Factors Associated With Lumbar and Femoral Bone Mineral Density in Kidney Transplants Candidates.
Data on risk factors associated with low bone mineral density are limited in patients with end-stage renal disease. This study evaluated the factors deemed associated with lumbar and femoral Z and T scores. Clinical and demographic data of 98 patients waiting for kidney transplantation were collected, as well as lumbar and femoral bone densitometries, before transplantation. Osteoporosis and osteopenia and factors associated with bone mineral density were assessed. According to the femoral T score, 38.8% (95% confidence interval [CI], 29.1% to 48.4%), 44.9% (95% CI, 35.1% to 54.7%), and 16.3% (95% CI, 9.0% to 23.6%) of the patients had normal bone density, osteopenia, and osteoporosis, respectively. According to the lumbar T score, 54.1% (95% CI, 44.2% to 63.9%), 33.7% (95% CI, 24.3% to 44.0%), and 12.2% (95% CI, 5.8% to 18.7%) of the patients had normal density, osteopenia, and osteoporosis, respectively. Age, serum levels of creatinine and parathyroid hormone, and use of calcitriol and calcium carbonate were associated with femoral densitometry scores. Serum total protein level, Rh-negative status, and B blood type were associated with the lumbar scores. Parathyroid hormone contributed to bone loss in our kidney transplant candidates, and B and Rh-negative blood types were associated with a higher risk of lumbar osteoporosis while total protein was negatively associated with the risk of bone loss. Calcitriol might improve femoral mineral density, but calcium carbonate was negatively associated with femoral bone density. Age and higher creatinine levels were associated with higher femoral bone densities.


Spatial covariance of herbivorous and predatory guilds of forest canopy arthropods along a latitudinal gradient.
In arthropod community ecology, species richness studies tend to be prioritised over those investigating patterns of abundance. Consequently, the biotic and abiotic drivers of arboreal arthropod abundance are still relatively poorly known. In this cross-continental study, we employ a theoretical framework in order to examine patterns of covariance among herbivorous and predatory arthropod guilds. Leaf-chewing and leaf-mining herbivores, and predatory ants and spiders, were censused on > 1000 trees in nine 0.1 ha forest plots. After controlling for tree size and season, we found no negative pairwise correlations between guild abundances per plot, suggestive of weak signals of both inter-guild competition and top-down regulation of herbivores by predators. Inter-guild interaction strengths did not vary with mean annual temperature, thus opposing the hypothesis that biotic interactions intensify towards the equator. We find evidence for the bottom-up limitation of arthropod abundances via resources and abiotic factors, rather than for competition and predation.


The last word on the so-called 'Rowell's syndrome'?
To date, 71 patients having the so-called 'Rowell's syndrome' (RS) have been reported in the literature. However, most of them did not show all the clinical and serological features first described by Rowell and co-workers in 1963. Moreover, since then, subacute cutaneous lupus erythematosus (SCLE) has been identified and the diagnostic criteria as well as the clinical features of erythema multiforme (EM) defined. Accordingly several authors have questioned the existence of RS over the past years. In the present paper, the main clinical, histopathological and immunopathological features of both SCLE and EM are described and all of the cases of RS reported in the literature are also reviewed in depth. A real association between discoid LE and EM was present only in a minority of cases and could be considered a mere coincidence. As for other associations, e.g. those between CLE and lichen planus or psoriasis, the coexistence of CLE and EM does not justify the framing of a separate syndrome as suggested by Rowell et al.


Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD72c allele.
An MRL/MpJ strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), composed of genomes derived from LG/J, AKR/J, C3H/Di and C57BL/6J mice, develops systemic vasculitis coincidentally with other collagen diseases, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. In a genome-wide screening of the MRL background genes mediating susceptibility to collagen diseases using N2 progeny mice MRL/lpr x (MRL/lpr x C3H/lpr)F1, we previously found that each collagen disease is controlled by a different set of genes. To clarify the candidate genes for vasculitis, we extended the linkage analysis of renal vasculitis to a larger number of N2 mice and to F2 intercross mice. Two distinct recessive susceptibility loci for vasculitis were mapped on chromosome (Chr) 4 at D4Mit89 and D4Mit147 in both progenies. The former was a novel locus for lupus phenotypes, which involved the MRL allele CD72(c) in contrast to the C3H allele CD72(b). The one on Chr 3 was a recessive locus which had an inhibitory effect on vasculitis. From their composition these loci seemed to be derived from AKR/J (for one) and LG/J (for another two) strains, and appeared to act in an additive manner on the development of vasculitis, indicating that vasculitis in MRL/lpr mice is inherited in a polygenic manner.


Electrochemical versus Enzymatic in Vitro Oxidations of 6-propyl-2-thiouracil: Identification, Detection, and Characterization of Metabolites.
6-Propylthiouracil, PTU, is a well-known antithyroid drug that has been the mainstay of treatment of Graves' disease. It is, however, also associated with liver toxicity and idiosyncratic toxicity. These toxicities are generally associated with metabolites derived from its bioactivation. In this manuscript, bioactivation of PTU was studied via two separate techniques: electrochemical oxidation and through the use of human liver microsomes. The aim of this work was to compare the bioactivation products of these two techniques. The electrochemical technique was studied online with a mass spectrometer, EC/ESI/MS. The microsomal oxidations were studied in tandem with liquid chromatography. The EC/ESI/MS technique was devoid of the normal reducing biological matrix prevalent in microsomal incubations. The predominant product at 400 mV was the dimeric PTU species with negligible formation of other metabolites. At higher potentials, complete desulfurization of PTU was observed with formation of sulfate. No sulfonic acid was observed, suggesting that the cleavage of the C-S bond was effected at the sulfinic acid stage, releasing a highly reducing sulfur species which is known to give rise to genotoxicity. The microsomal oxidations, surprisingly, showed formation of the unstable sulfenic acid, the S-oxide. Further incubation showed both the sulfinic and sulfonic acids. None of the systems showed any adducts with nucleophiles such as glutathione, showing that none of the reactive metabolites were stable enough to be adducted to nucleophiles in both the biological matrix and the electrochemical oxidizing environment.


Psychometric properties of an Arabic translation of the Big Three Perfectionism Scale-Short Form (BTPS-SF) in a community sample of adults.
Despite the high clinical relevance of the perfectionism construct as a transdiagnostic contributor to different mental health symptoms, and the recent burgeoning of research in this area across cultures in the past two decades, the Arab region was one of the cultural settings experiencing the slowest progress in this line of research. This study aimed to make a meaningful contribution to the literature by validating an Arabic-language version of the 16-item Big Three Perfectionism Scale-Short Form (BTPS-SF). In particular, we sought to examine structure and concurrent validity, internal consistency, and measurement invariance across gender groups. A web-based, convenience sampling method was adopted to collect a sample of Arabic-speaking adults from the general population of Lebanon (N = 515; aged 27.55 ± 10.92 years; 69.9% females). The forward-backward method was applied in translating the Arabic version of the BTPS-SF. The examination of the internal structure, using Confirmatory Factor Analysis (CFA), demonstrated that the three-factor model (i.e., rigid, self-critical, and narcissistic perfectionism) fitted well to the data. All three factors of the Arabic 16-item BTPS-SF yielded excellent reliability estimates, with both Cronbach's alpha and McDonald's omega ranging from 0.83 to 0.86. Multi-group CFA revealed that fit indices showed no significant difference in model fit at the configural, metric, and scalar levels, thus suggesting that the factor loadings, pattern structure, and item intercepts are invariant across gender groups. Finally, BTPS-SF subscales scores correlated positively with psychological distress (i.e., depression, stress and anxiety), and inversely with subjective well-being, indicating an acceptable concurrent validity. The present findings allow us to conclude that the Arabic BTPS-SF permits to capture reliably and validly three main factors of perfectionism. We hope that providing this psychometrically sound scale will encourage its large use not only in empirical research, but also in clinical applications, including psychological screening and treatment monitoring.


Excellent selectivity for actinides with a tetradentate 2,9-diamide-1,10-phenanthroline ligand in highly acidic solution: a hard-soft donor combined strategy.
In this work, we reported a phenanthroline-based tetradentate ligand with hard-soft donors combined in the same molecule, N,N'-diethyl-N,N'-ditolyl-2,9-diamide-1,10-phenanthroline (Et-Tol-DAPhen), for the group separation of actinides over lanthanides. The synthesis and solvent extraction as well as complexation behaviors of the ligand with actinides and lanthanides are studied experimentally and theoretically. The ligand exhibits excellent extraction ability and high selectivity toward hexavalent, tetravalent, and trivalent actinides over lanthanides in highly acidic solution. The chemical stoichiometry of Th(IV) and U(VI) complexes with Et-Tol-DAPhen is determined to be 1:1 using X-ray crystallography. The stability constants of some typical actinide and lanthanide complexes of Et-Tol-DAPhen are also determined in methanol by UV-vis spectrometry. Density functional theory (DFT) calculations reveal that the An-N bonds of the Et-Tol-DAPhen complexes have more covalent characters than the corresponding Eu-N bonds, which may in turn lead to the selectivity of Et-Tol-DAPhen toward actinides. This ligand possesses merits of both alkylamide and 2,9-bis-(5,6-dialkyl-1,2,4-triazin-3-yl)-1,10-phenanthroline (R-BTPhen) extractants for efficient actinide extraction and the selectivity toward minor actinides over lanthanides and hence renders huge potential opportunities in high-level liquid waste (HLLW) partitioning.


Lower bound on Transmission using Non-Linear Bounding Function in Single Image Dehazing.
The visibility of an image captured in poor weather (such as haze, fog, mist, smog) degrades due to scattering of light by atmospheric particles. Single image dehazing (SID) methods are used to restore visibility from a single hazy image. The SID is a challenging problem due to its ill-posed nature. Typically, the atmospheric scattering model (ATSM) is used to solve SID problem. The transmission and atmospheric light are two prime parameters of ATSM. The accuracy and effectiveness of SID depends on accurate value of transmission and atmospheric light. The proposed method translates transmission estimation problem into estimation of the difference between minimum color channel of hazy and haze-free image. The translated problem presents a lower bound on transmission and is used to minimize reconstruction error in dehazing. The lower bound depends upon the bounding function (BF) and a quality control parameter. A non-linear model is then proposed to estimate BF for accurate estimation of transmission. The proposed quality control parameter can be utilized to tune the effect of dehazing. The accuracy obtained by the proposed method for transmission is compared with state of the art dehazing methods. Visual comparison of dehazed images and objective evaluation further validates the effectiveness of the proposed method.


Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease.
Tolvaptan and related V(2)-specific vasopressin receptor antagonists have been shown to delay disease progression in animal models of polycystic kidney disease. Slight elevations in serum creatinine, rapidly reversible after drug cessation, have been found in clinical trials involving tolvaptan. Here, we sought to clarify the potential renal mechanisms to see whether the antagonist effects were dependent on underlying renal function in 20 patients with autosomal dominant polycystic kidney disease (ADPKD) before and after 1 week of daily split-dose treatment. Tolvaptan induced aquaresis (excretion of solute-free water) and a significant reduction in glomerular filtration rate (GFR). The serum uric acid increased because of a decreased uric acid clearance, and the serum potassium fell, but there was no significant change in renal blood flow as measured by para-aminohippurate clearance or magnetic resonance imaging (MRI). No correlation was found between baseline GFR, measured by iothalmate clearance, and percent change in GFR induced by tolvaptan. Blinded post hoc analysis of renal MRIs showed that tolvaptan significantly reduced total kidney volume by 3.1% and individual cyst volume by 1.6%. Preliminary analysis of this small cohort suggested that these effects were more noticeable in patients with preserved renal function and with larger cysts. No correlation was found between changes of total kidney volume and body weight or estimated body water. Thus, functional and structural effects of tolvaptan on patients with ADPKD are likely due to inhibition of V(2)-driven adenosine cyclic 3',5'-monophosphate generation and its aquaretic, hemodynamic, and anti-secretory actions.


[The impact of bronchial colonization in the quality of life of patients with chronic, stable bronchitis].
The aim of this study was to determine the impact of respiratory function and bacterial colonization of the lower airway on the quality of life of patients with chronic, stable bronchitis (CB). A series of 41 patients with stable CB was studied (age: 63.8; standard deviation (SD) 9.1 years; FVC% 91.0 (18.9); FEV1% 74.6 (23.7); FEV1/FEC 62.8 (11.2) with normal thoracic radiography. Patients with previous diagnosis of bronchiectasia, bronchial asthma and/or positive bronchodilatory tests (> 15%) were not included in the study. Bacterial growth in a sputum sample of grade 4-5 of the Murray-Washington scale was considered diagnostic of bronchial colonization. Measurement of the quality of life was performed with the Nottingham Health Profile (NHP) and the St. George Respiratory Questionnaire (SGRQ). The patients presented a moderate alteration in their quality of life with scores over 25 in most of the dimensions of the NHP and the SGRQ. In 9 out of 41 cases (22%), the sputum cultures demonstrated bronchial colonization with the most frequently isolated bacterias being Haemophilus influenzae and Moraxella catarrhalis. Multivariate analysis performed with the quality of life as the dependent variable showed an association between FEV1/FEC1 and the SGRQ score (R2 = 0.18), and energy (R2 = 0.09) and physical mobility (R2 = 0.05) of NHP. Bronchial obstruction is the main determinant in the quality of life in patients with stable CB. Colonization of the lower airway is observed in 22% of the patients and also influences the quality of life of the patients but to a much lesser extent.


Appropriate interface termination to improve imaging resolution of multilayered structures in the infrared and optical canalization regime.
Appropriate surface termination is used to improve dramatically the subwavelength imaging resolution of a multilayered positive-negative permittivity structure operating in the infrared or optical canalization regime. The imaging resolution of the improved multilayered structure resists practical material loss well, and it is not sensitive to the thickness of the interface layers, the total thickness, nor the period of the multilayered structure. Such a structure can be used to transfer a subwavelength image to a far distance through a thick structure.


Cervical Spine Spondylodiscitis After Esophageal Dilation in Patients With a History of Laryngectomy or Pharyngectomy and Pharyngeal Irradiation.
Dysphagia is a frequently reported sequela of treatment for head and neck cancer and is often managed with esophageal dilation in patients with dysphagia secondary to hypopharyngeal or esophageal stenosis. Reported complications of esophagoscopy with dilation include bleeding, esophageal perforation, and mediastinitis. These, though rare, can lead to substantial morbidity or mortality. In patients who have undergone irradiation, tissue fibrosis and devascularization may contribute to a higher incidence of these complications. To describe the occurrence of cervical spine spondylodiscitis (CSS) following esophageal dilation in patients with a history of laryngectomy or pharyngectomy and irradiation with or without chemotherapy. Medical records from a 5-year period (January 1, 2009, through December 31, 2014) in an academic tertiary care center were searched for patients with a history of laryngopharyngeal irradiation and a diagnosis of CSS following esophageal dilation. Four eligible patients were identified. Recognition and treatment of CSS in the study population. A total of 1221 patients underwent esophageal dilation for any reason. Of these, 247 patients carried a diagnosis of head and neck cancer at the following sites: piriform sinus, larynx, hypopharynx, epiglottis, oropharynx, base of the tongue, and tonsil. Of these, 4 patients with a diagnosis of CSS following esophageal dilation were included in this assessment. Prompt diagnosis and multidisciplinary management of CSS with intravenous antibiotics as well as spinal surgical debridement and stabilization led to recovery of full ability to take food by mouth in 3 of the 4 included patients. One patient remained dependent on the feeding tube. In patients with a history of laryngopharyngeal irradiation and esophageal dilation, complaints of neck pain or upper extremity weakness should trigger immediate evaluation for CSS; if present, prompt therapy is essential for prevention of substantial morbidity and mortality.


Isolation and Identification of Actinomycetes Strains from Switzerland and their Biotechnological Potential.
Actinomycetes strains isolated from different habitats in Switzerland were investigated for production of antibacterial and antitumoral compounds. Based on partial 16S rRNA gene sequences, the isolated strains were identified to genus level. Streptomyces as the largest genus of Actinobacteriawas isolated the most frequently. A screening assay using the OmniLog instrument was established to facilitate the detection of active compounds from actinomycetes. Extracts prepared from the cultivated strains able to inhibit Staphylococcus aureusand Escherichia coliwere further analysed by HPLC and MALDI-TOF MS to identify the produced antibiotics. In this study, the bioactive compound echinomycin was identified from two isolated Streptomycesstrains. Natural compounds similar to TPU-0037-C, azalomycin F4a 2-ethylpentyl ester, a derivative of bafilomycin A1, milbemycin-α8 and dihydropicromycin were detected from different isolated Streptomyces strains. Milbemycin-α8 showed cytotoxic activity against HT-29 colon cancer cells. The rare actinomycete,Micromonospora sp. Stup16_C148 produced a compound that matches with the antibiotic bottromycin A2. The draft genome sequence from Actinokineospora strain B136.1 was determined using Illumina and nanopore-based technologies. The isolated strain was not able to produce antibacterial compounds under standard cultivation conditions. The antiSMASH bioinformatics analyses of the genome from strain B136.1 identified biosynthetic gene clusters with identity values between 4% to 90% to known gene clusters encoding antibiotics. The combinations of cultivation conditions, screening assays, analytical methods and genome mining are important tools to characterize strains of actinomycetes for the identification of their potential to produce natural compounds with antimicrobial activity.


Structural Variations in Hybrid All-Nanoparticle Gibbsite Nanoplatelet/Cellulose Nanocrystal Multilayered Films.
Cellulose nanocrystals (CNCs) are promising biosourced building blocks for the production of high performance materials. In the last ten years, CNCs have been used in conjunction with polymers for the design of multilayered thin films via the layer-by-layer assembly technique. Herein, polymer chains have been replaced with positively charged inorganic gibbsite nanoplatelets (GN) to form hybrid "nanoparticle-only" composite films. A combination of atomic force microscopy and neutron reflectivity experiments was exploited to investigate the growth and structure of the films. Data show that the growth and density of GN/CNC films can be tuned over a wide range during preparation by varying the ionic strength in the CNC suspension and the film drying protocol. Specifically, thin and dense multilayered films or very thick, more porous mixed slabs, as well as intermediate internal structures, could be obtained in a predictable manner. The influence of key physicochemical parameters on the multilayer film buildup was elucidated and the film architecture was linked to the dominating interaction forces between the components. The degree of structural control over these hybrid nanoparticle-only films is much higher than that reported for CNC/polymer films, which offers new properties and potential applications as separation membranes or flame retardant coatings.


Assessment of older adults in the emergency department.
Older people make extensive use of emergency departments, yet there is evidence that optimum care is difficult to provide for those with complex health and social problems. Inappropriate hospital admissions for older people have also been documented. This article describes the establishment of an assessment team for older people (ATOP) that has been created to address these issues in a district general hospital. In the four months of the study period, the ATOP prevented admission of 178 of the 666 patients seen. Of these 178 patients, 19 re-attended the hospital and six were admitted.


Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus B lymphoblastoid cells.
T cell proliferation in response to antigen requires the presence of an antigen-presenting accessory cell. The accessory cell most commonly associated with antigen presentation has been the macrophage (Mo). This study demonstrates that B cells in the form of Epstein Barr virus-transformed B lymphoblasts (EBV-B) are able to present tetanus toxoid (TT) to human T cells and induce proliferation of these cells. T cells freshly isolated from peripheral blood were shown to undergo blast transformation and proliferation in response to TT and irradiated EBV-B cells. Furthermore, TT-reactive T cell blasts were shown to proliferate in the presence of EBV-B cells and TT, but not with other antigens. There was a progressive increase to a plateau in T blast proliferation with increasing numbers of EBV-B cells added to the culture. The concentration of TT required for optimal antigen presentation was similar for EBV-B cells and for Mo. TT-specific cloned T cells also proliferated in response to TT and EBV-B cells and could be continuously grown in culture with TT, interleukin 2-containing supernatant, and EBV-B cells in place of autologous Mo. EBV-B cells pulsed with TT could also act as antigen-presenting cells. The proliferative response of T cell clones to TT in the presence of EBV-B cells was inhibited by antiserum to human p29,34 glycoprotein but not by anti-beta 2-microglobulin. This inhibition was shown to result from interaction with Ia-like determinants on EBV-B cells. These results indicate that B lymphoblastoid cells in man are able, like Mo, to present antigen to T cells in the context of Ia-like determinants.


