on admission revealed right third nerve palsy, severe supranuclear vertical gaze palsy, almost complete convergence palsy, left hemiparesis and hyperreflexia with positive Babinski's sign on the left side. There was no sign of pupillary disturbance or no abnormality of the horizontal movements of the left eye. The vestibulo-ocular reflex of the left eye was preserved. There was no sensory disturbance. Cranial MRI had the advantages in demonstrating unilateral ischemic lesions at the cerebral peduncle and the thalamomesencephalic junction involving the unilateral riMLF on the right side. Recent reports have demonstrated that supranuclear vertical gaze palsy is caused by the unilateral riMLF lesion. We confirm that the unilateral riMLF lesion causes supranuclear vertical gaze palsy in our case and that cranial MRI has the advantages in demonstrating the specific lesion.


A novel mobile-cloud system for capturing and analyzing wheelchair maneuvering data: A pilot study.
The purpose of this pilot study was to provide a new approach for capturing and analyzing wheelchair maneuvering data, which are critical for evaluating wheelchair users' activity levels. We proposed a mobile-cloud (MC) system, which incorporated the emerging mobile and cloud computing technologies. The MC system employed smartphone sensors to collect wheelchair maneuvering data and transmit them to the cloud for storage and analysis. A k-nearest neighbor (KNN) machine-learning algorithm was developed to mitigate the impact of sensor noise and recognize wheelchair maneuvering patterns. We conducted 30 trials in an indoor setting, where each trial contained 10 bouts (i.e., periods of continuous wheelchair movement). We also verified our approach in a different building. Different from existing approaches that require sensors to be attached to wheelchairs' wheels, we placed the smartphone into a smartphone holder attached to the wheelchair. Experimental results illustrate that our approach correctly identified all 300 bouts. Compared to existing approaches, our approach was easier to use while achieving similar accuracy in analyzing the accumulated movement time and maximum period of continuous movement (p > 0.8). Overall, the MC system provided a feasible way to ease the data collection process and generated accurate analysis results for evaluating activity levels.


PredictBias: a server for the identification of genomic and pathogenicity islands in prokaryotes.
Pathogenicity Islands (PAIs) are the sub-sets of Genomic Islands (GIs) that are acquired by horizontal gene transfer (HGT) and are generally shown to have a significant deviation in G+C, dinucleotide or codon frequency from core genome. Major approaches used for PAI identification are based on composition bias and/or similarity with known PAIs. These approaches either limit the search to GIs or to regions similar to previously annotated PAIs. PredictBias is a web application for the identification of genomic and pathogenicity islands in prokaryotes based on composition bias, presence of insertion elements, proximity with virulence-associated genes and absence in related non-pathogenic species. A profile database of virulence factors (VFPD) has been developed using 213 protein families associated to virulence retrieved from Pfam and PRINTS database. PredictBias performs a RPSBLAST search for regions with significant composition bias against VFPD. If a region encodes for at least one protein related to virulence then it is marked as potential PAI (biased-composition) otherwise as GI. Regions involved in virulence but having unsuspicious composition bias due to ancient HGT are identified by scanning genome segments (8 ORFs) with more than four significant hits to VFPD and are marked as potential PAI (unbiased-composition). The relative absence of potential PAIs in related non-pathogenic species can be investigated using 'compare genome feature' of PredictBias that further aids in validating the results and defining boundaries for PAIs. Performance measure analysis showed that the output of PredictBias is in agreement with the known findings. PredictBias is available at www.davvbiotech.res.in/PredictBias.


Favorable outcome of individual regimens containing bedaquiline and delamanid in drug-resistant tuberculosis: A systematic review.
Drug-resistant tuberculosis (DR-TB) is a public health concern that is difficult to treat, requiring long and complex treatment with highly effective drugs. Bedaquiline and/or delamanid have already shown promising outcomes in patients with DR-TB, increasing the rate of culture conversion and lowering TB-related mortality. We comprehensively searched and evaluated the effectiveness of individual regimens containing bedaquiline and delamanid on culture conversion and treatment success. We assessed for quality either observational or experimental studies. We identified 14 studies that met the inclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart with 12 observational and 2 experimental studies. Of 1691 DR-TB patients enrolled in the included studies, 1407 of them concomitantly received regimens containing bedaquiline and delamanid. Overall multidrug resistant (MDR), preextensively drug resistant (XDR), and XDR-TB were seen in 21.4%, 44.1%, and 34.5%, respectively. Of 14 studies, 8 of them reported favorable outcomes including sputum culture conversion and cure rate at the end of treatment, meanwhile 6 studies only reported sputum culture conversion. Sputum culture conversion at the end of the 6th month was 63.6%-94.7% for observational studies, and 87.6%-95.0% for experimental studies. The favorable outcome at the end of treatment was 67.5%-91.4%. With high pre-XDR and XDR cases among DR-TB patients with limited treatment options, regimens containing bedaquiline and delamanid provide successful treatment. In DR-TB patients receiving regimens containing bedaquiline and delamanid, favorable outcomes were high including sputum conversion and cure rate.


Strain differences in the chronic mild stress animal model of depression and anxiety in mice.
Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in sucrose intake test (SIT) and open field test (OFT). However, the two strains showed quite different responses in forced swimming test (FST) and novelty-suppressed feeding (NSF) test after 3 weeks of CMS treatment. Only C57BL/6 mice displayed the depression- and anxiety-like behavioral effects in response to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression- and anxiety-like behaviors using CMS in ICR and C57BL/6 mice.


Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening.
To demonstrate the feasibility of presymptomatic diagnosis of spinal muscular atrophy (SMA) through newborn screening (NBS). We performed a screening trial to assess all newborns who underwent routine newborn metabolic screening at the National Taiwan University Hospital newborn screening center between November 2014 and September 2016. A real-time polymerase chain reaction (RT-PCR) genotyping assay for the SMN1/SMN2 intron 7 c.888+100A/G polymorphism was performed to detect homozygous SMN1 deletion using dried blood spot (DBS) samples. Then the exon 7 c.840C>T mutation and SMN2 copy number were determined by both droplet digital PCR (ddPCR) using the original screening DBS and multiplex ligation-dependent probe amplification (MLPA) using a whole blood sample. Of the 120 267 newborns, 15 tested positive according to the RT-PCR assay. The DBS ddPCR assay excluded 8 false-positives, and the other 7 patients were confirmed by the MLPA assay. Inclusion of the second-tier DBS ddPCR screening assay resulted in a positive prediction value of 100%. The incidence of SMA was 1 in 17 181 (95% CI, 1 in 8323 to 1 in 35 468). Two of the 3 patients with 2 copies of SMN2 and all 4 patients with 3 or 4 copies of SMN2 were asymptomatic at the time of diagnosis. Five of the 8 false-positives were caused by intragenic recombination between SMN1 and SMN2. Newborn screening can detect patients affected by SMA before symptom onset and enable early therapeutic intervention. A combination of a RT-PCR and a second-tier ddPCR can accurately diagnose SMA from DBS samples with no false-positives. ClinicalTrials.gov NCT02123186.


