Synchrotron-based X-ray fluorescence microscopy mapping the ionome of a toxic freshwater cyanobacterium.
Harmful algal blooms (HABs) pose a major environmental concern across the globe. In abundance, cyanobacteria, or so-called green-blue algae can produce extremely dangerous cyanotoxins that harm humans and animals. This study focused on the mapping and distribution of intracellular macro-and micronutrients of the wide-spread freshwater cyanobacteria Microcystis aeruginosa (M. aeruginosa). Towards a better understanding of trace metal uptake and homeostasis throughout the cell cycle, we quantitatively mapped the spatial distribution of the elements P, K, Fe, Ca, Zn, Mn, and Cu across the ultrastructure of frozen-hydrated single cells using state-of-the-art X-ray nanofluorescence imaging at the Advanced Photon Source (APS) at Argonne National Laboratory. Bulk cellular nutrient and trace metal content correlated well with the total intracellular elemental content in individual cells obtained by quantitative synchrotron X-ray fluorescence measurements. Multi-dimensional mappings showed P and K atoms colocalized as discrete semicircular hotspots that were analyzed with respect to their stoichiometry. Elevated Cu and Ca concentrations were detected along division plane of cells. P and K were found to have similar spatial elemental distribution with about 65% and 69% of the total cellular P and K, respectively, located at the hotspots. The P and K colocalization were refined further using nanotomography, showing a K envelope surrounding the P core. Inorganic P and organic P compounds were specified using solution-state 31P nuclear magnetic resonance (NMR) spectroscopy from M. aeruginosa. Of the total extracted P determined by 31P NMR spectroscopy, 47% were found to be nucleotides while only 11% were polyphosphates. Multimodal X-ray imaging provides a better understanding of intracellular biochemical processes in cyanobacteria, helping us monitor and combat an emerging environmental threat.


A preliminary investigation into postmortem changes in skinfold impedance during the early postmortem period in rats.
A highly accurate and reproducible technique was used to measure the electrical impedance (1 kHz) of a lateral abdominal skinfold, in each of eight rat cadavers stored at 9.0 +/- 0.7 degrees C, during the early postmortem period. Impedance increased exponentially between 1 and 120 h post mortem. Whether or not similar changes occur during the human postmortem period, and their potential value as a means of objective estimation of postmortem interval (PMI), remains to be established.


Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B.
Chronic hepatitis B (CHB) and liver fibrosis are associated with a high risk of hepatocellular carcinoma (HCC) development. We assessed whether entecavir (ETV) plus Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine, can further reduce the risk of HCC in treatment-naïve Chinese patients with CHB and an Ishak fibrosis score of ≥3 points derived from our parent double-blind randomized placebo-controlled trial. After a 72-week comparison between ETV+BRC and ETV+placebo treatment, participants were eligible to enter an open-label treatment phase and were followed up every 6 months. The primary [secondary] endpoints were the incidence of HCC [liver-related deaths, non-HCC events, and non-liver-related deaths]. Modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP) populations were defined for the time-to-event analysis. A total of 1,000 patients were recruited; the median age was 42.0 years; 69.9% were male and 58.3% were HBeAg positive. In the mITT population, the 7-year cumulative incidence of HCC [liver-related deaths] was 4.7% [0.2%] for ETV+BRC, which was significantly lower than 9.3% [2.2%] for ETV monotherapy (p = 0.008 [p = 0.030]). Notably, ETV+BRC treatment yielded a lower incidence of HCC in those who did not achieve regression of fibrosis at week 72 than ETV monotherapy (p = 0.018). There were no differences in the other 2 secondary endpoints or safety profiles between the groups. Multivariable Cox proportional regression analysis, including the treatment allocation as a parameter, also demonstrated that ETV+BRC treatment was associated with a reduced incidence of HCC. The ITT and PP analyses showed consistent results. ETV plus BRC combination treatment could further reduce the risk of HCC and liver-related deaths in patients with CHB and advanced fibrosis or cirrhosis, which may have important clinical implications for HCC prevention. Patients with chronic hepatitis B virus infection are at an increased risk of developing liver cancer (specifically hepatocellular carcinoma [HCC]). While there are effective antiviral treatments that can suppress the virus in chronically infected patients, the risk of HCC remains. Herein, we show that adding a traditional Chinese medicine called Biejia-Ruangan compound to an antiviral reduced the risk of HCC in patients with chronic hepatitis B.


Statistical control of the spectral quality index in electron beams.
In radiotherapy with electron linear accelerators, it is mandatory to guarantee the stability of beam output spectra. In this work we study the quality control of the magnitude that provides the beam spectral quality, by following statistical techniques usual in industry process. We establish the differences between the measurement of the reference quality index, R(50,ion), which involves usually a costly procedure, and that of the index used for the statistical control, which can be done in an easier way and with a higher frequency. The methodology developed is applied to a Siemens Mevatron KDS electron linear accelerator, specifically for the 6, 12 and 18 MeV modes. The uncertainties of both procedures are evaluated and are correlated. A retrospective analysis of the data registered during more than 13 years is carried out using CUSUM algorithmic and moving range charts. The larger uncertainties in R(50,ion) come from the measurement device and the observer. The uncertainty in the measurement of the statistical control variable, which is mainly due to the geometry setup, is negligible against its intrinsic variability. The application of CUSUM charts pointed out different out of control situations linked in much cases to assignable causes. In addition, moving range charts showed up situations of anomalous functioning of the LINAC. Algorithmic CUSUM charts permit a nice monitoring of R(50,ion). If the variability is not controlled, by using charts such as the moving range ones, the number of false alarms could increase without a change in the mean value of R(50,ion).


Fully automated 18F-fluorination of N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) for indirect labelling of nanobodies.
N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB), a widely used labeling agent to introduce the 4-[18F]fluorobenzoyl-prosthetic group, is normally obtained in three consecutive steps from [18F]fluoride ion. Here, we describe an efficient one-step labeling procedure of [18F]SFB starting from a tin precursor. This method circumvents volatile radioactive side-products and simplifies automatization. [18F]SFB was obtained after HPLC purification in a yield of 42 + 4% and a radiochemical purity (RCP) > 99% (n = 6). In addition, we investigate the automation of the coupling of [18F]SFB to a nanobody (cAbBcII10, targeting β-lactamase enzyme) and purification by size exclusion chromatography (PD-10 desalting column) to remove unconjugated reagent. Production and use of [18F]SFB were implemented on a radiosynthesis unit (Neptis®). The fully automated radiosynthesis process including purification and formulation required 160 min of synthesis time. [18F]SFB-labeled nanobody was obtained in a yield of 21 + 2% (activity yield 12 + 1% non-decay corrected) and a radiochemical purity (RCP) of > 95% (n = 3). This approach simplifies [18F]SFB synthesis to one-step, enhances the yield in comparison to the previous report and enables the production of radiolabeled nanobody on the same synthesis module.


