Valvulotomy in in situ vein bypasses performed by angioscope-assisted laser probe.
The objective of this study was to evaluate the use of an angioscope-assisted laser hot-tip probe for performing valvulotomies in in situ nonreversed canine veins used for arterial bypasses. In Group 1, 9 valvulotomies were performed in 7 bypass veins with a 2-mm probe activated by 12 W power, resulting in 4 vein perforations, 1 vein thrombosis, and 4 in situ grafts patent at removal after 2-28 days. In Group 2, 10 valvulotomies in 9 bypass veins were performed with a 1.5-mm probe at 14 W with no vein perforations, 3 vein thromboses, and 6 in situ grafts patent at removal after an interval of 1 to 6 weeks. We conclude that valvulotomy within in situ vein bypasses can be successfully performed using a 1.5-mm laser hot-tip probe at 14 W power, with patency of the grafts demonstrated at 6 weeks. Angioscope-assisted laser valvulotomy using a laser probe may significantly reduce the length of incisions and the time required for in situ vein bypasses and improve the technical accuracy of the procedure.


Insight into the correlation between microbial diversity and flavor profiles of traditional dry-cured duck from the metabolomic perspective.
The purpose of this work was to reveal the relationship between the microbial diversity and flavor profiles of traditional dry-cured duck from a metabolomic perspective. Enterococcus, Psychrobacter, Macrococcus, Salinivbrio, and Staphylococcus were the dominant bacterial genera, while Trichophyton, Kurtzmaniella, Blumeria, Cladosporium, Lysurus, Aspergillus, Starmerella and Debaryomyces were the dominant fungal genera of dry-cured duck. The results showed that aldehydes, alcohols, furan, and ketone compounds were the main volatile flavor compounds of dry-cured duck. Moreover, the identified metabolites of dry-cured duck were classified and included amino acids, amines, polypeptides, amino acid derivatives, polyols, fatty acids, organic acids, flavonoids and isoflavones. Heatmap analysis was used to illuminate the relationships between the microbial diversity and flavor profiles, as well as metabolites. These results will provide an effective theoretical reference for the standardization and modernization of dry-cured duck production.


Phenalenyl based neutral radical as a novel electrochromic material modulating visible to short-wave infrared light.
Applications for energy saving smart windows require materials which can switch from transmissive to black states in both the visible and short-wave IR range. We introduce an electrochromic phenalenyl based neutral radical small molecule and design devices capable of modulating light in both of these ranges.


Distribution of polycyclic aromatic hydrocarbons (PAHs) and sterols in termite nest, soil, and sediment from Great Kwa River, SE Nigeria.
Costal sediment samples from Great Kwa River as well as adjoining termite nest and soil samples were analyzed for quantitative determination of polycyclic aromatic hydrocarbons (PAHs) and sterols using gas chromatography-mass spectrometry (GC-MS) in order to access the possibility of transport of biologically produced PAHs/sterols from termite nest to the sediments. The total PAH concentrations (sum of parent and alkyl) for the sediments ranged between 131.96 and 139.35 ng/g dry weight (dw) while those for the nest and soil samples were in the range 9.51-9.71 and 71.85-77.26 ng/g dw, respectively. These levels of PAHs in sediments were relatively low compared to other urban/industrial Asian and American countries. No evidence of the usual biologically produced PAHs was found, thus reducing the likelihood of transport of these compounds from the nest to the sediments. The absence of parent and alkyl PAHs in central compartment of the nest may reflect the selective fern leaves feeding pattern of the dominant termite species prevalent in the vicinity of the study site. Utilization of six selected PAH ratios such as Fla/(Fla + Pyr) (0.4-0.5), Ant/(Ant + Phe) (0.25-0.90), BaA/(BaA + Chrys) (0.45-0.61), MP/P (0.05-6.81), 1,7/(1,7 + 2,6)-DMP (0.61-0.95), and LPAH/HPAH ( 2.80-3.80) allows discrimination of PAH sources for the samples to be made with a mixed source dominance observed. Examination of sterol distributions in the samples shows relatively high abundance of cholest-5-en-3β-ol in central compartment of the nest, considered here as a consequence of metabolic conversion of phyto-/fungi sterols in the tissues of the termite species. The relatively reduced levels of stanol compounds in central compartment of the nest may be associated with their utilization by the termites for growth and development.


Complications of closing wedge high tibial osteotomies for unicompartmental osteoarthritis of the knee.
We systematically reviewed the published literature on the complications of closing wedge high tibial osteotomy for the treatment of unicompartmental osteoarthritis of the knee. Publications were identified using the Cochrane Library, MEDLINE, EMBASE and CINAHL databases up to February 2012. We assessed randomised (RCTs), controlled group clinical (CCTs) trials, case series in publications associated with closing wedge osteotomy of the tibia in patients with osteoarthritis of the knee and finally a Cochrane review. Many of these trials included comparative studies (opening wedge versus closing wedge) and there was heterogeneity in the studies that prevented pooling of the results.


Universal Testing to Identify Lynch Syndrome Among Women With Newly Diagnosed Endometrial Carcinoma.
Lynch syndrome (LS) is an autosomal dominant cancer syndrome caused by a germline mutation in the mismatch repair (MMR) genes. Protocols based on immunohistochemical expression of MMR proteins in cancer are used to identify patients with LS. The universal LS screening protocol of the Tom Baker Cancer Centre (Calgary, AB) of all patients diagnosed between April 1, 2013 and April 1, 2015 with endometrioid carcinoma of the endometrium was audited through a retrospective chart review. LS status and frequency of protocol compliance at each of the key steps were calculated (Canadian Task Force Classification II-2). The cohort consisted of 375 patients. MMR immunohistochemical testing was requested for 321 (85.6%). Expression of at least one protein was lost in 86 (26.8%). Twenty-one (6.5%) patients were eligible for genetic counselling because PMS2, MSH2, or MSH6 protein expression was lost in 19, and two patients had a family history of LS. Eleven (91.7%) of 12 (57.1%) who attended had germline testing, and six (54.5%) showed a mutation diagnostic of LS. LS status among the cohort of 375 patients was positive in six (1.6%), negative in 294 (78.4%), and unknown in 75 (20%) because of protocol non-compliance. LS was confirmed in six (2%) of the 321 women who completed the protocol. This is the first audit of a Canadian-based universal LS screening protocol of patients with endometrial cancer. The success of the protocol is endorsed by the 80% compliance and by the 2% prevalence of LS, which is within the published range.


Modification of postoperative nitrogen balance with preoperative anabolic steroid.
Thirty six patients undergoing abdominal operations were randomly allocated to receive an anabolic steroid, stanozolol (50 mg) or placebo 24 h before surgery. Patients were fasted during the first four postoperative days. During this period the mean daily nitrogen balance was significantly less negative in the stanozolol group (-8.0+/-3.0 gN/day) than in the control group (-10.9+/-4.1 gN/day), although improvement in nitrogen balance was greater in male than in female patients. Muscle catabolism as measured by 3-methylhistidine excretion was similar in both treatment groups. Significant fluid retention occurred in the stanozolol treated group and was more marked in female patients. Improved nitrogen balance in the absence of a measurable change in muscle catabolism suggests that this anabolic steroid acts by improving protein synthesis in the early period after surgery.


First isolation of Trichinella britovi from a wild boar (Sus scrofa) in Belgium.
Since 1992, when the European Union Council Directive requires that wild boars (Sus scrofa) hunted in EU for commercial purpose should be examined for Trichinella, the infection has not been detected in wild boars from Belgium, despite serological evidence of the presence of anti-Trichinella antibodies in wildlife and previous reports of Trichinella larvae in this host species. In November 2004, Trichinella larvae were detected in a wild boar hunted near Mettet, Namur province (Southern Belgium). Larvae were identified as Trichinella britovi by polymerase chain reaction methods. This is the first report of the identification of Trichinella larvae from Belgium at the species level. The detection of T. britovi in wildlife in Belgium is consistent with findings of this parasite in other European countries and confirms the need to test game meat for Trichinella to prevent its transmission to humans.


Aberrant thyroid gland demonstrated by computed tomography.
Computed tomography (CT) demonstrated high attenuation values consistent with thyroid gland in scans of a patient with tumors in the base of the tongue and anterior median neck. Radioiodine scintigraphy revealed positive uptake in the same areas. This is an indication that CT attenuation values may be useful in the diagnosis of aberrant thyroid gland.


Large-scale identification and characterization of genetic variants in asthma candidate genes.
Asthma is a chronic inflammatory disorder of the airways, and a number of genetic loci are associated with the disease. Candidate gene association studies have been regarded as effective tools to study complex traits. Knowledge of the sequence variation and structure of the candidate genes is required for association studies. Thus, we investigated the genetic variants of 32 asthma candidate genes selected by colocalization of positional and functional candidate genes. We screened all exons and promoter regions of those genes using 12 healthy individuals and 12 asthma patients and identified a total of 418 single nucleotide polymorphisms (SNPs), including 270 known SNPs and 148 novel SNPs. Levels of nucleotide diversity varied from gene to gene (0.72 x 10(-4)-14.53 x 10(-4)), but the average nucleotide diversity between coding SNPs (cSNPs) and noncoding SNPs was roughly equivalent (4.63 x 10(-4) vs 4.69 x 10(-4)). However, nucleotide diversity of cSNPs was strongly correlated to codon degeneracy. Nucleotide diversity was much higher at fourfold degenerate sites than at nondegenerate sites (9.42 x 10(-4) vs 3.14 x 10(-4)). Gene-based haplotype analysis of asthma-associated genes in this study revealed that common haplotypes (frequency >5%) represented 90.5% of chromosomes, and they could be uniquely identified with five or fewer haplotype-tagging SNPs per gene. Therefore, our results may have important implications for the selection of asthma candidate genes and SNP markers for comprehensive association studies using large sample populations.