Assessment of gel-coated delayed self-gripping mesh.
Mesh hernia repair is one of the most frequently performed procedures in general surgery. Recently, use of the self-gripping mesh demonstrated a beneficial effect on postoperative pain in inguinal hernia repairs. However, in intra-abdominal placement, the use of this novel mesh requires greater laparoscopic skill and dexterity because of the mesh's tendency to fold and adhere to itself and to any surrounding tissues. We hypothesized that gel-like coverage of a self-gripping mesh with a water-soluble film would allow delaying the immediate surface adhesion of the mesh to the tissue, which may allow greater freedom and ease in mesh placement for laparoscopic surgeons. In this ex vivo animal study, gel-coated self-gripping mesh (ProGrip) was compared with a control uncoated mesh in bovine and porcine tissue specimens and assessed for dislodgement shear forces before and after dissolving of the gel. Gel coating of the mesh reduced preperitoneal dislodgement forces in a porcine abdominal wall specimen by 81% (8.05 ± 0.66 vs 1.53 ± 0.82 N, P < .01). Dissolving the gel markedly increased the anchoring forces (10.62 ± 3.70 vs 1.53 ± 0.82 N, P < .0001), and after dissolving the gel, the mesh shear dislodgement forces were similar and noninferior to the control mesh (8.05 ± 0.66 vs 10.62 ± 3.70 N, P = NS). We believe that water-soluble gel coating does not impair the adhesive features of the self-gripping mesh and may simplify its use in open and laparoscopic procedures by allowing controlled activation of the self-gripping mechanism.


The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors.
The mammalian natural killer gene complex (NKC) contains several families of type II transmembrane C-type lectin-like receptors (CLRs) that are best known for their involvement in the detection of virally infected or transformed cells, through the recognition of endogenous (or self) proteinacious ligands. However, certain CLR families within the NKC, particularly those expressed by myeloid cells, recognize structurally diverse ligands and perform a variety of other immune and homoeostatic functions. One such family is the 'Dectin-1 cluster' of CLRs, which includes MICL, CLEC-2, CLEC12B, CLEC9A, CLEC-1, Dectin-1 and LOX-1. Here, we review each of these CLRs, exploring our current understanding of their ligands and functions and highlighting where they have provided new insights into the underlying mechanisms of immunity and homeostasis.


A novel biomarker harvesting nanotechnology identifies Bak as a candidate melanoma biomarker in serum.
Melanoma represents only 4% of all skin cancers, but nearly 80% of skin cancer deaths. This manuscript applies several new measurement technologies with the purpose of elucidating molecular signatures of melanoma aggressiveness. We sought to determine whether low-abundant serum proteins related to apoptotic pathways could be measured and correlated with defined melanoma subtypes. Hydrogel core shell nanoparticles, a new technology capable of selectively entrapping low molecular weight proteins and protecting them from enzymatic degradation, were used to capture candidate serum biomarkers. Biomarker levels were correlated with confocal microscopy, thereby representing a combination of new technologies for in vivo histologic documentation. Among a panel of analyzed serum proteins, Bak was differentially expressed between nevi and melanomas. Melanomas with higher Bak serum levels exhibited more pronounced junctional activity on confocal imaging, whereas lesions with 'sparse' dermal nests had weak Bak expression. Our study links serum proteome analysis with confocal microscopic clinical in vivo histologic classification of melanomas. Bak has not been previously measured in serum. Bak differential expression among melanoma subtypes confirms the importance of the apoptotic pathway as a contributor to melanoma aggressiveness.


Fluorescent guanosine-nucleotide analogs suitable for photoaffinity-labeling experiments.
The synthesis and properties of strongly fluorescent derivative of inosine and its nucleotides are described. Reaction of 2-chloro-inosinic acid with sodium azide leads to a product bearing the tetrazole ring between position 2 and 3. Methylation at N1 was effected with dimethyl sulfate. The corresponding nucleosides and their 5'-triphosphates were also prepared. Only the non-methylated series is at equilibrium with small concentrations of their azido forms, and can be photolyzed by wavelengths above 300 nm. Both series are strongly fluorescent, their emission and excitation fluorescence spectra, as well as their quantum yields were measured. The nucleoside 5'-triphosphates are able to initiate and sustain polymerization of porcine brain tubulin.


A bioinformatic search for correspondence between differentially expressed genes of domestic versus wild animals and orthologous human genes altering reproductive potential.
One of the greatest achievements of genetics in the 20th century is D.K. Belyaev's discovery of destabilizing selection during the domestication of animals and that this selection affects only gene expression regulation (not gene structure) and inf luences systems of neuroendocrine control of ontogenesis in a stressful environment. Among the experimental data generalized by Belyaev's discovery, there are also f indings about accelerated extinc tion of testes' hormonal function and disrupted seasonality of reproduction of domesticated foxes in comparison with their wild congeners. To date, Belyaev's discovery has already been repeatedly conf irmed, for example, by independent observations during deer domestication, during the use of rats as laboratory animals, after the reintroduction of endangered species such as Przewalski's horse, and during the creation of a Siberian reserve population of the Siberian grouse when it had reached an endangered status in natural habitats. A genome-wide comparison among humans, several domestic animals, and some of their wild congeners has given rise to the concept of self-domestication syndrome, which includes autism spectrum disorders. In our previous study, we created a bioinformatic model of human self-domestication syndrome using differentially expressed genes (DEGs; of domestic animals versus their wild congeners) orthologous to the human genes (mainly, nervous-system genes) whose changes in expression affect reproductive potential, i. e., growth of the number of humans in the absence of restrictions caused by limiting factors. Here, we applied this model to 68 human genes whose changes in expression alter the reproductive health of women and men and to 3080 DEGs of domestic versus wild animals. As a result, in domestic animals, we identif ied 16 and 4 DEGs, the expression changes of which are codirected with changes in the expression of the human orthologous genes decreasing and increasing human reproductive potential, respectively. The wild animals had 9 and 11 such DEGs, respectively. This difference between domestic and wild animals was signif icant according to Pearson's χ2 test (p < 0.05) and Fisher's exact test (p < 0.05). We discuss the results from the standpoint of restoration of endangered animal species whose natural habitats are subject to an anthropogenic impact.