A new method for the assay of aminoacylase: elaboration of a fixed-incubation method for routine measurements.
A simple method suitable for routine determinations of aminoacylase (EC 188.8.131.52) in serum and tissue homogenates is described. It is based on the formation of red charge-transfer complexes from p-benzoquinone and amino acids liberated by cleavage of acylamino acids. Optimal substrates are trifluoroacetyl-L-methionine and chloroacetyl-L-methionine, the first being rapidly hydrolyzed by pancreatic tissue, the latter by liver and kidney homogenates. Sera preferentially split the chloroacetyl compound. Optimal conditions for the assay of serum activity are: 18-20 mm9l/l substrate concentration, 50 mmol/l phosphate buffer pH 6.0, no additives.


Acute effects on the lung and the liver of oral administration of cerium chloride on adult, neonatal and fetal mice.
We evaluated tissue changes associated with cerium chloride administration via gavage to adult mice, via milk to neonatal mice and transplacentally to fetal mice. Change in adults consisted of extensive pulmonary hemorrhage, pulmonary venous congestion, thickened alveolar septae, hepatic necrosis and neutrophil infiltrations. Those in fetal mice consisted of pulmonary and hepatic congestion. These results indicate that gavage cerium administration elicited subtle tissue changes, though oral toxicity is rather low. These changes were less severe in neonatal and fetal mice. When cerium was injected into adult mice through the tail vein, cerium was distributed mainly to the liver, spleen and lung dose-dependently with the cerium concentration gradually decreasing after 3 days. A study of cerium anticoagulation in mouse plasma showed that clotting time was significantly prolonged when cerium was added to plasma. These results suggest that cerium may disturb blood coagulation and cause pulmonary and hepatic vascular congestion.


Sociodemographic, health and lifestyle characteristics reported by discrete groups of adult dietary supplement users in Alberta, Canada: findings from The Tomorrow Project.
To determine the extent to which differences in sociodemographic, dietary and lifestyle characteristics exist between users of different types of dietary supplements and supplement non-users. We analysed cross-sectional data obtained from self-administered questionnaires completed at baseline by participants in The Tomorrow Project; a prospective cohort study in Alberta, Canada. Participants who used at least one type of dietary supplement at least weekly in the year prior to questionnaire completion were defined as supplement users, while the remainder were classified as non-users. Seven discrete user categories were created: multivitamins (+/- minerals) only, specific nutritional supplements only, herbal/other supplements only, and all possible combinations. Differences in sociodemographic, dietary and lifestyle characteristics between different groups of supplement users and non-users were analysed using Rao-Scott chi2 tests and multinomial logistic regression. Subjects were 5,067 men and 7,439 women, aged 35-69 years, recruited by random digit dialling throughout Alberta. Supplement use was extensive in this study population (69.8 %). Users of herbal/other supplements only, and women who used multivitamins only, tended to report dietary and lifestyle characteristics that were not significantly different from non-users. In contrast, those who reported using a combination of multivitamins, specific nutritional and herbal/other supplements were more likely than non-users to report behaviours and characteristics consistent with current health guidelines. Dichotomizing participants as supplement users or non-users is likely to mask further differences in sociodemographic, dietary and lifestyle characteristics among users of different types of supplements. This may have implications for analysis and interpretation of observational studies.


Inhibitors of DNA synthesis (aphidicolin and araC/HU) prevent the recovery of RNA synthesis after UV-irradiation.
UV-irradiation causes an immediate depression in the rate of RNA synthesis in human skin fibroblasts. RNA synthesis rates recover to greater than or equal to 90% of unirradiated levels within 90 min in normal cells. This recovery can be prevented by incubating the cells after irradiation with araC/HU or aphidicolin, potent inhibitors of DNA replication and excision repair. The effect of these inhibitors on the recovery of RNA synthesis can also be observed in non-dividing cells; it is thus independent of their effects on DNA replication.


Assessment of a mechanism for reactive inhibition of carboxypeptidase A with QM/MM methods.
The mechanism for inhibition of carboxypeptidase A (CPA) by the two enantiomers of a reactive inhibitor, N-(2-chloroethyl)-N-methylphenylalanine, has been investigated using computational methods. Quantum mechanical and molecular mechanical (QM/MM) methods have been employed to find likely enzyme binding conformations by comparison with the observed rates of inactivation of the enzyme. The study has shown that the enzyme active site appears to be flexible enough to allow the nucleophilic deactivation reactions of both the (R) and (S) forms of a model of the inhibitor to be catalysed by the Zn(II) cofactor of CPA.


The concept of the 'organic individual' in Haeckel's writings.
Biological individuality was a hotly debated concept in nineteenth-century German biology, both in botany and in zoology. Much discussion centered on a comparison of higher plants with colonial organisms that are subject to polymorphism and exhibit division of labor among their parts. Building on the work of Matthias Jakob Schleiden, Johannes Müller, Rudolf Leuckart, and especially the botanist Alexander Braun, Haeckel in his writings continued to refine his theory of relative individuality. Haeckel recognized three kinds of individuality: physiological, morphological, and genealogical, the latter two hierarchically structured. These distinctions allowed him to embed in his theory of relative (biological) individuality the threefold parallelism of ontogeny, phylogeny, and classification. For Haeckel, this threefold parallelism provided the strongest proof for Darwin's theory of descent with modification.