Estimation of an inter-rater intra-class correlation coefficient that overcomes common assumption violations in the assessment of health measurement scales.
Intraclass correlation coefficients (ICC) are recommended for the assessment of the reliability of measurement scales. However, the ICC is subject to a variety of statistical assumptions such as normality and stable variance, which are rarely considered in health applications. A Bayesian approach using hierarchical regression and variance-function modeling is proposed to estimate the ICC with emphasis on accounting for heterogeneous variances across a measurement scale. As an application, we review the implementation of using an ICC to evaluate the reliability of Observer OPTION5, an instrument which used trained raters to evaluate the level of Shared Decision Making between clinicians and patients. The study used two raters to evaluate recordings of 311 clinical encounters across three studies to evaluate the impact of using a Personal Decision Aid over usual care. We particularly focus on deriving an estimate for the ICC when multiple studies are being considered as part of the data. The results demonstrate that ICC varies substantially across studies and patient-physician encounters within studies. Using the new framework we developed, the study-specific ICCs were estimated to be 0.821, 0.295, and 0.644. If the within- and between-encounter variances were assumed to be the same across studies, the estimated within-study ICC was 0.609. If heteroscedasticity is not properly adjusted for, the within-study ICC estimate was inflated to be as high as 0.640. Finally, if the data were pooled across studies without accounting for the variability between studies then ICC estimates were further inflated by approximately 0.02 while formerly allowing for between study variation in the ICC inflated its estimated value by approximately 0.066 to 0.072 depending on the model. We demonstrated that misuse of the ICC statistics under common assumption violations leads to misleading and likely inflated estimates of interrater reliability. A statistical analysis that overcomes these violations by expanding the standard statistical model to account for them leads to estimates that are a better reflection of a measurement scale's reliability while maintaining ease of interpretation. Bayesian methods are particularly well suited to estimating the expanded statistical model.


Cutaneous pharmacodynamics of transdermally delivered isosorbide dinitrate.
Laser doppler velocimetry (LDV) has been used to assess the cutaneous pharmacodynamics of isosorbide dinitrate (ISDN) following transdermal delivery of the drug from prototypal patches. The delivery systems, which were saturated with ISDN, (a) produced various degrees of skin occlusion and (b) spanned a six-fold range of adhesiveness. The patches were applied to the ventral forearm skin of 10 healthy volunteers and the local ISDN-induced increase in local skin blood flow was determined using LDV by locating the probe in a central hole in the delivery system. Measurements were made for 1.5 hr and the pharmacodynamics were quantified by (i) the maximum LDV response and (ii) the area under the LDV response versus time curve. These parameters were not sensitive to patch occlusivity. They were significantly (P less than 0.01) dependent on patch adhesiveness, though, and decreased with increasing adhesion. Although this observation suggested that ISDN diffusion through the adhesive could determine, at least in part, the rate of drug delivery, it was subsequently demonstrated that ISDN release (in vitro, into a perfect "sink") was unaffected by the level of cross-linking in the adhesive polymer. Because the drug was present in all systems at unit thermodynamic activity, these results cannot be explained on the basis of altered ISDN partitioning at the device-stratum corneum interface. We speculate that the in vivo-in vitro discrepancy may be due to the efficiency of skin contact achieved by different adhesives: that is, the more adhesive, less flexible systems make poorer contact with the skin surface, thereby decreasing the effective surface area of drug delivery.(ABSTRACT TRUNCATED AT 250 WORDS)


Pik3c3 deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1β production.
The PIK3C3/VPS34 subunit of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex plays a role in both canonical and noncanonical autophagy, key processes that control immune-cell responsiveness to a variety of stimuli. Our previous studies found that PIK3C3 is a critical regulator that controls the development, homeostasis, and function of dendritic and T cells. In this study, we investigated the role of PIK3C3 in myeloid cell biology using myeloid cell-specific Pik3c3-deficient mice. We found that Pik3c3-deficient macrophages express increased surface levels of major histocompatibility complex (MHC) class I and class II molecules. In addition, myeloid cell-specific Pik3c3 ablation in mice caused a partial impairment in the homeostatic maintenance of macrophages expressing the apoptotic cell uptake receptor TIM-4. Pik3c3 deficiency caused phenotypic changes in myeloid cells that were dependent on the early machinery (initiation/nucleation) of the classical autophagy pathway. Consequently, myeloid cell-specific Pik3c3-deficient animals showed significantly reduced severity of experimental autoimmune encephalomyelitis (EAE), a primarily CD4+ T-cell-mediated mouse model of multiple sclerosis (MS). This disease protection was associated with reduced accumulation of myelin-specific CD4+ T cells in the central nervous system and decreased myeloid cell IL-1β production. Further, administration of SAR405, a selective PIK3C3 inhibitor, delayed disease progression. Collectively, our studies establish PIK3C3 as an important regulator of macrophage functions and myeloid cell-mediated regulation of EAE. Our findings also have important implications for the development of small-molecule inhibitors of PIK3C3 as therapeutic modulators of MS and other autoimmune diseases.


Amputations and foot ulcers in patients newly diagnosed with type 2 diabetes mellitus and observed for 19 years. The role of age, gender and co-morbidity.
To determine the prevalence of foot ulcers and the incidence of amputations in patients with Type 2 diabetes observed for 19 years after diagnosis. We investigated the role of gender, age and co-morbidities. From the Diabetes Care in General Practice study, 1381 patients were included and examined at diabetes diagnosis, at 6 years and at 14 years after diagnosis. Register-based follow-up was for 19 years. Foot ulcers and amputations were related to gender, age and co-morbidities by odds and hazard ratios from logistic and Cox regression models, respectively. The incidence of any amputation and major amputation was 400 (95% CI 307-512) and 279 (95% CI 203-375) per 100,000 patient-years, respectively. At the three observation points, the foot ulcer prevalences were 2.76% (95% CI 1.89-3.63), 2.93% (95% CI 1.86-4.00) and 4.96% (95% CI 3.10-6.82). Multivariate analyses showed associations between foot ulcers and peripheral neuropathy, peripheral arterial disease, male gender, retinopathy and myocardial infarction. After multivariate adjustment, significant predictors (hazard ratio; 95% CI) of any amputation were peripheral neuropathy (hazard ratio 2.09; 95% CI 1.19-3.69), peripheral arterial disease (hazard ratio 3.43; 95% CI 1.65-7.12), microalbuminuria (hazard ratio 2.11; 95% CI 1.21-3.67), retinopathy (hazard ratio 6.42; 95% CI 2.59-15.90), impaired vision (hazard ratio 6.92; 95% CI 2.35-20.38) and male gender (hazard ratio 2.40; 95% CI 1.31-4.41). For women, the risk of amputation increased with age, but for men the risk was higher when diagnosed with diabetes at a younger age. Despite improved treatment regimens, the incidence of amputations is still high in this population-based patient sample. Men diagnosed with diabetes before age 65 years and patients with diabetes-related co-morbidities are at particularly high risk of foot ulcers and amputations.


beta-Catenin regulation during matrigel-induced rat hepatocyte differentiation.
Hepatocytes in primary cultures de-differentiate and re-differentiate following addition of Engelbreth-Holm-Swarm mouse sarcoma (matrigel) to the cultures. The Wnt/beta-catenin pathway has been shown to be important in liver growth and development. Here, we investigate changes in beta-catenin and its mechanism, during matrigel-induced hepatocyte differentiation. Primary rat hepatocytes were cultured for 8 days, and matrigel was added to half of the cultures. Total and nuclear protein and total RNA were extracted at different days of culture and examined for beta-catenin and other Wnt pathway components. A significant increase in total beta-catenin protein was observed upon matrigel addition, during hepatocyte differentiation, despite a decrease in beta-catenin and frizzled-1 (Wnt receptor) expression. A concurrent decrease in the glycogen synthase kinase-3beta (GSK3beta), axin, and ser45/thr41-phosphorylated beta-catenin proteins was observed in matrigel-treated cultures, implying decreased degradation of beta-catenin. Interestingly, a decrease in nuclear beta-catenin and total active beta-catenin was observed in the presence of matrigel. Matrigel also induced an increased association of beta-catenin with Met (hepatocyte growth factor receptor), whereas association with E-cadherin remained unchanged. This coexisted with decreased beta-catenin tyrosine phosphorylation. Thus, beta-catenin undergoes multifactorial regulation during matrigel-induced hepatocyte differentiation and maturation; this induces its stabilization and membrane translocation, possibly contributing to hepatocyte differentiation.


Estimation of the total number of hippocampal CA1 pyramidal neurons: new methodology applied to helpless rats.
We have recently reported that in the learned helplessness model of depression, the less hippocampal spine synapses rats have, the more helpless they become. It remains unclear, however, whether the observed synaptic changes are associated with the loss of CA1 pyramidal cells. Cell bodies in the CA1 pyramidal layer are very densely packed, making cell counting difficult in this hippocampal subregion. To address this issue, we developed a new approach that (1) yields excellent preservation of the three-dimensional tissue structure; (2) utilizes osmium tetroxide to unambiguously label nucleoli; and (3) facilitates and accelerates unbiased, reliable counting of densely packed cell bodies. Our method provides an improved tool for studies aiming to evaluate hippocampal atrophy and cell loss, the most characteristic features in many neurodegenerative diseases, such as Alzheimer's disease, temporal lobe epilepsy and ischemia, as well as in several psychiatric disorders. Using this new method, we demonstrated no significant changes in the number of CA1 pyramidal cells in the rat learned helplessness paradigm. In addition, volumes of the CA1 pyramidal cell layer and the entire CA1 subfield remained unchanged among treatment groups. We conclude that previously observed synaptic alterations in helpless rats are not associated with CA1 pyramidal cell loss. This finding suggests that behavioral outcome in the learned helplessness paradigm is related to plastic events at the synaptic level, rather than at the level of principal cells.


High-resolution manometry and swallow outcomes after vocal fold injection medialization for unilateral vocal fold paralysis/paresis.
Injection medialization is performed to improve glottic closure, thereby airway protection. Overall objective to determine if unilateral injection medialization changes glottal area with concomitant adjustments in penetration/aspiration scale (PAS) scores and pharyngeal high-resolution manometry (HRM) parameters. Enrolled 17 adults with unilateral vocal fold paralysis/paresis and aspiration/penetration. Fiberoptic endoscopic evaluation of swallowing and pharyngeal HRM completed at (1) baseline (within 1 week before injection), (2) postinjection (within 1 week post injection), and (3) 1-month postinjection. Comparisons between time points for PAS scores, glottal area, pharyngeal pressure, and timing. No significant differences in normalized glottal area. No significant differences in PAS scores, for any consistency. Significantly increased rate of mesopharynx pressure rise and maximum pressure at 1 month postinjection (P = .01 and .02, respectively) compared to baseline. Significant decrease in mesopharynx integral from baseline to 1 week postoperative (P = .03). Findings suggest unilateral vocal fold injection medialization had limited effect on swallow function.


