Electrical conductivity of nonideal carbon and zinc plasmas: experimental and theoretical results.
Electrical conductivities of nonideal carbon and zinc plasmas have been measured in this paper. The plasma is produced by vaporizing a wire placed in a glass capillary within some hundred nanoseconds. In the case of carbon, vaporization occurs with good reproducibility when utilizing a preheating system. The particle density is in the range of n=(1-10) x 10(21) cm(-3). The plasma temperature, which is obtained by fitting a Planck function to the measured spectrum, is between 7-15 kK. Plasma radius and behavior of the plasma expansion were studied with a streak, a framing or an intensified charge coupled device camera. We compare the measured electrical conductivities with theoretical results, which were obtained solving quantum kinetic equations for the nonideal partially ionized plasmas. In this approach, the transport cross sections are calculated on the level of a T-matrix approximation using effective potentials. The plasma composition is determined from a system of coupled mass action laws with nonideality corrections.


Anesthetic complications in surgery for congenital heart disease.
Anesthetic complications in 500 consecutive operations for congenital heart disease were studied and their contribution to mortality and morbidity were assessed. The great majority of the cases were young and sick children in ASA Class III, IV, or V with complex congenital heart disease. Anesthetic mortality was zero and hospital mortality was 6.3%. Anesthetic complications occurred in 2% of the cases. Four major complications were seen, including two tension pneumothoraces, one episode of severe hypotension on induction, and a breathing circuit malfunction on induction leading to bradycardia and hypotension. Six minor complications included two cases of premature extubation that required reintubation postoperatively, one case of subglottic edema, airway obstruction from inadvertent tracheal insertion of an esophageal temperature probe, one corneal abrasion, and one case of erosion of the nasal ala secondary to a nasotracheal tube. Half of the complications were probably preventable, but the other half of the complications occurred despite specific attempts at their prevention.


Diverticulosis of the colon is rare amongst immigrants living in the Zaanstreek region in the Netherlands.
Data on prevalence of diverticulosis related to ethnicity or race in the Western world are very sparse. A cross-sectional study was done in patients undergoing endoscopy of the colon in order to assess the prevalence of diverticulosis and relate the presence to ethnicity. An analysis was undertaken of the endoscopy reports from all consecutive patients undergoing endoscopy of the colon. As a reference group all patients in whom no abnormalities were detected were used. In the Zaanstreek region a large population of immigrants, mostly of Turkish descent, is present. These immigrants were studied separately. In a period of 12 years 3004 patients were diagnosed with diverticulosis. Of these 2975 were authentic Dutch. The remainder 29 patients were immigrants. Diverticulosis was diagnosed significantly more often in immigrant men (P < 0.0001). Immigrants with diverticulosis were significantly younger than the authentic Dutch, P < 0.001. There was no major difference in representation of immigrants with diverticular disease in different age cohorts. The reference group consisted of 3356 patients. In this group 2998 patients were authentic Dutch, while 358 patients were immigrants. There was no difference in numbers of men and women amongst the immigrants. Of the patients with a normal colon and rectum 11% is immigrant. In the group of patients with diverticulosis only 0.9% was immigrant. This study clearly shows that prevalence of diverticular disease is very low in immigrants. The majority of these immigrants are of Turkish descent. In addition, the majority of immigrants with diverticulosis was male.


Serum procalcitonin is a marker for prediction of readmission from an intermediate care to an acute care hospital in neurosurgical patients.
Readmission of patients to acute hospitals contributes significantly toward inefficient utilization of healthcare resources, with studies quoting up to 90% being preventable. We aim to report and analyze the factors involved in the readmission of neurosurgical patients who had been previously transferred to an intermediate step-down care facility, and explore possible predictive markers for such readmissions. We conducted a retrospective analysis of all 129 neurosurgical patients who were transferred from out acute tertiary hospital to an intermediate care facility. The cases were segregated into those who were readmitted and those who were not readmitted back to our acute center. The demographic data, clinical features, diagnoses, treatment modalities, pretransfer laboratory findings, and inpatient complications were compared with readmission rate. There were 23 patients (17.8%) who were readmitted to our acute hospital. The most common causes of readmission was infection (n = 12, 52.2%). We found a statistically significant correlation between the higher pretransfer procalcitonin levels with the readmission of our patients (P = 0.037). There was also a significant difference noted between ethnic groups (P = 0.026) and having no complications of disease or treatment (P = 0.008), with readmission. Procalcitonin is a pro-hormone known to correlate with infection and poor neurological status. We have found that its serum values correlate significantly with the readmission rates of neurosurgical patients in our study. We postulate that by ensuring normality in procalcitonin levels prior to transfer to an intermediate care facility, potentially half of neurosurgical readmissions can be prevented.


Endoscopic Methods for Control of Non-variceal Gastrointestinal Bleeding.
Flexible upper gastrointestinal endoscopy has a well established place in the diagnosis of upper gastrointestinal bleeding. Increasing experience with a variety of modalities has made endoscopic therapy appropriate for many significant bleeding lesions of the upper GI tract. In many instances endoscopic therapy will eliminate the need for surgical control of the bleeding lesion. In other patients the temporary endoscopic control of bleeding may allow appropriate surgical intervention to be postponed until optimal stabilisation can be accomplished.


TRUC or the need for a new microbial classification.
Microbes were defined in the 19th century by L. Pasteur. Prokaryotes and eukaryotes, which are divided into two worlds of microbes, were introduced by E. Chatton in 1925. R. Woese divided this world into three domains based on ribosomal analysis (Bacteria, Archaea, and Eukarya). The discovery of Mimivirus and other Megavirales, that are microbes, led to divide the microbiological world into four branches. I introduced the name TRUC (Things Resisting Uncompleted Classifications) to accommodate the division in four of the currently known microbiological world.


Biochemical assessment and prediction of gestational well-being.
It is apparent from this brief review of serum markers that there is no ideal biochemical screen available to either assure fetal well-being or reliably predict fetal compromise. At present, MSAFP has become the dominant serum marker, but much work needs to be done to refine its usefulness as a screen and its utility in association with other measurements of fetoplacental well-being. The trend in modern obstetric management is toward an array of biophysical tests of fetal well-being, particularly in the last trimester of pregnancy. Biochemical screening in early gestation is used increasingly to assess future fetoplacental status and to predict risk for later pregnancy complications. Combinations of these biochemical and biophysical modalities will likely achieve the greatest predictive success in assessing fetal and placental well-being.


Foraging activity is reduced in a mouse model of depression.
Depression interferes with the human ability to make decisions. Multiple criteria have been adopted for the diagnosis of depression in humans, but no clear indicators are available in animal models to reflect the depressive mood, involving higher cognitive functions. The act of foraging is a species-specific behaviour which is believed to involve the decision-making and higher cognitive functions. We previously established a method to detect the foraging behaviour of rodents, in which our results demonstrated that NMDA and dopamine receptors were involved. Conversely, increased NMDA receptors and reduced dopamine have been reported in depression model rodents. However, we hypothesise that foraging activities may also be impaired in depression. To test the theory, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm. Most interestingly, the food foraging activity of mice after CUMS was significantly reduced. In addition, the treatment of anti-depressant fluoxetine reversed most depressive symptoms and reduced glial fibrillary associated protein (GFAP) expression in the hippocampus, but was less effective in the reduction of foraging activities. However, clozapine reversed all symptoms of CUMS-exposed mice including reduction of GFAP expression in the hippocampus and impaired foraging activity. Our findings of GFAP expression as a marker to validate the CUMS protocol provide further validation of our hypothesis, that the reduced food foraging is probably a new behavioural finding of depression in which the serotoninergic system could not be singly involved. Our study suggests that NMDA receptors, serotoninergic and dopaminergic systems are differentially involved in these food foraging behaviours. Our data suggest that the foraging test in rodents can be a useful tool to assess the ability of decision-making in depression.


[The stereotaxic biopsy of tumors in the pineal area].
The outcomes of stereotactic biopsy (STB) of pineal tumors are presented. This diagnostic approach was applied in 51 patients aged 7 to 59 years (mean 23 years) and its main indication is to develop an adequate treatment policy by specifying the histological structure of a tumor. Informative morphological samples were taken in 42 (82%) cases. One patient died, another developed a persistent neurological defect after STB. A third of all cases was diagnosed as having germinomas and other 5 patients were found to have germinative cellular tumors of mixed structure, which reflects the views on the policy of examination and treatment of patients with pineal tumors and indications for the biopsy, which have been established at the N. N. Burdenko Institute of Neurosurgery, Russian Academy of Medical Sciences. In 14 cases, STB diagnosis was verified from 1 to 46 weeks of postbioptic surgery connected with tumor removal or autopsy. There was 100% coincidence in histological diagnosis. Indications for STB in patients with pineal tumors, the significance of its findings, methodological and technical aspects, as well as the clinical value of this diagnostic procedure are dealt with in the paper.


Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal Cancer in Kashmiri Population: a Case Control Study.
Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p<0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.


Allogeneic stem cell transplantation with reduced-intensity conditioning is potentially feasible as an outpatient procedure.
Allogeneic stem cell transplantation (allo-SCT) after a reduced-intensity conditioning (RIC) protocol is associated with decreased short-term toxicity. This suggests that the procedure could be performed on an outpatient basis. We analysed the incidence and risk factors of grade >or=2 conditioning-related toxicities (CRTs) as a hallmark for hospital admission, in 41 consecutive patients allografted from an HLA identical sibling after RIC. The RIC regimen consisted of fludarabine plus melphalan for lymphoid malignancies, and fludarabine plus busulphan for myeloid malignancies. In all, 11 patients (27%) did not experience any toxicity. The more frequent CRTs observed were neutropenic fever and gastrointestinal toxicity. The median duration of hospitalisation was 27 (range, 17-50) days. If allo-SCT had been planned as an outpatient procedure and admission indicated only in the case of >or=2 CRTs, the inpatient period would have decreased to 9 (range, 0-33) days (P<0.001). No risk factors for CRTs were identified. Allo-SCT after an RIC regimen is a well-tolerated procedure. Our results warrant a prospective pilot trial of nonmyeloablative allo-SCT performed in the outpatient setting.