Polysaccharides with sulfate groups are human T cell mitogens and murine polyclonal B cell activators (PBAs) II. Cellulose sulfate and dextran sulfate with two different lower molecular weights.
In our previous paper, we reported that various types of carrageenan, dextran sulfate and fucoidan, which are sulfated homopolysaccharides with high molecular weights, were human T cell mitogens and murine polyclonal B cell activators (PBAs) and that heparin, a sulfated heteropolysaccharide, was a very weak human mitogen and mouse PBA. Here we used cellulose sulfate (Mr 7-9 X 10(3], dextran sulfate with two different low molecular weights (Mr 5 X 10(3) and 8 X 10(3], two different condroitin sulfates (Mr 3.5 X 10(4], polyvinyl sulfate and polygalacturonic acid to investigate mitogenic activities of polysaccharides in detail. The following results were obtained. Low-molecular-weight sulfated homopolysaccharides, dextran sulfate and cellulose sulfate, were very weak or not human T cell mitogens. However, they were better murine PBAs. Sulfated heteropolysaccharides, chondroitin 4-sulfate and chondroitin 6-sulfate, hardly induced mitogenic changes in human T cells and mouse B cells, even though the molecular weight of these substances was more than 1 X 10(4). There were no other polymers examined so far which activated both human T cells and murine B cells. The relationship among molecular size, sulfate groups and lymphocyte activation is discussed in detail.


Molecular cloning and sequence determination of four different cDNA species coding for alpha-subunits of G proteins from Xenopus laevis oocytes.
A cDNA library prepared from Xenopus laevis oocytes in lambda gt10 was screened with a mixture of three oligonucleotide probes designed to detect sequences found in different mammalian genes coding for alpha-subunits of G-proteins. In addition to a clone coding for a G alpha o-type subunit previously reported [(1989) FEBS Lett. 244, 188-192] four additional clones have been found coding for different G alpha protein subunits. By comparison with mammalian alpha-subunits, these oocyte cDNAs correspond to two closely related G alpha s-1a, to a G alpha i-1 and to a G alpha i-3 species. The derived amino acid sequences showed that both G alpha s species contain 379 residues, corresponding to the short species without the serine residue and with a calculated Mr of 42720. The G alpha i-1 gene encodes a 354 amino acid protein with an Mr of 39,000 and the G alpha i-3 encodes an incomplete open reading frame of 345 residues, lacking the first 9 amino acid residues at the NH2 terminus. All these G alpha-subunits showed high identity with their respective mammalian counterparts (75-80%), indicating a great degree of conservation through the evolution and the important cellular regulatory function that they play.


Radial osteotomy for the correction of forearm deformities in hereditary multiple osteochondroma.
Forearm deformities are often observed in patients with hereditary multiple osteochondroma, resulting in functional disability and cosmetic impairment. The aim of this study was to assess clinical and radiological outcomes after corrective osteotomy of the radius (COR). We performed a retrospective analysis of clinical and radiologic data from patients with forearm deformities who underwent COR combined with osteochondroma resection between 1978 and 2015. Seventeen patients (17 forearms) were included. The mean (range) age at surgery was 11.8 years (3.2-14.4), and the mean interval between surgery and last follow-up was 8.2 years (2-34.2). Range of motion was moderately increased and postoperative radiological assessments found significant improvements in ulnar variance, radial articular angle, bowing of the radius, and carpal slip. At last follow-up, a loss of ulnar variance correction was noted in 11 cases (mean loss: 4mm). The mean score on the Quick Disabilities of the Arm, Shoulder and Hand self-administered questionnaire was 13.9. Our results show that a forearm deformity in a patient with hereditary multiple osteochondroma is an appropriate indication for COR combined with osteochondroma resection and should be performed at the end of growth. This simple, safe technique corrects bowing of the radius and radius-ulna length discrepancy and could limit the risk of radial head dislocation. LEVEL OF EVIDENCE: IV.


Correlation between the key aroma compounds and gDNA copies of Bacillus during fermentation and maturation of natto.
The aim of the study was to analyze the correlation between the key aroma compounds and gDNA copies of Bacillus natto during fermentation and maturation of natto. Solvent-assisted flavor evaporation (SAFE) techniques were employed to extract volatile organic compounds. Aroma compounds were separated and analyzed through gas chromatography-olfactometry-mass spectrometry (GC-MS/O) using DB-5 and DB-Wax capillary columns. Seventy-nine compounds were extracted and identified, including 17 ketones, 17 alcohols, 9 aldehydes, 6 acids, 7 esters, 8 pyrazines, 8 aromatics, and 7 others. Twenty-two compounds were identified as the key aroma compounds of natto by aroma extraction dilution analysis (AEDA). Pyrazines played a key role in the flavor of natto both during the fermentation and maturation. 2,5-Dimethylpyrazine, 2,3,5-trimethylpyrazine, 2,3,5,6-tetramethylpyrazine, and 2,3,5-methyl-6-ethylpyrazine contributed substantially to natto flavor. They presented significant positive and negative correlations with the gDNA copies of Bacillus natto during fermentation and maturation, respectively.


Design and synthesis of novel poly (aryl ether ketones) containing trifluoromethyl and trifluoromethoxy groups.
The high-frequency and high-speed communication in the 5 G era puts forward requirements for the dielectric properties of polymers. Introducing fluorine into poly(ary ether ketone) can improve its dielectric properties. In this work, by introducing the fluorine group strategy, we successfully designed and synthesized three novel trifluoromethyl (-CF3) or trifluoromethoxy (-OCF3)-containing bisphenol monomers and their F-substitution PEK-based polymers (PEK-Ins). All these PEK-Ins exhibited good thermal, mechanical and dielectric properties. The T d5% of the three polymers is all higher than 520℃. The free volume fraction of novel polymers increased from 3.75% to 5.72%. Among the three polymers, exhibited the lowest dielectric constant of the films is 2.839, and the dielectric loss is 0.0048, ascribing to the increasing free volume. The Young's modulus of the polymer film is as high as 2.9 GPa and the tensile strength is as high as 84 MPa. PEK-Ins reduced the dielectric constant by introducing a low fluorine content. This study provides a new way to design PEK to synthesize low dielectric constant polymers.