Crosstalk among dietary polyunsaturated fatty acids, urolithiasis, chronic inflammation, and urinary tract tumor risk.
Based on a consistent bulk of experimental and epidemiologic works, we proposed that abnormal metabolism and/or dietary deprivation of essential polyunsaturated fatty acids by inducing a chronic and subclinical essential fatty acid deficiency (EFAD) in urothelial cell membranes may enhance the risk for urinary tract tumor (UTT) development. This threat may be enhanced by the unusual fact that the fatty-acid profile of the normal urothelium is similar to that reported in EFAD. The risk for UTT may be worsened when coexisting with a low-grade chronic inflammation (LGCI) state induced by urolithiasis or disbalance management of peroxides, free radical molecules, and their quenchers. There is cumulative evidence linking the LGCI of the urinary tract mucosa, calculi, and UTT, due to the long-standing release of promitotic, promutagen, and pro-inflammatory antiapoptotic cytokines in these conditions. The dual role played by pro- and anti-inflammatory eicosanoids and bioactive lipids, cytokines, and the disbalance of lipid peroxidation is discussed, concluding that the moderate, long-standing consumption or dietary supplementation of ω-3 PUFAs may improve the chances of avoiding UTT development.


Efficacy of plasma exchange in acute attacks of neuromyelitis optica spectrum disorders: A systematic review and meta-analysis.
Plasma exchange (PE) has usually to be considered as a rescue therapy when intravenous corticosteroids is insufficient in acute attacks of neuromyelitis optica spectrum disorders (NMOSD). The efficacy of PE has not been quantified. This system review and meta-analysis was aimed to evaluate the efficacy of PE therapy in acute attacks of NMOSD. Studies evaluating the efficacy of PE in patients with NMOSD were identified from PubMed and Embase. Changes of Expanded Disability Status Scale (EDSS) score between before and after PE therapy, and the rate of response to PE, were defined as the main efficacy outcomes. Meta-regression was performed to identify the sources of heterogeneity. Subgroup meta-analysis were performed based on the interval of initiation PE after attack onset and AQP4-IgG serostatus of patients. Twenty-four studies containing 528 patients with NMOSD were included in this meta-analysis. As a rescue therapy when patients failed to respond to intravenous corticosteroids (PE rescue), PE treatment resulted in a reduction in the mean EDSS score by 1.69 (95% CI: 0.88-2.50), with a response rate of 75%(95%CI: 66%-83%). As a first-line therapy being used alone or simultaneously with intravenous corticosteroids (PE first-line), PE resulted in a reduction in the mean EDSS score by 2.34 (95% CI: 1.69-2.98), with a response rate of 71%(95%CI: 44%-93%). Overall, PE resulted in a reduction in the mean EDSS score by 1.83 (95% CI: 1.19-2.47), with a response rate of 74% (95%CI: 66%-82%). Subgroup analysis suggested that earlier PE initiation and AQP4-IgG seronegative patients seemed to be associated with a superior response to PE therapy. Plasma exchange, whether used as rescue or as first-line therapy, is an effective therapeutic method in patients during acute attacks of NMOSD.


[Larval development and determinism of nymphal diapause in a Lepidoptera, Actias selene Hbn. (Attacidae) (author's transl)].
Actias selene has been reared under different conditions of lights, photophases and temperatures. The red light (630-670 nm) corresponding to the maximum of absorption of pterobilin and phorcabilin chromoproteins reduces the average length of development from 29 days to 50 days and totally inhibits the nymphal diapause. The results are discussed.


Purification and structure analysis of mycolic acids in Corynebacterium glutamicum.
Corynebacterium glutamicum is widely used for producing amino acids. Mycolic acids, the major components in the cell wall of C. glutamicum might be closely related to the secretion of amino acids. In this study, mycolic acids were extracted from 5 strains of C. glutamicum, including ATCC 13032, ATCC 13869, ATCC 14067, L-isoleucine producing strain IWJ-1, and L-valine producing strain VWJ-1. Structures of these mycolic acids were analyzed using thin layer chromatography and electrospray ionization mass spectrometry. More than twenty molecular species of mycolic acid were observed in all 5 strains. They differ in the length (20-40 carbons) and saturation (0-3 double bonds) of their constituent fatty acids. The dominant species of mycolic acid in every strain was different, but their two hydrocarbon chains were similar in length (14-18 carbons), and the meromycolate chain usually contained double bonds. As the growth temperature of cells increased from 30°C to 34°C, the proportion of mycolic acid species containing unsaturated and shorter hydrocarbon chains increased. These results provide new information on mycolic acids in C. glutamicum, and could be useful for modifying the cell wall to increase the production of amino acids.


Artificial small RNA-mediated growth inhibition in Escherichia coli and Salmonella enterica serovar Typhimurium.
We developed a synthetic RNA approach to identify growth inhibition sequences by cloning random 24-nucleotide (nt) sequences into an arabinose-inducible expression vector. This vector expressed a small RNA (sRNA) of ∼140 nt containing a 24 nt random sequence insert. After transforming Escherichia coli with the vector, 10 out of 954 transformants showed strong growth defect phenotypes and two clones caused cell lysis. We then examined growth inhibition phenotypes in the Salmonella Typhimurium LT2 strain using the twelve sRNAs that exerted an inhibitory effect on E. coli growth. Three of these clones showed strong growth inhibition phenotypes in S. Typhimurium LT2. The most effective sRNA contained the same insert (N1) in both bacteria. The 24 nt random sequence insert of N1 was abundant in guanine residues (ten out of 24 nt), and other random sequences causing growth defects were also highly enriched for guanine (G) nucleotides. We, therefore, generated clones that express sRNAs containing a stretch of 16 to 24 continuous guanine sequences (poly-G16, -G18, -G20, -G22, and -G24). All of these clones induced growth inhibition in both liquid and agar plate media and the poly-G20 clone showed the strongest effect in E. coli. These results demonstrate that our sRNA expression system can be used to identify nucleotide sequences that are potential candidates for oligonucleotide antimicrobial drugs.


Characterization of dynamics in complex lyophilized formulations: II. Analysis of density variations in terms of glass dynamics and comparisons with global mobility, fast dynamics, and Positron Annihilation Lifetime Spectroscopy (PALS).
Amorphous HES/disaccharide (trehalose or sucrose) formulations, with and without added polyols (glycerol and sorbitol) and disaccharide formulations of human growth hormone (hGH), were prepared by freeze drying and characterized with particular interest in methodology for using high precision density measurements to evaluate free volume changes and a focus on comparisons between "free volume" changes obtained from analysis of density data, fast dynamics (local mobility), and PALS characterization of "free volume" hole size. Density measurements were performed using a helium gas pycnometer, and fast dynamics was characterized using incoherent neutron scattering spectrometer. Addition of sucrose and trehalose to hGH decreases free volume in the system with sucrose marginally more effective than trehalose, consistent with superior pharmaceutical stability of sucrose hGH formulations well below Tg relative to trehalose. We find that density data may be analyzed in terms of free volume changes by evaluation of volume changes on mixing and calculation of apparent specific volumes from the densities. Addition of sucrose to HES decreases free volume, but the effect of trehalose is not detectable above experimental error. Addition of sorbitol or glycerol to HES/trehalose base formulations appears to significantly decrease free volume, consistent with the positive impact of such additions on pharmaceutical stability (i.e., degradation) in the glassy state. Free volume changes, evaluated from density data, fast dynamics amplitude of local motion, and PALS hole size data generally are in qualitative agreement for the HES/disaccharide systems studied. All predict decreasing molecular mobility as disaccharides are added to HES. Global mobility as measured by enthalpy relaxation times, increases as disaccharides, particularly sucrose, are added to HES.


MicroRNAs in central nervous system diseases: A prospective role in regulating blood-brain barrier integrity.
Given the essential role of the blood-brain barrier (BBB) in the central nervous system (CNS), cumulative investigations have been performed to elucidate how modulation of BBB structural and functional integrity affects the pathogenesis of CNS diseases such as stroke, traumatic brain injuries, dementia, and cerebral infection. Recent studies have demonstrated that microRNAs (miRNAs) contribute to the maintenance of the BBB and thereby mediate CNS homeostasis. This review summarizes emerging studies that demonstrate cerebral miRNAs regulate BBB function in CNS disorders, emphasizing the direct role of miRNAs in BBB molecular composition. Evidence presented in this review will encourage a deeper understanding of the mechanisms by which miRNAs regulate BBB function, and facilitate the development of new miRNAs-based therapies in patients with CNS diseases.


Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.
Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs). This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy. In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR). The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%. In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients.


Milk and Plasma Lutein and Zeaxanthin Concentrations in Chinese Breast-Feeding Mother-Infant Dyads With Healthy Maternal Fruit and Vegetable Intake.
While others have reported that milk from coastal Chinese women contains high levels of lutein and zeaxanthin, no research has determined the corresponding infant plasma response. Whether infant plasma levels increase commensurately provides important guidance for supplementation of these increasingly intriguing carotenoids in breast-feeding mothers and formula-fed infants. Fifty-six mother-infant pairs with a maternal diet rich in eggs, green leafy vegetables, and fruit were enrolled between 6 and 16 weeks of lactation. Milk samples and blood samples from both the mother and infant were collected at entry. Maternal 3-day dietary records and a second milk sample were collected 1 to 3 weeks later. Mean milk lutein concentrations in samples 1 and 2 were 6.5 and 7.7 μg/dL (range 1-22.5 μg/dL), and for zeaxanthin, 1.6 and 1.7 μg/dL (range 1-5.9 μg/dL). Lutein concentrations in infant plasma (18.2 μg/dL) were similar to those in maternal plasma (21.6 μg/dL); zeaxanthin was lower than lutein in both maternal (3.1 μg/dL) and infant (2.9 μg/dL) plasma. Infant and maternal mean plasma lutein and zeaxanthin concentrations were higher than those in both milk samples 1 and 2 (lutein, 6.9 and 8.2 μg/dL; zeaxanthin, 1.9 and 2.0 μg/dL). Infant plasma lutein and zeaxanthin concentrations positively correlated with those in milk sample 1 (lutein, r2 = 0.15, p = 0.004; zeaxanthin, r2 = 0.21, p < 0.001). Together, these results reveal that high milk concentrations of lutein and zeaxanthin driven by healthy maternal intakes of xanthophyll rich foods are associated with high infant plasma concentrations. These findings will be useful for determining appropriate lutein fortification strategies. Clinical Study.gov registration number: NCT01669655.