Heterochromatin protein HP1Hsbeta (p25beta) and its localization with centromeres in mitosis.
Some autoimmune sera containing anticentromere autoantibodies also recognize a doublet of Mr 23 000 (p23) and 25 000 (p25) in addition to CENP (centromere protein)-A (Mr 19 000), -B (Mr 80 000), and -C (Mr 140 000). A p25 antigen (HP1(Hsalpha)) has been shown to be a human homolog of Drosophila HP1 (heterochromatin protein 1). We have isolated a cDNA clone encoding another form of p25 (HP1(Hsbeta ) or p25beta) from a lambdaZap HepG2 library using human autoimmune serum. The deduced amino acid sequence of the clone contained a conserved chromodomain (chromatin modifier domain) in the N-terminal region and a heterochromatin binding domain in the C-terminal region. In immunofluorescence experiments, only affinity purified antibodies reactive with the C-terminal (amino acids 70-185) domain showed nucleoplasmic and heterochromatin staining, whereas N-terminal (amino acids 1-115) specific antibodies were nonreactive. In metaphase chromosome spreads, the C-terminal domain antibody was also localized to the centromeric regions of chromosomes. Association with centromeres was most prominent at anaphase and changed to a more generalized association with whole chromosomes in telophase. The cooccurrence of autoantibodies to centromere proteins and HP1 in certain autoimmune diseases might be a reflection of coordinated immune responses to these closely associated sets of proteins.


Arterolane, a new synthetic trioxolane for treatment of uncomplicated Plasmodium falciparum malaria: a phase II, multicenter, randomized, dose-finding clinical trial.
Drug-resistant Plasmodium falciparum malaria necessitates development of novel drugs for treatment.The present study assessed the efficacy and safety of 3 dose levels of arterolane (RBx 11160), a synthetic trioxolane, for treatment of acute uncomplicated falciparum malaria. In this randomized, double-blind, multicenter, parallel-group, dose-finding, phase II trial, 230 patients from 4 centers in Thailand, India, and Tanzania (mainland and Zanzibar) received either 50 mg (n=78), 100mg (n=76), or 200 mg (n=76) of arterolane once daily for 7 days. Patients (aged 13-65 years) with asexual parasite density of 1000-100,000 parasites/microL were included and were followed up for 28 days. The median time to 90% parasite clearance (PC90) was evaluated. The median PC90 was longer in the group receiving the 50-mg dose (19.4 h), compared with the groups receiving the 100-mg dose (12.8 h) and 200-mg dose (12.6 h) (P < .01). The polymerase chain reaction-corrected adequate clinical and parasitological responses on day 28 were 63%, 71%, and 72% for the groups receiving the 50-mg, 100-mg, and 200-mg doses, respectively, by intention-to-treat analysis (odds ratio, 1.55; 95%confidence interval, 0.78-3.06, for comparison of the 200-mg and 50-mg dose groups). Treatment was generally well tolerated. No patient died or experienced any serious adverse event. Mild complaints were reported in <10%of the patients and were similar in the 3 groups. Biochemistry and hematological analyses did not show any signof drug toxicity in any patient. Arterolane at daily doses of 100 and 200 mg is a rapidly acting, effective, and safe synthetic antimalarial drug, which may potentially represent an alternative to artemisinin derivatives in antimalarial combination therapy. ClinicalTrials.gov identifier NCT00362050.


Comparison of the Analgesic and Sedative Effects of Midazolam-Ketamine and Propofol-Sufentanil Combinations in Painful Procedures of Children with Haematologic Malignancy.
Bone marrow aspiration and lumbar puncture play essential roles in the diagnosis and treatment of haematological disorders. These repeated invasive procedures lead to considerable pain and stress in children, which is emotionally stressful for their parents. This study aimed to compare the effectiveness and outcomes of two combinations of midazolam-ketamine (MK) and propofol-sufentanil (PS) in painful procedures of children with haematologic malignancy. In this prospective, randomised, double-blind clinical trial, we enrolled 80 eligible patients with haematologic malignancy aged 2-14 years. We randomly allocated them to the MK and PS groups. We recorded and compared the level of sedation, pain severity, hemodynamic indices, the onset of effect, duration of recovery and complications during and after procedure in the two groups. We analysed the data using the SPSS software. We used Mann-Whitney U, independent t-test, chi-square and Fisher's exact tests to compare continuous and categorical variables. From initially enrolled patients, 68 patients completed the study (38 in PS and 30 in MK group). The levels of sedation and the mean score of pain intensity were significantly lower in the MK group than those in the PS group (p<0.05). Movements and the needs to repeat the dose were significantly lower in the MK group than those in the PS group (p<0.05). During bone marrow aspiration and lumbar puncture procedures in children with haematologic malignancy, the findings of this trial suggest that MK combination therapy provides better sedation and analgesia than PS.


Immediate Effects of Lower Limb Sensory Simulation Using Smart Socks to Stabilize Gait in People with Parkinson's Disease.
People with Parkinson's disease (PD) experience gait impairment that can lead to falls and poor quality of life. Here we investigate the feasibility of using smart socks to stimulate the lower limbs of people with PD to reduce excessive step time variability during walking. We hypothesised that rythmic excitation of lower limb afferents, matched to a participant's comfortable pace, would entrain deficient neuro-muscular signals resulting in improved gait. Five people with mild to moderate PD symptoms (70 ± 9 years) were tested on medication before and after a 30-minute familierization session. Paired t-tests and Cohen's d were used to assess gait changes and report effect sizes. Participant experiences were recorded through structured interviews. Lower limb stimulation resulted in an acute 15% increase in gait speed (p=0.006, d=0.62), an 11% increase in step length (p=0.04, d=0.35), a 44% reduction in step time variability (p=0.03, d=0.91), a 22% increase in perceived gait quality (p=0.04, d=1.17), a 24% reduction in mental effort to walk (p=0.02, d=0.79) and no statistical difference for cadence (p=0.16). Participants commented positively on the benefit of stimulation during training but found that stimulation could be distracting when not walking and the socks hard to put on. While the large effects for step time variability and percieved gait quality (Cohen's d > 0.8) are promising, limitations regarding sample size, potential placebo effects and translation to the home environment should be addressed by future studies.Clinical Relevance- This study demonstrates the feasibility of using smart stimulating socks to reduce excessive step time variability in people with PD. As step time variability is a risk factor for falls, the use of smart textiles to augment future rehabilitation programs warrants further investigation.


Undernourished adults and acetylation phenotype.
The acetylation phenotype of two groups of well-nourished and undernourished male adults living in South India was studied using sulfadimidine as test substance. About 60% of the subjects in both groups were slow acetylators. Nutritional status did not seem to influence the extent of sulfadimidine acetylated when subjects belonged to the same phenotype class. Thus we concluded that undernutrition does not alter the acetylation phenotype of male adults.


Regular exercise training prevents aortic valve disease in low-density lipoprotein-receptor-deficient mice.
Regular exercise training (ET) slows the progression of atherosclerotic lesions, reduces oxidative stress, and increases nitric oxide bioavailability, all of which may be expected to improve degenerative aortic valve disease. Four-week-old low-density lipoprotein-receptor-deficient mice (n=94) were randomly divided into 4 groups: Group 1 (control group), normal diet plus sedentary activity; group 2 (cholesterol group), cholesterol diet plus sedentary activity; group 3 (regular ET group), cholesterol diet plus regular ET (60 min/day, 5 days/week) for 16 weeks; and group 4 (occasional exercise group), cholesterol diet plus occasional ET (1 day/week) for 16 weeks. At 20 weeks of age, histological analysis was performed. A significant increase in aortic valve thickness was evident in the cholesterol group compared with the control group. Importantly, regular but not occasional ET significantly reduced aortic valve thickness compared with the cholesterol group (control 31.3+/-3.0 mum, cholesterol 50.1+/-3.4 mum, regular exercise 30.4+/-1.2 mum, and occasional exercise 48.9+/-3.2 mum). Immunohistochemistry revealed that a cholesterol diet disrupted and regular ET preserved endothelial integrity on the aortic valve surface. Furthermore, serum myeloperoxidase, accumulation of macrophages and oxidized low-density lipoprotein, in situ superoxide, activated myofibroblasts/osteoblast phenotypes, and mineralization were increased in the cholesterol group but were decreased by regular ET. Polymerase chain reaction revealed increased messenger RNA expression for alpha-smooth muscle actin, bone morphogenetic protein-2, runt-related transcription factor-2, and alkaline phosphatase in the cholesterol group, whereas these were diminished by regular ET. Moreover, regular ET significantly increased circulating levels of fetuin-A compared with the cholesterol group. In the low-density lipoprotein-receptor-deficient mouse, regular ET prevents aortic valve sclerosis by numerous mechanisms, including preservation of endothelial integrity, reduction in inflammation and oxidative stress, and inhibition of the osteogenic pathway.


Contribution of warm habitat to cold-water fisheries.
A central tenet of landscape ecology is that mobile species depend on complementary habitats, which are insufficient in isolation, but combine to support animals through the full annual cycle. However, incorporating the dynamic needs of mobile species into conservation strategies remains a challenge, particularly in the context of climate adaptation planning. For cold-water fishes, it is widely assumed that maximum temperatures are limiting and that summer data alone can predict refugia and population persistence. We tested these assumptions in populations of redband rainbow trout (Oncorhynchus mykiss newberrii) in an arid basin, where the dominance of hot, hyperproductive water in summer emulates threats of climate change predicted for cold-water fish in other basins. We used telemetry to reveal seasonal patterns of movement and habitat use. Then, we compared contributions of hot and cool water to growth with empirical indicators of diet and condition (gut contents, weight-length ratios, electric phase angle, and stable isotope signatures) and a bioenergetics model. During summer, trout occurred only in cool tributaries or springs (<20 °C) and avoided Upper Klamath Lake (>25 °C). During spring and fall, ≥65% of trout migrated to the lake (5-50 km) to forage. Spring and fall growth (mean [SD] 0.58% per day [0.80%] and 0.34 per day [0.55%], respectively) compensated for a net loss of energy in cool summer refuges (-0.56% per day [0.55%]). In winter, ≥90% of trout returned to tributaries (25-150 km) to spawn. Thus, although perennially cool tributaries supported thermal refuge and spawning, foraging opportunities in the seasonally hot lake ultimately fueled these behaviors. Current approaches to climate adaptation would prioritize the tributaries for conservation but would devalue critical foraging habitat because the lake is unsuitable and unoccupied during summer. Our results empirically demonstrate that warm water can fuel cold-water fisheries and challenge the common practice of identifying refugia based only on summer conditions.


[Cost effective and quality assured (adeno)tonsillectomy in children].
The issues of whether minor surgery should be performed in private or public clinics and/or be funded by the national health service are under continuous debate in Norway. A prospective study of the benefit of (adeno)tonsillectomies in 120 children is presented. Surgery included in the study was performed on an inpatient as well as an outpatient basis and in public as well as private clinics. There was no difference in patient satisfaction or in the quality of surgery depending on the type of organisation. Relief of symptoms associated with (adeno)tonsillar infections and obstruction following surgery was consistent. Less euresis was found in the study population following surgery. Increased haemoglobin concentration and less protoporfyrin IX in erythrocytes indicate an improved erythropoiesis following (adeno)tonsillectomy. Less manpower was needed to perform (adeno)tonsillectomies in private compared to public clinics. We suggest that the Norwegian national health system opens up for funding surgery of established quality irrespective of whether it is performed in a public or a private clinic.