Emerging Tick-Borne Viruses in the Twenty-First Century.
Ticks, as a group, are second only to mosquitoes as vectors of pathogens to humans and are the primary vector for pathogens of livestock, companion animals, and wildlife. The role of ticks in the transmission of viruses has been known for over 100 years and yet new pathogenic viruses are still being detected and known viruses are continually spreading to new geographic locations. Partly as a result of their novelty, tick-virus interactions are at an early stage in understanding. For some viruses, even the principal tick-vector is not known. It is likely that tick-borne viruses will continue to emerge and challenge public and veterinary health long into the twenty-first century. However, studies focusing on tick saliva, a critical component of tick feeding, virus transmission, and a target for control of ticks and tick-borne diseases, point toward solutions to emerging viruses. The aim of this review is to describe some currently emerging tick-borne diseases, their causative viruses, and to discuss research on virus-tick interactions. Through focus on this area, future protein targets for intervention and vaccine development may be identified.


Cooperative binding of 2,2'-bipyridine into polynucleotide poly(A)-poly(U-) in an alkaline aqueous solution.
UV absorption data analysis has been used to evaluate equilibrium constants of the pH-induced interaction of 2,2'-Bipy with polyadenylnic-polyuridylic acid in aqueous solution. The conditional probabilities hard model has been adopted in treatment of concentration diagrams calculated by the soft modelling-based Multivariate Curve Resolution-Alternating Least Squares approach. Intrinsic binding constant (lgKg = 1.93), and the cooperativity parameter (ω = 340), were calculated as the best fit. The plot of the experimental binding constant versus 2,2'-Bipy equilibrium concentration shows two modes of ligand with polymer interactions. The equilibrium hard model correctly reproduced the binding constant variations observed in the experiment. The results indicated that ligand binding in two steps is governed by a cooperative process, that is, the enhancement of deprotonated structure stability. It would appear that proposed calculation approach can be used in future combined hard modelling theoretical and soft modelling experimental works.


[Validation of the questionnaire for screening frailty].
For screening frailty in daily practice, we developed the questionnaire relating issues of weight loss, impaired vision and hearing, injuries related to falls, mood decline, cognitive impairment, urinary incontinence, and mobility difficulties. 356 outpatients from Moscow were included in the study (mean age 74,9±6,1 years, women - 80,4 %). Patients were interviewed using the questionnaire and underwent a comprehensive geriatric assessment. The phenotype model of frailty was determined by L. Fried criteria, the frailty index model - by K. Rockwood criteria. ROC-analysis demonstrated a satisfactory agreement between the result of the survey by the questionnaire and assessment the phenotype model of frailty and the frailty index model (AUC=0,765 and 0,731, respectively). The results statistically significantly correlated with the assessment of the phenotype model of frailty and the frailty index model (Spearman correlation = 0,4 and 0,41, p<0,001). Optimal characteristics of the questionnaire for the frailty screening were consistent to cut-off ≥3 and ≥ 4 points. We propose to use a cut-off ≥ 3 point, since it corresponds to a higher value of sensitivity (85,7 and 93,3 % compared with the phenotype model of frailty and the frailty index model respectively). The proportion of patients who scored ≥ 3 points (58,4 %) indicates a high prevalence of geriatric syndromes among outpatients in Moscow.


Measuring the strong electrostatic and magnetic fields with proton radiography for ultra-high intensity laser channeling on fast ignition.
In order to investigate the intense laser propagation and channel formation in dense plasma, we conducted an experiment with proton deflectometry on the OMEGA EP Laser facility. The proton image was analyzed by tracing the trajectory of mono-energetic protons, which provides understanding the electric and magnetic fields that were generated around the channel. The estimated field strengths (E ∼ 10(11) V/m and B ∼ 10(8) G) agree with the predictions from 2D-Particle-in-cell (PIC) simulations, indicating the feasibility of the proton deflectometry technique for over-critical density plasma.


Relational continuity of care in integrated maternity and child health clinics improve parents' service experiences.
In the Finnish primary health care, relational continuity of care is implemented in integrated maternity and child health clinics where the same nurse takes care of the family from the pregnancy until the child reaches school age. The aim of this study was to clarify the association between this relational continuity of care and the availability, utilisation and selected features of the maternity and child health clinic services, as evaluated by the parents. A comparative, cross-sectional service evaluation survey was used. Eighteen months after their baby's delivery, mothers (N = 987) and fathers (N = 835) from Southwest Finland evaluated specific maternity and child health clinic services. Comparisons were made between the parents who had relational continuity of care in the integrated maternity and child health clinics and those who did not. Home visits were more frequently provided when relational continuity of care in integrated maternity and child health clinics existed. Parents who had this relational continuity of care, evaluated several features of the service, especially provided support, more positively than parents who did not. Relational continuity of care in integrated maternity and child health clinics seems to increase parents' satisfaction with the services and might increase the provision of home visits.


Effect of recruitment strategy on types of subjects entered into a primary prevention clinical trial.
Clinical trials typically recruit subjects through referrals or media promotion, with generalizability of the results often uncertain. As part of a primary prevention trial to evaluate strategies for increasing physical activity in sedentary men and women, two recruitment sources, a random-digit-dial telephone survey and a community media campaign, were used to identify subjects. Baseline characteristics of 357 randomized men and women aged 50 to 65 years were compared by recruitment source. Whereas there were few differences between recruitment sources for demographic variables, telephone survey recruitment was particularly successful in recruiting smokers and persons with other cardiovascular risk factors into the trial. Counter to expectations, subsequent exercise adherence rates did not differ by recruitment source. The results suggest that the survey method, while more expensive, may be particularly useful for locating higher-risk subjects who could especially benefit from increases in physical activity but who rarely are recruited through more traditional approaches.


Trypsin purification by affinity binding to small unilamellar liposomes.
A novel protein purification process using affinity-ligand-modified liposomes and membrane ultrafiltration is described. The feasibility of the process was tested using trypsin as the model protein and p-aminobenzamidine (PAB) as the affinity ligand for trypsin. The affinity liposomes were prepared by covalently attaching PAB to the surface of small unilamellar liposomes via the hydrophilic spacer arm diglycolic acid. The liposomes were comprised of dimyristoyl phosphatidyl choline, cholesterol, and dimyristoyl phosphatidyl ethanolamine to which the diglycolic acid was attached. The equilibrium binding constant between trypsin and immobilized PAB was shown to be dependent on the PAB density of the liposome surface. Bound trypsin was eluted from the liposomes by the trypsin inhibitor benzamidine. Trypsin was purified from a trypsin/chymotrypsin mixture and from one of its naturally occurring sources, porcine pancreatic extract. A recovery yield from the crude mixture of 68% was obtained with a trypsin purity of 98%. The affinity-modified liposomes were stable in the complex mixture and retained their trypsin binding capacity after multiple adsorption/elution cycles over a 30-day period.