Complete genome sequence of Leuconostoc gelidum subsp. gasicomitatum KG16-1, isolated from vacuum-packaged vegetable sausages.
Leuconostoc gelidum subsp. gasicomitatum is a predominant lactic acid bacterium (LAB) in spoilage microbial communities of different kinds of modified-atmosphere packaged (MAP) food products. So far, only one genome sequence of a poultry-originating type strain of this bacterium (LMG 18811(T)) has been available. In the current study, we present the completely sequenced and functionally annotated genome of strain KG16-1 isolated from a vegetable-based product. In addition, six other vegetable-associated strains were sequenced to study possible "niche" specificity suggested by recent multilocus sequence typing. The genome of strain KG16-1 consisted of one circular chromosome and three plasmids, which together contained 2,035 CDSs. The chromosome carried at least three prophage regions and one of the plasmids encoded a galactan degradation cluster, which might provide a survival advantage in plant-related environments. The genome comparison with LMG 18811(T) and six other vegetable strains suggests no major differences between the meat- and vegetable-associated strains that would explain their "niche" specificity. Finally, the comparison with the genomes of other leuconostocs highlights the distribution of functionally interesting genes across the L. gelidum strains and the genus Leuconostoc.


The involvement of the semantic neural network in rule identification of mathematical processing.
The role of the visuospatial network in mathematical processing has been established, but the involvement of the semantic network in mathematical processing is still poorly understood. The current study utilized a number series completion paradigm with the event-related potential (ERP) technique to examine whether the semantic network supports mathematical processing and to find the corresponding spatiotemporal neural marker. In total, 32 right-handed undergraduate students were recruited and asked to complete the number series completion as well as the arithmetical computation task in which numbers were presented in sequence. The event-related potential and multi-voxel pattern analysis showed that the rule identification process involves more semantic processing when compared with the arithmetical computation processes, and it elicited higher amplitudes for the late negative component (LNC) in left frontal and temporal lobes. These results demonstrated that the semantic network supports the rule identification in mathematical processing, with the LNC acting as the neural marker.


Refinement of the rodent pentylenetetrazole proconvulsion assay, which is a good predictor of convulsions in repeat-dose toxicology studies.
The pentylenetetrazole (PTZ)-induced seizure assay in rodents is an established method for investigating drug-induced alterations in seizure threshold such as proconvulsant effects. The standard procedure in our laboratory was to administer the test item prior to 75-120 mg/kg subcutaneous PTZ. However, this dose range is associated with a high incidence of mortality, including approximately 40% or greater deaths of control animals. The predictivity of the PTZ-induced seizure assay was retrospectively evaluated by relating drug plasma levels associated with proconvulsant effects to exposures observed during convulsions in repeat-dose toxicology studies. Margins to estimated efficacious doses were also considered. To investigate potential refinements, a high PTZ dose (80 mg/kg, subcutaneously) was compared to two lower doses (40 and 60 mg/kg), and a range of doses of theophylline was orally administered as positive control. The PTZ-induced proconvulsion assay proved to be a good predictor of convulsions in toxicology studies. In the refinement study, theophylline potentiated PTZ-induced seizures over all doses tested. At 60 mg/kg PTZ, the proconvulsant dose-dependency of theophylline was best observed. At both 40 and 60 mg/kg PTZ, mortality in control animals was significantly reduced. Risk assessment at an early stage of drug development supports candidate selection and, along that approach, the PTZ proconvulsion assay was proven to be a good predictor of convulsions in subsequent toxicology studies. It was also demonstrated that a relatively lower PTZ dose (60 mg/kg) improved the dose-response-curve of the positive control tested, decreased mortality overall and, therefore, contributes to refining this standard procedure for CNS safety evaluation.


["En face" optical coherence tomography for multiple evanescent white dot syndrome].
Multiple evanescent white dot syndrome (MEWDS) is a rare, usually unilateral, retinal disease associated with transient loss of vision. Its pathogenesis remains elusive. The purpose of this study was to determine the spatial location of the lesions in the neurosensory retina of a patient with MEWDS, using a new technology, i.e. "en face" optical coherence tomography ("en face" OCT). A 21-year-old woman presenting with bilateral MEWDS underwent Cirrus(®) OCT with advanced "en face" reconstructions of the various retinal layers and inner choroid, fluorescein angiography, and infracyanine green angiography (ICGA). During the acute stage of MEWDS, advanced "en face" visualization mode of the IS/OS photoreceptor junction and the inner choroid showed areas of strong signal attenuation, forming a spot pattern identical to that of the hypofluorescent IGCA dots. One month later, visual acuity returned to 20/25 in both eyes and the reflectivity map of the IS/OS junction and inner choroid displayed no areas of signal attenuation. "En face" OCT is a new, noninvasive technology, capable of visualizing specific attenuation of the IS/OS junction in MEWDS, which form a spot pattern identical to those revealed by ICGA.


The occurrence of vasculitis in perianeurysmal fibrosis.
The histological findings of retroperitoneal fibrosis in 17 operated patients are described. Of these patients 6 showed a simultaneous aneurysm of the abdominal aorta verified either by computerized tomography, ultrasound, arteriography or during an operation. Of the patients 14 were operated on primarily because of ureteral obstruction, 2 because of aortic aneurysm and 1 because of rupture of the abdominal aorta. Advanced fibrosis with varying amounts of inflammation was detected in all 17 patients. The same histological pattern was present in patients with aneurysm of the abdominal aorta and in those without aneurysm. Accompanying vasculitis with destruction of the vascular wall was noted in 8 patients, including 6 with an abdominal aortic aneurysm. In 3 patients who underwent aneurysm resection as well as in 1 patient with aortic rupture the process extended into the aortic wall. The only patient with vasculitis and no aortic process suffers from severe rheumatoid arthritis. On the basis of the different histological findings we suggest that retroperitoneal fibrosis with vasculitis and aneurysm may represent a distinct pathological entity.


In vivo complement activation by polyanion--polycation complexes: evidence that C5a is generated intravascularly during heparin--protamine interaction.
In vitro studies have established the complement-activating potency of polyanion-polycation interaction. By transferring the heparin-protamine model to an animal (rabbit) system that picks up ongoing intravascular complement activation by documenting acute granulocytopenia due to margination, evidence that intravascular polyanion-polycation complexing leads to instantaneous activation of the C system in vivo that goes beyond C1, C4, and C2, and results in generation of biologically highly reactive products, such as C5a, is provided. Dependence of the phenomenon on an activable complement system is documented by its complete abolishment when animals were complement depleted by cobra venom factor administration. Therefore, activation of the complement system may play a causative role for untoward effects following heparin neutralization by protamine under clinical conditions. Furthermore, these studies suggest an in vivo role of nonimmune generation of inflammatory mediators by interaction of naturally occurring polyions.


[Insulinoma presenting as pseudo-drug-resistant focal epilepsy].
We describe a case of insulinoma presenting as a refractory frontal lobe epilepsy in a 44-year-old man with a history of severe head trauma. Despite escalating treatment, his seizure frequency worsened during the previous year. He also developed psychomotor slowing and sweating occurring early in the morning. He gained weight. Insulinoma was diagnosed based on the presence of episodes of hypoglycemia, abnormal insulin/blood glucose ratio and a tumor in the pancreas (echo-ultrasound). After partial pancreatectomy, the patient became seizure free and anti-epileptic drugs were progressively stopped, with a follow-up of five years. Insulinoma should be considered in patients with no reason for having drug-resistant epilepsy, especially when seizures occur early in the morning or when episodes of neuropsychiatric symptoms with sweating are present.


Enzymes of the human intestinal brush border membrane. Identification after gel electrophoretic separation.
The postition of a number of human intestine brush border membrane enzyme activities in polyacrylamide gels after electrophoresis has been determined. These activities are, in order from the origin, maltase/glucoamylase, lactase/phlorizin hydrolase, maltase/sucrase/isomaltase, enteropeptidase, trehalase and gamma-glutamyl-transferase. Leucylnaphthylamide hydrolyzing activity was inactivated by sodium dodecylsulfate and its position was not determined. The positions of the activities have been correlated with the positions of protein bands previously determined. One such band situated between enteropeptidase and alkaline phosphatase has not been identified.


Utility of intrathecal baclofen pump in primary lateral sclerosis.
Primary lateral sclerosis is a disorder categorized by insidious onset of progressive upper motor neuron dysfunction without lower motor neuron involvement. PLS often presents with gradual-onset, progressive lower extremity stiffness and pain due to muscle spasticity. Intrathecal Baclofen pumps (ITB) have been used to effectively treat spasticity in several neurologic conditions including MS and spinal cord injury. This study aimed at reviewing a cohort of PLS patients with spasticity requiring ITB to assess the clinical course, benefits, and complications in these patients. A series of 5 patients were identified who were diagnosed with PLS and received ITB as treatment for spasticity. The average age of the patients at the time of ITB insertion was 56.4 years. The average length of treatment was 10.4 years with a range of 4-15 years. All patients reported improvement in spasticity as measured by clinical examinations and Ashworth scores; 1/5 had complications with the pump related to migration of catheter. No patients required permanent removal of the ITB. ITB is a safe and effective treatment for spasticity in PLS and should be considered in other patients.


Hypnosis Versus Placebo During Atrial Flutter Ablation: The PAINLESS Study: A Randomized Controlled Trial.
The aim of this study was to assess the superiority of hypnosis versus placebo on pain perception and morphine consumption during typical atrial flutter (AFL) ablation. AFL ablation commonly requires intravenous opioid for analgesia, which can be associated with adverse outcomes. Hypnosis is an alternative technique with rising interest, but robust data in electrophysiological procedures are lacking. This single center, randomized controlled trial compared hypnosis and placebo during AFl ablation. In addition to the randomized intervention, all patients were treated according to the institution's standard of care analgesia protocol (administration of 1 mg of intravenous morphine in case of self-reported pain ≥5 on an 11-point numeric rating scale or on demand). The primary endpoint was perceived pain quantified by patients using a visual analog scale. Between October 2017 and September 2019, 113 patients (mean age 70 ± 12 years, 21% women) were randomized to hypnosis (n = 56) or placebo (n = 57). Mean pain score was 4.0 ± 2.2 in the hypnosis group versus 5.5 ± 1.8 in the placebo group (p < 0.001). Pain perception, assessed every 5 min during the whole procedure, was consistently lower in the hypnosis group. Patients' sedation scores were also better in the hypnosis group than in the placebo group (8.3 ± 2.2 vs. 5.4 ± 2.5; p < 0.001). Finally, morphine requirements were significantly lower in the hypnosis group (1.3 ± 1.3 mg) compared with the placebo group (3.6 ± 1.8 mg; p < 0.001). In this first randomized trial, hypnosis during AFL ablation was superior to placebo for alleviating pain and reducing morphine consumption.