Effects of lysophosphatidyl choline and phospholipase A on the lens.
Lenses incubated for 24 or 63 hours in media containing either lysophosphatidyl choline or phospholipase A gained Na+ ions and water. Electrolyte imbalances and damage to lens fiber membranes occurred at lysophosphatidyl choline and phospholipase A concentrations of 7.5 mug per milliliter and 0.25 mug per milliliter, respectively. Intravitreal injection of 250 mug of lysophosphatidyl choline or 0.4 mug of phospholipase A induced posterior subcapsular cataracts which progressed to maturity only in the latter instance. This is the first demonstration of the cataractogenic effects of a naturally occurring aqueous humor phospholipid or its generating enzyme.


Effect of p62/SQSTM1 polyubiquitination on its autophagic adaptor function and cellular survival under oxidative stress induced by arsenite.
Oxidative stress induced by arsenite [As(III)] affects protein folding and results in increased levels of misfolded proteins or protein aggregates. Accumulation of misfolded protein aggregates may act as a cue signal for the oligomerization of the autophagic adaptor protein p62, which facilitates recognition of misfolded protein aggregates that are polyubiquitinated with K63 linkages. However, as the autophagic flux is impaired under exposure to As(III), p62 oligomers cannot be cleared by autophagy and accumulate as aggregates with Keap1. This results in the sequestration of Keap1 and the stabilization of Nrf2, which activates the non-canonical Nrf2-Keap1 pathway as an antioxidant response. In this study, we found that polyubiquitination of p62 itself increased upon exposure to As(III) to prevent further oligomerization of p62 and to increase the availability of functional free monomeric p62. We also found that monomeric p62 could also interact with ubiquitinated proteins and that the forced dimerization of p62 was sufficient to increase the interactions with ubiquitinated proteins, probably polyubiquitinated with K63 linkages. Upon exposure to As(III), (1) inability to form oligomeric p62 because of a mutation in the PB1 dimerization domain, or (2) reduced capability to generate monomeric p62 owing to diminished polyubiquitination of p62 itself, resulted in reduced viability of cells. Therefore, upon exposure to As(III), p62 initially needs to form oligomers to activate an antioxidant response pathway. Subsequently, p62 is polyubiquitinated to prevent further oligomerization and ensure the availability of free p62 monomers. We propose that the polyubiquitination of p62 under exposure to As(III) plays an important role in overcoming the impaired autophagic flux by regulating the oligomerization status of p62.


Three-Dimensional Image Transmission of Integral Imaging through Wireless MIMO Channel.
For the reconstruction of high-resolution 3D digital content in integral imaging, an efficient wireless 3D image transmission system is required to convey a large number of elemental images without a communication bottleneck. To support a high transmission rate, we herein propose a novel wireless three-dimensional (3D) image transmission and reception strategy based on the multiple-input multiple-output (MIMO) technique. By exploiting the spatial multiplexing capability, multiple elemental images are transmitted simultaneously through the wireless MIMO channel, and recovered with a linear receiver such as matched filter, zero forcing, or minimum mean squared error combiners. Using the recovered elemental images, a 3D image can be reconstructed using volumetric computational reconstruction (VCR) with non-uniform shifting pixels. Although the received elemental images are corrupted by the wireless channel and inter-stream interference, the averaging effect of the VCR can improve the visual quality of the reconstructed 3D images. The numerical results validate that the proposed system can achieve excellent 3D reconstruction performance in terms of the visual quality and peak sidelobe ratio though a large number of elemental images are transmitted simultaneously over the wireless MIMO channel.


Aggregation behavior of a conjugated C3-symmetric molecule: a description based on chiro-optical experimental and theoretical spectroscopies.
A new chiral octopolar C(3)-symmetric molecule is synthesized and its optical and chiro-optical properties are analyzed with the help of density functional theory. In all the cases, the work relates these spectroscopic properties with the phenomena of aggregation. Ultraviolet-visible absorption, infrared and Raman spectroscopies, and ECD and VCD chiro-optical spectroscopies are presented in combination with theoretical chemistry. In this regard, optical spectroscopies are insensitive to the supramolecular effects, while electronic and vibrational circular dichroism spectroscopies delivered adequate proof for the detection of aggregation. We have simulated the effect of molecular self-assembly by means of a docking process that provides a stable dimer on which all the spectroscopic properties have been theoretically calculated. The shape of this dimer provides us with a guideline to propose a helicoidal aggregate that is the responsibility of the chiro-optical spectra amplified by self-assembly.


Effects of 2450 MHz electromagnetic fields with a wide range of SARs on methylcholanthrene-induced transformation in C3H10T1/2 cells.
This study examined whether 2450 MHz continuous wave high frequency electromagnetic fields (HFEMF) could induce cancer-like changes in mouse C3H10T1/2 cells, and whether HFEMF could initiate malignant or synergistic transformation. Transformed foci, Type II and Type III, were independently counted as the experiment endpoint. The cells were exposed to HFEMF alone at a wide range of specific absorption rates (SARs) of 5 to 200 W/kg for 2 h and/or were treated with a known initiating chemical, methylcholanthrene (MC) (2.5 microg/ml). No significant differences were observed in the malignant transformation (Type II + Type III) frequency between the controls and HFEMF with or without 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.5 ng/ml), a tumor promoter that could enhance transformation frequency initiated by MC in multistage carcinogenesis. However, the transformation frequency for HFEMF at SAR of more than 100 W/kg with MC or MC plus TPA was increased compared with MC alone or MC plus TPA. On the other hand, the corresponding heat groups (heat alone, heat + MC, and heat + MC + TPA) did not increase transformation compared with each control level in C3H10T1/2 cells. This result suggests that 2450 MHz HFEMF could not contribute to the initiation stage of tumor formation, but it may contribute to the promotion stage at the extremely high SAR (100 W/kg).


A Five-Year Study of Intrapleural Fibrinolytic Therapy in Loculated Pleural Collections.
Pleural fluid loculations due to complicated parapneumonic effusion (CPE), empyema, tubercular effusion and traumatic hemothorax can be managed either by video-assisted thoracoscopic surgery (VATS) or intrapleural ibrinolytic therapy (IPFT). The former is more invasive, not easily available and is also more expensive. On the other hand, IPFT is less invasive, cheaper, easily accessible and if used early, in loculated pleural collections, break loculations and early pleural peel, thereby facilitating pleural space drainage. To study the efficacy of IPFT in facilitating pleural space drainage in loculated pleural collections of diverse aetiologies. A five-year retrospective, observational study of 200 patients, with loculated pleural collections and failed tube drainage and managed with IPFT was carried out. Responders were defined as those with significant volume of fluid drained and significant radiological resolution. There were 106 (53%) cases of CPE, 59 (29.5%) cases of tubercular effusion, 23 (11.5%) cases of empyema and 12 (6%) cases of hemothorax. Responders were 148 (74%) in number. The distribution of responders as per type of loculated pleural collection was as follows: CPE 88 (83%), tubercular 37 (62.7%), empyema 14 (60.8%) and traumatic hemothorax 11 (91.6%). The adverse effects were mild and included chest pain in six patients and low-grade transient fewer in three cases. Intrapleural fibrinolytic therapy is a safe and cost-effective option in the management of selected patients with loculated pleural effusions.


Lung recruitment in unilateral lung disease.
The treatment of unilateral lung injury is supportive. Gas exchange can be improves by positioning the patient with the "good lung down" and applying differential ventilation with selective PEEP in some patients. However, both strategies have serious limitations in clinical practice. Basic research have shown that the application of selective TGI and the combination of selective TGI and PLV permitted a reduction in tidal volume with resultant decrease in airway pressures and improvement in lung compliance, without any adverse effects on CO2 elimination. Experimental models have shown that the use of selective TGI and PLV at low tidal volume is a simple method to provide regional recruitment, enhancing gas exchange while reducing cyclic lung stretch and shear stresses associated with mechanical ventilation. These experimental studies cannot be extrapolated to clinical practice because further studies are needed to determine human applications of these therapies.


Phase I and pharmacokinetic study of arabinofuranosyl-5-azacytosine (fazarabine, NSC 281272).
A Phase I clinical trial of 1-beta-D-arabinofuranosyl-5-azacytosine (ara-AC or fazarabine) given as a 72-h continuous infusion on a 21-day cycle was conducted in 27 adult patients with refractory cancer. The major toxicity was reversible granulocytopenia and thrombocytopenia. Dose-limiting toxicity was observed at a dose rate of 1.96 mg/m2/h in which Grade IV leukopenia (WBC less than 1,000/mm3) occurred in 4 of 11 patients and Grade IV thrombocytopenia (platelets less than 25,000/mm3) occurred in 3 of 11 patients. Plasma steady-state levels ranged from 0.13 to 0.6 microM for doses of 1.25 to 5.94 mg/m2/h. Mean total body clearance was 647 ml/min/m2. Minor clinical responses were seen in one patient with testicular cancer, one patient with colon cancer, one patient with breast cancer, and one patient with acute nonlymphocytic leukemia. Another patient with adenocarcinoma of unknown primary had stable disease during 13 cycles of therapy. Based on the results of this study, the recommended dose for Phase II studies of 1-beta-D-arabinofuranosyl-5-azacytosine administered as a 72-h continuous infusion is 2.0 mg/m2/h (48 mg/m2/day).


Bactericidal synergy between penicillin or ampicillin and aminoglycosides against antibiotic-tolerant lactobacilli.
The bactericidal activities of penicillin G and ampicillin alone were compared with those of their combinations with streptomycin or gentamicin against 17 strains of lactobacilli classified as tolerant to various beta-lactam antibiotics. The penicillin G combinations with streptomycin and gentamicin were synergistic against 17 and 16 of these strains, respectively, whereas the corresponding ampicillin-aminoglycoside combinations were synergistic against 12 and 15 strains, respectively. Importantly, synergy was manifested at concentrations of these antibiotics that are attained in serum after their administration in conventional dose regimens. In no instances were combinations antagonistic. These in vitro observations provide a partial explanation for the favorable results obtained in preliminary clinical evaluations of the benefits of combination regimens in the treatment of lactobacillus infections refractory to single-drug therapy.


Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging.
Background. Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluorescent dyes, EC17 and OTL38, which both target folate receptor but have different fluorochromes. Materials. HeLa and KB cells lines were used for in vitro and in vivo comparisons of EC17 and OTL38 brightness, sensitivity, pharmacokinetics, and biodistribution. In vivo experiments were then performed in mice. Results. The peak excitation and emission wavelengths of EC17 and OTL38 were 470/520 nm and 774/794 nm, respectively. In vitro, OTL38 required increased incubation time compared to EC17 for maximum fluorescence; however, peak signal-to-background ratio (SBR) was 1.4-fold higher compared to EC17 within 60 minutes (p < 0.001). Additionally, the SBR for detecting smaller quantity of cells was improved with OTL38. In vivo, the mean improvement in SBR of tumors visualized using OTL38 compared to EC17 was 3.3 fold (range 1.48-5.43). Neither dye caused noticeable toxicity in animal studies. Conclusions. In preclinical testing, OTL38 appears to have superior sensitivity and brightness compared to EC17. This coincides with the accepted belief that near infrared (NIR) dyes tend to have less autofluorescence and scattering issues than visible wavelength fluorochromes.


The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR).
Induction of cytochrome P450 3A (CYP3A) by xenobiotics may lead to clinically relevant drug interactions. In contrast with other CYP3A family members, studies on the inducibility of CYP3A5 indicate conflicting results. We report the induction of CYP3A5 mRNA in 13 of 16 hepatocyte preparations exposed to rifampin. Furthermore, induction of CYP3A5 mRNA was observed in intestinal biopsies in three of eight probands following exposure to the antibiotic. The highest absolute levels of CYP3A5 transcripts were found following rifampin treatment in hepatocytes and intestines from carriers of CYP3A5*1 alleles. Elucidation of the mechanism involved in CYP3A5 induction revealed that constitutively activated receptor (CAR) and pregnane X receptor (PXR) transactivated the CYP3A5 promoter (-688 to +49) and that the transactivation was dependent on an everted repeat separated by 6 bp (ER6-dependent). Treatment with the prototypical PXR ligand rifampin led to a 2-fold induction of the CYP3A5 promoter activity. In agreement with these observations, PXR and CAR bound specifically to the ER6 motif. Hepatic expression of PXR correlated with that of CYP3A5 mRNA levels in a bank of liver samples. Taken together, studies here revealed the presence of a functional ER6 motif in the CYP3A5 promoter located -100 bp upstream from the transcription start site, suggesting that CYP3A5 is inducible by mechanisms similar to those involved in CYP3A4 induction. Enhanced expression of CYP3A5 caused by exposure to inducers may phenocopy the effects of the high expression allele CYP3A5*1. In this manner, induction of CYP3A5 may contribute to the overall importance of this P450 in drug metabolism and drug interactions.


Exocytosis proteins as novel targets for diabetes prevention and/or remediation?
Diabetes remains one of the leading causes of morbidity and mortality worldwide, affecting an estimated 422 million adults. In the US, it is predicted that one in every three children born as of 2000 will suffer from diabetes in their lifetime. Type 2 diabetes results from combinatorial defects in pancreatic β-cell glucose-stimulated insulin secretion and in peripheral glucose uptake. Both processes, insulin secretion and glucose uptake, are mediated by exocytosis proteins, SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes, Sec1/Munc18 (SM), and double C2-domain protein B (DOC2B). Increasing evidence links deficiencies in these exocytosis proteins to diabetes in rodents and humans. Given this, emerging studies aimed at restoring and/or enhancing cellular levels of certain exocytosis proteins point to promising outcomes in maintaining functional β-cell mass and enhancing insulin sensitivity. In doing so, new evidence also shows that enhancing exocytosis protein levels may promote health span and longevity and may also harbor anti-cancer and anti-Alzheimer's disease capabilities. Herein, we present a comprehensive review of the described capabilities of certain exocytosis proteins and how these might be targeted for improving metabolic dysregulation.


Surgical Site Infection due to a Preauricular Sinus: A Rare Complication after Craniotomy.
Wound infection due to a preauricular sinus after craniotomy has not been previously reported. A 71-year-old woman visited our institute with subarachnoid hemorrhage. The aneurysm was surgically clipped with external decompression. Sixteen days after surgery, a focal erythema and discharging were observed at the inferior end of the skin incision. Careful inspection revealed a small pit there, which was diagnosed as a preauricular sinus. After the infection subsided, the sinus was completely excised. Neurosurgeons must be aware of this rare condition and must opt for complete excision to prevent infectious sequelae even if the preauricular sinus is asymptomatic.


Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered.
High dose of corticosteroids has been previously shown to protect against controlled mechanical ventilation (CMV)-induced diaphragmatic dysfunction while inhibiting calpain activation. Because literature suggests that the calpain inhibiting effect of corticosteroid depends on the dose administered, we determined whether lower doses of corticosteroids would also provide protection of the diaphragm during CMV. This may be important for patients undergoing mechanical ventilation and receiving corticosteroids. Rats were assigned to controls or to 24 hours of CMV while being treated at the start of mechanical ventilation with a single intramuscular administration of either saline, or 5 mg/kg (low MP) or 30 mg/kg (high MP) of methylprednisolone. Diaphragmatic force was decreased after CMV and this was exacerbated in the low MP group while high MP rescued this diaphragmatic dysfunction. Atrophy was more severe in the low MP group than after CMV while no atrophy was observed in the high MP group. A significant and similar increase in calpain activity was observed in both the low MP and CMV groups whereas the high dose prevented calpain activation. Expression of calpastatin, the endogenous inhibitor of calpain, was decreased in the CMV and low MP groups but its level was preserved to controls in the high MP group. Caspase-3 activity increased in all CMV groups but to a lesser extent in the low and high MP groups. The 20S proteasome activity was increased in CMV only. Administration of 30 mg/kg methylprednisolone during CMV protected against CMV-induced diaphragm dysfunction while 5 mg/kg was more deleterious. The protective effect is due mainly to an inhibition of the calpain system through preservation of calpastatin levels and to a lesser extent to a caspase-3 inhibition.


Role of mitral valve repair in infective endocarditis.
Mitral valve reconstruction (MVP) is currently the standard treatment for degenerative mitral regurgitation (MR). However, when MR is due to infective endocarditis (IE) the range of pathophysiology present often makes any repair challenging. Hence, the authors' clinical experience of MVP to treat MR caused by IE was analyzed. Between September 2004 and March 2011, a total of 26 patients (20 males, six females) who had been diagnosed with MR due to IE (single surgeon, retrospective review) were operated on. Among the 26 patients (17 active, nine healed; six Carpentier type I, 20 Carpentier type II), MVP was performed in 11 patients (42.3%), of which six were active cases and five were healed. All MVP procedures included ring annuloplasty. A variety of repair techniques was used, including triangular resection (n = 3), pericardial patch reconstruction (n = 4), commissuroplasty (n = 4), artificial chordoplasty (n = 1), chordae transfer (n = 2), and secondary chordae resection (n = 1). Six of 17 patients who had a pathology favorable for repair underwent valve replacement; the etiologies were underlying valvular disease (n = 2, rheumatic pathology), Child's group C liver cirrhosis (n = 1), second redo sternotomy (n = 1), multivalvular disease (n = 1), and critical medical condition (n = 1, septic shock). The mean follow up duration was 35.7 months (range: 0.1-84.9 months). Among the repair group, none of the patients showed residual MR on postoperative echocardiography. There were no early or late deaths, and no patient showed newly developed MR during the follow up. Among the replacement group, three patients died of noncardiac causes during the follow up (two early deaths and one late death). MVP for MR due to IE showed successful clinical outcomes. Valve replacement was performed in some patients with a repair-favorable pathology, after taking into consideration any comorbidities. Whilst standard repair techniques were sufficient, careful decision-making was the key to achieving excellent results for MVP.


[Effect of MT01/PEN complexes on the expression of osteoprotegerin and receptor activator of nuclear factor κB ligand in human osteoblast-like cell line MG63].
This study aims to synthesize MTO1 (a kind of oligodeoxynucleotides) and N-isopropylacrylamide-modified polyethylenimines (PEN) complexes (MT01/PEN) as well as to investigate the effect of the complexes on the expression of osteoprotegerin (OPG) and the receptor activator of nuclear factor κB ligand (RANKL) in the human osteoblast-like cell line MG63. MG63 cells were transfected by MT01/PEN complexes formed with three different mass ratios (1:2, 1:4, 1:6) of MT01 to PEN. MT01 and MT01-s were used as positive control. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were performed to estimate the amount of OPG and RANKL released into the culture media and in MG63 at 24, 48, 72 h. MG63 responded to the MT01/PEN complexes by significantly upregulating the OPG on the protein and mRNA levels (P < 0.05). The protein and mRNA levels of RANKL were lower in most of the groups with complexes, and the OPG/RANKL ratio were higher (P < 0.05). MG63 were affected by the MT01/PEN complexes with different mass ratios, particularly when the ratio was 1:6. MT01 can enhance the promotion of ossification by establishing the delivery system with PEN.


Demosaicing Based on Directional Difference Regression and Efficient Regression Priors.
Color demosaicing is a key image processing step aiming to reconstruct the missing pixels from a recorded raw image. On the one hand, numerous interpolation methods focusing on spatial-spectral correlations have been proved very efficient, whereas they yield a poor image quality and strong visible artifacts. On the other hand, optimization strategies, such as learned simultaneous sparse coding and sparsity and adaptive principal component analysis-based algorithms, were shown to greatly improve image quality compared with that delivered by interpolation methods, but unfortunately are computationally heavy. In this paper, we propose efficient regression priors as a novel, fast post-processing algorithm that learns the regression priors offline from training data. We also propose an independent efficient demosaicing algorithm based on directional difference regression, and introduce its enhanced version based on fused regression. We achieve an image quality comparable to that of the state-of-the-art methods for three benchmarks, while being order(s) of magnitude faster.