[Type I Chiari malformation associated with cerebellar atrophy. Case report].
Chiari malformation is characterized by caudal displacement of the cerebellar tonsils that penetrate into the spinal canal through the foramen magnum, achieving reach the atlas or axis. trunk and any drop of the fourth ventricle is observed. Typically is seen in young adults. In some cases scoliosis and Syringomyelic cavities may occur. The authors present (as far as they know) the first case in the literature with long term follow-up, of a caucasian woman with an unusual form of cerebellar atrophy and Chiari Type I malformation, suffering from weakness in his upper and lower extremities with rapidly progression. The patient was successfully treated with suboccipital decompression and C1 laminectomy.


Nonlinear Resonance Vibration Assessment to Evaluate the Freezing and Thawing Resistance of Concrete.
Under cold environments, the freezing and thawing cycles of water in concrete reduce the lifetime and durability of concrete structures. For enhanced freezing and thawing resistance, entrained air voids are generally required, but malfunctioning of air entrainment is sometimes reported in the field. To evaluate the quality of air entrainment, this study proposes a nondestructive method that is a preceding evaluation before damage to the concrete. A nonlinear resonance vibration method is adopted in samples having an identical air void content. The durable concrete sample with resistance to freezing and thawing cycles shows higher nonlinearity in its resonance. Thus, the quality of air entrainment and, furthermore, the potential freezing and thawing resistance can possibly be evaluated by measuring the nonlinearity parameter of the concrete, which is preliminary study to attempt the preceding evaluation of freezing and thawing resistance using nondestructive method.


Borderline ER-Positive Primary Breast Cancer Gains No Significant Survival Benefit From Endocrine Therapy: A Systematic Review and Meta-Analysis.
Endocrine responsiveness of primary breast cancers with borderline estrogen receptor expression (ER+ [1%-9%]) remains unclear. We aimed at investigating differences in endocrine responsiveness, prognosis, and clinicopathological characteristics between the ER+ (1%-9%) cohort and the ER- cohort or ER+ (≥10%) cohort. Eligible literature published from inception to November 20, 2016 was retrieved from the PubMed database on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on survival outcomes were extracted and pooled odds ratios (ORs), 95% confidence intervals (CIs), and 2-tailed P values are reported. P values of the χ2 test for comparison of clinicopathological characteristics among included patients in the ER+ (1%-9%) cohort and the other 2 cohorts were calculated respectively. The analysis included 6 studies with 16,606 patients. Significant differences were detected between the ER+ (1%-9%) cohort and the other 2 cohorts on the basis of clinicopathological characteristics respectively. When taking all of the patients into analysis without consideration of treatment modality, the ER+ (1%-9%) cohort presented better prognosis than the ER- group in terms of 5-year disease-free survival (OR, 1.47; P = .046) and 5-year overall survival (OR, 1.23; P = .046). However, patients with ER+ (1%-9%) breast cancer who received endocrine therapy seemed to have a prognosis similar to those without any endocrine therapy (P = .684) and those with ER- carcinoma who received endocrine therapy (P = .145). Patients with ER+ (≥10%) tumors had better endocrine responsiveness compared with their ER+ (1%-9%) counterparts (OR, 0.52; P = .034, ER+ [1%-9%] vs. ER+ [≥10%]). Our results indicate that primary breast cancer patients with ER+ (1%-9%) expression gained no significant survival benefit from endocrine therapy, but manifested overall better prognosis than those with ER- cancer.


[Biomonitoring in workers exposed to pesticides: development and application of method detecting imidacloprid in urine].
Imidacloprid is a relatively new insecticide in neonicotinoids chemical class with neuroactivity in insects, being one of the most widely used insecticides in the world. For biomonitoring in workers exposed to pesticides, the authors designed a method detecting low levels of Imidacloprid in urine of operators, based on tandem liquid mass-spectrometry with ionization source--electrostatic dispersion (positive ionization) in multi-reaction monitoring regime with subsidiary ion (mass/charge) 209 for quantitative assessment and ion 175.1 for confirmation onion ratio. The study incorporated diurnal urine, about 100 ml of average sample was frozen and kept at temperature -20C for analysis. Before extraction, the sample was unfrozen, an aliquot of 5 ml was selected, diluted with 5 ml of 0.1% formic acid. The substance was concentrated out of the urine samples via solid-phase extraction with application of cartridges based on octadecylsilane, eluition--1 ml of methanol. Lower limit of Imidacloprid detection in urine is 0.02 ng/ml, of the quantitative assessment--0.1 ng/ ml, linear range of concentrations measured 0.1-10 ng/ml. The method was tested for monitoring in workers exposed to Imidacloprid preparations in natural conditions of pesticides application in agriculture, with various processing technologies. Imidacloprid was identified in urine of two professional operators after work in seed treatment and the subsequent seeding at lower limit of detection (0.02 ng/ml) and 0.34 ng/ml.


Ante mortem cerebrospinal fluid tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration.
To test the hypotheses that (1) antemortem cerebrospinal fluid (CSF) tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration (FTLD) and (2) tauopathy patients have higher phosphorylated-tau levels compared to transactivation response element DNA-binding protein 43 (TDP-43) proteinopathy patients while accounting for Alzheimer's disease (AD) copathology. Patients had autopsy-confirmed FTLD with tauopathy (n = 31), TDP-43 proteinopathy (n = 49), or AD (n = 26) with antemortem CSF. CSF tau levels were compared between groups and correlated with digital histology measurement of postmortem tau pathology averaged from three cerebral regions (angular gyrus, mid-frontal cortex, and anterior cingulate gyrus). Multivariate linear regression tested the association of ante mortem CSF tau levels with postmortem tau pathology adjusting for demographics. Multivariate regression found an independent association of ante mortem CSF phosphorylated tau levels with postmortem cerebral tau pathology in FTLD (Beta = 1.3; 95% confidence interval = 0.2-2.4; p < 0.02). After excluding patients with coincident AD-associated tau pathology accompanying sporadic FTLD, we found lower CSF phosphorylated tau levels in the TDP-43 group (median = 7.4pg/ml; interquartile range [IQR] = 6.0, 12.3; n = 26) compared to the tauopathy group (median = 12.5pg/ml; IQR = 10.7, 15.0; n = 23; Z = 2.6; p < 0.01). CSF phosphorylated-tau levels are positively associated with cerebral tau burden in FTLD. In vivo detection of AD copathology in sporadic FTLD patients may help stratify clinical cohorts with pure neuropathology in which low CSF phosphorylated-tau levels may have diagnostic utility to distinguish TDP-43 proteinopathy from tauopathy. Autopsy-confirmed samples are critical for FTLD biomarker development and validation. Ann Neurol 2017;82:247-258.