Survey analysis and chemical characterization of solid inhomogeneous samples using a general homogenization procedure including acid digestion, drying, grinding and briquetting together with X-ray fluorescence.
A survey analysis and chemical characterization methodology for inhomogeneous solid waste samples of relatively large samples (typically up to 100g) using X-ray fluorescence following a general homogenization procedure is presented. By using a combination of acid digestion and grinding various materials can be homogenized e.g. pure metals, alloys, salts, ores, plastics, organics. In the homogenization step, solid material is fully or partly digested in a mixture of nitric acid and hydrochloric acid in an open vessel. The resulting mixture is then dried, grinded, and finally pressed to a wax briquette. The briquette is analyzed using wave-length dispersive X-ray fluorescence with fundamental parameters evaluation. The recovery of 55 elements were tested by preparing samples with known compositions using different alloys, pure metals or elements, oxides, salts and solutions of dissolved compounds. It was found that the methodology was applicable to 49 elements including Na, Mg, Al, Si, P, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Cd, In, Sn, Sb, Te, Cs, Ba, La, Ce, Ta, W, Re, Ir, Pt, Au, Tl, Pb, Bi, and Th, that all had recoveries >0.8. 6 elements were lost by volatilization, including Br, I, Os, and Hg that were completely lost, and S and Ge that were partly lost. Since all lanthanides are chemically similar to La and Ce, all actinides are chemically similar to Th, and Hf is chemically similar to Zr, it is likely that the method is applicable to 77 elements. By using an internal standard such as strontium, added as strontium nitrate, samples containing relatively high concentrations of elements not measured by XRF (hydrogen to fluorine), e.g. samples containing plastics, can be analyzed.


Antimicrobial Efficacy of Commercially Available Low-fluoride and Fluoride-free Dentifrices for Children.
The objective of this study was to evaluate and compare the antimicrobial efficacy of low-fluoride and fluoride-free dentifrices against Streptococcus mutans. The antimicrobial efficacy of four commercially available low-fluoride child formula dentifrices and four fluoride-free dentifrices against S. mutans was determined using the agar diffusion test. Fifty microliters of various dilutions (1:1, 1:2, 1:4) of each dentifrice were inoculated on the assigned plates under aseptic conditions. Saline was taken as negative control and 0.2% chlorhexidine was considered as a positive control. The plates were incubated at 37°C for 24 hours and the zone of inhibition around the wells was measured. All the tested low-fluoride dentifrices showed varying degrees of antimicrobial activity against S. mutans with F2 (Pediflor®) and F4 (Cheerio™) showing greater zones of inhibition when compared to F1 (Colgate®kids) and F3 (Kidodent). When the mean zones of inhibition produced by non-fluoridated dentifrices were compared with that of fluoridated dentifrices, no statistically significant difference was noted between NF1, NF3, NF4, and F2, F4. The antibacterial activity of F1 and F3 was significantly lower when compared to others. However, no antibacterial activity was noted with NF2. Both low-fluoride and fluoride-free formulations tested in the study exhibited antimicrobial activity against S. mutans. In very young children where the risk of fluorosis is of concern, fluoride-free formulations can be considered as safe alternatives to fluoride formulations. Several dentifrices, both fluoride-free and low-fluoride formulations, are being aggressively marketed for young children. Though these toothpastes are being very commonly used by young parents for their infants and toddlers, there is very little published literature available on their antimicrobial activity and this study focuses on addressing this. Reddy D, Selvan A, Paul ST, et al. Antimicrobial Efficacy of Commercially Available Low-fluoride and Fluoride-free Dentifrices for Children. Int J Clin Pediatr Dent 2021;14(2):183-186.


Spin trapping study of antioxidant properties of neopterin and 7,8-dihydroneopterin.
Previously, it has been shown that pteridine derivatives are capable of modulating the action of free radicals and both prooxidant and antioxidant properties have been described. However, the mechanism of manifestation of these properties is still unclear. We studied the radical scavenging properties of 7,8-dihydroneopterin and neopterin using the spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO). It was found that dihydroneopterin acts generally as a radical scavenger. In the presence of dihydroneopterin the ESR signal was reduced by 30 to 90% compared to the control signal. The rate constants for the reactions of 7,8-dihydroneopterin with superoxide (10(3) M(-1) s(-1)) and peroxyl radicals (10(7) M(-1) s(-1)) were determined. Neopterin in contrast showed no reduction of the ESR signal except with superoxide radicals produced by xanthine oxidase. However, this effect was shown to be due to an inhibition of enzyme rather than to radical scavenging. Our results provide a basis for understanding previous observations of radical scavenger activity of 7,8-dihydroneopterin.


U.V.C.-induction of p53 activation and accumulation is dependent on cell cycle and pathways involving protein synthesis and phosphorylation.
Transcriptional activation and stabilization of p53 is a major response of mammalian cells to U.V.-light induced genetic damages, and possibly responsible for cell damage control. We have studied here by gel mobility shift and immunoblotting assays the activation and accumulation of p53 by U.V.C. and its dependency on cell cycle, protein synthesis and protein phosphorylation. In G0/G1 synchronized cells U.V.C.-induced p53 DNA-binding activity, but not its accumulation, whereas both events took place in G1/S and S-phase cells. The kinetics of p53 activation by U.V.C. were slow requiring at least 1 h and slowly increasing thereafter with full activation observed at 6 h. Treatment of cells with cycloheximide (CHX) prevented the activation of p53 in all phases of the cell cycle and its accumulation in G1/S and S. However, removing CHX-block allowed full activation and accumulation of p53 with fast kinetics even if 4 h had lapsed since the initial U.V.C. insult. This suggests that the protein synthesis-dependent signal initiating p53 activation by U.V.C. remains continuous in the cells. The requirement of protein phosphorylation as mediator of p53 activation by U.V.C. was studied by using chemical protein kinase inhibitors. Of the tested inhibitors, only staurosporine, a known inhibitor of protein kinase C (PKC) and various other kinases, inhibited both p53 activation and accumulation, whereas specific PKC inhibitors, tyrosine kinase inhibitors and a serine/threonine kinase inhibitor did not. PKC-mediation of the p53 U.V.-response was further ruled out by the reactivity of the activated p53 to C-terminal antibody PAb 421. Kinetic studies showed that staurosporine-mediated inhibition of p53 function is an early event in cell damage response. Thus dual, kinetically different events, de novo protein synthesis and staurosporine-inhibited protein phosphorylation are required for p53 activation and accumulation in all phases of the cell cycle. Notably, in the absence of U.V.-induced accumulation in G0/G1 cells, p53 activation is still subject to inhibition of protein synthesis.


The relationship between facilitators' questions and the level of reflection in postsimulation debriefing.
Simulation-based education is a learner-active method that may enhance teamwork skills such as leadership and communication. The importance of postsimulation debriefing to promote reflection is well accepted, but many questions concerning whether and how faculty promote reflection remain largely unanswered in the research literature. The aim of this study was therefore to explore the depth of reflection expressed in questions by facilitators and responses from nursing students during postsimulation debriefings. Eighty-one nursing students and 4 facilitators participated. The data were collected in February and March 2008, the analysis being conducted on 24 video-recorded debriefings from simulated resuscitation teamwork involving nursing students only. Using Gibbs' reflective cycle, we graded the facilitators' questions and nursing students' responses into stages of reflection and then correlated these. Facilitators asked most evaluative and fewest emotional questions, whereas nursing students answered most evaluative and analytic responses and fewest emotional responses. The greatest difference between facilitators and nursing students was in the analytic stage. Only 23 (20%) of 117 questions asked by the facilitators were analytic, whereas 45 (35%) of 130 students' responses were rated as analytic. Nevertheless, the facilitators' descriptive questions also elicited student responses in other stages such as evaluative and analytic responses. We found that postsimulation debriefings provide students with the opportunity to reflect on their simulation experience. Still, if the debriefing is going to pave the way for student reflection, it is necessary to work further on structuring the debriefing to facilitate deeper reflection. Furthermore, it is important that facilitators consider what kind of questions they ask to promote reflection. We think future research on debriefing should focus on developing an analytical framework for grading reflective questions. Such research will inform and support facilitators in devising strategies for the promotion of learning through reflection in postsimulation debriefings.


Dibiphytanyl ether lipids in nonthermophilic crenarchaeotes.
The kingdom Crenarchaeota is now known to include archaea which inhabit a wide variety of low-temperature environments. We report here lipid analyses of nonthermophilic crenarchaeotes, which revealed the presence of cyclic and acyclic dibiphytanylglycerol tetraether lipids. Nonthermophilic crenarchaeotes appear to be a major biological source of tetraether lipids in marine planktonic environments.


Peripheral Auditory Nerve Impairment in a Mouse Model of Syndromic Autism.
Dysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing, including hypersensitivity. Altered sound sensitivity is frequently observed in autism spectrum disorder (ASD), suggesting that AN deficits and changes in auditory information processing may contribute to ASD-associated symptoms, including social communication deficits and hyperacusis. The MEF2C transcription factor is associated with risk for several neurodevelopmental disorders, and mutations or deletions of MEF2C produce a haploinsufficiency syndrome characterized by ASD, language, and cognitive deficits. A mouse model of this syndromic ASD (Mef2c-Het) recapitulates many of the MEF2C haploinsufficiency syndrome-linked behaviors, including communication deficits. We show here that Mef2c-Het mice of both sexes exhibit functional impairment of the peripheral AN and a modest reduction in hearing sensitivity. We find that MEF2C is expressed during development in multiple AN and cochlear cell types; and in Mef2c-Het mice, we observe multiple cellular and molecular alterations associated with the AN, including abnormal myelination, neuronal degeneration, neuronal mitochondria dysfunction, and increased macrophage activation and cochlear inflammation. These results reveal the importance of MEF2C function in inner ear development and function and the engagement of immune cells and other non-neuronal cells, which suggests that microglia/macrophages and other non-neuronal cells might contribute, directly or indirectly, to AN dysfunction and ASD-related phenotypes. Finally, our study establishes a comprehensive approach for characterizing AN function at the physiological, cellular, and molecular levels in mice, which can be applied to animal models with a wide range of human auditory processing impairments.SIGNIFICANCE STATEMENT This is the first report of peripheral auditory nerve (AN) impairment in a mouse model of human MEF2C haploinsufficiency syndrome that has well-characterized ASD-related behaviors, including communication deficits, hyperactivity, repetitive behavior, and social deficits. We identify multiple underlying cellular, subcellular, and molecular abnormalities that may contribute to peripheral AN impairment. Our findings also highlight the important roles of immune cells (e.g., cochlear macrophages) and other non-neuronal elements (e.g., glial cells and cells in the stria vascularis) in auditory impairment in ASD. The methodological significance of the study is the establishment of a comprehensive approach for evaluating peripheral AN function and impact of peripheral AN deficits with minimal hearing loss.