Cultural competence among pre-graduate nursing students, new graduate nurses, nurse mentors, and registered nurses: A comparative descriptive study.
Achieving and improving cultural competence in nursing is an ongoing process, beginning in the student period and continuing through the professional career. The present study aims to compare pre-graduate students, newly graduated nurses, registered nurses, and nurse mentors in Taiwan in terms of their respective levels of cultural competence, and to determine associated influencing factors. A comparative cross-sectional study. Three universities and three hospitals (one regional hospital and two teaching hospitals) in Taiwan. A total of 756 nurses/students (103 pre-graduate nurses, 321 newly graduated nurses, 101 registered nurses, and 231 nurse mentors). The Cultural Competence Scale for Pre-Graduated Students to Licensed Professionals was used to measure the cultural competence level. One-way analysis of variance and hierarchical regression analysis were used for statistical analysis. For overall cultural competence and the subscales of knowledge, awareness, and skills, the pre-graduate students scored lower than the other three groups. Experience of caring for patients from diverse cultures and countries significantly influenced the cultural competence of all four groups. Ability to speak fluent English and receiving cultural competence education during nursing education only significantly influenced the cultural competence of the pre-graduate and new graduate nurses. Current job position and primary practice setting significantly influenced the cultural competence of the registered nurses and nurse mentors. Pre-graduate students, newly graduated nurses, registered nurses, and nurse mentors have differing levels of cultural competence and differing influencing factors. Cultural competence education that accords with the influencing factors for each nursing position would continuously cultivate nursing staff's cultural competence.


Ultrasound-assisted extraction of phenolic compounds from strawberries prior to liquid chromatographic separation and photodiode array ultraviolet detection.
Ultrasound-assisted extraction was used for the determination of phenolic compounds present in strawberries. The optimization study of the extraction was carried out using spiked samples (100 mg/kg). The sample immersed in an aqueous solution containing hydrochloric acid (0.4 M) was sonicated for 2 min (duty cycle 0.2 s, output amplitude 20% of the nominal amplitude of the converter, applied power 100 W with the probe placed 1cm from the bottom of the water bath and 5 cm from the walls of the precipitate glass). Subsequent separation was carried out by liquid chromatography (LC) with photodiode array UV detection. Calibration curves using the standard addition in green strawberries typically gave linear dynamic ranges of 2-300 mg/l for all analytes; R(2) values exceeded 0.996 in all cases. The method was applied to two types of strawberries to demonstrate the applicability of the proposed method, which is much faster and produces less analyte degradation than methods as solid-liquid, subcritical water and microwave-assisted extraction.


Study of the revisited, revised, and expanded Silva pattern system for Chinese endocervical adenocarcinoma patients.
As a new pattern-based classification, the Silva pattern system has been recently developed to evaluate invasive lymph node metastasis and the prognosis of endocervical adenocarcinoma (EAC). Therefore, our study was conducted to explore the reproducibility and prognostic significance of this system in a multi-institutional Chinese cohort, with the goal of revising and expanding its application. The clinicopathological data of 191 EAC patients from 3 medical centers were examined in a retrospective manner. The Silva pattern system demonstrated great prognostic value, significance in guiding treatment selection, and acceptable reproducibility in 191 patients that included additional histologic variants and 124 usual-type EAC patients. Collectively, compared with usual-type EAC, the whole cohort demonstrated similar statistical significance for relevant clinicopathological parameters, such as International Federation of Gynecology and Obstetrics stage (R = 0.612 versus R = 0.600), tumor thickness (P < .0001 versus P < .0001), lymphovascular invasion (P < .0001 versus P < .0001), lymph node metastasis (P = .033 versus P = .018), perineural invasion (P = .003 versus P = .001), and recurrence-free survival (P = .047 versus P = .020). Moreover, perineural invasion was significantly correlated (P = .001) with the Silva pattern system and appeared in most Silva C tumors. In conclusion, the Silva pattern system is consistent with the biological behavior of EAC and has acceptable reproducibility. Compared with International Federation of Gynecology and Obstetrics stage, it can predict patient prognosis before surgery. We suggest revising the Silva C criteria by adding perineural invasion as a factor and propose expanding the Silva pattern system to include more histologic variants. It seems that the Silva pattern system can be applied in routine clinical practice to guide EAC therapeutic strategies in the near future.


A Programmable Dual-Regime Spray for Large-Scale and Custom-Designed Electronic Textiles.
Increasing demand for wearable healthcare synergistically advances the field of electronic textiles, or e-textiles, allowing for ambulatory monitoring of vital health signals. Despite great promise, the pragmatic deployment of e-textiles in clinical practice remains challenged due to the lack of a method in producing custom-designed e-textiles at high spatial resolution across a large area. To this end, a programmable dual-regime spray that enables the direct custom writing of functional nanoparticles into arbitrary fabrics at sub-millimeter resolution over meter scale is employed. The resulting e-textiles retain the intrinsic fabric properties in terms of mechanical flexibility, water-vapor permeability, and comfort against multiple uses and laundry cycles. The e-textiles tightly fit various body sizes and shapes to support the high-fidelity recording of physiological and electrophysiological signals on the skin under ambulatory conditions. Pilot field tests in a remote health-monitoring setting with a large animal, such as a horse, demonstrate the scalability and utility of the e-textiles beyond conventional devices. This approach will be suitable for the rapid prototyping of custom e-textiles tailored to meet various clinical needs.


Fe (III) complexes of a bis-benzimidazolyl diamide ligand: spectral and catalytic studies.
A new tetradentate bis benzimidaozlyl diamide ligand N,N'-Bis (benzimidazol-2-yl-methyl)-hexane-1,6-dicarboxamide (GBSA) has been synthesized and utilized to prepare new Fe(III) complexes with exogenous anionic ligand X=Cl(-) and NO(3)(-). Isomer shift values are in the range found for Iron in the +3 oxidation state while Quadrupole Splitting indicates large distortion from a six coordinate geometry, a finding supported by low temperature EPR work. The E(1/2) values are found to be quite cathodic indicating stability of the Iron (III) complexes. The oxidation of alcohols was investigated using [Fe(GBSA)Cl(3)] as the catalyst with TBHP as an alternate source of oxygen. The respective carbonyl products have been isolated and characterized by (1)H NMR, electronic spectroscopy, mass and IR spectral studies.


Cell-based immobilization strategy for sensitive piezoelectric immunoassay of total prostate specific antigen.
A novel yeast cell-based strategy for the immobilization of antibodies using an amine-terminated self-assembly film has been proposed. A quartz crystal microbalance sensor was according fabricated by coupling with anti-prostate specific antigen (anti-PSA) for PSA immunoassay. The crystal was modified with cysteamine to deposit yeast cells, on which anti-PSA antibodies were immobilized. The surface topologies of the as-prepared crystals were characterized by use of scanning electron microscopy. In contrast to the traditional glutaraldehyde (GLU) approach, the yeast cells could allow antibody molecules bound with higher bioactivity and achieve better immunoreaction capability. Results indicate that immunoassay prepared using the developed yeast cell-binding procedure exhibits increased analytical performance compared with that produced using the GLU cross-linking procedure. A PSA serum concentration in the range of 5.0-604.0 ng ml(-1) can be determined by this new system.


Intravenous isosorbide dinitrate during open-heart surgery and its role in the treatment of right-sided congestive heart failure.
Recent awareness of the importance of the functional integrity of the right ventricle and the effect of raised pulmonary vascular resistance on cardiac output after cardiopulmonary bypass has focused attention on means of protecting right ventricular myocardium and reducing right ventricular afterload during open-heart surgery. A study of the acute effects of bolus intravenous isosorbide dinitrate (ISDN) has shown that after cardiopulmonary bypass, bolus intravenous ISDN produced highly significant (p less than 0.001) decreases in mean pulmonary arterial pressure (13%), pulmonary vascular resistance (23%) and the ratio of pulmonary to systemic vascular resistance (20%), indicating that active pulmonary vasodilation had occurred in the absence of other hemodynamic changes. The results suggest that possibly the acute effect of low-dose ISDN after cardiopulmonary bypass is predominantly exerted on the right ventricular afterload if systemic arterial pressure is not elevated. Two different clinical situations are described in which intravenous ISDN proved beneficial, one being acute pulmonary hypertension after protamine sulphate and the second being acute right-sided congestive heart failure with systemic hypotension unresponsive to conventional therapeutic measures. Thus, ISDN may prove a useful agent for alleviating right ventricular dysfunction at a time of not infrequent cardiovascular instability, the period after bypass.


Apparent prevalence of Mycoplasma wenyonii, Candidatus Mycoplasma haemobos, and bovine leukemia virus in Wisconsin and Michigan dairy cattle herds.
Mycoplasma wenyonii (formerly Eperythrozoon wenyonii) is a hemotrophic, epicellular bacterial parasite of cattle that has been associated with clinical disorders, including hemolytic anemia, decreased milk yield, and peripheral edema. Mycoplasma wenyonii and a related organism, Candidatus Mycoplasma haemobos, have been detected in both ill and apparently healthy cattle, but little is known about their prevalence in US dairy cattle. The objective of this prospective, cross-sectional study was to determine herd-level apparent prevalence of M. wenyonii and C. M. haemobos in dairy cattle located in Wisconsin and Michigan compared with seroprevalence of bovine leukemia virus (BLV) in the same herds. In summer 2018, researchers collected blood samples from 30 lactating cows per herd from randomly recruited farms in selected dairy-intensive counties in each state. During the farm visit, a brief survey was used to collect herd management information. Detection of M. wenyonii and C. M. haemobos were based on PCR testing, and ELISA was used to test for antibodies to BLV. Blood samples were collected from lactating cows located in 64 Wisconsin herds (n = 1,930 samples) and 18 Michigan herds (n = 591 samples). Herd-level apparent prevalence was 100% for both M. wenyonii and C. M. haemobos. Herd-level seroprevalence for BLV was 83 and 100% for Wisconsin and Michigan herds, respectively. Estimated within-herd apparent prevalence of M. wenyonii was 71.7% ± 1.0% (ranging from 23.3 to 93.5%) and for C. M. haemobos was 77.3% ± 1.0% (ranging from 16.7 to 100%). Within-herd prevalence of BLV positive samples was 39.8% ± 1.0% and ranged from 0 to 86.7%. About 22% of cows were concurrently positive for all 3 organisms. Parity and stage of lactation were recorded for 2,317 cows. Prevalence of positive cows for parity groups 1, 2, and ≥3 were 72.0, 73.8, and 67.7% for M. wenyonii; 80.9, 76.8, and 74.9% for C. M. haemobos; and 25.3, 39.7, and 55.5% for BLV, respectively. None or only minor differences in apparent prevalence were observed based on stage of lactation. This is the first report of the prevalence of hemotrophic mycoplasmas in Wisconsin and Michigan dairy herds and indicates that infection with these organisms is endemic. The impact of infection on cattle health and productivity remains unknown, and risk factors associated with infection warrant further study.