Low-signal-intensity rim on susceptibility-weighted imaging is not a specific finding to progressive multifocal leukoencephalopathy.
Low-signal-intensity (LSI) rim along deep layers of the cerebral cortex is reportedly a susceptibility-weighted imaging (SWI) finding in progressive multifocal leukoencephalopathy (PML). We aimed to evaluate whether this finding can be identified in diseases other than PML. We retrospectively reviewed brain MR images from 5605 patients who underwent SWI at 3T; 370 patients with various diseases, who showed cortical and subcortical FLAIR high-signal lesions including U-fiber, were enrolled. The presence or absence of LSI rim on thin-slice SWI and hyperintense cortical signal (HCS) on T1-weighted images adjacent to LSI rim was analyzed. Signal changes of the LSI rim were assessed on serial SWI, if available. Twenty-five of the 370 patients (6.8%) showed SWI LSI rim, in infarct (n=22) and encephalitis (n=3). HCS was apparent adjacent to SWI LSI rim in 17 patients (15 infarct, 2 encephalitis). Serial SWI was available for 17 patients, of whom 10 patients (8 infarct, 2 encephalitis) presented LSI rim later than 45days after onset. LSI rim can be observed in infarct and encephalitis. Therefore, this finding is not specific to PML. LSI rim appears to be associated with HCS.


-572 G/C single nucleotide polymorphism of interleukin-6 and sepsis predisposition in chronic renal disease.
Single nucleotide polymorphisms (SNPs) of interleukin (IL)-6 are associated with the development of chronic renal disease (CRD). Their impact for sepsis in the field of CRD was investigated. One control cohort of 115 patients with CRD without infection and another case cohort of 198 patients with CRD and sepsis were enrolled. Genotyping at the -174 (rs1800795) and -572 positions of IL-6 (rs1800796) was done by restriction fragment length polymorphism. Circulating IL-6 was measured by an enzyme immunoassay. The GG genotype of rs1800796 was more frequent among cases (78.3%) than controls (62.6%). No difference in the genotype frequencies of rs1800795 between cases and controls were found. Odds ratio for sepsis was 2.07 (95%CI 1.24-3.44, p = 0.005) with the GG genotype of rs1800796, which was confirmed by logistic regression analysis taking into consideration the presence of chronic comorbidities. All-cause mortality until day 28 was similar between patients with the GG genotype and the GC/CC genotypes of rs1800796, but death caused from cardiovascular events not-related with infection was more frequent with the GG genotype (14.6% vs 2.4%, p = 0.031). Circulating IL-6 was greater among patients of the GC/CC genotypes of rs1800796 and multiple organ dysfunction (p = 0.013). The GG genotype of rs1800796 predisposes to sepsis in CRD and to 28-day mortality by sepsis-unrelated cardiovascular phenomena.


Wheat-dependent exercise-induced anaphylaxis in mice is caused by gliadin and glutenin treatments.
Various foods may be associated with food-dependent exercise-induced anaphylaxis (FDEIAn). However, although the most frequently reported cause of FDEIAn has been wheat, the mechanism of FDEIAn for wheat has remained largely uninvestigated. To investigate the effect of wheat-fractionated proteins on FDEIAn, female B10.A mice (16-20 g) were divided into four groups; i.e. salt-soluble (S-group), gliadin-rich (GLI-group), and glutenin-rich (GLU-group)-sensitized mice, and unsensitized mice. The three sensitized groups were run on a treadmill after oral intake of each wheat-fractionated protein. The mice showed a significant increase in serum IgE, especially in the GLI- and GLU-group. After oral administration of each wheat-fractionated protein, the running time until exhaustion was remarkably shorter for the GLI- and GLU-group than for the S-group and unsensitized mice. The level of intestinal erosion was higher in all the sensitized mice than that in the unsensitized ones after exhaustive running. Furthermore, moderate exercise for 30 min after oral ingestion of each wheat-fractionated protein also induced intestinal erosion in the GLI- and GLU-group. In addition, we observed leaking of gliadin and glutenin proteins out of the intestine into the liver. These results indicated that the main factor involved in wheat-dependent exercise-induced anaphylaxis might be the gliadin and glutenin in wheat proteins.


A Poisson regression approach for modelling spatial autocorrelation between geographically referenced observations.
Analytic methods commonly used in epidemiology do not account for spatial correlation between observations. In regression analyses, omission of that autocorrelation can bias parameter estimates and yield incorrect standard error estimates. We used age standardised incidence ratios (SIRs) of esophageal cancer (EC) from the Babol cancer registry from 2001 to 2005, and extracted socioeconomic indices from the Statistical Centre of Iran. The following models for SIR were used: (1) Poisson regression with agglomeration-specific nonspatial random effects; (2) Poisson regression with agglomeration-specific spatial random effects. Distance-based and neighbourhood-based autocorrelation structures were used for defining the spatial random effects and a pseudolikelihood approach was applied to estimate model parameters. The Bayesian information criterion (BIC), Akaike's information criterion (AIC) and adjusted pseudo R2, were used for model comparison. A Gaussian semivariogram with an effective range of 225 km best fit spatial autocorrelation in agglomeration-level EC incidence. The Moran's I index was greater than its expected value indicating systematic geographical clustering of EC. The distance-based and neighbourhood-based Poisson regression estimates were generally similar. When residual spatial dependence was modelled, point and interval estimates of covariate effects were different to those obtained from the nonspatial Poisson model. The spatial pattern evident in the EC SIR and the observation that point estimates and standard errors differed depending on the modelling approach indicate the importance of accounting for residual spatial correlation in analyses of EC incidence in the Caspian region of Iran. Our results also illustrate that spatial smoothing must be applied with care.


Abnormalities of the gallbladder, clinical effects.
The aim of this review of the literature was to present and discuss the anatomical and embryological basis of congenital abnormalities of the gallbladder, based on a case of volvulus. In the rare cases of ectopic gallbladder, diagnosis of a biliary disease could be difficult. In such cases surgery can also be dangerous, especially when it is associated with abnormalities of the intra-hepatic biliary and vascular tree. This study, based on the embryology of the extra hepatic bile duct, focused on the most frequent gallbladder abnormalities to keep them in mind.


Application of Perovskite Quantum Dots as an Absorber in Perovskite Solar Cells.
Perovskite quantum dots (QDs) preserve the attractive properties of perovskite bulk materials and present additional advantages, owing to their quantum confinement effect, leading to their suitability as an absorber in perovskite solar cells. In this Review, the issues and advantages of perovskite QDs are analyzed in the context of purification, device fabrication with perovskite QDs, light absorption, charge transport, and stability. In addition, promising strategies to enhance perovskite QDs and QD-based solar cells are elucidated based on exchange chemistry (ion and ligand exchange), passivation engineering (ion and ligand passivation), and structure engineering (conventional/inverted, planar/mesoscopic and dimensionally graded structures). These discussions will give a clue to the further development of perovskite QDs and thus the advancement of QD-based solar cells.