Ankle arthrodesis. Clinical and conceptual applications.
Ankle fusion provides an excellent salvage for an otherwise intolerable deformity or painful joint derangement. It is the only available alternative for a failed ankle prosthesis. It produces a serviceable foot when done in proper perspective for the appropriate indication. It produces a good result when consolidation occurs and the remaining tarsal joints have preserved integrity. Improvement in occupational and daily activities can be anticipated when arthrodesis and correct alignment are obtained.


Metabolic syndrome in the pediatric population: a short overview.
The metabolic syndrome (MS) in adults is defined as a concurrence of obesity, disturbed glucose and insulin metabolism, hypertension and dyslipidemia, and is associated with increased morbidity and mortality from cardiovascular diseases and type 2 diabetes. Studies now indicate that many of its components are also present in children and adolescents. Moreover, the clustering of these risk factors has been documented in some children, who are at increased cardiovascular risk in adulthood. The MS is highly prevalent among overweight children and adolescents. Identifying these children is important for early prevention and treatment of different components of the syndrome. The first-line treatment comprises lifestyle modification consisting of diet and exercise. The most effective tool for prevention of the MS is to stop the development of childhood obesity. The first attempt at consensus-based pediatric diagnostic criteria was published in 2007 by the International Diabetes Federation. Nevertheless, national prevalence data, based on uniform pediatric definition, protocols for prevention, early recognition and effective treatment of pediatric MS are still needed.The aim of this article is to provide a short overview of the diagnosis and treatment options of childhood MS, as well as to present the relationships between MS and its individual components.


Relevance of partially structured states in the non-classical secretion of acidic fibroblast growth factor.
Acidic fibroblast growth factor (aFGF) is a signal peptide-less protein that is secreted into the extracellular compartment as part of a multiprotein release complex, consisting of aFGF, S100A13 (a calcium binding protein), and a 40 kDa (p40) form of synaptotagmin (Syt1), a protein that participates in the docking of a variety of secretory vesicles. p40 Syt1, and specifically its C2A domain, is believed to play a major role in the non-classical secretion of the aFGF release complex mediated by the interaction of aFGF and p40 Syt1with the phospholipids of the cell membrane inner leaflet. In the present study, we investigate the structural characteristics of aFGF and the C2A domain of p40 Syt1 under acidic conditions, using a variety of biophysical techniques including multidimensional NMR spectroscopy. Urea-induced equilibrium unfolding (at pH 3.4) of both aFGF and the C2A domain are non-cooperative and proceed with the accumulation of stable intermediate states. 1-Anilino-8-napthalene sulfonate (ANS) binding and size-exclusion chromatography results suggest that both aFGF and the C2A domain exist as partially structured states under acidic conditions (pH 3.4). Limited trypsin digestion analysis and 1H-15N chemical shift perturbation data reveal that the flexibility of certain portions of the protein backbone is increased in the partially structured state(s) of aFGF. The residues that are perturbed in the partially structured state(s) in aFGF are mostly located at the N- and C-terminal ends of the protein. In marked contrast, most of the interactions stabilizing the native secondary structure are preserved in the partially structured state of the C2A domain. Isothermal titration calorimetry data indicate that the binding affinity between aFGF and the C2A domain is significantly enhanced at pH 3.4. In addition, both aFGF and the C2A domain exhibit much higher lipid binding affinity in their partially structured states. The translocation of the multiprotein FGF release complex across the membrane appears to be facilitated by the formation of partially structured states of aFGF and the C2A domain of p40 Syt1.


[Distribution, determinants and reference values of left ventricular parameters in the general population--results of the MONICA/KORA echocardiography studies].
For successful fighting against the burden of cardiovascular disease in the community a comprehensive knowledge about the prevalence and the impact of underlying risk factors is important. The present paper summarises some studies undertaken on more than 2000 persons from the MONICA/KORA-studies (parts of S1 and S3) where left ventricular mass (LVM) and other left ventricular parameters were determined by echocardiography. We especially investigated the associations of LVM with blood pressure and obesity. A special focus was on sex-specific factors in the determination of LVM and the influence of different indices of body size when normalising LVM. It could be shown that hypertension and obesity are major determinants of LV hypertrophy. Especially women with both hypertension and obesity on showed a high prevalence of concentric hypertrophy, significantly more than men. We also showed that the prevalence of LV hypertrophy in a representative sample of the general population (25 to 74 years) is 17.5 % for men, and 18.5 % for women. This underscores the need for primary and secondary prevention regarding the development of LV hypertrophy. Finally, our data in a selected group of normal subjects (reference sample) may be used for the development of reference values for left ventricular parameters in the general German population.


Echo enhanced ultrasound: a new valid initial imaging approach for severe acute pancreatitis.
This prospective study aimed to compare the accuracy of echo enhanced ultrasound with spiral computed tomography (CT) in assessing acute pancreatitis and to explore the correlation between ultrasound findings and clinical outcome. Thirty one patients (24 men and 7 women, median age 39 years, range 19-67 years) with acute pancreatitis were investigated by contrast enhanced CT and echo enhanced ultrasound within 72 hours after admission. Echo enhanced ultrasound (with intravenous injection of 2.4 ml SonoVue, pulse inversion technique, mechanical index 0.1 to 0.2, Siemens Elegra) was performed following conventional ultrasound. Balthazar's grading system was used to measure CT and ultrasound severity indices (CTSI and USSI). Correlations between CTSI and USSI and between USSI and clinical parameters were tested by Spearman's rank correlation coefficient. A strong correlation was demonstrated between CTSI and USSI (r = 0.807, p<0.01). Ultrasound correlated with the following: the Ranson score (r = 0.401, p<0.05), C-reactive protein levels 48 hours after admission (r = 0.536, p<0.01), duration of hospitalisation (r = 0.422, p<0.05), and clinical outcome regarding morbidity, including local and systemic complications (r = 0.363, p<0.05). Based on CT findings as the gold standard, sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound for detecting severe acute pancreatitis based on imaging criteria (Balthazar score D or E and/or presence of hypoperfusion compatible with necrosis and/or SI>/=3) were, respectively, 82% (95% CI 61 to 93), 89% (95% CI 57 to 98), 95% (95% CI 75 to 99), and 67% (95% CI 39 to 86). Echo enhanced ultrasound produces excellent results in the staging of acute pancreatitis severity. The procedure is cheaper and has fewer contraindications than CT. Further multicentre studies need to be performed before including the method in the diagnostic algorithm of patients with acute pancreatitis.


Fenoprofen therapy in large-joint osteoarthritis: double-blind comparison with aspirin and longterm experience.
This study, designed to evaluate fenoprofen in patients with osteoarthritis, consisted of two phases: I. A double-blind crossover comparison of fenoprofen, 200 to 600 mg every six hours, to aspirin, 325 to 975 mg every six hours; II. Longterm use of fenoprofen in an open study design. During the first part of the study, both fenoprofen and aspirin were significantly better than placebo in relieving the severity and duration of pain, and in reducing stiffness. In most of the variables fenoprofen was also slightly better than aspirin. The most frequently observed side effects were abdominal discomfort, headache, pruritus, nervousness, and tinnitus. Longterm administration demonstrated the safety of fenoprofen or periods exceeding two years. Fenoprofen did not precipitate or aggravate chronic disorders, nor did it mask the symptoms of any developing disease. No interaction with concomitant drug therapy was observed.


Clinical Feature, Lifestyle Behavior and Non-Communicable Diseases Comorbidities Among Psoriasis Patients in Shanghai: Gender Disparity Analysis Based on a Cross-Sectional Study.
Gender difference is prevalent in clinical feature, disease severity for noncommunicable diseases (NCD), but studies on gender disparity in clinical feature, disease severity and NCD comorbidity among psoriasis patients are limited. This cross-sectional study explores gender differences in clinical feature, lifestyle behavior and NCD comorbidity among psoriasis patients. Psoriasis patients were recruited through cluster survey method in two hospitals, and questionnaire interviews were applied to collect the demographic feature, lifestyle habits, clinical feature and NCD among patients. A total of 2102 psoriasis patients included 1332 males (63.4%), 70% were over 35 years old and approximately 50% of them were overweight or obesity. The median value for psoriasis initiation age and disease duration was 33 years old (34 for male and 32 for female) and 9 years (10 for male and 7 for female), respectively. The psoriasis recurrence was mainly in winter (73.4%) and autumn (34.2%) both for patients. The prevalence of tobacco smoking and alcohol drinking was 31.2% and 12.6%. Male patients had higher prevalence of tobacco smoking (odds ratio (OR) = 13.26, 95% confidence interval (CI): 9.54-18.44) and alcohol drinking (OR = 14.44, 95% CI: 7.90-26.40). The prevalence of diabetes, hypertension, hyperlipidemia, and metabolic syndrome were 13.2%, 28.5%, 23.4% and 21.5%, respectively. Male patients had higher prevalence of diabetes (OR = 1.53, 95% CI: 1.16-2.02), hypertension (OR = 1.87, 95% CI: 1.52-2.30), hyperlipidemia (OR = 2.34, 95% CI: 1.85-2.95) and metabolic syndrome (OR = 2.06, 95% CI: 1.63-2.62) than female patients. The proportions for 4 types of NCDs diagnosed after psoriasis onset were over 58%, which were also higher in males than females. Female patients had shorter disease duration and with less NCD, and male patients had more body weight issue, with fewer sleep time and higher prevalence of tobacco smoking and alcohol drinking and NCDs. We recommend that dermatologist should notice the gender disparity in psoriasis patients, which is helpful for the disease diagnosis and treatment.