Role of nitric oxide in a nonseptic shock model induced by zymosan in the rat.
Nitric oxide (NO) is a short-lived mediator, the synthesis of which is induced by various cytokines during inflammatory processes. Recently, it has been proposed that zymosan, a nonbacterial agent, causes inflammation by inducing the production of various cytokines and proinflammatory mediators. In the present study we investigated the role of NO in a nonseptic shock model induced by zymosan administration in the rat. Administration of zymosan (500 mg/kg, intraperitoneally) in the rat induced acute peritonitis, as assessed by a marked increase in the leukocytes count in the exudate, as well as by an increase in the exudate nitrate/nitrite concentration. Zymosan-treated rats developed a severe hypotension and showed signs of systemic illness, significant loss of body weight, and a high mortality rate (53% of animals died within 72 h). Elevated plasma levels of nitrite and nitrate were also observed in zymosan-treated rats compared with control rats (67 +/- 4 microM and 23 +/- 2 microM, respectively; p < .01). In ex vivo experiments, vascular reactivity was studied in thoracic aorta rings of zymosan-treated rats. The contractile responses to norepinephrine (100 nM) and endothelin-1 (5 nM) were significantly reduced. An impairment of the endothelial-dependent relaxation in response to acetylcholine was also observed. Pretreatment of zymosan-shocked rats with NG-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMA), (10 mg/kg, subcutaneously, 15 min before zymosan) decreased mortality, prevented the development of peritonitis, improved ex vivo vascular reactivity, and significantly reduced hypotension. Our data suggest that overproduction of NO plays a role in the zymosan-induced peritonitis and cardiovascular derangements in the rats.


Deficits in sustained attention in schizophrenia and affective disorders: stable versus state-dependent markers.
The authors compared sustained attention deficits measured by the Continuous Performance Test in patients with various affective disorders and patients with schizophrenia and examined whether Continuous Performance Test deficits in patients with affective disorders improve with remission of affective disorder symptoms. Patients with schizophrenia (N=41), major depression without psychotic features (N=22), bipolar disorder without psychotic features (N=22), and bipolar disorder with psychotic features (N=46) completed Continuous Performance Test sessions with an undegraded version of the test and a 25% degraded version in which the stimulus images were visually distorted. Subjects were also interviewed with the Chinese version of the Diagnostic Interview for Genetic Studies. All inpatients with schizophrenia (N=41) and bipolar disorder (N=15) were assessed both at admission and discharge. Subjects' Continuous Performance Test scores were standardized in comparison with scores for a community sample of 345 subjects, with adjustment for age, sex, and level of education. Compared with the general population, all patient groups except the group with nonpsychotic major depression were significantly impaired in their ability to discriminate target stimuli from nontarget stimuli on the Continuous Performance Test. Patients with schizophrenia had the severest impairment, followed by patients with bipolar disorder with psychotic features and those with bipolar disorder without psychotic features. From admission to discharge, Continuous Performance Test deficits in schizophrenia remained unchanged, but inpatients with bipolar disorder showed significant improvement on the degraded Continuous Performance Test. All patients adopted a similar response criterion (the amount of perceptual evidence the person requires to decide that a stimulus is a target) to that in the general population, except that the patients with schizophrenia had a less stringent response criterion during the degraded Continuous Performance Test. Continuous Performance Test deficits are stable vulnerability indicators for schizophrenia, mediating indicators for bipolar disorder, and state-dependent indicators for major depression.


Knowledge and practice regarding dengue and chikungunya: a cross-sectional study among Healthcare workers and community in Northern Tanzania.
To investigate knowledge and prevention practices regarding dengue and chikungunya amongst community members, as well as knowledge, treatment and diagnostic practices among healthcare workers. We conducted a cross-sectional survey with 125 community members and 125 healthcare workers from 13 health facilities in six villages in the Hai district of Tanzania. A knowledge score was generated based on participant responses to a structured questionnaire, with a score of 40 or higher (of 80 and 50 total scores for community members and healthcare workers, respectively) indicating good knowledge. We conducted qualitative survey (n = 40) to further assess knowledge and practice regarding dengue and chikungunya fever. 15.2% (n = 19) of community members had good knowledge regarding dengue, whereas 53.6%, (n = 67) of healthcare workers did. 20.3% (n = 16) of participants from lowland areas and 6.5% (n = 3) from highland areas had good knowledge of dengue (χ2 = 4.25, P = 0.03). Only 2.4% (n = 3) of all participants had a good knowledge score for chikungunya. In the qualitative study, community members expressed uncertainty about dengue and chikungunya. Some healthcare workers thought that they were new diseases. There is insufficient knowledge regarding dengue and chikungunya fever among community members and healthcare workers. Health promotion activities on these diseases based on Ecological Health Mode components to increase knowledge and improve preventive practices should be developed.


Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours.
Beclin 1 is is an autophagy gene, the role of which as a tumour suppressor has recently been recognized in a few studies. We examined the expression of Beclin 1 protein in 212 primary human brain tumours, including 97 high-grade glial tumours, 29 low-grade glial tumours, 4 grade III meningiomas, 19 grade II meningiomas, 52 grade I meningiomas, and 11 medulloblastomas. In 94 cases, including 56 glial tumours, 35 meningiomas, and 3 medulloblastomas we also assessed Beclin 1 mRNA expression by real-time RT-PCR. In most high-grade astrocytic, ependymal neoplasms and atypical meningiomas we found a decrease of cytoplasmic protein expression that was, instead, high in the majority of low-grade tumours and in medulloblastomas. The expression level of Beclin 1 mRNA was significantly lower in glioblastomas than in grade II (p=0.04) and grade I (p=0.01) astrocytomas; in grade III than in grade I astrocytomas (p=0.01); in grade II than in grade I meningiomas (p=0.03); and in all glial tumours when compared to all meningiomas (p<0.0001). Cytoplasmic expression is thought to be linked to the functional protein. Our observations are in line with studies that demonstrated decreased expression of Beclin 1 in human breast, ovarian, prostate and ovarian cancer and furtherly support its involvement also in brain tumours, which had previously been demonstrated in a few experimental studies, both in spontaneous and in therapy-induced autophagy. Furthermore, our study suggests possible differences of Beclin 1 involvement and its role among the different histotypes of brain neoplasms. Further studies are needed to highlight Beclin 1 function in tumour suppression and/or in tumour survival through autophagy and other related programmed cell death processes in brain tumours.