[Effectiveness and efficiency of stationary geriatric treatment of old and very old patients].
In this study we compared characteristics and treatment results in patients of 60 to 79 (group I, n = 682) and of 80 to 100 years of age (group II, n = 593) treated in a geriatric hospital. Neurologic diseases (mainly stroke) predominated in group I (38%), and patients with fractures in group II (53%). Diabetes mellitus and hyperlipidemia were less frequent in patients of group II, but overt cardial insufficiency was more frequent than in group I. While the effectiveness of geriatric treatment was identical in both groups, the efficiency-defined as progress per day-was in some parts slightly higher in group II. There are three independent variables strongly related to the decision of transfer into a nursing home: 1) Barthel Index on discharge; 2) Household-Size (living alone/living not allone); 3) Age.


Peptide fragment of thymosin β4 increases hippocampal neurogenesis and facilitates spatial memory.
Although several studies have suggested the neuroprotective effect of thymosin β4 (TB4), a major actin-sequestering protein, on the central nervous system, little is understood regarding the action of N-acetyl-serylaspartyl-lysyl-proline (Ac-SDKP), a peptide fragment of TB4 on brain function. Here, we examined neurogenesis-stimulative effect of Ac-SDKP. Intrahippocampal infusion of Ac-SDKP facilitated the generation of new neurons in the hippocampus. Ac-SDKP-treated mouse hippocampus showed an increase in β-catenin stability with reduction of glycogen synthase kinase-3β (GSK-3β) activity. Moreover, inhibition of vascular endothelial growth factor (VEGF) signaling blocked Ac-SDKP-facilitated neural proliferation. Subchronic intrahippocampal infusion of Ac-SDKP also increased spatial memory. Taken together, these data demonstrate that Ac-SDKP functions as a regulator of neural proliferation and indicate that Ac-SDKP may be a therapeutic candidate for diseases characterized by neuronal loss.


Dual effects of glutathione-S-transferase pi on As2O3 action in prostate cancer cells: enhancement of growth inhibition and inhibition of apoptosis.
To determine the effects of glutathione-S-transferase pi (GSTpi) on the actions of As2O3, As2O3-induced growth inhibition and apoptosis was studied in three prostate cancer cell lines: DU-145, PC-3 and LNCaP cells. As2O3 inhibited cell proliferation of DU-145 and PC-3 cells (both cells express GSTpi), but not of LNCaP cells (which lack GSTpi expression) at concentrations below 1 microM. LNCaP cells stably transfected and expressed GSTpi (LNCaP/GSTpi) became sensitive to As2O3 growth inhibition. As2O3 arrested cell growth of DU-145, PC-3 and LNCaP/GSTpi cells in the G2/M phase of the cell cycle at low concentrations (<2 microM), but did not induce apoptosis. At higher concentrations (10-20 microM), As2O3 induced apoptosis in LNCaP cells, but not in DU-145 or PC-3 cells. The apoptosis induction due to As2O3 treatment of LNCaP cell correlated with the activation of JNK and p38 and induction of p53 protein. LNCaP/GSTpi cells became insensitive to As2O3-induced apoptosis with reduced JNK activition. These data indicate that GSTpi increases growth inhibition due to As2O3 treatment and prevents As2O3-induced apoptosis in prostate cancer cells. Therefore, it appears that As2O3 inhibits cell growth and induces apoptosis through different mechanisms.


Donor-recipient risk assessment tools in heart transplant recipients: the Bad Oeynhausen experience.
Some risk assessment tools have been developed to categorize mortality risk in heart transplant recipients, but it is unclear whether these tools can be used interchangeable in different transplant regions. We performed a retrospective single-centre study in 1049 adult German heart transplant recipients under jurisdiction of Eurotransplant. Univariable and multivariable Cox regression analysis was used to generate a risk scoring system. C-statistics were used to compare our score with a US score and a French score regarding their ability to discriminate between 1 year survivors and non-survivors within our study cohort. Of 38 parameters assessed, seven recipient-specific parameters [age, height, dilated cardiomyopathy (DCM), ischaemic cardiomyopathy (ICM), total bilirubin, extracorporeal membrane oxygenation (ECMO), and biventricular assist device/total artificial heart (BVAD/TAH) implant], one donor-specific parameter (cold ischaemic time), and one recipient-independent and donor-independent other parameter (late transplant era) were statistically significant in predicting 1 year mortality. The initial score was generated by using the regression coefficients from the multivariable analysis as follows: 1.70 * ln age - 4.0 * ln height - 0.9 * diagnosis (= 1 if diagnosis = DCM) - 0.67 * diagnosis (= 1 if diagnosis = ICM) + 0.33 * ln total bilirubin + 1.74 * ln cold ischaemic time + 0.98 * mechanical circulatory support (MCS) implant (= 1 if MCS implant = ECMO) + 0.47 * MCS implant (= 1 of MCS implant = BVAD/TAH) - 0.66 * transplant era (= 1 if transplant era = 2017-2018). The initial score was converted into the Bad Oeynhausen (BO) score as a positive integer variable by means of the following formula: BO score = (initial score + 8) * 3. In patients scoring 2 to <7 points (n = 112), 7 to <11 points (n = 580), 11 to <15 points (n = 339), and 15 to 20 points (n = 18), 1 year survival was 93.1%, 84.2%, 66.9%, and 27.8%, respectively. The c-index of our score was 0.73 [95% confidence interval (CI): 0.69-0.77]. Values were in our cohort for the US and French scores 0.66 (95% CI: 0.62-0.70) and 0.63 (95% CI: 0.59-0.67), respectively. Data indicate that our score, but also risk assessment tools from other transplant regions, may be used as a reliable support for risk-adjusted organ allocation and potentially help to improve outcomes in heart transplantation. Further developments will have to include as yet unaccounted risk factors for even more reliable predictions.