Evaluation of Outcome Prediction of Flow Diversion for Intracranial Aneurysms.
Identifying and predicting which aneurysms are likely to quickly occlude and which ones are likely to remain open following treatment with flow-diverting devices is important to develop optimal patient management strategies. The purpose of this study was to evaluate predictions based on computational fluid dynamics models using the elastase rabbit aneurysm model. A series of 13 aneurysms created in rabbits were treated with flow diverters, and outcomes were angiographically assessed at 8 weeks' follow-up. Computational fluid dynamics models were constructed from pretreatment 3D rotational angiograms and Doppler ultrasound flow velocity measurements. Postimplantation mean aneurysm inflow rate and flow velocity were used to prospectively predict aneurysm occlusion blinded to the actual outcomes. Specifically, if both variables were below their corresponding thresholds, fast occlusion was predicted, while if one of them was above the threshold, slow or incomplete occlusion was predicted. Of the 13 aneurysms included, 8 were incompletely occluded 8 weeks after treatment, and 5 were completely occluded. A total of 10 computational fluid dynamics-based predictions agreed with the angiographic outcome, reaching 77% accuracy, 80% sensitivity, and 75% specificity. Posttreatment mean velocity alone was able to achieve the same predictive power as the combination of inflow rate and velocity. Subject-specific computational fluid dynamics models of the hemodynamic conditions created immediately after implantation of flow-diverting devices in experimental aneurysms created in rabbits are capable of prospectively predicting, with a reasonable accuracy, which aneurysms will completely occlude and which ones will remain incompletely occluded.


Biomechanics of footwear.
This article discusses biomechanical principles that indicate a number of basic design criteria for shoes and the properties of good footwear in terms of normal daily activities at home, at school, and at work. These properties also apply to normal occupational footwear and safety footwear.


Adherence to Recess Guidelines in the United States Using Nationally Representative Data: Implications for Future Surveillance Efforts.
National adherence to the recess recommendations of the Centers for Disease Control and Prevention (CDC) has not been comprehensively studied in the United States. Data from 6 nationally representative data sets over the last decade (Classification of Laws Associated with School Students, Early Childhood Longitudinal Study, National Health and Nutrition Examination Survey, National Youth Fitness Survey, School Health Policies and Practices Survey, and the School Nutrition and Meal Cost Study) provided estimates for adherence to CDC recess guidelines. While approximately 65-80% of elementary school-children receive the recommended 20+ minutes of daily recess according to parent-, principal-, and school-report, adherence declines by sixth grade, and little information is available for middle/high school students. Adherence to playground safety was high (90%), but adherence to recommendations about recess before lunch (<50%), withholding recess as punishment (∼50%), and training recess staff (<50%) were lower. School policy and practice should align with CDC recommendations, with the aim of providing sufficient quality recess to all youth, K-12th grade. Comprehensive, on-going national surveillance of multiple recess domains is needed to inform policy and ensure equitable provision of recess.


Alloscardovia omnicolens gen. nov., sp. nov., from human clinical samples.
The taxonomic position of 12 isolates tentatively assigned to the genus Bifidobacterium on the basis of a limited phenotypic characterization was examined. The isolates were collected between 1978 and 2005 in Belgium, Sweden and Norway, and originated from various human clinical samples, including urine, blood, urethra, oral cavity, tonsil, and abscesses of lung and aortic valve. On the basis of band number and clustering analysis, repetitive DNA element-based PCR fingerprinting using the BOXA1R and (GTG)(5) primers indicated that the clinical isolates represented a taxon probably not belonging to the genus Bifidobacterium. Analysis of 16S rRNA gene sequence similarities revealed that the isolates were most closely affiliated to Parascardovia denticolens LMG 18312(T) (93.0-93.2 %), Scardovia inopinata LMG 18313(T) (92.9-93.1 %) and other members of the Bifidobacteriaceae, indicating that the isolates belong to a novel genus within that family. This observation was further substantiated by the results of partial sequencing of the heat-shock protein 60 gene (hsp60) and determination of the DNA G+C contents (47.3-48.3 mol%). Members of the novel taxon can be phenotypically distinguished from S. inopinata, P. denticolens and Gardnerella vaginalis by the ability to grow on agar under aerobic conditions and on the basis of positive reactions for acid production from L-arabinose, raffinose, salicin and D-xylose. Unambiguous phenotypic differentiation from Aeriscardovia aeriphila and Bifidobacterium species may be difficult, so phenotypic analyses should be complemented by molecular methods. The values for DNA-DNA binding among four members of the novel genus were in the range of 89-100 %, indicating that the strains should be considered as a single novel species of a novel genus, for which the name Alloscardovia omnicolens gen. nov., sp. nov. is proposed. The type strain of Alloscardovia omnicolens is CCUG 31649(T) (=LMG 23792(T)).


Fast-response fiber-optic anemometer with temperature self-compensation.
We report a novel fiber-optic anemometer with self-temperature compensation capability based on a Fabry-Pérot interferometer (FPI) formed by a thin silicon film attached to the end face of a single-mode fiber. Guided in the fiber are a visible laser beam from a 635 nm diode laser used to heat the FPI and a white-light in the infrared wavelength range as the signal light to interrogate the optical length of the FPI. Cooling effects on the heated sensor head by wind is converted to a wavelength blueshift of the reflection spectral fringes of the FPI. Self-temperature-compensated measurement of wind speed is achieved by recording the difference in fringe wavelengths when the heating laser is turned on and then off. Large thermal-optic coefficient and thermal expansion coefficient of silicon render a high sensitivity that can also be easily tuned by altering the heating laser power. Furthermore, the large thermal diffusivity and the small mass of the thin silicon film endow a fast sensor response.


Cytomegalovirus retinitis and viral resistance: ganciclovir resistance. CMV Retinitis and Viral Resistance Study Group.
Cytomegalovirus (CMV) retinitis is among the most common opportunistic infections in patients with AIDS and a substantial cause of visual loss. With long-term therapy, resistant CMV may develop. In a prospective study of 108 patients with CMV retinitis, 80.6% of patients were found to have either a positive blood culture or positive urine culture for CMV at the diagnosis of retinitis. At diagnosis of retinitis, 0.9% and 2.7% of patients had a ganciclovir-resistant blood culture isolate and urine culture isolate, respectively. Of 76 patients initially treated with ganciclovir, 11.4% had a resistant blood or urine culture isolate by 6 months of treatment and 27.5% by 9 months. The development of ganciclovir resistance during follow-up correlated with the occurrence of CMV retinitis in the contralateral eye (odds ratio = 9.06, P = .003).


Outcome of antenatally suspected congenital cystic adenomatoid malformation of the lung: 10 years' experience 1991-2001.
To determine the outcome of antenatally suspected congenital cystic adenomatoid malformation of the lung (CCAM) over a 10 year period. This is a retrospective study of all babies diagnosed antenatally in the Prenatal Diagnosis Unit and delivered in Oxford between 1991 and 2001. Data were obtained from the Oxford Congenital Anomaly Register, theatre records, and histopathology reports. Twenty eight cases of CCAM were diagnosed antenatally. Five pregnancies were terminated. Data are available on all 23 of the pregnancies that continued and resulted in two neonatal deaths and 21 surviving babies. Eleven of the 23 cases (48%) showed some regression of the lesion antenatally, and four of these cases appeared to resolve completely on prenatal ultrasound. Three of the 23 babies (13%) were symptomatic in the early neonatal period, and three developed symptoms shortly afterwards. Seventeen of the 23 babies (74%) were asymptomatic, of whom 12 had abnormalities on chest radiograph or computed tomography scan and had elective surgery. Two babies (8%) had completely normal postnatal imaging, and three had abnormalities which resolved in the first year of life. Seventeen of the 23 babies (74%) had surgery. Histology at surgery was heterogeneous. Of the 23 live births, all 21 survivors (91%) are well at follow up or have been discharged. All babies diagnosed antenatally with CCAM require postnatal imaging with computed tomography irrespective of signs of antenatal resolution. In asymptomatic infants, the recommendations are close follow up and elective surgery for persistent lesions within the first year of life. Histology at surgery was heterogeneous, and this should be considered when counselling parents.


[Immunohistological study of an intestinal antigen].
The localization of an intestinal antigen in different normal and malignant tissues was studied by indirect immunoperoxidase technique. It was shown that this antigen is characteristic for the cells of the intestinal epithelium. The antigen was revealed in 94.3% of primary and metastatic colonic tumors, 50% of gastric tumors and in all samples of the enterolysed gastric mucosa. The intestinal antigen was not found in colonic carcinoids or in the overwhelming majority of tumors of different origins.


Detection of Epstein-Barr virus in transformations of low-grade B-cell lymphomas after fludarabine treatment.
Fludarabine is a highly effective chemotherapeutic agent for chronic lymphocytic leukemia/small lymphocytic lymphoma and is also active in other B-cell lymphoproliferative disorders. Although highly efficacious in destroying the malignant B-cells, fludarabine also causes T-cell lymphopenia and immunosuppression. We present five patients given fludarabine for low-grade B-cell lymphoproliferative disorders who showed transformation of the primary neoplasm to a higher grade tumor. Immunohistologic antibody studies were performed on paraffin-embedded tissue sections of the initial tissue (when available) and on the follow-up biopsy specimens for CD20, CD3, CD45RO, CD43, CD30, CD15, and latent membrane protein (LMP-1) for Epstein-Barr virus (EBV). The initial diagnoses in these five patients included chronic lymphocytic leukemia/small lymphocytic lymphoma (three cases), follicle center lymphoma (one case), and Waldenstrom's macroglobulinemia (one case). All of the follow-up biopsy specimens showed scattered Hodgkin's-like cells, and two of the five also showed foci of large-cell transformation. The Hodgkin's-like cells showed CD30 immunoreactivity in four of the five cases and CD15 immunoreactivity in three of the five. Strong immunoreactivity of the large, atypical, Hodgkin's-like cells for LMP-1 of EBV was noted in four cases; in the remaining case, this finding was equivocal. In situ hybridization for EBV-encoded RNA was positive in four of the five cases. Molecular studies by polymerase chain reaction (PCR) showed the presence of EBV in three of the five cases. PCR for detection of immunoglobulin heavy chain demonstrated identical monoclonal rearrangements in the original lymphoma and transformation in one case with available material. The CD4 lymphocyte count in each patient was less than 550/microL, indicating cellular dysfunction. Transformation of low-grade non-Hodgkin's lymphomas after fludarabine therapy might be associated with EBV and severe immunosuppression.