Cooperative learning in interdisciplinary education for the allied health professions.
The need for interdisciplinary education in allied health has often been cited, but few studies have been made concerning appropriate learning strategies in such courses. This study examines the concept of cooperative goal structuring and assesses the effect of one cooperative learning technique (group consensus examinations) on the perceptions and achievement of allied health students in an interdisciplinary course. The results indicated that when compared with the traditional (individual) mode of testing, group consensus examinations had a significant positive effect on the perceptions of students regarding the clarity and importance of course topics. Achievement on the unit quizzes was higher, and although no difference was found between the two treatment groups on final examination scores, student performance was superior to that of previous years. A large majority of students indicated they preferred group consensus examinations in this type of course.


Tailoring Experimental Configurations to Probe Transition Dipoles of Fluorescent Nanoemitters by Polarimetry or Fourier Imaging with Enhanced Sensitivity.
Probing the transition dipoles responsible for the luminescence of a nanoemitter is essential to understanding its physical properties, its interactions with its environment, and its potential applications. Various methods in photoluminescence microscopy, based on polarimetry or Fourier imaging, have been developed to measure an emitter's dipole properties: the number of radiating dipoles, the oscillator strength ratio between them, and their orientation. In this article, we model the most used of these protocols and show that their sensitivity depends crucially on the experimental conditions: substrate material, presence of another lower or upper layer, and objective numerical aperture. We develop guidelines to optimize the measurement sensitivity by tailoring the experimental conditions, depending on the type of protocol used and the dipole property to be measured.


GSR is not essential for the maintenance of antioxidant defenses in mouse cochlea: Possible role of the thioredoxin system as a functional backup for GSR.
Glutathione reductase (GSR), a key member of the glutathione antioxidant defense system, converts oxidized glutathione (GSSG) to reduced glutathione (GSH) and maintains the intracellular glutathione redox state to protect the cells from oxidative damage. Previous reports have shown that Gsr deficiency results in defects in host defense against bacterial infection, while diquat induces renal injury in Gsr hypomorphic mice. In flies, overexpression of GSR extended lifespan under hyperoxia. In the current study, we investigated the roles of GSR in cochlear antioxidant defense using Gsr homozygous knockout mice that were backcrossed onto the CBA/CaJ mouse strain, a normal-hearing strain that does not carry a specific Cdh23 mutation that causes progressive hair cell degeneration and early onset of hearing loss. Gsr-/- mice displayed a significant decrease in GSR activity and GSH/GSSG ratios in the cytosol of the inner ears. However, Gsr deficiency did not affect ABR (auditory brainstem response) hearing thresholds, wave I amplitudes or wave I latencies in young mice. No histological abnormalities were observed in the cochlea of Gsr-/- mice. Furthermore, there were no differences in the activities of cytosolic glutathione-related enzymes, including glutathione peroxidase and glutamate-cysteine ligase, or the levels of oxidative damage markers in the inner ears between WT and Gsr-/- mice. In contrast, Gsr deficiency resulted in increased activities of cytosolic thioredoxin and thioredoxin reductase in the inner ears. Therefore, under normal physiological conditions, GSR is not essential for the maintenance of antioxidant defenses in mouse cochlea. Given that the thioredoxin system is known to reduce GSSG to GSH in multiple species, our findings suggest that the thioredoxin system can support GSSG reduction in the mouse peripheral auditory system.


A Cross-Sectional Pharmacoepidemiological Study of the Utilization Pattern of Pre-Anesthetic Medications in Major Surgical Procedures in a Tertiary Care Hospital.
A study of the utilization pattern of pre-anesthetic medications in major surgical procedures. A cross-sectional, pharmacoepidemiological study was conducted among patients undergoing surgical procedures in routine or emergency conditions under general anesthesia. The utilization of pre-anesthetic medicines in all patients was reported. A total of 110 patients (mean age - 42.36 years; 57.27% males) were enrolled. The major (>10%) indications for surgery were carcinoma/tumor - 25 (22.73%), perforation peritonitis - 20 (18.18%), and intestinal obstruction - 11 (10%). All patients received ranitidine plus metoclopramide. Injections of ondansetron, midazolam, pentazocin, anticholinergic agents, and fentanyl were used in 103 (93.64%), 103 (93.64%), 92 (83.64%), 84 (76.36%), and 23 (20.91%) patients, respectively. The dosage of ondansetron was 4 mg in 95 patients (86.36%), while 89.09% patients received 1 mg of midazolam. In 86 patients (78.18%), pentazocine was used in a 15 mg dose. Among the anticholinergic agents, glycopyrrolate was used in 76 patients (69.09%). Glycopyrrolate was used in a 0.2 mg dose in 74 patients (97.37%). The major indications for the use of fentanyl were carcinoma - 8 (34.8%), perforation peritonitis - 4 (17.4%), and surgery for intestinal obstruction - 3 (13%). The administration of ondansetron, midazolam, and pentazocin is very common (>80% patients) as pre-anesthetic medication. Glycopyrrolate was the preferred anticholinergic agent. In cancer patients, the use of fentanyl is common.


THE EVOLUTION OF CARBON ALLOCATION TO PLANT SECONDARY METABOLITES: A GENETIC ANALYSIS OF COST IN DIPLACUS AURANTIACUS.
Diplacus aurantiacus contains large amounts of a leaf phenolic resin, an important deterrent to a leaf-eating caterpillar, Euphydryas chalcedona. The resin can also retard water loss during drought. Furthermore, the leaf resin content differs among plants and populations. This study investigates the existence of heritable variation (h2 ) in resin production and tests for a genetic correlation (rG ) between carbon allocation to secondary metabolites and growth rate, as well as with three other vegetative traits. Nine dam and 10 sire plants were chosen randomly at a field site and used to generate 78 full-sib families (19 half-sib families) by crossing all males to all females in a factorial design. Heritability was estimated in two ways, and genetic correlations were estimated by three methods. We found: (1) the heritability of resin production estimated by the regression of offspring on sires was significantly greater than zero (hs2=0.32, P<0.01); (2) the maternal variance in resin content was significantly greater than zero (21.3% of total phenotypic variance); (3) significant negative genetic correlation between resin content and growth rate was observed from two of three methods and was consistent with the phenotypic correlation; and (4) the cost of resin could be assessed quantitatively. The genetic cost of 1 mg in resin is equivalent to 25 mg of dry shoot-biomass growth, but the phenotypic cost is only 2.1 mg. This study indicates that carbon allocation to these secondary metabolites may respond to natural selection, and the phenotypic cost of resin production has a genetic basis in D. aurantiacus. This trade-off suggests that once selection occurs, increased phenolic resin production may result in decreased growth, or vice versa.