Transcriptomic features of trophoblast lineage cells derived from human induced pluripotent stem cells treated with BMP 4.
Early development of the human placenta remains poorly understood due to the lack of proper model systems. Previous reports have demonstrated that human induced pluripotent stem cells (hiPSCs) treated with bone morphogenetic protein 4 (BMP4) can differentiate into extraembryonic tissues as useful models of the early stage of trophoblast (TB) differentiation. In our previous study, we optimized the culture conditions of hiPSC-derived TB lineages, but the differentiated cells were heterogeneous. In order to characterize the hiPSC-derived TB lineage cells, four types of hiPSCs were treated with 50 ng/mL of BMP4 for 10 days. Subsequently, cells that were positive for the pan-TB marker keratin 7(KRT7) were purified from the differentiated cells using flow cytometry and identified with a DNA microarray. Comparisons of our microarray data with the human transcriptome in a previous large-scale analysis showed that the gene expression patterns of KRT7+ cells were similar to the placenta. In total, 259 upregulated genes were commonly expressed in all four KRT7+ groups, including well-known TB markers. Among these upregulated genes, several with poorly investigated expression patterns and functions were confirmed as expressed in the primary placenta. While only XAGE2 and KCNQ2 were expressed in TB layers, XAGE2 was expressed throughout pregnancy and KCNQ2 was expressed only in cytotrophoblasts of the first trimester placenta. BMP4-treated KRT7+ cells were in the course of the human placental development. In addition, this approach allowed the identification of new genes that might be involved in placentation. However, further studies are needed to confirm their functions.


Topological phase transition in quasi-one dimensional organic conductors.
We explore topological phase transition, which involves the energy spectra of field-induced spin-density-wave (FISDW) states in quasi-one dimensional (Q1D) organic conductors, using an extended Su-Schrieffer-Heeger (SSH) model. We show that, in presence of half magnetic-flux FISDW state, the system exhibits topologically nontrivial phases, which can be characterized by a nonzero Chern number. The nontrivial evolution of the bulk bands with chemical potential in a topological phase transition is discussed. We show that the system can have a similar phase diagram which is discussed in the Haldane's model. We suggest that the topological feature should be tested experimentally in this organic system. These studies enrich the theoretical research on topologically nontrivial phases in the Q1D lattice system as compared to the Haldane topological phase appearing in the two-dimensional lattices.


Diagnostic value of the femoral vein flow pattern for the detection of an iliocaval venous obstruction.
Identification of iliocaval obstructions has traditionally been difficult due to the lack of a reliable noninvasive screening technique. Although femoral vein flow patterns have been used to detect outflow obstructions, the diagnostic accuracy of indirect Doppler parameters has not yet been fully elucidated. The purpose of this study was to establish the diagnostic value of the femoral vein waveform in detecting chronic iliocaval venous lesions. Medical records of consecutive patients with chronic venous disease classified as Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) C3-6 between March 2011 and December 2012 were assessed retrospectively. The results of common femoral vein duplex ultrasound examinations, based on the presence or absence of respiratory variation in the femoral flow as well as its response to the Valsalva maneuver, were compared with contrast venography and intravascular ultrasound imaging of the inferior vena cava and the bilateral common and external iliac veins. Three types of flow patterns in the common femoral vein were identified with duplex ultrasound examination: phasic flow correlated with respiration, minimally phasic flow (showing some phasicity but no cessation with respiration), and monophasic flow (continuous flattened flow). In addition, three types of responses to the Valsalva maneuver were recorded: complete cessation of flow, reversal of flow, and continuation of flow. The study evaluated 86 patients (63 men, 23 women) with a mean age 40.3 ± 1.5 years. Contrast venography and intravascular ultrasound imaging were used to detect venous obstructions in the inferior vena cava and the right and left iliac veins in 16.3%, 32.6%, and 80.2% of patients, respectively. When various flow parameters were evaluated, the combination of common femoral vein monophasic flow at rest and continuous flow during the Valsalva maneuver had the highest diagnostic value for iliocaval venous obstructions. The sensitivity, specificity, positive predictive value, and negative predictive value of the combination of monophasic flow at rest and unceasing forward flow during the Valsalva maneuver for the diagnosis of any degree of iliac venous obstruction were 38.1%, 100%, 100%, and 55.8%, respectively. The sensitivity and negative predictive value of these diagnostic parameters increased as the degree of obstruction increased. An iliocaval venous obstruction is a frequent feature of chronic venous disease. Doppler examination of the common femoral vein can be used as a screening test for iliocaval venous obstructions. The monophasic flow of the common femoral vein is a reliable diagnostic tool for the detection of possible iliac vein obstructions.


Specificity of the inhibition of DNA synthesis by extracts from cloned normal, sarcoma-virus-transformed and revertant 3T3 cells.
Extracts containing tissue-specific DNA-inhibitory activity were prepared from normal FL (Swiss) and BALBc3T3 cells, from these cells transformed with sarcoma virus and from revertants cloned from the transformed cell lines. By testing all extracts on all cell lines we found that (1) production of and susceptibility to the inhibitors were decreased in transformed BALB/c cells (2) specificity varied with expression of the transforming genome, as an extract from a given cell line inhibited the growth of its cell of origin, e.g. revertant, more than normal or transformed cells, and (3) there was also a DNA-synthesis stimulator.


Quantitative trait loci for electrocardiographic parameters and arrhythmia in the mouse.
Cardiac arrhythmias associated with sudden death are influenced by multiple biological pathways and are modulated by numerous genetic and environmental factors. Elevated heart rate and prolonged ECG indices of conduction and repolarization have been associated with risk of sudden death. Insight into the genetic underpinnings of these parameters thus provides an important means to the dissection of the genetic components modulating risk of sudden cardiac death. In this study we mapped quantitative trait loci (QTL) modulating heart rate, ECG indices of conduction and repolarization, and susceptibility to arrhythmia, in a conduction disease-sensitized F(2) mouse population. Heart rate, P-duration, PR-, QRS- and QT-interval were measured at baseline (n=502) and after flecainide administration (n=370) in mutant F(2) progeny (F(2)-MUT) resulting from the FVB/NJ-Scn5a1798(insD/+) X 129P2-Scn5a1798(insD/+) mouse cross. Episodes of sinus arrhythmia and ventricular tachyarrhythmia occurring post-flecainide were treated as binary traits. F(2)-MUT mice were genotyped using a genome-wide 768 single nucleotide polymorphism (SNP) panel. Interval mapping uncovered multiple QTL for ECG parameters and arrhythmia. A sex-interacting scan identified QTL displaying sex-dependency, and a two-dimensional QTL scan unmasked locus-locus (epistasis) interactions influencing ECG traits. A number of QTL coincided at specific chromosomal locations, suggesting pleiotropic effects at these loci. Through transcript profiling in myocardium from the parental mouse strains we identified genes co-localizing at the identified QTL that constitute highly relevant candidates for the observed effects. The detection of QTL influencing ECG indices and arrhythmia is an essential step towards identifying genetic networks for sudden, arrhythmic, cardiac death.