The debate about over-the-counter emergency contraceptive pills.
Many prescription drugs have been converted to over-the-counter (OTC) status in recent years. Another drug that has been proposed for OTC status is a levonorgestrel-only emergency contraceptive pill. The debate surrounding OTC access to emergency contraceptive pills echoes issues encountered in previous reclassification processes and raises new challenges. This article discusses the emergency contraceptive pill, the evolution of its access options, and the context and implications of changing its status from a prescription to an OTC medication.


Silicone and rheumatic diseases.
Silicone generally has been regarded as a biologically inert material. However, recent reports suggest that inflammatory responses to silicone occur. There is some experimental and clinical evidence of a direct inflammatory response to the presence of liquid or particulate silicone. These include granulomatous skin reaction to injected silicone, synovitis around silicone prosthetic joints, and lymphadenopathy proximal to silicone prostheses. There are case reports of systemic rheumatic disease following silicone prostheses, but no definitive proof of a direct relationship between silicone prostheses and systemic disease. The clinical features of the reported cases following breast augmentation include breast tenderness, axillary adenopathy, sclerodermatous skin changes, arthritis, Raynaud's phenomenon, rheumatoid factors, and ANAs. Prior epidemiologic evidence and the number and consistency of our own and others' clinical findings suggest that silicone may indeed be associated with inflammatory processes and rheumatic diseases.


A new Spanish family with Hb Louisville.
The clinical, hematological, and biochemical characteristics of a new family with heterozygous hemoglobin (Hb) Louisville are described. The family showed a decrease in both oxygen affinity and cooperativity with the normal Bohr effect. This family has the greatest number of affected members reported to date. Among the descendants, two first cousins (III-10 and III-11), both of whom are affected by the heterozygous trait of Hb Louisville, had had three abortions of undetermined causes.


Evaluation of insulin sensitivity in patients with Klinefelter's syndrome: a hyperinsulinemic euglycemic clamp study.
Patients with Klinefelter's syndrome have a higher incidence of diabetes mellitus and the percentage of insulin resistance was reported to be high in these patients. However, little is known about the insulin sensitivity assessed by the hyperinsulinemic euglycemic clamp in these patients. In the present study, subjects included 13 newly diagnosed patients with Klinefelter's syndrome, and 9 age- and body mass index-matched healthy males. The hyperinsulinemic euglycemic clamp was performed in all patients and controls. Insulin resistance was present in five (38.5%) patients with Klinefelter's syndrome. Compared with control subjects, patients with Klinefelter's syndrome had elevated plasma concentrations of fasting insulin, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin, whereas they had reduced plasma free testosterone and total testosterone concentrations. The multivariate linear regression analysis showed that fasting glucose, fasting insulin, free testosterone, and total testosterone were independently associated with M-value. In conclusion, the present study by using hyperinsulinemic euglycemic clamp indicates the high prevalence of insulin resistance in Klinefelter's syndrome patients. However, these patients did not have reduced mean M-values compared with the controls, although their plasma insulin levels were significantly elevated. It is possible that hyperinsulinemia may be the primary metabolic abnormality rather than insulin resistance.


Metastatic spinal cord compression in non-small cell lung cancer patients. Prognostic factors in a series of 356 patients.
Patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC) have an unfavorable prognosis compared to most other MSCC patients. This study was performed to identify prognostic factors for functional outcome and survival in these patients after radiotherapy (RT) alone. Data of 356 patients irradiated for MSCC from NSCLC were retrospectively analyzed. Ten potential prognostic factors were investigated including age, gender, Eastern cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to RT of MSCC, time developing motor deficits before RT, and the radiation schedule. On multivariate analysis, better functional outcome was associated with pre-RT ambulatory status (estimate: - 0.84, p = 0.022), no visceral metastases (estimate: - 1.15, p < 0.001), interval from cancer diagnosis to RT of > 15 months (estimate: + 0.48, p = 0.019), and slower (> 7 days) development of motor deficits (estimate: + 1.56, p < 0.001). On multivariate analysis, improved survival was significantly associated with female gender (risk ratio (RR) 1.32, p = 0.043), ECOG-PS 1-2 (RR 1.45, p = 0.034), pre-RT ambulatory status (RR 0.58, p < 0.001), no other bone metastases (RR 1.38, p = 0.010), no visceral metastases (RR 2.87, p < 0.001), interval from cancer diagnosis to RT of > 15 months (RR 0.84, p = 0.035), and slower (> 7 days) development of motor deficits (RR 0.78, p < 0.001). This study identified additional independent prognostic factors for outcomes after radiotherapy of MSCC from NSCLC. These prognostic factors can be used for stratification in future trials and can help develop prognostic scores for MSCC from NSCLC.


A prospective comparative study of two regimens of diphenylcyclopropenone (DPCP) in the treatment of alopecia areata.
Alopecia areata (AA) is a chronic disorder and the best treatment regimen for it is unknown. Currently, one of the best documented treatment modalities for AA is topical immunotherapy. To evaluate the safety and efficacy of a novel method (multi-concentration patch test) versus standard protocol for topical immunotherapy. A prospective randomized clinical trial was conducted on 30 patients with Alopecia areata, half of them received DPCP with a novel method using multi-concentration patch test to determine the optimal initiating concentration of DPCP (case group) and the other half experienced immunotherapy according to the standard protocol (control group). Percentage of hair regrowth after 6 months of treatment and the incidence of drug-related adverse effects were evaluated and compared between the two groups. (IRCT registration code: IRCT20141209020250N5). Absolute and relative hair regrowth percentages were reported 25% and 41.49% in case group and 8.2% and 14.21% in control group respectively. Considerable response (more than 75% hair regrowth) was observed in 4 (26.6%) patients in case and 1 (6.6%) patient in control group. The clinical response was initiated about 7 weeks sooner in case compared to the control group (14 versus 7.38 weeks, P: 0.001). Overall, clinical response was higher in patients received new protocol, compared to control group. Moreover, patients who experienced new protocol had a higher level of treatment satisfaction in comparison with patients having standard protocol (P: 0.012). This study revealed the effectiveness and safety of the novel multi-concentration patch test DPCP therapy for AA and its priority to conventional method, at least in terms of shortened duration of DPCP immunotherapy.


Case report: systolic murmur associated with pulmonary embolism.
This case study's novelty lies in the potential to link a new sign in pulmonary embolism diagnosis which does not increase cost but could lead to more rapid treatment. Early intervention in these cases is vital to decrease morbidity and mortality. An otherwise healthy 20-year-old female patient presents to the emergency department for evaluation of a syncopal episode which occurred just prior to arriving to the emergency department. Patient also complains of ongoing shortness of breath while performing activities of daily living for 3 weeks. In this patient with no known valvular disease, physical exam revealed a systolic murmur heard only posteriorly. Subsequent emergency department workup revealed bilateral massive pulmonary emboli. A new flow murmur heard in atypical locations could be an early sign to aid in the detection and diagnosis of pulmonary embolism. This is especially important in rural community hospitals with limited access to advanced imaging modalities.


Sediment and residual feed from aquaculture water bodies threaten aquatic environmental ecosystem: Interactions among algae, heavy metals, and nutrients.
The effect of sediment and residual fish feed on aquaculture water bodies has gained increasing attention to alleviate the eutrophication and heavy metals enrichment induced by aquaculture. Thus, this study intended to reveal the possible interactions among nutrients, heavy metals, and Chlorella vulgaris (C. vulgaris) in aquaculture water bodies containing fish feed and sediment. The analyses showed that consistent with the composition of heavy metals in fish feed, manganese (Mn) and zinc (Zn) accounted for the highest proportions (68-78%) of heavy metals in sediment. Meanwhile, sediment in the centre of aquaculture water bodies (S2) contained more heavy metals than those in the perimeter (S1), but the released concentrations and rates (Rrelease) of heavy metals from S1 were higher than those from S2. Moreover, the biomass, growth rate, specific growth rate, and nitrogen and carbon fixation rate of C. vulgaris increased with adding fish feed, whereas superoxide dismutase (SOD) and malondialdehyde (MDA) decreased. In addition, with C. vulgaris, influenced by the release process from sediment and the uptake by C. vulgaris, the concentration and Rrelease of Mn, Pb, Cu, Mn, Cr and Cd from sediments coexisting with fish feed in water first increased and then decreased in general. The C. vulgaris biomass was significantly negatively related to Mn, Pb, Cu, Ni, Cr, and Cd and PO43-P (P < 0.05), which was caused by the uptake of C. vulgaris and indicated that C. vulgaris biomass is easily affected by these factors. Accordingly, the input of residual fish feed and sediment should be controlled.


Sources and nature of variation in DNA analysis of follicular thyroid adenoma.
We investigated the sources and nature of variation that may occur in the DNA analysis of thyroid adenomas from cytological and histological samples. Imprints and smears gave identical results. However, the nuclear area was higher in smears where the optical density of the nuclei was lower. In measuring imprints, the interactive selection of nuclei was preferred to the automatic, because the risk of measuring nuclear fragments or undesired objects was thus avoided. The reproducibility and the variation of the DNA measurements depended on the degree of observer training in quantitative pathology, the method of field selection, and the type of instrumentation. Biological variation in the spatial distribution of nuclei with different ploidy values in some adenomas seemed to hide the influence of section thickness on measurements. Our data seem to suggest that it is best to apply a constant section thickness and 5 micron sections seem acceptable.