CCR7, CCR8, CCR9 and CCR10 in the mouse hippocampal CA1 area and the dentate gyrus during and after pilocarpine-induced status epilepticus.
The present study showed CCR7, CCR8, CCR9 and CCR10 in the normal Swiss mouse hippocampus at both protein and mRNA levels. CCR7, CCR9 and CCR10 were mainly localized in hippocampal principal cells and some interneurons. CCR9 was also found in the mossy fibres and/or terminals, suggesting an axonal or presynaptic localization, and CCR10 in apical dendrites of pyramidal neurons in the CA1 area. CCR8 was observed in interneurons. Double-labelling immunocytochemistry revealed that most of calbindin (CB)-, calretinin (CR)- and parvalbumin (PV)-immunopositive neurons expressed CCR7-10, except CR-immunopositive cells in which only 10 to 12% expressed CCR8. During and after pilocarpine-induced status epilepticus, progressive changes of each of CCR7, CCR8, CCR9 and CCR10 proteins occurred in different patterns at various time points. Sensitive real-time PCR showed similar change patterns at mRNA level. At the chronic stage, i.e. at 2 months after pilocarpine-induced status epilepticus, significant reduction of CCR7-10 expression in CB-, CR- and PV-immunpositive interneurons may suggest the phenotype change of surviving interneurons. Double labelling of CCR7, CCR8 and CCR9 with glial fibrillary acidic protein (GFAP) at the chronic stage may suggest an induced expression in reactive astrocytes. The present study may, therefore, for the first time, provide evidence that CCR7-10 may be involved in normal hippocampal activity. The demonstration of the progressive changes of CCR7-10 during and after status epilepticus may open a new area to reveal the mechanism of neuronal loss after status epilepticus and of epileptogenesis.


Evaluating information prescriptions in two clinical environments.
The research sought to evaluate whether providing personalized information services by libraries can improve satisfaction with information services for specific types of patients. Adult breast cancer (BrCa) clinic patients and mothers of inpatient neonatal intensive care unit (NICU) patients were randomized to receive routine information services (control) or an IRx intervention. The BrCa trial randomized 211 patients and the NICU trial, 88 mothers. The BrCa trial showed no statistically significant differences in satisfaction ratings between the treatment and control groups. The IRx group in the NICU trial reported higher satisfaction than the control group regarding information received about diagnosis, treatments, respiratory tradeoffs, and medication tradeoffs. BrCa patients posed questions to librarians more frequently than did NICU mothers, and a higher percentage reported using the website. Questions asked of the librarians by BrCa patients were predominantly clinical and focused on the areas of treatment and side effects. Study results provide some evidence to support further efforts to both implement information prescription projects in selected settings and to conduct additional research on the costs and benefits of services.


Testis-specific proteins and their role in contraceptive vaccine development.
Development of a vaccine(s) based on sperm antigens represents a promising approach for contraception. The utility of an antigen in immunocontraception is contingent upon its testis/sperm specificity and involvement in spermatogenesis and/or fertilization. The aim of the present article is to review the information regarding the proteins that have been reported to be testis/sperm-specific and may have an important function in spermatogenesis and/or fertilization. The potential role of these proteins in the development an antisperm contraceptive vaccine(s) is discussed.


MF-Storm: a maximum flow-based job scheduler for stream processing engines on computational clusters to increase throughput.
A scheduling algorithm tries to schedule multiple computational tasks on a cluster of multiple computing nodes to maximize throughput with optimal utilization of computational and communicational resources. A Stream Processing Engine (SPE) is deployed to run streaming applications (computational tasks) on a computational cluster which helps execution and coordination of these applications. It is observed that there is a gap in the optimal mapping of a computational and communicational load of a streaming application on the underlying computational and communication power of the resources (cluster). Frequently communicated tasks are scheduled at different processing nodes with relatively slow communicating links. This increases network latency with a decrease in resource utilization. Hence, reduces the achieved throughput of the cluster significantly. MF-Storm, a max-flow min-cut based job scheduler is presented to achieve a near-optimum schedule to maximize throughput. It schedules a streaming application by considering the processing, communication demands, available computational and communicational resources in a heterogeneous cluster, dynamically with minimized scheduling cost. To keep the scheduling cost minimum, the scheduler is built in a pipeline with two major stages: in the first stage, the application's tasks graph is partitioned using the max-flow min-cut algorithm to minimize inter-partition traffic, and in the second stage, these partitions are assigned to computing nodes according to the computational power of the cluster's nodes. Extensive experiments were done to evaluate the performance of MF-Storm using different topologies with multiple scenarios on a physical cluster implementation. Results showed on average 148% improvement in throughput with 30% less computational resources as compared to different state-of-the-art schedulers.


Xenobiotic C-sulfonate derivatives; metabolites or metabonates?
1. The production of sulfate conjugates is a well-known and established pathway within the field of xenobiotic metabolism. In addition to the usual attachment of a sulfonate grouping via an oxygen atom (O-sulfonates) to yield a sulfate conjugate, so-called "N-sulfates" (N-sulfonates) have been reported and "S-sulfates" (S-sulfonates) mooted to exist. 2. The few examples cited in the literature where the sulfur atom of the sulfonate group was attached directly to a carbon atom of the xenobiotic (C-sulfonates) and subsequently excreted as a metabolite have been collated, examined and reviewed. 3. The potential mechanisms of formation of these C-sulfonates are discussed, both biological and chemical; the potential role of the gut microbiome raised and hopefully by highlighting this curiosity further fruitful investigation will be stimulated.


Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease.
Alzheimer's disease (AD) is a multifactorial, fatal neurodegenerative disorder characterized by the abnormal accumulation of Aβ and Tau deposits in the brain. There is no cure for AD, and failure at different clinical trials emphasizes the need for new treatments. In recent years, significant progress has been made toward the development of miRNA-based therapeutics for human disorders. This study was designed to evaluate the efficiency and potential safety of miRNA replacement therapy in AD, using miR-15/107 paralogues as candidate drug targets. We identified miR-16 as a potent inhibitor of amyloid precursor protein (APP) and BACE1 expression, Aβ peptide production, and Tau phosphorylation in cells. Brain delivery of miR-16 mimics in mice resulted in a reduction of AD-related genes APP, BACE1, and Tau in a region-dependent manner. We further identified Nicastrin, a γ-secretase component involved in Aβ generation, as a target of miR-16. Proteomics analysis identified a number of additional putative miR-16 targets in vivo, including α-Synuclein and Transferrin receptor 1. Top-ranking biological networks associated with miR-16 delivery included AD and oxidative stress. Collectively, our data suggest that miR-16 is a good candidate for future drug development by targeting simultaneously endogenous regulators of AD biomarkers (i.e., Aβ and Tau), inflammation, and oxidative stress.


Rational Design of Hypoallergenic Vaccines: Blocking IgE-binding to Polcalcin Using Allergen-specific IgG Antibodies.
Chenopodium album polcalcin (Che a 3) is characterized as a major cause of cross-reactivity inallergic patients to the Chenopodiaceae family. Therefore, the present study was conducted to develop a hypoallergenic Che a 3 derivatives as the candidate vaccine for type 1 allergy. Four derivatives were generated from Che a 3. The first was a mosaic peptide derivative computationally identified in Che a 3 which was coupled to keyhole limpet hemocyanin (KLH). The second one was a mutant Che a 3, and the other two derivatives included N- and C-terminal halves of Che a 3 that both coupled to KLH. The IgE-binding capacity of Che a 3 and its derivatives and also their ability to induce there combinant Che a 3 (rChe a 3)-specific IgG antibody, were determined using the enzyme-linked immune sorbent assay (ELISA). Moreover, the lymphopro liferative capacity of rChe a 3 or its derivatives and their pro-inflammatory cytokine response interleukin (IL)-5 and IL-13 were measured in the human peripheral blood mononuclear cells (PBMCs). Among all derivatives, the N-terminal half peptide and mosaic peptide exhibited the lowest IgE-binding capacity. In addition, in comparison to other antigens, KLH-coupled mosaic peptide induced the highest level of the recombinant Che a 3 (rChe a 3)-specific IgG antibody and ther Che a 3 specific-blocking IgG antibody in mice. Moreover, the mosaic peptide lacked lymphopro liferative capacity and down-regulated expression of pro-allergic IL-5 and IL-13 cytokines. Therefore, a peptide-carrier fusion vaccine, composed of the B-cell epitope coupled to the carrier, could be considered as one of the promising hypoallergenic vaccines to treat patients with allergy to low molecular weight allergens such as Che a 3.


Direct synthesis of long single-walled carbon nanotube strands.
In the processes that are used to produce single-walled nanotubes (electric arc, laser ablation, and chemical vapor deposition), the typical lengths of tangled nanotube bundles reach several tens of micrometers. We report that long nanotube strands, up to several centimeters in length, consisting of aligned single-walled nanotubes can be synthesized by the catalytic pyrolysis of n-hexane with an enhanced vertical floating technique. The long strands of nanotubes assemble continuously from arrays of nanotubes, which are intrinsically long.


Spironolactone for acne in women.
Overview of: Santer M, Lawrence M, Renz S, et al. Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ. 2023;381:e074349.


Newly Discovered Occurrences and Gene Tree of the Extracellular Globins and Linker Chains from the Giant Hexagonal Bilayer Hemoglobin in Metazoans.
Multicellular organisms depend on oxygen-carrying proteins to transport oxygen throughout the body; therefore, proteins such as hemoglobins (Hbs), hemocyanins, and hemerythrins are essential for maintenance of tissues and cellular respiration. Vertebrate Hbs are among the most extensively studied proteins; however, much less is known about invertebrate Hbs. Recent studies of hemocyanins and hemerythrins have demonstrated that they have much wider distributions than previously thought, suggesting that oxygen-binding protein diversity is underestimated across metazoans. Hexagonal bilayer hemoglobin (HBL-Hb), a blood pigment found exclusively in annelids, is a polymer comprised up to 144 extracellular globins and 36 linker chains. To further understand the evolutionary history of this protein complex, we explored the diversity of linkers and extracellular globins from HBL-Hbs using in silico approaches on 319 metazoan and one choanoflagellate transcriptomes. We found 559 extracellular globin and 414 linker genes transcribed in 171 species from ten animal phyla with new records in Echinodermata, Hemichordata, Brachiopoda, Mollusca, Nemertea, Bryozoa, Phoronida, Platyhelminthes, and Priapulida. Contrary to previous suggestions that linkers and extracellular globins emerged in the annelid ancestor, our findings indicate that they have putatively emerged before the protostome-deuterostome split. For the first time, we unveiled the comprehensive evolutionary history of metazoan HBL-Hb components, which consists of multiple episodes of gene gains and losses. Moreover, because our study design surveyed linkers and extracellular globins independently, we were able to cross-validate our results, significantly reducing the rate of false positives. We confirmed that the distribution of HBL-Hb components has until now been underestimated among animals.