Assessment of Bipolar Radiofrequency Ablation Combined with Coronary Artery Bypass Surgery for Management of Atrial Fibrillation in Cardiac Patients.
Atrial fibrillation (AF) is a common problem in patients undergoing coronary artery bypass graft (CABG). For AF ablation, bipolar radiofrequency ablation (BRA) achieves complete transmural ablation lines and reduces the risk of treatment failure. We analyzed the efficacy of BRA for sinus rhythm restoration in patients with AF undergoing CABG. This prospective study included patients with permanent or paroxysmal AF scheduled to undergo BRA combined with CABG in our institution from May 2014 to June 2020. After discharge from hospital, all patients were seen every 6 months over 5 years to evaluate survival, sinus rhythm restoration, and New York Heart Association (NYHA) class. We enrolled 168 patients, 97 (57.7%) with permanent AF (group I) and 71 (42.3%) with paroxysmal AF (group II) at 60 months. We found that group II patients had better sinus rhythm restoration rates after BRA with CABG than group I patients (P = .005). Overall mortality at 60 months was significantly lower in group II patients (2 [2.8%]) than patients in group I (14 [14.4%]; P = .01). The survival rate was significantly higher in group II than in group I (94% versus 72%; P = .0003) as shown by Kaplan-Meier analysis. The 95% confidence interval of the Cox hazards survival regression ratio was significantly different between groups (0.1792 [0.04069 to 0.7896]; P = .006). Long-term AF (>3 years) before BRA with CABG and permanent AF type were identified as predictors of post-BRA recurrent AF (P = .0001 and P = .005, respectively). NYHA class improved significantly at 60 months compared with baseline (P < .0001). This study identified preoperative AF type and duration as predictors of the success of BRA combined with CABG.


A mini review on manipulation of carbohydrate for better use in surimi and surimi products: modification and compounding.
Carbohydrate is widely used in the production of surimi and surimi products to improve their qualities, such as anti-freezing capability, gelling ability, nutrition, flavor and 3D printability. More and more native carbohydrates have been modified through physical methods (e.g., ball milling, irradiation and differential sedimentation), chemical method (e.g., deacetylation, hydroxypropylation and acetic acid esterification) or enzymatic method (e.g., chitosanase) before being used in the processing of surimi and surimi products in recent years. At the same time, different carbohydrates are compounded and applied to surimi and surimi products. The modified and compounded carbohydrates in surimi have been proved to improve quality of surimi and surimi products more pronouncedly than native carbohydrates. Therefore, this review summarizes the manipulation of carbohydrate by modification and compounding to improve the qualities of surimi and surimi products. Moreover, the prospects for carbohydrate modification and compounding for use in surimi and surimi products are discussed. © 2023 Society of Chemical Industry.


The relationship between maternal and paternal psychological symptoms and ratings of adolescent functioning.
Families with an adolescent between the ages of 11 and 18 years participated in a study examining the relationship between parental depressive and anxiety symptomatology and parental ratings of adolescents' functioning. This study indicated that mothers, fathers, and adolescents exhibited significant cross-informant correspondence (i.e. correlations) and very few significant differences in ratings of adolescents' functioning. After controlling for demographic variables and the ratings of other informants, mothers' depressive symptomatology was a significant predictor of mothers' ratings of adolescents' internalizing and externalizing behavior problems and competence. With regard to fathers' ratings, fathers' depressive symptomatology was a significant predictor of adolescents' internalizing behavior problems and competence, whereas fathers' depressive and anxious symptomatology was a significant predictor of adolescents' externalizing behavior problems. The findings of this study suggested the importance of considering maternal and paternal depressive symptomatology when parents are asked to provide ratings of their adolescents' functioning.


Validity, reliability and usefulness of smartphone and kinovea motion analysis software for direct measurement of vertical jump height.
Jumping is a simple exercise determined by several biomechanical and physiological factors. Measures of vertical jump height are common and easy to administer tests of lower limb muscle power that are carried out with several types of equipment. This study aimed to validate and address the usefulness of the combination of smartphone and computer-based applications (Smartphone-Kinovea) against a laboratory-based Motion Capture System. One hundred and twelve healthy adults performed three maximal-effort countermovement jumps each. Both instruments measured the heights of the 336 trials concurrently while tracking the excursion of the body center of gravity. The vertical velocity at take-off vto and the impulse J were computed with jump height h measures. Intraclass correlation coefficient (ICC) results indicated very high agreement for h and vto (0.985) and almost perfect agreement for J (0.997), and Cronbach's α=0.99. Low mean differences were observed between instruments for h: -0.22 ± 1.15 cm, vto: -0.01 ± 0.04 m/s, and J: -0.56 ± 2.92 Ns, all p<0.01. The smallest worthwhile change (SWC) and the typical error of measurement (SEM) were 1.34 cm, 0.81 cm for h; 1.15 m/s, 0.03 m/s for vto, and 2.93 Ns, 2.25 Ns for J, so the usefulness of the method is established (SWC/SEM>1). Bland-Altman plots showed very low mean systematic bias ± random errors (-0.22 ± 2.25 cm; -0.01 ± 0.08 m/s; -0.56 ± 5.73 Ns), without association between their magnitudes (r2=0.005, r2=0.005, r2=0.001). Finally, very high to practically perfect correlation between isntruments were observed (r = 0.985; r = 0.986; r = 0.997). Our results suggest that the Smartphone-Kinovea method is a valid and reliable, low-cost instrument to monitor changes in jump performance in a healthy, active population diverse in gender and physical condition.