Simvastatin induces adverse effects on proliferation and mineralization of human primary osteoblasts.
Frequently statins were administered to reduce the LDL-concentration in circulating blood. Especially simvastatin (SV) is an often prescribed statin. Pleiotropic effects of these drugs were reported. Thus, the aim of this study was to evaluate effects of SV on osteoblastic mineralization. After informed consent primary osteoblasts were collected from tissue surplus after treatment of 14 individuals in the Department of Cranio-Maxillofacial Surgery, University Hospital Münster. The cells were passaged according to established protocols. Viability, mineralization capability and osteoblastic marker (alkaline phosphatase) were determined at day 9, 13 and 16 after adding various SV concentrations (0.05 μM, 0.1 μM, 0.5 μM, 1.0 μM). Statistical analysis was performed using the Kruskal-Wallis-test. The cell cultures showed a time and dose-dependent significantly decreased viability (p < 0.01) and a significantly increased mineralization (p < 0.01) in a late mineralization stage after adding SV. The typical alteration of the alkaline phosphatase (ALP) levels during osteogenic differentiation was not recognizable. The pleiotropic effects found for different SV concentrations were possibly originated from other mineralization pathways beside the ALP induced one. Additionally, possible alterations of protein expression levels during mineralization and investigation of possible deviating application of SV in other treatment fields can be considered after gaining a deeper insight in the affected mechanisms.


Aldicarb and carbofuran transport in a Hapludalf influenced by differential antecedent soil water content and irrigation delay.
Pesticide use in agroecosystems can adversely impact groundwater quality via chemical leaching through soils. Few studies have investigated the effects of antecedent soil water content (SWC) and timing of initial irrigation (TII) after chemical application on pesticide transport and degradation. The objectives of this study were to investigate the effects of antecedent soil water content (wet vs dry) and timing of initial irrigation (0h Delay vs 24h Delay) on aldicarb [(EZ)-2-methyl-2-(methylthio)propionaldehyde O-methylcarbamoyloxime] and carbofuran [2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate] transport and degradation parameters at a field site with Menfro silt loam (fine-silty, mixed, superactive, mesic Typic Hapludalf) soils. Aldicarb and carbofuran were applied to plots near field capacity (wet) or near permanent wilting point (dry). Half of the dry and wet plots received irrigation water immediately after chemical application and the remaining plots were irrigated after a 24h Delay. The transport and degradation parameters were estimated using the method of moments. Statistical significance determined for SWC included averages across TII levels, and significance determined for TII included averages across SWC levels. For the dry treatment, aldicarb was detected 0.10 m deeper (P<0.01) on two of the four sampling dates and carbofuran was detected at least 0.10 m deeper (P<0.05) on all of the sampling dates compared to the wet treatment. Pore water velocity was found to be higher (P<0.10) in the dry vs wet treatments on three of four dates for aldicarb and two of four dates for carbofuran. Retardation coefficients for both pesticides showed similar evidence of reduced values for the dry vs wet treatments. These results indicate deeper pesticide movement in the initially dry treatment. For aldicarb and carbofuran, estimated values of the degradation rate were approximately 40-49% lower in the initially dry plots compared to the initially wet plots, respectively. When the initial irrigation was delayed for 24h, irrespective of antecedent moisture conditions, a 30% reduction in aldicarb degradation occurred. This study illustrates the deeper transport of pesticides and their increased persistence when applied to initially dry soils.


Hypertension as a risk factor for retinal vein occlusion in menopausal women: A nationwide Korean population-based study.
Retinal vein occlusion (RVO) is an important cause of blindness. Hypertension is a well-known risk factor for RVO. Although the prevalence of hypertension increases in women after menopause, the relationship between blood pressure and RVO in women before and after menopause has not been studied in detail.We retrospectively analyzed 2,619,206 patients from the Korean National Health Insurance System database. A Cox proportional hazard regression model was used to evaluate the independent association between blood pressure and the risk of RVO development and identify differences between premenopausal and postmenopausal women.The incidence of RVO was higher among postmenopausal women than in premenopausal women. In the model adjusted for socioeconomic and clinical variables, there was an association between blood pressure and RVO development in premenopausal and postmenopausal women; however, this was stronger than premenopausal women.Both systolic and diastolic blood pressure are associated with an increased risk of RVO, and their effects are more potent in premenopausal women than postmenopausal women. Thus, comprehensive management of hypertension in premenopausal women is essential to reduce the risk of RVO.


Patient Safety Leadership WalkRounds at Partners Healthcare: learning from implementation.
Brigham and Women's Hospital (BWH) began Patient Safety Leadership WalkRounds in January 2001; its experience, along with that of three other Partner Healthcare hospitals, is reported. COLLECTING DATA ON WALKROUNDS: Data were obtained from interviews with patient safety personnel, WalkRounds scribes, and senior leaders. A total of 233 one-hour WalkRounds during 28 months yielded 1,433 comments--30% related to equipment, 13% to communications, 7% to pharmacy, and 6% to workforce. Actions occurred quickly in small hospitals. Formal processes for managing larger issues were necessary in large organizations. Implementation feasibility featured more prominently than severity in determining actions. The study generated essential guidelines for success--for example, the supporting resources must include the maintenance of effective information databases that identify actions taken, and the discussions during WalkRounds are influenced by who in leadership is participating, their ability to quietly listen, and whether they have clinical or nonclinical backgrounds. WalkRounds appears to be an effective tool for engaging leadership, identifying safety issues, and supporting a culture of safety.


The Influence of Greenspace Exposure on Affect in People With and Those Without Schizophrenia: Exploratory Study.
Exposure to natural vegetation (ie, "greenspace") is related to beneficial outcomes, including higher positive and lower negative affect, in individuals with and those without mental health concerns. Researchers have yet to examine dynamic associations between greenspace exposure and affect within individuals over time. Smartphone-based ecological momentary assessment (EMA) and passive sensors (eg, GPS, microphone) allow for frequent sampling of data that may reveal potential moment-to-moment mechanisms through which greenspace exposure impacts mental health. In this study, we examined associations between greenspace exposure and affect (both self-reported and inferred through speech) in people with and those without schizophrenia spectrum disorder (SSD) at the daily level using smartphones. Twenty people with SSD and 14 healthy controls reported on their current affect 3 times per day over 7 days using smartphone-based EMA. Affect expressed through speech was labeled from ambient audio data collected via the phone's microphone using Linguistic Inquiry and Word Count (LIWC). Greenspace exposure, defined as the normalized difference vegetation index (NDVI), was quantified based on continuous geo-location data collected from the phone's GPS. Overall, people with SSD used significantly more positive affect words (P=.04) and fewer anger words (P=.04) than controls. Groups did not significantly differ in mean EMA-reported positive or negative affect, LIWC total word count, or NDVI exposure. Greater greenspace exposure showed small to moderate associations with lower EMA-reported negative affect across groups. In controls, greenspace exposure on a given day was associated with significantly lower EMA-reported anxiety on that day (b=-0.40, P=.03, 95% CI -0.76 to -0.04) but significantly higher use of negative affect words (b=0.66, P<.001, 95% CI 0.29-1.04). There were no significant associations between greenspace exposure and affect at the daily level among participants with SSD. Our findings speak to the utility of passive and active smartphone assessments for identifying potential mechanisms through which greenspace exposure influences mental health. We identified preliminary evidence that greenspace exposure could be associated with improved mental health by reducing experiences of negative affect. Future directions will focus on furthering our understanding of the relationship between greenspace exposure and affect on individuals with and those without SSD.


Teratoma of the tongue in neonates: report of a case and review of the literature.
A female newborn presented with a huge mass protruding from the mouth. She had no respiratory distress but had difficulty swallowing. The mass originated from the tongue and was completely extirpated on the day of birth. The histologic diagnosis was mature teratoma. Three days later, another mass measuring 1 cm in diameter was found attached to the upper pharyngeal wall and was also completely extirpated 20 days after birth. The histologic diagnosis was also mature teratoma. The infant had a complete cleft palate, but no other malformation was found. Two years after surgery there is no sign of recurrence.


Stigma management during reintegration of older incarcerated adults with mental health issues: A qualitative analysis.
The number of older prisoners with mental health issues released from prisons and forensic psychiatric institutions is rising. Their successful integration is important due to its implications for the public's safety and the individual's health and well-being. However, reintegration efforts are hampered due to the double stigma attached to 'mental illness' and 'incarceration history'. To alleviate the burden of such stigma, affected persons and their social networks employ stigma management strategies. This study sought to investigate the stigma management strategies of mental health professionals supporting older incarcerated adults with mental health issues in their reintegration process. Semi-structured interviews with 63 mental health professionals from Canada and Switzerland were carried out as part of the overall project. To address the reintegration topic, data from 18 interviews were used. Data analysis followed the thematic analysis approach. Mental health professionals emphasized the double stigmatization of their patients which impaired their quest for housing. Lengthy searches for placement frequently resulted in patients' unnecessary long stays in forensic programs. Nevertheless, participants outlined that they were at times successful in finding appropriate housing for their patients due to the use of certain stigma management strategies. They stated that they, first, established initial contacts with outside institutions, second, educated them about stigmatizing labels and, third, provided ongoing collaboration with public institutions. Incarcerated persons with mental health issues face double stigmatization that affects their reentry process. Our findings are interesting as they illustrate ways in which stigma can be reduced, and how the reentry process can be streamlined. Future research should include the perspectives of incarcerated adults with mental health issues to shed more light on the various options that they seek for successful reintegration after imprisonment.