[Relationship between the tonus of the walls of the internal carotid artery and cyclic adenylmonophosphate].
Experiments were carried out in dogs with the use of resistography of circulatory-isolated internal carotid artery. Both activation of adenyl cyclase by adenosine and inhibition of phosphodiesterase by theophylline in the vascular wall result in a significant decrease in the vasoconstrictor effect of prestaglandin E2. On the contrary, inhibition of adenyl cyclase by the beta-blocker propranolol or activation of phosphodiesterase by imidazol in the vascular wall causes potentiation of vasoconstriction brought about by prostaglandin E2. Thus the endogenous cyclic AMP either antagonizes the vasoconstrictor effect of prostaglandin E2, or the latter affects vascular smooth muscles by influencing the activity of enzymes that are responsible for the cyclic AMP level in the vascular wall.


A data-oriented self-calibration and robust chemical-shift encoding by using clusterization (OSCAR): Theory, optimization and clinical validation in neuromuscular disorders.
Multi-echo Chemical Shift-Encoded (CSE) methods for Fat-Water quantification are growing in clinical use due to their ability to estimate and correct some confounding effects. State of the art CSE water/fat separation approaches rely on a multi-peak fat spectrum with peak frequencies and relative amplitudes kept constant over the entire MRI dataset. However, the latter approximation introduces a systematic error in fat percentage quantification in patients where the differences in lipid chemical composition are significant (such as for neuromuscular disorders) because of the spatial dependence of the peak amplitudes. The present work aims to overcome this limitation by taking advantage of an unsupervised clusterization-based approach offering a reliable criterion to carry out a data-driven segmentation of the input MRI dataset into multiple regions. Results established that the presented algorithm is able to identify at least 4 different partitions from MRI dataset under which to perform independent self-calibration routines and was found robust in NMD imaging studies (as evaluated on a cohort of 24 subjects) against latest CSE techniques with either calibrated or non-calibrated approaches. Particularly, the PDFF of the thigh was more reproducible for the quantitative estimation of pathological muscular fat infiltrations, which may be promising to evaluate disease progression in clinical practice.


Thoracoscopic sympathicolysis for essential hyperhidrosis: effects on pulmonary function.
Bilateral interruption of the upper dorsal sympathetic chain at the D2 and D3 level represents the only permanent cure for essential hyperhidrosis. Following surgical sympathectomy, significant and symptomatic changes in pulmonary function have been observed. Since functional effects of the surgical intervention cannot be excluded, we wondered whether such alterations also occurred after thoracoscopic sympathicolysis; these should then be attributable to the surgical denervation itself. Pulmonary function tests (PFTs), including spirometry and body plethysmographic measurement of lung volumes and airway resistance and conductance, were compared before and 6 weeks after thoracoscopic sympathicolysis in 47 patients. In order to virtually exclude any effects of thoracoscopy on the test results PFTs were repeated 6 months after thoracoscopic sympathicolysis in 35 patients. Essential hyperhidrosis was completely relieved in all patients, thereby confirming the interruption of the D2-D3 sympathetic chain. None of the patients developed respiratory symptoms after thoracoscopic sympathicolysis. Forced expiratory volume in one second (FEV1) (-3%), forced expiratory flow after exhaling 75% of vital capacity (FEF75) (-8%) and total lung capacity (TLC) (-3%) were slightly but significantly reduced at six weeks after thoracoscopic sympathicolysis; whereas airway resistance (Raw) had increased (+12%). After correction for the small decrease in lung volume (FEV1/forced vital capacity (FVC), specific airway resistance (sRaw), specific airway conductance (sGaw))significant changes in "volume-dependent" PFT parameters were no longer observed. Smoking status had no influence on the reduction in FEF75. At 6 months after thoracoscopic sympathicolysis, TLC had returned to preoperative values, whereas FEF75 remained decreased (-8.6%). The decrease in airway calibre was confirmed by small but significant changes in FEV1/FVC (-2%) and Raw (+29%). We conclude that thoracoscopic sympathicolysis in patients with essential hyperhidrosis causes only minimal and subclinical changes in pulmonary function secondary to a temporary small decrease in lung volume, which in turn is probably inherent to the thoracoscopic procedure. D2-D3 sympathicolysis, in itself, is responsible only for a small and permanent decrease in forced expiratory flow, which suggests that, at least in essential hyperhidrosis patients, airway bronchomotor tone is influenced by sympathetic innervation.


Building the technological European Community through education: European mobility and training programmes in the 1980s.
The Community Action Programme for Education and Training for Technology (COMETT) played a key role in paving the way for increased cooperation between the member states of the European Community (EC) in the field of education and in the promotion of intra-Europe mobility. In this article, COMETT is considered as a non-traditional education and training programme for solving economic challenges in the context of technological change that was focused on the training of a highly skilled workforce. The process of setting the agenda for COMETT is studied through an analysis of official EC policy documents and archival material from the EU's historical archives in Florence. Our analysis suggests that the challenge posed by new information technologies acted as a catalyst for a new approach to education governance that was based on closer cooperation between European universities and industry. Promoting intra-Europe mobility among highly skilled workers and students was a key part of the programme, which defined an economic and social strategy for Europe in response to technological change. Educational and social goals were secondary in the design and implementation of the COMETT programme, which, first and foremost, was motivated by the EC agenda to boost the competitiveness of European industry.


Implementation of the ECHO® telementoring model for the treatment of patients with hepatitis C.
We aimed to implement the Extension for Community Healthcare Outcomes (ECHO) telementoring model for hepatitis C and to evaluate its outcomes in the health providers. Following the ECHO model, an hepatitis C teleECHO clinic was established at the Hospital Italiano in Argentina. The teleECHO clinic provides support and training to physicians from Patagonia who treat patients with hepatitis C. In order to evaluate the teleECHO clinic outcomes, physicians completed a survey focused on skills and competence in hepatitis C before and after 6 months of participating in the project. The survey consisted of 10 questions, which participants rated from 1 to 7 (1 no ability; 7 highest ability). To analyze the difference before and after participation in the project, Wilcoxon signed-rank test was used. During the first 6 months of implementation of the model, a total of 14 physicians from 12 sites in Patagonia agreed to participate in the survey. The median age of the participants was 42 years. Participants' primary specialties were Hepatology (55%), Infectious Diseases (25%), General Practice (10%), and other (10%). A significant improvement was observed in all the evaluated fields after 6 month of the participation in the teleECHO clinic, namely fibrosis staging, determining appropriate candidates for treatment, and selecting appropriate HCV treatment. In addition, their general interest in hepatitis C increased. We successfully replicated and implemented the first teleECHO clinic in Argentina. Physicians improved their ability to provide best practice care for patients with Hepatitis C. J. Med. Virol. 89:660-664, 2017. © 2016 Wiley Periodicals, Inc.


Transaortic endoclamp for mitral valve operation through right minithoracotomy in 369 patients.
: The effects and benefits of a transaortic endoclamp for mitral valve operation through right minithoracotomy have not been established. : The records were examined in 671 patients undergoing mitral valve operation using aortic cannulation through a 6-cm right minithoracotomy in the fourth intercostal space. The ascending aorta was cannulated with a 24-Fr cannula through a 12-mm port in the first intercostal space. The experience from 1998 to 2006 with aortic endoclamping (group A, N = 436) was compared with the experience from 2006 to 2009 with external aortic clamping (group B, N = 235). Aortic endoclamping was achieved with a 30 mL endoclamp introduced through the aortic cannula into the ascending aorta to provide aortic endoclamping, anterograde cardioplegia, and root venting. Percutaneous femoral venous cannulation was used. : Group A and group B had similar demographics. Endoclamp availability (group A) resulted in significantly less fibrillatory arrest (no clamping) in 67 of 436 (15%) versus 104 of 235 (44%) patients in group B (P = 0.001). In patients with aortic clamping, endoclamp (group A) versus external clamp (group B) was not a determinant of clamp time or pump time. Hospital and late outcomes were not different between groups. No patient complications could be attributed to the endoclamp. : Aortic endoclamping requires no more clamp or pump time than external clamping and can provide a more bloodless field than ventricular fibrillation without obstructing hardware. Aortic endoclamping is a safe alternative for mitral surgery through right minithoracotomy.


Tumor-Educated Platelets as a Noninvasive Biomarker Source for Cancer Detection and Progression Monitoring.
Liquid biopsies represent a potential revolution in cancer diagnostics as a noninvasive method for detecting and monitoring diseases, complementary to or even replacing current tissue biopsy approaches. Several blood-based biosources and biomolecules, such as cell-free DNA and RNA, proteins, circulating tumor cells, and extracellular vesicles, have been explored for molecular test development. We recently discovered the potential of tumor-educated blood platelets (TEP) as a noninvasive biomarker trove for RNA biomarker panels. TEPs are involved in the progression and spread of several solid tumors, and spliced TEP RNA surrogate signatures can provide specific information on the presence, location, and molecular characteristics of cancers. So far, TEP samples from patients with different tumor types, including lung, brain, and breast cancers, have been tested, and it has been shown that TEPs from patients with cancer are distinct from those with inflammatory and other noncancerous diseases. It remains to be investigated how platelets are "educated," which mechanisms cause intraplatelet RNA splicing, and whether the relative contribution of specific platelet subpopulations changes in patients with cancer. Ultimately, TEP RNA may complement currently used biosources and biomolecules employed for liquid biopsy diagnosis, potentially enhancing the detection of cancer in an early stage and facilitating noninvasive disease monitoring. Cancer Res; 78(13); 3407-12. ©2018 AACR.


Some mathematical problems of excitability.
The description of the electrical behaviour of nerve and muscle is one of the most quantitative areas of cellular physiology. There are detailed biophysical measurements of currents and potentials, that may be summarised as Master equations or stochastic differential equations for membrane channel and noise recordings, and nonlinear differential equations for macroscopic voltage clamp recordings. Propagation in excitable media is described by nonlinear reaction-diffusion equations. Computational approaches can provide solutions to these equations, but without qualitative studies on simplified caricatures contribute little to mathematical or physiological understanding.


Ipsilateral corticomotor excitability is associated with increased gait variability in unilateral transtibial amputees.
Ipsilateral primary motor cortex (M1) reorganisation after unilateral lower-limb amputation may degrade function of the amputated limb. We hypothesised unilateral lower-limb amputees would have a bilateral increase in corticomotor excitability, and increased excitability of ipsilateral M1 would be associated with increased step-time variability during gait. Twenty transtibial amputees (16 male) aged 60.1 years (range 45-80 years), and 20 age- and gender-matched healthy adult controls were recruited. Single-pulse transcranial magnetic stimulation assessed corticomotor excitability. Two indices of corticomotor excitability were calculated. An index of corticospinal excitability (ICE) determined relative excitability of ipsilateral and contralateral corticomotor projections to alpha-motoneurons innervating the quadriceps muscle (QM) of the amputated limb. A laterality index (LI) assessed relative excitability of contralateral projections from each hemisphere. Spatial-temporal gait analysis was performed to calculate step-time variability. Amputees had lower ICE values, indicating relatively greater excitability of ipsilateral corticomotor projections than controls (P = 0.04). A lower ICE value was associated with increased step-time variability for amputated (P = 0.04) and non-amputated limbs (P = 0.02). This association suggests corticomotor projections from ipsilateral M1 to alpha-motoneurons innervating the amputated limb QM may interfere with gait. Cortical excitability in amputees was not increased bilaterally, contrary to our hypothesis. There was no difference in excitability of contralateral M1 between amputees and controls (P = 0.10), and no difference in LI (P = 0.71). It appears both hemispheres control one QM, with predominance of contralateral corticomotor excitability in healthy adults. Following lower-limb amputation, putative ipsilateral corticomotor excitability is relatively increased in some amputees and may negatively impact on function.