Analyzing complex patients' temporal histories: new frontiers in temporal data mining.
In recent years, data coming from hospital information systems (HIS) and local healthcare organizations have started to be intensively used for research purposes. This rising amount of available data allows reconstructing the compete histories of the patients, which have a strong temporal component. This chapter introduces the major challenges faced by temporal data mining researchers in an era when huge quantities of complex clinical temporal data are becoming available. The analysis is focused on the peculiar features of this kind of data and describes the methodological and technological aspects that allow managing such complex framework. The chapter shows how heterogeneous data can be processed to derive a homogeneous representation. Starting from this representation, it illustrates different techniques for jointly analyze such kind of data. Finally, the technological strategies that allow creating a common data warehouse to gather data coming from different sources and with different formats are presented.


High-resolution electron microscopic studies on the quaternary structure of ornithine aminotransferase from pig kidney.
The ornithine aminotransferase (OAT) from pig kidney has been studied on the basis of high-resolution electron microscopy and the morphological appearance of the apoenzyme and holoenzyme have been examined. The quaternary structure of the OAT molecules in the presence of 5 mM pyridoxal 5'-phosphate could be established. The enzyme molecule appears to be built up of two morphological units, called M1. The native holoenzyme, termed morphological unit M2, measures 10.9 nm in length and 5.8 nm in width and its molecular mass is approximately 168 kDa, based on electron microscopical calculations. Since the enzyme is composed of only one type of 45-kDa subunit, the holoenzyme is a homotetramer. Each M1 is composed of two subunits and, as seen in top-view projection, has an oval to triangular shape. Upon tilting to 40 degrees the triangular shape changes into three distinct centers of mass. This morphological differentiation reflects the inner organization of M1, i.e. the shape of the individual subunit deviates from strictly globular proteins. This observation is compatible with the notion that the 45-kDa subunit consists of one large and one small domain. By tilting to 40 degrees, both large domains in M1 represent two of the three centers of mass, while the third center of mass is attributed to the superposition of both small domains. Thus, the four domains of both subunits in M1, in accordance with the triangular top-view projection, are quasi-tetrahedrally arranged. Since the change in shape of M1 upon tilting is only obvious in one of the two halves of the native OAT, it suggests that both morphological units of M2 are oriented asymmetrically relative to one another.


Reverse pneumatic artificial muscles (rPAMs): Modeling, integration, and control.
Despite offering many advantages over traditional rigid actuators, soft pneumatic actuators suffer from a lack of comprehensive, computationally efficient models and precise embedded control schemes without bulky flow-control valves and extensive computer hardware. In this article, we consider an inexpensive and reliable soft linear actuator, called the reverse pneumatic artificial muscle (rPAM), which consists of silicone rubber that is radially constrained by symmetrical double-helix threading. We describe analytical and numerical static models of this actuator, and compare their performance against experimental results. To study the application of rPAMs to operate underlying kinematic linkage skeletons, we consider a single degree-of-freedom revolute joint that is driven antagonistically by two of these actuators. An analytical model is then derived, and its accuracy in predicting the static joint angle as a function of input pressures is presented. Using this analytical model, we perform dynamic characterization of this system. Finally, we propose a sliding-mode controller, and a sliding mode controller augmented by a feed-forward term to modulate miniature solenoid valves that control air flow to each actuator. Experiments show that both controllers function well, while the feed-forward term improves the performance of the controller following dynamic trajectories.


Truncated gag products encoded by Gv-1-responsive endogenous retrovirus loci.
The conversion of endogenous or exogenous murine retroviruses to a leukemogenic phenotype involves recombination with retroviral sequences present in host genomic DNA. In the 129 Gix+ inbred strain, these endogenous sequences are replication defective but still express retroviral proteins under the apparent transcriptional control of the Gv-1 regulatory locus. To study the protein-coding potential of Gv-1-regulated endogenous retroviral loci, we used oligonucleotide probes directed to env deletion breakpoints identified in previously characterized cDNA clones. Four endogenous retroviral loci were isolated from a library of 129 Gix+ genomic DNA with these probes. Three loci cloned with the env deletion probe del env-1 had virtually identical proviral inserts by restriction analysis. A unique locus was identified and cloned with the del env-2 probe, which must therefore represent a Gv-1-responsive element. Restriction enzyme and nucleotide sequence analyses indicated that the del env-1 and del env-2 loci represented members of the polytropic and modified polytropic classes of endogenous retrovirus, respectively. Despite this divergence, members of both classes contained identical deletions of 19 nucleotides within p30gag and of 1,474 nucleotides from p10gag into the reverse transcriptase-coding region of pol, suggesting that a recombination event had occurred between these proviral sequences prior to insertion within the genome. The del env-1 and del env-2 loci retained coding capacity for truncated gag polyproteins, confirmed by in vitro translation and immunoprecipitation of the protein products. Nucleotide sequence comparison of the untranslated leader (L) regions of the del env-1 and del env-2 loci to a replication-competent ecotropic virus indicated regions that might be important to dispersion of these endogenous retroviral elements throughout the host genome.


Dietary fats, fish, and blood pressure.
In humans any effects of dietary saturated fats or omega-6 polyunsaturates on blood pressure appear to be mediated by changes in caloric intake and long-term weight changes. In contrast, omega-3 fatty acids have a mild antihypertensive effect which is seen most clearly in untreated subjects with higher blood pressures, in older people, and during sodium restriction. The mechanism may be due to a combination of effects consequent to incorporation of omega-3 fatty acids into vascular phospholipids, leading to reduced formation of endothelial contractile substances in larger vessels and impairment of sympathetic neuroeffector and other vasoconstrictor mechanisms in resistance vessels.


High-flexion, motion-guided total knee arthroplasty: who benefits the most?
A multicenter study was performed to determine which patients have the most potential to benefit from total knee arthroplasty (TKA) with a high-flexion, guided-motion design. In 201 consecutive TKAs, the mean gain in range of motion (ROM) was 14 degrees at 3 months and 24 degrees at 6 months. The gain in flexion was significant at 3 and 6 months postoperatively. No differences were found based on preoperative diagnosis, age, or sex. There was a poor correlation between body mass index and ROM. Pre- and postoperative flexion also displayed a weak correlation. Patients with the least preoperative flexion (<90 degrees) gained the most degrees of flexion (26 degrees). We conclude that the use of a high-flexion, guided-motion TKA allows a significant functional improvement in patients with preoperative stiffness and the preservation of good flexion in patients with normal preoperative flexion.


Polyoxygenated Stigmastane-Type Steroids from Vernonia kotschyana Sch. Bip. ex Walp. and Their Chemophenetic Significance.
Four polyoxygenated stigmastanes (1-4) alongside known analogues (7-8) and flavonoids (5-6) were isolated from a dichloromethane/methanol (1:1, v/v) extract of the whole plant of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae). Their structures were determined by means of spectroscopic and spectrometric analysis. The relative stereochemistry of the new compounds was established and confirmed via biosynthesis evidence and cyclization of 1 under acidic conditions. A plausible biosynthetic pathway to the new compounds and the chemophenetic significance of the isolated constituents were also discussed. The crude extract, fractions, and compounds (1-3) were assessed for their antibacterial activity against five highly prevalent bacterial strains. The fractions and compounds showed low to moderate activity with minimal inhibitory concentrations (MICs) > 125 µg/mL.


Strategies for overcoming imatinib mesylate resistance in chronic myelogenous leukemia.
Imatinib mesylate was approved for the treatment of chronic myelogenous leukemia more than 5 years ago. This drug enabled us to put a very high percentage of patients into hematologic, cytogenetic, and molecular remission. Some patients were resistant to Imatinib from the onset of the treatment whereas others became resistant after showing an initial response to Imatinib mesylate. Various strategies have been tried to overcome the resistance to this drug including using newer combinations, higher dosage of Imatinib and development of newer compounds. This article will discuss these strategies in detail.


Coxsackie A10 virus infection among infectious hepatitis contacts.
During an outbreak of infectious hepatitis at a housing development, Coxsackie A10 virus was recovered from the stools of 45 different contacts and from the blood of four others. Caution should be exercised in attributing an etiological role to any given isolate of a Group A Coxsackie virus in view of the widespread distribution of these organisms. Nevertheless, the recovery of Coxsackie A10 viruses from the blood and stools of contacts with hepatitis cases appears to warrant record.


The ability of enteric diarrhoeal pathogens to ferment starch to short-chain fatty acids in vitro.
Short-chain fatty acids (SCFA), produced in the normal colon by bacterial fermentation, are decreased in acute diarrhoea. This may have deleterious effects on epithelial function in the colon. The ability of several diarrhoeal pathogens to produce SCFA when incubated with starch in vitro was studied. Isolated pathogens were incubated for 24 h with either no added substrate, glucose, or starch under anaerobic conditions, and SCFA were quantitated by gas-liquid chromatography. Unlike the normal colonic flora, the pathogens produced acetate but not propionate or butyrate. D-Lactate was also produced by all the pathogens studied. When the pathogens were incubated in anaerobic medium containing starch, significantly greater amounts of acetate and significantly lesser amounts of lactate were produced. The inability of enteric pathogens to produce butyrate may impair epithelial cell function, whereas production of D-lactate may enhance mucosal damage in diarrhoeal disease. The presence of luminal starch may be helpful in shifting the fermentation profile to a more favourable pattern.