Comb-type polymer-hybridized MXene nanosheets dispersible in arbitrary polar, nonpolar, and ionic solvents.
Solution-based processing of two-dimensional (2D) nanomaterials is highly desirable, especially for the low-temperature large-area fabrication of flexible multifunctional devices. MXenes, an emerging family of 2D materials composed of transition metal carbides, carbonitrides, or nitrides, provide excellent electrical and electrochemical properties through aqueous processing. Here, we further expand the horizon of MXene processing by introducing a polymeric superdispersant for MXene nanosheets. Segmented anchor-spacer structures of a comb-type polymer, polycarboxylate ether (PCE), provide polymer grafting-like steric spacings over the van der Waals range of MXene surfaces, thereby reducing the colloidal interactions by the order of 103, regardless of solvent. An unprecedented broad dispersibility window for Ti3C2Tx MXene, covering polar, nonpolar, and even ionic solvents, was achieved. Furthermore, close PCE entanglements in MXene@PCE composite films resulted in highly robust properties upon prolonged mechanical and humidity stresses.


Choline availability: effects on the toxicity of centrally active drugs.
The effect of chronic choline supplementation was studied on the toxicity of various pharmacological agents in rats and mice. Choline prevented both the incidence of seizures and the consequent lethality of nicotine, paraoxon, pentylenetetrazol, and strychnine. Nicotine toxicity was most markedly affected, and the prophylactic effects of choline were present in both rats and mice following either dietary or parenteral supplementation. Results suggest that chronic choline availability may alter neuronal membrane excitability.


[Hemiparesis and torsade de pointes under low-dose sotalol therapy].
An 81-year-old woman with recurrent epileptic attacks, hemiparesis and rapidly changing consciousness is described in whom the most probable reason for the clinical picture was polymorphous ventricular tachycardia (torsade de pointes). Sotalol (Sotalex), which the patient received for two weeks at a dose of 80 mg twice daily because of asymptomatic ectopic ventricular beats, was identified as the causative agent. Torsade de pointes disappeared after a single intravenous injection of 2 g magnesium sulfate. The patient left the hospital a few days later completely recovered from all neurological deficits.


Atomic cobalt on nitrogen-doped graphene for hydrogen generation.
Reduction of water to hydrogen through electrocatalysis holds great promise for clean energy, but its large-scale application relies on the development of inexpensive and efficient catalysts to replace precious platinum catalysts. Here we report an electrocatalyst for hydrogen generation based on very small amounts of cobalt dispersed as individual atoms on nitrogen-doped graphene. This catalyst is robust and highly active in aqueous media with very low overpotentials (30 mV). A variety of analytical techniques and electrochemical measurements suggest that the catalytically active sites are associated with the metal centres coordinated to nitrogen. This unusual atomic constitution of supported metals is suggestive of a new approach to preparing extremely efficient single-atom catalysts.


Ribosome Mediated Quinary Interactions Modulate In-Cell Protein Activities.
Ribosomes are present inside bacterial cells at micromolar concentrations and occupy up to 20% of the cell volume. Under these conditions, even weak quinary interactions between ribosomes and cytosolic proteins can affect protein activity. By using in-cell and in vitro NMR spectroscopy, and biophysical techniques, we show that the enzymes, adenylate kinase and dihydrofolate reductase, and the respective coenzymes, ATP and NADPH, bind to ribosomes with micromolar affinity, and that this interaction suppresses the enzymatic activities of both enzymes. Conversely, thymidylate synthase, which works together with dihydrofolate reductase in the thymidylate synthetic pathway, is activated by ribosomes. We also show that ribosomes impede diffusion of green fluorescent protein in vitro and contribute to the decrease in diffusion in vivo. These results strongly suggest that ribosome-mediated quinary interactions contribute to the differences between in vitro and in vivo protein activities and that ribosomes play a previously under-appreciated nontranslational role in regulating cellular biochemistry.


Effect of nicergoline on cerebral blood flow.
Cerebral blood flow (CBF) was measured before and after intravenous injection of the cerebral vasodilator nicergoline in 13 patients with cerebrovascular disease. CBF increased in seven. The possibility that the effect of the drug in the remainder may have been masked by a fall of CBF which occurs during sequential measurement of patients at rest is discussed.


An adipo-biliary-uridine axis that regulates energy homeostasis.
Uridine, a pyrimidine nucleoside present at high levels in the plasma of rodents and humans, is critical for RNA synthesis, glycogen deposition, and many other essential cellular processes. It also contributes to systemic metabolism, but the underlying mechanisms remain unclear. We found that plasma uridine levels are regulated by fasting and refeeding in mice, rats, and humans. Fasting increases plasma uridine levels, and this increase relies largely on adipocytes. In contrast, refeeding reduces plasma uridine levels through biliary clearance. Elevation of plasma uridine is required for the drop in body temperature that occurs during fasting. Further, feeding-induced clearance of plasma uridine improves glucose metabolism. We also present findings that implicate leptin signaling in uridine homeostasis and consequent metabolic control and thermoregulation. Our results indicate that plasma uridine governs energy homeostasis and thermoregulation in a mechanism involving adipocyte-dependent uridine biosynthesis and leptin signaling.


Control of contact-inhibition by 4E-BP1 upregulation.
Although contact inhibition is a fundamental process for multicellular organisms, how proliferation is inhibited at high cellular densities remains poorly characterized. Here we show that 4E-BP1, one major repressor of cap-dependent translation, plays a critical role in density-mediated cell cycle arrest. 4E-BP1 promoter is activated and 4E-BP1 protein amount increases as cells reach confluence. Conversely, a much less marked density-dependent inhibition of cell proliferation is observed upon 4E-BP1 silencing. We further show that at high density, progression through the G₁ phase of the cell cycle is faster and Cyclin D1 protein is induced in different cell types where 4E-BP1 has been either downregulated (stable shRNA expression or transient siRNA transfection) or removed (knock-out). Thus 4E-BP1 appears as an important mediator of contact inhibition.


The cardiology and endocrinology connection between amiodarone and thyrotoxicosis: case report and review of the literature.
Amiodarone is used in a large number of cardiac conditions. Amiodarone-induced thyroid dysfunction has been reported to affect up to 20% of users. Amiodarone can lead to both amiodarone-induced hypothyroidism (AIH) and less commonly amiodarone-induced thyrotoxicosis (AIT). There are two main forms of AIT. Type 1 AIT, a form of io-dine-induced hyperthyroidism, and type 2, a drug-induced destructive thyroiditis. Type 1 AIT develops on individuals with underlying thyroid disease. Treatment of Type 1 AIT includes the use of antithyroid drugs and discontinuation of amiodarone. Type 2 AIT is commonly self-limiting in nature. In this article wedescribe a patient with Amiodarone-induced thyrotoxicosis discussing its clinical features and medical therapeutic approach.