Temporal profile of adverse drug reactions and associated clinical factors: a prospective observational study in a neonatal intensive care unit.
Although adverse drug reactions (ADRs) are quite common in hospitalised neonates, pharmacovigilance activities in this public are still incipient. This study aims to characterise ADRs in neonates in a neonatal intensive care unit (NICU), identifying causative drugs, temporal profile and associated factors. Prospective observational study. NICU of a public maternity hospital in Natal/Brazil. All neonates admitted to the NICU for more than 24 hours and using at least one medication were followed up during the time of hospitalisation. Incidence rate and risk factors for ADRs. The ADRs were detected by an active search in electronic medical records and analysis of spontaneous reports in the hospital pharmacovigilance system. Six hundred neonates were included in the study, where 118 neonates had a total of 186 ADRs. The prevalence of ADRs at the NICU was 19.7% (95% CI 16.7% to 23.0%). The most common ADRs were tachycardia (30.6%), polyuria (9.1%) and hypokalaemia (8.6%). Tachycardia (peak incidence rate: 57.1 ADR/1000 neonates) and hyperthermia (19.1 ADR/1000 neonates) predominated during the first 5 days of hospitalisation. The incidence rate of polyuria and hypokalaemia increased markedly after the 20th day, with both reaching a peak of 120.0 ADR/1000 neonates. Longer hospitalisation time (OR 0.018, 95% CI 0.007 to 0.029; p<0.01) and number of prescribed drugs (OR 0.127, 95% CI 0.075 to 0.178; p<0.01) were factors associated with ADRs. ADRs are very common in NICU, with tachycardia and hyperthermia predominant in the first week of hospitalisation and polyuria and hypokalaemia from the third week onwards.


Pulmonary gas exchange and ventilatory responses to brief intense intermittent exercise in young trained and untrained adults.
To investigate pulmonary gas exchange and ventilatory responses to brief intense intermittent exercise and to study the effects of physical fitness on these responses, nine trained and nine untrained healthy male subjects aged 18-33 years performed the force-velocity (F-v) exercise test. This test consisted of 6-s sprints against increasing braking forces (F) separated by 5-min recovery periods. Oxygen uptake (VO2), carbon dioxide output (VCO2), and ventilation (VE) were continuously measured during the test and the magnitudes of their responses to the sprints were then calculated. For all subjects VO2 increased rapidly after beginning the sprints, and the peaks of the responses (F = 13.4; P < 0.001), end of recovery values (F = 6.5; P < 0.01), and VO2 magnitudes of response (F = 12.4; P < 0.001) rose significantly with the repetition of the sprints. The VO2 magnitudes of response correlated with the corresponding sprint power outputs (r = 0.55; P < 0.001) and with the sprint repetitions (r = 0.51, P < 0.001). The VCO2 (F = 7.1; P < 0.01) and VE (F = 5.0; P < 0.01) peaks of response increased with the initial load incrementation, then stabilized when the subjects attained peak power output. End of recovery VCO2 (F = 18.0; P < 0.001) and VE (F = 14.1; P < 0.001) values rose with increasing F. The F-v peak VO2, VCO2, VE, tidal volume and respiratory frequency responses attained 53%, 40%, 44%, 66%, and 82% of the peak values measured at exhaustion of maximal graded exercise, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)


Tailoring the Synergistic Bronsted-Lewis acidic effects in Heteropolyacid catalysts: Applied in Esterification and Transesterification Reactions.
In order to investigate the influences of Lewis metals on acidic properties and catalytic activities, a series of Keggin heteropolyacid (HPA) catalysts, HnPW11MO39 (M = Ti(IV), Cu(II), Al(III), Sn(IV), Fe(III), Cr(III), Zr(IV) and Zn(II); for Ti and Zr, the number of oxygen is 40), were prepared and applied in the esterification and transesterification reactions. Only those cations with moderate Lewis acidity had a higher impact. Ti Substituted HPA, H5PW11TiO40, posse lower acid content compared with Ti(x)H(3-4x)PW12O40 (Ti partial exchanged protons in saturated H3PW12O40), which demonstrated that the Lewis metal as an addenda atom (H5PW11TiO40) was less efficient than those as counter cations (Ti(x)H(3-4x)PW12O40). On the other hand, the highest conversion reached 92.2% in transesterification and 97.4% in esterification. Meanwhile, a good result was achieved by H5PW11TiO40 in which the total selectivity of DAG and TGA was 96.7%. In addition, calcination treatment to H5PW11TiO40 make it insoluble in water which resulted in a heterogeneous catalyst feasible for reuse.


Therapeutic efficacy of the HMG-CoA-reductase inhibitor pravastatin in hyperlipoproteinaemia type II.
The efficacy and safety of the HMG-CoA-reductase inhibitor pravastatin was assessed in a double-blind, placebo controlled study. Thirty patients (51 y) with hyperlipoproteinaemia Type IIa (N = 22) or IIb (N = 8) received for 16 weeks either pravastatin 5 mg b.d. for 8 weeks followed by 10 mg b.d. for 8 weeks (Group I), or 10 mg b.d. for 8 weeks followed by 20 mg b.d. to 16 weeks (Group II), or placebo (Group III). In Groups I and II, mean serum total cholesterol was reduced by -26% and -22%, respectively; low-density lipoprotein (LDL)-cholesterol decreased by -28% and -27%, apolipoprotein B by -25% and -23%, and apolipoprotein E by -9% (NS) and -16%, respectively. Serum high-density lipoprotein (HDL)-cholesterol was increased by 11% in Group II, and so the total/HDL-cholesterol ratio fell by 33%. Apoprotein A1 and A2 were not significantly changed. No serious clinical and laboratory abnormalities were observed. The data suggest considerable therapeutic efficacy of pravastatin in the treatment of Type II hyperlipoproteinaemia.


Perioperative Neurofilament Light Plasma Concentrations and Cognition before and after Cardiac Surgery: A Prospective Nested Cohort Study.
Neurofilament light is a marker of neuronal injury and can be measured in blood. Postoperative increases in neurofilament light have been associated with delirium after noncardiac surgery. However, few studies have examined the association of neurofilament light changes with postdischarge cognition in cardiac surgery patients, who are at highest risk for neuronal injury and cognitive decline. The authors hypothesized that increased neurofilament light (both baseline and change) would be associated with worse neuropsychological status up to 1 yr after cardiac surgery. This observational study was nested in a trial of cardiac surgery patients, in which blood pressure during bypass was targeted using cerebral autoregulation monitoring. Plasma concentrations of neurofilament light were measured at baseline and postoperative day 1. Neuropsychological testing was performed at baseline, 1 month after surgery, and 1 yr after surgery. Primary outcomes were baseline and change from baseline in a composite z-score of all cognitive tests. Among 167 patients, cognitive outcomes were available in 80% (134 of 167) and 61% (102 of 167) at 1 month and 1 yr after surgery, respectively. The median baseline concentration of neurofilament light was 18.2 pg/ml (interquartile range, 13.4 to 28.1), and on postoperative day 1 was 28.5 pg/ml (interquartile range, 19.3 to 45.0). Higher baseline log neurofilament light was associated with worse baseline cognitive z-score (adjusted slope, -0.60; 95% CI, -0.90 to -0.30; P < 0.001), no change in z-score from baseline to 1 month (0.11; 95% CI, -0.19 to 0.41; P = 0.475), and improvement in z-score from baseline to 1 yr (0.56; 95% CI, 0.31 to 0.81; P < 0.001). Whereas some patients had an improvement in cognition at 1 yr and others a decline, an increase in neurofilament light from baseline to postoperative day 1 was associated with a greater decline in cognition at 1 yr. Higher baseline neurofilament light concentration was associated with worse baseline cognition but improvement in cognition at 1 yr. A postoperative increase in neurofilament light was associated with a greater cognitive decline at 1 yr.


The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives.
PALB2 has been recently identified as breast cancer susceptibility gene in western populations. To investigate the contribution of PALB2 mutations to Chinese non-BRCA1/BRCA2 hereditary breast cancer, we screened all coding exons and intron-exon boundaries of PALB2 in 360 Chinese women with early-onset breast cancer or affected relatives from five breast disease clinical centers in China by utilizing PCR-DHPLC and DNA sequencing analysis. Some genetic variants identified in the cases were then studied in 864 normal controls with no personal or family history of breast cancer. Two protein-truncating PALB2 mutations, 751C>T and 1050_1051delAAinsTCT, were identified in three separate families, and 751C>T was a recurrent mutation. Neither of them, however, were present in the controls (P=0.025). All the truncating mutations occurred in exon 4 of PALB2, and there were still three unclassified variants were detected in the same fragment. We found that exon 4 accounted for 44.1% (15/34) of the person-times carrying with any variant in our study. PALB2 mutations were responsible for approximately 1% of Chinese women with early-onset breast cancer and affected relatives. Our results suggested that a detection of exon 4 before the assay of the whole PALB2 gene might be a cost-effective approach to the screening of Chinese population.


Fracturing rings to understand lantibiotics.
Haloduracin is a bacterially produced antibiotic system of two alkali-stable peptides (Halalpha and Halbeta) that have extensive posttranslational modifications, including lanthionine rings. Now, Cooper et al. (2008) revise the structure of Halbeta and demonstrate that some of the lanthionine rings are not essential for bioactivity.


An unusual presentation of carcinoma of the lung: 26 patients with cervical node metastases.
Carcinoma of the lung should be considered in the search for an unknown primary lesion when there is evidence of cervical lymph node involvement. Of 1,686 patients with a final diagnosis of bronchogenic carcinoma seen during a 10-year period at the University of Louisville Hospitals, 26 presented one or more clinically positive cervical nodes. The frequency of lung cancer in such instances varies from 1.5% (in the present report) to 32%, possibly because the term "cervical node" is used without clarification. More precise description of such metastases is urged.


Idiotypic receptors for soluble antigens on human T lymphocyte clones.
T lymphoblasts sensitized in vitro to tetanus toxoid (TT) in 6 day cultures, acquire the capacity of stimulating the blastogenic response of "resting" autologous T lymphocytes in primary AMLC reactions. The response of lymphocytes primed against autologous-TT-sensitized-lymphoblasts (ATTSL) seems to be specific for idiotypic receptors for TT, expressed by ATTSL. Evidence to this effect derive from restimulation experiments in which anti-ATTSL primed lymphocytes (PL) were shown to display memory responses only when challenged with ATTSL, and not when exposed to the antigen alone, or to autologous lymphoblasts that had been sensitized to other antigens. Memory responses were induced, however, by allogeneic lymphoblasts primed to TT, even when the latter shared no HLA-DR antigen with the responding anti-ATTSL-PL. This indicated that the recognition of idiotypic receptors for TT is not DR-restricted. By generating T cell clones reacting to PPD and anti-idiotypic T cell clones which respond to anti-PPD sensitized blasts, we have been able to analyze the idiotype-anti-idiotype T cell interreaction at the clonal level. We found that anti-idiotypic T cell clones discriminate between determinants expressed by various autologous anti-PPD clones. Certain idiotypic determinants seem to prevail, however, as they were recognized in concert by the same cluster of anti-idiotypic clones.