Functional T lymphocytes are required for a murine retrovirus-induced immunodeficiency disease (MAIDS).
Athymic nu/nu mice were found to be resistant to the immunodeficiency disease and lethality induced in normal mice by the injection of the LP-BM5 mixture of murine retroviruses (LP-BM5 MuLV). Susceptibility to disease induction was reconstituted by injection of nu/nu mice with purified, mature T lymphocytes. The extent of viral replication of both the ecotropic and mink cell focus forming (MCF) components of LP-BM5 MuLV was equivalent in both nu/nu and normal animals. Retrovirally-induced immunodeficiency disease in mice (MAIDS) is thus dependent upon the presence of functional T lymphocytes, and high virus titers in athymic mice have little or no effect on the immune system.


Retention and splicing complex (RES) - the importance of cooperativity.
One of the great challenges to structural biologists lies in explaining the complexities of the spliceosome - a ribosome-sized molecular machine that is assembled in a step-wise manner and is responsible for pre-mRNA splicing. The spliceosome is both fascinating and difficult to work with, because of its dynamic nature. At each discrete step of splicing tens of proteins come and go orchestrating the functional transition through massive structural rearrangements. The retention and splicing complex (RES) is an important splicing factor interacting with pre-mRNA at the onset of the first transesterification reaction. RES is a specific splicing factor for a number of genes and is important for controlling pre-mRNA retention in the nucleus. RES is a 71 kDa heterotrimer composed of the 3 proteins Pml1p, Bud13p and Snu17p. We solved the 3-dimensional structure of the core of the RES complex as well as the 2 dimers, Snu17p-Bud13p and Snu17p-Pml1p. Further biophysical analysis revealed an astounding cooperativity that governs the assembly of this trimeric complex as well as its interaction with pre-mRNA. The more than 100-fold cooperativity originates from the progressive rigidification of Snu17p upon coupled binding-and-folding of protein regions, which are disordered in the unbound state. Our work highlights the role of cooperativity in the spliceosome and poses new questions about the structure and assembly of the spliceosome.


Prospective study of residual neuromuscular block and postoperative respiratory complications in patients reversed with neostigmine versus sugammadex.
Postoperative residual curarization (PORC) is an important complication of neuromuscular blocking drug (NMBD) use. This study evaluates the incidence of PORC in the Postanesthesia Care Unit (PACU), its relation to the type of muscle relaxant and reversal agent used, and its implication in the development of postoperative respiratory complications. A prospective observational study of cohorts was made with 558 patients operated under general anesthesia. Data regarding patient history, muscle relaxation (train-of-four [TOF]) monitoring, type of relaxants and reversal agents used, and TOF upon admission to the PACU was collected. Four groups were established: cisatracurium, cisatracurium-neostigmine, rocuronium, and rocuronium-sugammadex. An evaluation was made on the incidence of PORC (TOF ratio [TOFr] <0.9) in PACU, and its relation to the relaxants and reversal agents used and to the development of postoperative respiratory complications - minor and major (pneumonia, atelectasis). From a total of 558 patients, 27.9% presented with PORC. According to the NMBD used and the administration or not of a reversal agent, the incidence of PORC in the four groups was: cisatracurium 34%, cisatracurium-neostigmine 28.6%, rocuronium 34%, and rocuronium-sugammadex 1.15%. The global incidence of minor critical respiratory events (CREs) was 14.5%: cisatracurium 27.5%, cisatracurium-neostigmine 17.4%, rocuronium 10.5%, and rocuronium-sugammadex 2.3%, with statistically significant differences. The global incidence of major CREs was 7.5%, and was significantly higher in patients with TOFr<0.9 upon admission to the PACU. PORC in the PACU is associated to a greater incidence of major and minor respiratory complications. The use of rocuronium-sugammadex significantly reduces the incidence of PORC in the PACU.


Lymphocyte sensitization to thymus and lymph node antigen in multiple sclerosis and other neurological diseases.
Circulating lymphocytes from patients with multiple sclerosis are sensitized to saline homogenate of human thymus. They also show a minor degree of sensitization to lymph node extract. The sensitization to thymus is greater in multiple sclerosis than it is in other neurological disease (except dementia paralytica) and this may be related to the degree of parenchymatous destruction which provides the antigen stimulus or to astroglial overgrowth in these diseases. The observations support the view that human brain and thymus may share antigen(s) of the type known as ø-antigen in mice.


B(C6 F5 )3 -Catalyzed Ring Opening and Isomerization of Unactivated Cyclopropanes.
Catalytic amounts of B(C6 F5 )3 promote the ring opening and subsequent isomerization of a series of unactivated cyclopropanes to afford terminal olefins in good yields when a hydrosilane and 2,6-dibromopyridine are employed as additives.


[Cardiac arrest after sudden cessation of alcohol consumption].
Chronic alcohol abuse can cause both acute and chronic health problems. Unfortunately, sudden cessation is problematic, with risk of complications ranging from mild to lethal. We report a case of a 60-year-old man with substantial alcohol abuse, who suffered cardiac arrest after sudden withdrawal of alcohol. No other cause of death was found despite thorough examination. Alcohol withdrawal syndrome is a potentially fatal condition and the risks of sudden withdrawal should be recognized and treated.


Tuning clustering in random networks with arbitrary degree distributions.
We present a generator of random networks where both the degree-dependent clustering coefficient and the degree distribution are tunable. Following the same philosophy as in the configuration model, the degree distribution and the clustering coefficient for each class of nodes of degree k are fixed ad hoc and a priori. The algorithm generates corresponding topologies by applying first a closure of triangles and second the classical closure of remaining free stubs. The procedure unveils an universal relation among clustering and degree-degree correlations for all networks, where the level of assortativity establishes an upper limit to the level of clustering. Maximum assortativity ensures no restriction on the decay of the clustering coefficient whereas disassortativity sets a stronger constraint on its behavior. Correlation measures in real networks are seen to observe this structural bound.


Emotional health across the transition to first and second unions among emerging adults.
The link between romantic relationships and emotional health has been extensively examined and suggests that marriage provides more emotional health benefits than cohabiting or dating relationships. However, the contemporary context of intimate relationships has changed and these associations warrant reexamination among emerging adults in the 2000s. We examined the change in emotional health across the entrance into first and second unions, including cohabiting unions, direct marriage (marriage without premarital cohabitation), and marriage preceded by cohabitation. Using the National Longitudinal Survey of Youth, 1997, a nationally representative panel study of youth born between 1980 and 1984 in the United States, pooled fixed-effects regression models indicated that entrance into first cohabiting unions and direct marriages, and all second unions, were significantly associated with reduced emotional distress. Gender differences were found for first unions only; for men, only direct marriage was associated with an emotional health benefit, while both direct marriage and cohabitation benefited women's emotional health.


1,25-Dihydroxyvitamin D3 inhibits myelopoiesis but not B-lymphopoiesis in long-term bone marrow cultures.
The biologically active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been demonstrated to have differentiative and antiproliferative effects on myeloid tumors of human or murine origin. Its effects on normal murine hemopoiesis were tested by addition of the seco-steroid to long-term bone marrow cultures optimized for either myelopoiesis or B-lymphopoiesis. The addition of 10(-8) M 1,25(OH)2D3, but not 10(-8) M 25(OH)D3, to myeloid bone marrow cultures (MBMC) resulted in a complete cessation of hemopoiesis by 4 weeks, because no hemopoietic cells or colony-forming units were detected. This result was observed whether or not the cultures were initiated and maintained in hydrocortisone. A potential effect of 1,25(OH)2D3 on the production of myeloid growth factors by adherent layer cells in the cultures was examined, but this function was not affected by 1,25(OH)2D3 treatment. Further, adherent layers that had been treated with 1,25(OH)2D3 for 3 weeks were capable of supporting myelopoiesis upon seeding with a stromal cell-depleted population of bone marrow cells. Transfer of MBMC to lymphoid bone marrow culture (LBMC) conditions results in the cessation of myelopoiesis and the initiation of B-cell production. Lymphopoiesis did not initiate in 1,25(OH)2D3-pretreated MBMC that were transferred to LBMC conditions, indicating that the pool of B-cell precursors present in MBMC had been depleted by exposure of MBMC to 1,25(OH)2D3. When 1,25(OH)2D3 (10(-8) M) was added to MBMC at the time of transfer to LBMC conditions, the seco-steroid did not affect induction of B-lymphopoiesis, although the overall cellularity was less in 1,25(OH)2D3-treated cultures than in control cultures.


[Knockdown of ATG5 enhances the sensitivity of human renal carcinoma cells to sunitinib].
Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown. Proliferation rate of A-498 cells in control group and ATG5 low expression group was determined by flow cytometry. Finally, the survival rate was detected by MTT assay after A-498 cells were treated with different concentrations of sunitinib. Results The expression levels of ATG5 and LC3 in renal clear cell carcinoma tissues were significantly higher than those in para-tumor tissues. The expression levels of ATG5 and LC3 were associated with classification, histological grade, TNM stage and survival rate, rather than gender, age, location, tumor size. Compared with the control group, the protein expressions of ATG5 and LC3 significantly decreased in A-498 cells with ATG5 low expression. The cell proliferation rate in ATG5 downregulation group was lower than that in the control group. Compared with control group, the survival rate in ATG5 low expression group were significantly reduced in a dose-dependent manner after sunitinib treatment. Conclusion Autophagy is active in renal clear cell carcinoma, and the drug sensitivity to sunitinib in renal cancer cells can be enhanced by the downregulation of ATG5.