Effects of IL-6 Polymorphisms on Individual Susceptibility to Allergic Diseases: A Systematic Review and Meta-Analysis.
Background: Many studies have assessed the potential link between interleukin-6 polymorphisms and susceptibility to allergic diseases. However, the results are still conflicting. Therefore, a comprehensive meta-analysis can not only resolve differences but also provide clues for future projects. Methods: A systematic electronic search was conducted on the databases of Web of Science, PubMed, and Cochrane Library to retrieve all published studies. Revman and Stata software were used for statistical analysis. Results: This meta-analysis included 11 studies. The results revealed that there was a statistically significant association between IL-6 rs1800795 polymorphism and the risk of asthma and allergic rhinitis in the general population. Subgroup analyses demonstrated that rs1800795 affected allergic diseases risk in different populations. Conclusion: Our findings suggested that IL-6 rs1800795 was associated with allergic diseases susceptibility among Asians and Caucasians in opposite trends, and it might influence the risk of asthma and allergic rhinitis. None of the IL-6 polymorphisms were shared risk variants of allergic diseases.


Resveratrol inhibits phosphorylation within the signal transduction and activator of transcription 3 signaling pathway by activating sirtuin 1 in SW1353 chondrosarcoma cells.
The present study assessed the mechanism by which resveratrol (Res) inhibits the growth of SW1353 chondrosarcoma cells and examined whether sirtuin 1 (Sirt1) activation affects phosphorylation within the signal transduction and activator of transcription 3 (STAT3) signaling pathway. The present study used SW1353 chondrosarcoma cells in the logarithmic phase of growth (control and treatment groups). The latter group was treated with Res at 25 and 50 µmol/l for 24 h, and cell viability, proliferation and apoptosis were analyzed using the cell counting kit‑8 assay, colony counting and Hoechst staining, respectively. The expression levels of caspase‑3, cleaved caspase‑3, B‑cell lymphoma‑2 (BCL‑2), BCL-2 associated X protein (Bax), STAT3 and phosphorylated (p‑)STAT3) were measured by Western blotting. SW1353 cells were transfected with small interfering (si)RNA targeting Sirt1 and the expression levels of Sirt1, STAT3 and p-STAT3 were assessed. Exposure of SW1353 cells to Res reduced cell viability in a dose‑dependent manner (P<0.01). Additionally, cell proliferation was significantly inhibited and the cell nuclei exhibited apoptotic characteristics. Cleaved caspase‑3, Sirt1 and Bax levels were upregulated. The expression levels of BCL‑2 and p‑STAT3 were downregulated. Additionally, the BCL‑2/Bax ratio was reduced compared with the control group. The total STAT3 level was unaffected. Res treatment activated Sirt1, however, in cells transfected with Sirt1‑siRNA, the ability of resveratrol to suppress p‑STAT3 expression was compromised. Overall, it was revealed that Res treatment induced apoptosis, inhibited proliferation and affected phosphorylation within the STAT3 signaling pathway by activating Sirt1 in SW1353 chondrosarcoma cells.


Bridging Income Generation with Group Integrated Care for cardiovascular risk reduction: Rationale and design of the BIGPIC study.
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with >80% of CVD deaths occurring in low and middle income countries (LMICs). Diabetes mellitus and pre-diabetes are risk factors for CVD, and CVD is the major cause of morbidity and mortality among individuals with DM. There is a critical period now during which reducing CVD risk among individuals with diabetes and pre-diabetes may have a major impact. Cost-effective, culturally appropriate, and context-specific approaches are required. Two promising strategies to improve health outcomes are group medical visits and microfinance. This study tests whether group medical visits integrated into microfinance groups are effective and cost-effective in reducing CVD risk among individuals with diabetes or at increased risk for diabetes in western Kenya. An initial phase of qualitative inquiry will assess contextual factors, facilitators, and barriers that may impact integration of group medical visits and microfinance for CVD risk reduction. Subsequently, we will conduct a four-arm cluster randomized trial comparing: (1) usual clinical care, (2) usual clinical care plus microfinance groups only, (3) group medical visits only, and (4) group medical visits integrated into microfinance groups. The primary outcome measure will be 1-year change in systolic blood pressure, and a key secondary outcome measure is 1-year change in overall CVD risk as measured by the QRISK2 score. We will conduct mediation analysis to evaluate the influence of changes in social network characteristics on intervention outcomes, as well as moderation analysis to evaluate the influence of baseline social network characteristics on effectiveness of the interventions. Cost-effectiveness analysis will be conducted in terms of cost per unit change in systolic blood pressure, percent change in CVD risk score, and per disability-adjusted life year saved. This study will provide evidence regarding effectiveness and cost-effectiveness of interventions to reduce CVD risk. We aim to produce generalizable methods and results that can provide a model for adoption in low-resource settings worldwide.


Brain Strokes Related to Aortic Aneurysma - the Analysis of three Cases.
Brain stroke connected with aortic blood flow disturbances is a rare disease and its incidence is difficult to assume. Nevertheless, 10-50% of patients with aortic dissection may not experience any pain. In case of 18-30% patients with aortic dissection neurological signs are first disease presentation and among them ischemic stroke is the most common. The most popular aortic dissection classification is with use of Stanford system. Type A involves the ascending aorta and type B is occurring distal to the subclavian artery. Aortic dissection risk factors include hypertension, cystic medionecrosis, bicuspid aortic valve and Marfan's or Ehlers-Danlos syndrome.


[Evaluation of hepatic damage in personnel in the anesthesiology- resuscitation department in relation to halothane exposure].
In a simple uncontrolled toxicological study 27 workers of an anesthesiology-resuscitation department of a hospital type III were examined. Besides detailed clinical examination, determination of basic hematological and biochemical parameters as well as ultrasonography, also selected parameters of proteosynthetic function of the liver, some so-called proteins of the acute phase and the biological half-life of antipyrine were established in the workers under study. The occurrence of pathological findings in the picture of the examinations performed was related to long-term professional exposure to halothane over the period of one year before the examination. With regard to the possibility of chronic hepatotoxic damage, appropriate attention should be paid to workers of anesthesiology-resuscitation departments, concerning particularly entrance medical examinations and regular screening and follow-up of their health condition, including check-ups hepatic parameters. (Tab. 4, Ref. 23.)