Differentiated Levels of Ganciclovir Resistance Conferred by Mutations at Codons 591 to 603 of the Cytomegalovirus UL97 Kinase Gene.
Diagnostic mutations in the cytomegalovirus UL97 kinase gene are used to assess the level of associated ganciclovir resistance and therapeutic options. The best-known mutations at codons 460, 520, or 591 to 607 individually confer 5- to 10-fold-decreased ganciclovir susceptibility, except that a 3-fold decrease occurs in the case of the amino acid substitution C592G. Less common point and in-frame deletion mutations at codons 591 to 603 remain incompletely characterized. The ganciclovir susceptibilities of 17 mutants in this codon range were evaluated by use of the same recombinant phenotyping system and extensive assay replicates in two types of cell cultures. Amino acid substitutions K599E and T601M conferred no ganciclovir resistance, while A591V conferred 3.8-fold-decreased susceptibility. In-frame deletions of three or more codons conferred at least 8-fold-increased ganciclovir resistance, while the level of resistance conferred by one- or two-codon deletions varied from 4- to 10-fold, depending on their location. Measured levels of ganciclovir resistance were closely comparable when assays were performed in either fibroblasts or modified retinal epithelial cells. The significant revision of a few previously published resistance phenotypes and the new data strengthen the interpretation of genotypic testing for cytomegalovirus drug resistance.


Reimplantation Bypass Using One Limb of a Double-Origin Posterior Inferior Cerebellar Artery for Treatment of a Ruptured Fusiform Aneurysm: Case Report.
Posterior inferior cerebellar artery (PICA) aneurysms are uncommon, and aneurysms associated with anatomical PICA variants are even rarer. Although often treated endovascularly, aneurysms associated with anatomical PICA variants may not be suitable for endovascular intervention because of the risk of compromise of brainstem perforators and may be more amenable to open techniques. This case report describes the successful treatment of an aneurysm associated with a double-origin PICA (DOPICA) by distally reimplanting one of the PICA limbs. A 78-yr-old man with a Hunt-Hess grade III, Fisher grade IV subarachnoid hemorrhage secondary to a ruptured distal right PICA aneurysm associated with a DOPICA was treated with PICA-PICA bypass and trapping of the aneurysm. This is the first reported case in the literature of successful bypass of a DOPICA-associated aneurysm. Radiographically, the bypass remained patent with successful obliteration of the aneurysm, and at discharge from the hospital, the patient had a Glasgow Coma Scale score of 15 and modified Rankin Scale score of 3. This case demonstrates a novel reimplantation bypass for a ruptured aneurysm that exploits this rare variant anatomy of a DOPICA.


[The first experience of small intestinal autotransplantation for advanced digestive cancer].
Usually, gastrointestinal tumors (GIT) invading great vessels are acknowledged to be irresectable. Along with that, we can expect positive oncological results only when there is combination treatment with radical surgery (R0 resection). In this article we share the first experience of small intestinal autotransplantation as a method of radical surgery in locally advanced GIT. We conducted the analysis of outcomes of three patients (with pancreas cancer (n=2) and neuroendocrine tumor of caecum (n=1), with neoplastic process involving to superior mesenteric artery and vein. We analyzed intraoperative aspects and algorithm of small intestinal autotransplantation. Long-term outcomes with 1.5-13 months of observing time are presented. On the basis of conducted analysis the authors suggest the possibility of small intestinal autotransplantation in referral centers with strict personalized approach and multidisciplinary surgical team.


Clinical, serologic, and pathologic changes in calves with experimentally induced Trypanosoma brucei infection.
In 7 calves inoculated with Trypanosoma brucei and observed for 105 days, the minimal clinical signs were occasional lethargic periods associated with parasitemia. Rectal temperatures increased by postinoculation day (pid), 10, remained moderately high until PID 50 to 60, and then returned to base line. Moderate anemia occurred between PID 15 and 25. Slightly increased lymphocyte count with relative decrease in neutrophil count was found in 3 calves. Monocytosis of minimal degree occurred 14 days after parasitemia. Trypanosome counts of low level and irregular frequency were found throughout the infection. The average number of trypanosomes in blood was approximately 1,000/ml. Antibody titers, as determined by the indirect immunofluorescent antibody method, appeared on PID 22 and stayed at moderate levels. The immunoglobulin M first increased at PID 5 and remained high (av 216% of base line value) throughout infection, but immunoglobulin G was never increased. Histopathologic study revealed proliferative changes in the lymph nodes and spleen characteristic of humoral antibody (B-cell) response. Mononuclear cell infiltration (lymphocytes and plasma cells), eosinophols, and edema were common in the lymph nodes, spleen, liver, heart, brain, hypophysis, testes, kidney, skeletal muscle, adrenal gland, pancreas, and uterus.


Black phosphorus photodetector for multispectral, high-resolution imaging.
Black phosphorus is a layered semiconductor that is intensely researched in view of applications in optoelectronics. In this letter, we investigate a multilayer black phosphorus photodetector that is capable of acquiring high-contrast (V > 0.9) images both in the visible (λVIS = 532 nm) as well as in the infrared (λIR = 1550 nm) spectral regime. In a first step, by using photocurrent microscopy, we map the active area of the device and we characterize responsivity and gain. In a second step, by deploying the black phosphorus device as a point-like detector in a confocal microsope setup, we acquire diffraction-limited optical images with submicron resolution. The results demonstrate the usefulness of black phosphorus as an optoelectronic material for hyperspectral imaging applications.


Polyphenolic compounds from Korean Lonicera japonica Thunb. induces apoptosis via AKT and caspase cascade activation in A549 cells.
Lonicera japonica Thunb. (L. japonica T.) has historically been used in Korean herbal medicine due to its anticancer and protective effects on the respiratory system. In the present study, the polyphenolic compounds in L. japonica T. were investigated using high-performance liquid chromatography coupled with tandem mass spectrometry, and its anticancer effects on A549 non-small-cell lung cancer cells were studied. Polyphenolic compounds potentially inhibit A549 cells in a dose-dependent manner. Flow cytometry and western blot analysis demonstrated that polyphenolic compounds induce apoptosis by regulating the protein expression levels of caspases, poly-(ADP-ribose) polymerase and the B-cell lymphoma-2-associated X-protein/B-cell lymphoma-extra large ratio. Furthermore, polyphenolic compounds inhibited mitochondrial membrane potential activity. Caspase-3 activity was increased in a dose-dependent manner and polyphenolic compounds inhibited the activation of protein kinase B by dephosphorylation. These results suggest that polyphenolic compounds in A549 cells indicate the anticancer activity through the induction of apoptosis.


Con-A-stimulated superoxide production by granulocytes: reversible activation of NADPH oxidase.
Stimulation of granulocyte (PMN) superoxide (O2-) production by concanavalin-A (Con-A) can be monitored continuously in the spectrophotometer. Both the rate of activation and final activity of the O2--generating system is dependent on the concentration of Con-A. Alpha methylmannoside (alpha MM) can prevent Con-A, but not phorbol myristate acetate (PMA) or zymosan, induced O2- production. Alpha MM inhibits both the rate of activation and the final rate of O2- production. When alpha MM is added after the attainment of a maximal rate of O2- production with Con-A, O2- production continues for another minute before it ceases. When PMA is added to such treated cells, it restores O2- production. Although the inhibition of O2- production by alpha MM on previously activated cells requires time, most of the bound concanavalin-A is removed immediately after the addition of alpha MM. Treatment of cells with L-1-tosylamido-2-phenylethyl-chloromethyl ketone (TPCK) prevents activation of PMN by Con-A to a greater extent than it does for either PMA or zymosan. TPCK has no effect on the binding of Con-A. TPCK, when added after Con-A, will inactivate O2- production by the cells. The addition of PMA after TPCK treatment restores O2--generating activity. Membrane-enriched particles from PMN activated with Con-A, alpha MM, and PMA demonstrate that the change in O2- production seen by whole cells is due to an alteration of the activity of the NADPH oxidase. Thus, Con-A stimulation of human PMN O2- production can be prevented and reversed by the addition of either alpha MM or TPCK and that PMA can reactivate Con-A and either alpha MM- or TPCK-treated cells. The activation, inactivation, and reactivation occur as a result of changes in the plasma membrane NADPH-dependent O2--generating enzyme.


Expression of Key Androgen-Activating Enzymes in Ovarian Steroid Cell Tumor, Not Otherwise Specified.
To characterize the expression of steroidogenic enzymes implicated in the development of ovarian steroid cell tumors, not otherwise specified (SCT-NOS). We present 4 ovarian SCT-NOS evaluated by immunohistochemical staining of steroidogenic enzymes as an approach to define this entity pathologically. All 4 ovarian SCT-NOS showed increased expression for cholesterol side-chain cleavage enzyme (CYP11A1), 17α-hydroxylase (CYP17A1), 17β-hydroxysteroid dehydrogenase 1 (HSD17B1), aldo-ketoreductase type 1 C3 (AKR1C3), 3β-hydroxysteroid dehydrogenase 2 (HSD3B2), 5α-reductase type 2 (SRD5A2), steroid sulfatase (SULT2A1), estrogen sulfotransferase (EST), and aromatase (CYP19A1). Expression was negative for 21-hydroxylase (CYP21A2) and 17β-hydroxysteroid dehydrogenase 2 (HSD17B2). 17β-hydroxysteroid dehydrogenase 3 (HSD17B3) and 5α-reductase type 1 (SRD5A1) showed variable expression. Our analysis reveals a novel finding of increased expression of AKR1C3, HSD17B1, SRD5A2, SULT2A1, and EST in ovarian SCT-NOS, which is clinically associated with androgen excess and virilization. Further studies are needed to validate these enzymes as new markers in the evaluation of hyperandrogenic ovarian conditions.