Hepatitis C infection in risk groups.
Hepatitis C infection is important global health problem with wide spectrum of health, social and economic consequences. The goal of this research was to estimate prevalence of hepatitis C virus infection in risk groups, and to determine association hepatitis C virus (HCV) infection and risk factors. Research included 4627 subjects divided in two groups. Test group included 2627 subjects divided in 4 subgroups with risk for HCV infection: those who received blood transfusion without screening on HCV (it was introduced in 1995) (700); intravenous drug users (60); patients on hemodialysis (168) and health care workers (1699). Control group included 2000 healthy volunteer blood donors. In all subjects anti-HCV antibodies were tested with third generation ELISA test. Positive serum samples were tested for presence of HCVRNA, using reaction of reverse transcription and polymerase chain reaction. In all anti-HCV positive subjects further epidemiological and clinical workup was performed. Prevalence of HCV infection in risk groups was: 4.6% in subjects who have received blood transfusions without HCV blood screening, 35% in intravenous drug users, 58.9% in patients on chronic dialysis, and 0.4% in health care workers. In control group prevalence was low (0.2%). In the group of 158 anti-HCV positive subjects, 73.4% had HCVRNA. The largest number of subjects with HCV infection was in the age group of 30-49 years (45.8%). This study showed that multiple blood transfusions before introducing the blood screening for HCV, longer duration of intravenous drug abuse, longer duration of hemodialysis treatment, larger number of accidental injuries in health care workers are independent and statistically significant risk factors for those groups examined. Results of this study confirm that general screening for HCV infection is recommended in risk groups for HCV infection in order to identify to prevent and to treat it.


Analysis of Growing Season Normalized Difference Vegetation Index Variation and Its Influencing Factors on the Mongolian Plateau Based on Google Earth Engine.
Frequent dust storms on the Mongolian Plateau have adversely affected the ecological environmental quality of East Asia. Studying the dynamic changes in vegetation coverage is one of the important means of evaluating ecological environmental quality in the region. In this study, we used Landsat remote sensing images from 2000 to 2019 on the Mongolian Plateau to extract yearly Normalized Difference Vegetation Index (NDVI) data during the growing season. We used partial correlation analysis and the Hurst index to analyze the spatiotemporal characteristics of the NDVI before and after the establishment of nature reserves and their influencing factors on the GEE cloud platform. The results showed that (1) the proportion of the region with an upwards trend of NDVI increased from 52.21% during 2000-2009 to 67.93% during 2010-2019, indicating a clear improvement in vegetation due to increased precipitation; (2) the increase in precipitation and positive human activities drove the increase in the NDVI in the study region from 2000 to 2019; and (3) the overall trend of the NDVI in the future is expected to be stable with a slight decrease, and restoration potential is greater for water bodies and grasslands. Therefore, it is imperative to strengthen positive human activities to safeguard vegetation. These findings furnish scientific evidence for environmental management and the development of ecological engineering initiatives on the Mongolian Plateau.


Digital image storage.
Film has long been considered the gold standard for displaying and storing clinical images. But that may be changing. Digital technology--specifically digital imaging and storage technology--has advanced to the point where it can now deliver on the promises envisioned years ago. That is, the ability to provide any image, virtually anywhere, at any time--a goal that could never be achieved with film. Achieving this goal, however, requires a properly implemented digital infrastructure, including effective digital image storage. As early adopters will attest, digital image storage can be difficult to implement. It requires the careful selection and implementation of storage technologies and the continuous management of storage operations. In this Guidance Article, we address many of the issues facing the healthcare professionals charged with managing this process: We introduce the topic of medical digital storage, discussing how it is accomplished and why storing images is not that different from storing other forms of data. We review the available storage alternatives, from fast-access hard drives and RAIDs to long-term magnetic tape and optical disc storage. We delve into the issue of image compression, describing what compression is and how much can be used without affecting patient care. And we review the pertinent legal, regulatory, and management issues. When committing to a digital image workflow, it is essential that a healthcare facility give careful consideration to data storage issues, since poor choices can lead to significant long-term costs for the facility.


Effects of gender and listeners' preference on magnitude-estimation scaling of rock music.
The purpose of the present study was to examine the effects of gender and listener preference on magnitude-estimation scaling of rock music. Four groups of young adults were tested: 14 women who liked rock music, 14 women who disliked rock music, 14 men who liked rock music, and 14 men who disliked rock music. Subjects were instructed to assign numerical values to a random series of nine suprathreshold intensity levels of a 10-sec. sample of rock music. Analysis indicated that there was no difference in scaling performance between women and men. There was a difference in scaling performance between the group of women who liked rock music and the group of women who disliked rock music. There was no difference in the way the two groups of men performed the scaling task. These results suggest that men and women perform magnitude-estimation scaling of rock music similarly. Women, however, allow preference to influence how they choose numbers during magnitude-estimation scaling tasks whereas men do not.


How boys become dogs: stigmatization and marginalization of uninitiated xhosa males in East London, South Africa.
Male circumcision is practiced in South Africa among the Xhosa people as a rite of passage from boyhood to manhood. The manhood status achieved after the ritual accords men power and authority in the community over women and uncircumcised men. Therefore, uninitiated men experience great pressures to get circumcised. We describe the experience of newly initiated Xhosa men in East London, South Africa. Interpretive phenomenology was used as the inquiry of choice. Data were collected through focus group discussions in which 14 men participated. The theme of marginalization of uninitiated Xhosa males emerged with two categories: (a) rejection, and (b) lack of respect. The participants revealed that uninitiated men are rejected by the community, their own families, friends, and women. We frame the discussion around the concept of stigma. Acknowledging that uninitiated males are stigmatized can help mitigate stigma, and in turn, the incidence of medical complications from botched circumcisions.


A lab-on-a-chip-based multiplex platform to detect potential fraud of introducing pig, dog, cat, rat and monkey meat into the food chain.
Food forgery has posed considerable risk to public health, religious rituals, personal budget and wildlife. Pig, dog, cat, rat and monkey meat are restricted in most religions, but their sporadic adulteration are rampant. Market controllers need a low-cost but reliable technique to track and trace suspected species in the food chain. Considering the need, here we documented a lab-on-a-chip-based multiplex polymerase chain reaction (PCR) assay for the authentication of five non-halal meat species in foods. Using species-specific primers, 172, 163, 141, 129 and 108-bp sites of mitochondrial ND5, ATPase 6 and cytochrome b genes were amplified to detect cat, dog, pig, monkey and rat species under complex matrices. Species-specificity was authenticated against 20 different species with the potential to be used in food. The targets were stable under extreme sterilisation (121°C at 45 psi for 2.5 h) which severely degrades DNA. The assay was optimised under the backgrounds of various commercial meat products and validated for the analysis of meatballs, burgers and frankfurters, which are popular fast food items across the globe. The assay was tested to detect 0.1% suspected meats under commercial backgrounds of marketed foods. Instead of simplex PCR which detects only one species at a time, such a multiplex platform can reduce cost by at least fivefolds by detecting five different species in a single assay platform.


Durability of tunnel restorations in general practice: a three-year multicenter study.
Twelve dentists, clinically experienced and familiar with the tunnel technique, placed 374 tunnel restorations in permanent teeth. Mean age of the patients was 19.1 years (range 10-74). The filling material used was a glass cermet cement, Ketac Silver. After 1, 2 and 3 years the teeth were controlled by the dentists. The bitewing radiographs from baseline, 1, 2 and 3 years were also analyzed by 2 of the authors, independently. The baseline radiographs showed technical defects in 6% and indicated remaining dentin caries in 8% of the restorations. After 3 years, 305 restorations were accessible for examination. The cumulative replacement rate was 20%. The main reasons for replacement were marginal ridge fracture (14%) and dentin caries (3%). The number of restorations showing untreated progressive caries increased during the study. After 3 years, untreated dentin caries was seen in 28 cases (11%) and almost half of the left enamel lesions showed progression.


Reproducibility of the assessment of the Fränkel manoeuvre for the evaluation of sagittal skeletal discrepancies in Class II individuals.
The Fränkel manoeuvre is a procedure by which the mandible of Class II individuals is postured forward in dental Class I relationship. The evaluation of the resulting facial profile provides information concerning the components determining the sagittal discrepancy. Data concerning the reproducibility of its assessment are not available. This study aimed to evaluate the intra-observer and inter-observer reproducibility of the assessment of the manoeuvre and to assess whether the amount of clinical experience affects its reproducibility. Two lateral photographs, one in centric occlusion, and the other with the mandible postured forward (Fränkel manoeuvre) of 100 Angle Class II individuals aged between 9 and 13 years were evaluated by six orthodontists (T0). Each examiner was asked whether the facial profile worsen or not with the manoeuvre after being trained by an expert orthodontist. The test was repeated after 2 weeks interval (T1). Intra-observer and inter-observer agreement were evaluated by computing the Cohen's K. The agreement (K values) between observations (T0 versus T1) for each examiner ranged from 0.49 to 0.72. The overall agreement was 0.65 [95% confidence interval (CI) = 0.54-0.75]. The agreement in the group with less clinical experience was 0.61 (95% CI = 0.46-0.76), while it was 0.68 (95% CI = 0.53-0.83) in the more experienced group. The amount of clinical experience did not affect intra-observer agreement (P = 0.50). The overall agreement between the examiners and the trainer was 0.74 (95% CI = 0.65-0.83) and 0.73 (95% CI = 0.64-0.83) at T0 and T1 respectively. The assessment of the Fränkel manoeuvre is reproducible and it is not influenced by the amount of clinical experience.


Clinicians' evaluation of clinical ethics consultations in Norway: a qualitative study.
Clinical ethics committees have existed in Norway since 1996. By now all hospital trusts have one. An evaluation of these committees' work was started in 2004. This paper presents results from an interview study of eight clinicians who evaluated six committees' deliberations on 10 clinical cases. The study indicates that the clinicians found the clinical ethics consultations useful and worth while doing. However, a systematic approach to case consultations is vital. Procedures and mandate of the committees should be known to clinicians in advance to ensure that they know what to expect. Equally important is bringing all relevant facts, medical as well as psychosocial, into the discussion. A written report from the deliberation is also important for the committees to be taken seriously by the clinicians. This study indicates that the clinicians want to be included in the deliberation, and not only in the preparation or follow-up. Obstacles for referring a case to the committee are the medical culture's conflict aversion and its anxiety of being judged by outsiders. The committees were described as a court by some of the clinicians. This is a challenge for the committees in their attempt to balance support and critique in their consultation services.


Quality of life and stress response symptoms in long-term and recent spouses of testicular cancer survivors.
The aim of this study was to gain insight into the quality of life (QoL) and stress response of female spouses of men cured of testicular cancer in the long-term. Time since treatment completion varied from 0.5 to 23.8 years. Two hundred and fifty nine testicular cancer survivors and their spouses completed the Dutch version of the MOS Short Form (SF)-36 and the Impact of Event Scale. QoL data from a reference group of women were used for comparison. Spouses who had relationship with the testicular cancer survivor before the diagnosis (spouses during testicular cancer) had better functioning scores than the reference group, especially with respect to the physical QoL domains. Spouses who had started a relationship after treatment (spouses after testicular cancer) experienced more problems with psychological QoL domains than spouses during testicular cancer and than the reference group. The stress response of spouses during testicular cancer was related to that of the testicular cancer survivors and to the extent of treatment they had received. Although stress response levels were low, spouses during testicular cancer reported more stress response than the testicular cancer survivors. Time since completion of treatment did not affect QoL or stress response. This study showed that spouses during testicular cancer had a good QoL and little stress response. Functioning of spouses after testicular cancer was poorer with respect to various QoL domains, particularly the psychological measures.


Clinical Value of FDG-PET/CT for the Evaluation of Rheumatic Diseases: Rheumatoid Arthritis, Polymyalgia Rheumatica, and Relapsing Polychondritis.
FDG is a tracer for visualizing glucose metabolism. PET/CT using FDG is widely used for the diagnosis of cancer, because glycolysis is elevated in cancer cells. Similarly, active inflammatory tissue also exhibits elevated glucose metabolism because of glycolysis in activated macrophages and proliferating fibroblasts. Elevated FDG uptake by active inflammatory tissues, such as those affected by arthritis, vasculitis, lymphadenitis, and chondritis, has enabled the diagnosis of inflammatory diseases using FDG-PET/CT. Rheumatoid arthritis (RA) is a systemic, chronic inflammation of the joints resulting in synovitis. Several clinical studies of RA have demonstrated that FDG uptake in affected joints reflects the disease activity of RA, with strong correlations between FDG uptake and various clinical parameters having been noted. Furthermore, the use of FDG-PET for the sensitive detection and early monitoring of the response to RA therapy has been reported. RA is sometimes associated with subclinical vasculitis, which is related to systemic inflammation. FDG-PET/CT can be used to evaluate subclinical vasculitis in the aorta or carotid artery. Polymyalgia rheumatica (PMR) is an autoimmune musculoskeletal disease of unknown etiology characterized by pain and stiffness in the shoulder, neck, and pelvic girdle, but not in the small finger joints in the hands, together with fever, fatigue, and weight loss. There is no specific test for PMR, and its diagnosis is based on clinical diagnostic criteria and the exclusion of other diseases with similar symptoms. However, FDG-PET/CT reveals a characteristic FDG uptake by the bursitis in ischial tuberosity, greater trochanter, lumbar or cervical spinous process, and scapulohumeral joint. A combination of FDG-PET/CT findings showed a high diagnostic value for PMR in a differential diagnosis from RA. FDG-PET/CT is also very useful for evaluating large vessel vasculitis, which is often associated with PMR. Relapsing polychondritis is a rare multisystem disease of unknown etiology involving cartilaginous and proteoglycan-rich structures. Its rarity and diversity of symptoms often result in a delayed diagnosis. FDG-PET/CT reveals unique FDG uptake findings for chondritis in the auricular, nasal, trachea, bronchial tree, and costal cartilage and in the cartilage of joints. Thus, the spread of knowledge regarding these very specific FDG-PET/CT findings could promote the early diagnosis and improved disease control of relapsing polychondritis.


[Experience with Prasugrel in the Treatment of Patients with Acute Coronary Syndrome].
Dual antiplatelet therapy (DAPT) with aspirin and one of inhibitors of P2Y12 receptors (clopidogrel, ticagrelor, prasugrel) is an international standard of receptors (clopidogrel, ticagrelor, prasugrel) is an international standard of is an international standard of treatment strategy in patients with acute coronary syndrome (ACS). to analyze experience of prasugrel use in the National Medical Cardiology Research Center in comparison to similar groups of patients treated with other P2Y12 inhibitors for determination of optimal place of DAPT with prasugrel in ACS patients. Materials and methods. We included in this retrospective study 40 patients who received therapy with prasugrel, ticagrelor, or clopidogrel in connection with urgent percutaneous coronary intervention (PCI) performed in the Department of Urgent Cardiology from May to December 2018. We analyzed specific characteristics of prasugrel treated patients including disease history, features of clinical presentation and coronary anatomy, use of strategies of escalation and de-escalation, as well as inhospital mortality, development of complications and side effects. Results. New P2Y12 inhibitors were more effective in patients with higher risk of atherothrombosis compared with risk of bleeding. Median of implanted stents in ticagrelor and clopidogrel groups was equal to 1, in the prasugrel group - 2 stents per PCI. When multivascular stenting was performed the choice usually was made in favor of prasugrel or ticagrelor, excluding cases with presence of limiting factors - use of oral anticoagulants (OAC) (n=4) and prehospital thrombolytic therapy (n=5). Of note was close to statistical significance high number of side effects related to ticagrelor use (n=3, 23.08%, p=0.057). There were no significant differences between groups in rates of unfavorable outcomes and complications. Conclusion. Administration of prasugrel can be considered in patients with high risk of atherothrombosis: with diabetes, with large number of implantable stents. The choice between ticagrelor and prasugrel can be made with consideration of the potential for side effects that significantly impair the quality of life of patients. Main limitations for application of both prasugrel and ticagrelor are the need to permanent use of OAC, prehospital thrombolytic therapy, and higher cost compared to clopidogrel.


Different pattern of recovery of fast and slow muscles following nerve injury in the rat.
The sciatic nerve was crushed in 5-6-day-old rats and the time course of recovery and changes in physiological and morphological properties of reinnervated fast and slow muscles was compared. The maximal tetanic tension developed by the reinnervated muscles was recorded at different times from about 18 days of age, when functional recovery was first seen, until 2 months. The maximal indirectly elicited tetanic tension of the reinnervated slow soleus muscle gradually increased from 55% of normal at 18 days to 75% of normal at 2 months. In contrast, the tension of the reinnervated fast muscle extensor digitorum longus (e.d.l.) fell sharply from 70% of normal at 18 days to 40% at 21 days and remained at that level till the end of the study. The total number of muscle fibres in control, reinnervated and denervated e.d.l. muscles was counted. At 18 days the number of fibres in the reinnervated e.d.l. was similar to normal but by 1 month it had fallen to one-third. This decrease did not take place in permanently denervated muscles until at least 35 days. Loss of fibres in the reinnervated soleus was small. During the early stages of reinnervation the contraction and relaxation of the fast muscles was very prolonged. By 1 month the time taken to reach peak twitch tension had decreased to normal values but the relaxation was still slower and remained so for several months. The study of fatigue resistance showed that at 18 days the reinnervated fast muscles were as fatigable as normal muscles from animals of the same age. The fatigability of normal muscles increased with age to adult levels, but the reinnervated muscles became more fatigue resistant and remained so. Our findings suggest that fast muscles become selectively impaired after nerve injury at 6 days because they lose a large number of fibres after reinnervation.


Hemolytic activity of the nematocyst venom from the sea anemone Bunodosoma caissarum.
The nematocyst venom of the sea anemone Bunodosoma caissarum obtained by electric stimulation of the animals has hemolytic activity on fish, toad, snake, mice and rat erythrocytes. The hemolytic action was dose-dependent and the ED50 varied between 2.9 and 7.6 micrograms venom/ml erythrocyte suspension (0.5%, v/v). Toad erythrocytes were the most sensitive while rat erythrocytes were the most resistant to the sea anemone venom. The hemolytic activity of venom in mice was partially inhibited by preincubation of the venom with sphingomyelin for 1 h. The ED50 was increased 3.8-fold when 10.0 micrograms sphingomyelin per ml erythrocyte suspension was used. Venom concentrations above 33.6 micrograms/ml erythrocyte suspension produced approximately 95% hemolysis and were inhibited only by 40.0 micrograms sphingomyelin. The hemolysin activity was inhibited by heating to 90 degrees C but not to 70 degrees C.


An instant measurement of oxidoreductase activity above 100 degrees C by monitoring the absorbance change.
A conventional absorbance monitoring method using a cuvette covered with a tight rubber cap was found to be applicable for measuring oxidoreductase activity at temperatures up to 115 degrees C. Using this method, the optimal temperatures of the enzymes, including oxygen-sensitive enzymes from a hyperthermophilic archaeon Thermococcus profundus, were determined.


Adherence to disease-modifying therapy in multiple sclerosis: Part II.
Multiple sclerosis (MS) is a chronic, debilitating disease for which there is no cure; however, the recent introduction of injectable immunomodulating agents has reduced the rate of relapsing episodes and possibly slowed the progression of the disease. These disease-modifying agents are recommended by the National MS Society, but their true potential cannot be realized if patients do not accept them and healthcare professionals do not promote them. Since MS has an unpredictable course, and treatments can produce side effects, adherence to the recommended therapy is a complex and challenging issue. Improved understanding of the obstacles to adherence and the identification of possible solutions should be of value to nurses, who have numerous opportunities to encourage patients to initiate and continue therapy. Part I of this article, published in the September/October 2001 issue of Rehabilitation Nursing, described the particular problems of treatment adherence in MS. Part II proposes that the transtheoretical model of behavior change can be a useful tool in achieving both patient acceptance and treatment goals. This model is founded upon the concept that readiness for change is crucial, and that attempts at intervention should be sensitive to the patients' changing conditions and states of mind.


Polymers zippered-up by electric charge reveal themselves.
In the current issue of ACS Nano, Löbling, Haataja et al. craft polymeric nanoparticles with a hierarchy of nontrivial surface structures by combining conventional interpolyelectrolyte complexation with steric control from an uncharged copolymer block. Remarkable cylindrical and lamellar nanodomains are produced on the polyionic coronae of spherical micelles. Here, we discuss generalizing this elegant self-assembly strategy and provide speculative perspectives for its future potential for new nanomaterials.