Bottom-Up Photosynthesis of an Air-Stable Radical Semiconductor Showing Photoconductivity to Full Solar Spectrum and X-Ray.
Single-component semiconductors with photoresponse to full solar spectrum are highly desirable to simplify the device structure of commercial photodetectors and to improve solar conversion or photocatalytic efficiency but remain scarce. This work reports bottom-up photosynthesis of an air-stable radical semiconductor using BiI3 and a photochromism-active benzidine derivative as a photosensitive functional motif. This semiconductor shows photoconductivity to full solar spectrum contributed by radical and non-radical forms of the benzidine derivative. It has also the potential to detect X-rays because of strong X-ray absorption coefficient. This finding opens up a new synthetic method for radical semiconductors and may find applications on extending photoresponsive ranges of perovskites, transition metal sulfides, and other materials.


Development of a pentaplex X-chromosomal short tandem repeat typing system and population genetic studies.
Quadruplex and pentaplex systems for polymerase chain reaction amplification of X-chromosomal short tandem repeats DXS101, HPRTB, DXS8377, DXS981 (STRX1) and DXS6789 were developed for automated profiling of liquid and membrane-bound DNA samples. Chinese, Japanese and Thai populations were typed using a quadruplex system, while German and Philippine populations were analyzed using a five-locus system. Out of 88 meioses studied in Philippine family samples at each locus, a possible one repeat deletion (allele 51 to 50) at DXS8377 was observed in a father-daughter pair. Exact tests performed on genotype data from females in the Philippine, German and Thai populations indicated that these groups conform to Hardy-Weinberg equilibrium. Exact tests for population differentiation indicate significant variations in allele distributions, particularly at loci DXS101, DXS981 and DXS6789. Considered individually, DXS8377 was the most polymorphic and HPRTB the least polymorphic locus in these five populations. When the forensic efficiency of the quadruplex system was calculated, the combined power of discrimination among males (PD(M)) was no lower than 0.998, while among females the combined PD(F) was at least 0.9999 in all populations. The combined power of paternity exclusion was a minimum of 0.998 in trio cases and 0.98 in motherless cases. The addition of locus DXS6789 to the German and Philippine population databases using a pentaplex increased the forensic efficiency of the analysis system.


Species and tissue distribution of cholecystokinin/gastrin-like substances in some invertebrates.
Twenty-six species of invertebrates representing eight phyla were surveyed for the presence of cholecystokinin/gastrin-like (CCK/gastrin-like) peptides by radioimmunoassay of various tissue extracts. This is the first report of the presence of CCK/gastrin-like peptides in representatives of the phylum Ectoprocta, the arthropodan classes Crustacea and Merostomata, and in the nervous systems of the gastropod mollusc Aplysia californica and the oligochaete annelid Lumbricus terrestris. It has been proposed that CCK/gastrin evolved in the invertebrates as a neural peptide and was subsequently exploited by the vertebrates as a regulatory peptide in both the nervous system and the gastrointestinal endocrine system. The present results indicate that some gastropod molluscs, a merostomatan arthropod, and an annelid have detectable CCK/gastrin in both nervous and gut tissue. However, extractable CCK/gastrin was found only in gut tissue and not in the central nervous system of a crustacean arthropod. The tissue origin of the extracted CCK/gastrin in Bugula (phylum Ectoprocta) was not determined. Final resolution of the question of the nervous versus gut endocrine cellular origin of CCK/gastrin in invertebrates awaits further investigation. CCK/gastrin-like peptides are widely distributed among the invertebrates, which thus provide a rich source of comparative material for study of these regulatory substances.


Genetic Modifiers of Sickle Cell Disease.
Sickle cell disease (SCD) is characterized by tremendous phenotypic heterogeneity across patients, but this clinical variability is poorly understood, thus motivating the search for genetic modifiers. The early identification of genetic variants that control fetal hemoglobin levels-a strong modifier of severity in SCD-served as a powerful example in support of these genetic experiments. Although there have been successful discoveries (eg, UGT1A, APOL1), many of the reported genetic associations remain controversial. The emergence of large-scale SCD cohorts and their integration into genetic and other omic-type research programs should bring SCD patients closer to the promises of precision medicine.


DO/ART4 gene sequencing in sub-Saharan cohorts and African migrants: useful data describing the diversity and spreading of rare variants.
Due to the unavailability of immunological reagents, the Dombrock blood group is insufficiently explored in African populations and can be a source of alloimmunization. A large study including pygmoid and nonpygmoid ethnic groups from East, Central, and West continental Africa, together with African migrants like Comorians, Afro-Caribbean from Martinique, and Maroons from French Guiana would be helpful to increase transfusion safety. Using genomic DNA extracted from blood samples collected from 336 nonpygmoid and 51 pygmoid Africans as well as 268 samples of African descent, DO coding regions were PCR-amplified and sequenced. DO*A and DO*B alleles were detected in almost all groups, with a clear predominance of DO*B in every cohort tested. DO*JO and DO*HY allele frequencies reached 10% or more in several ethnic groups. DO*B-SH-Gln149Lys, DO*B-Ile5Thr, and DO*DODE variants were identified both in African ethnic groups and outside Africa. Twelve novel variants were characterized on a DO*A or a DO*B background. Five of them were found in both African and migrant cohorts, the others were restricted to either within or outside Africa. No DO*DOYA, DO*DOLG, DO*DOLC, nor DO*DOMR variants were observed. A first phylogenetic tree was proposed including all variant alleles. This study across continental Africa and countries with African migrants provides a useful overview of Dombrock allele diversity and distribution. The identification of 12 new alleles underlines the importance of genotyping for Dombrock alleles, particularly to improve transfusion safety in countries hosting migrant populations of African descent.


Furosemide kinetics and dynamics in aged patients.
Furosemide (F) is frequently used by elderly persons. We wanted to know whether age-related changes in the disposition or the effect of F occurred and whether these changes could be predicted or explained. Kinetics and diuretic effects were studied after intravenous F injection in geriatric patients (70 to 93 yr of age). The changes in kinetics were as follows: slightly enlarged volume of distribution (0.16 +/- 0.04 l) inversely related to serum albumin, diminished total body clearance (73 +/- 27 ml/min), decreased renal clearance (40 +/- 18 ml/min), and prolonged elimination t1/2 (180 +/- 87 min). F effects were unchanged only if the decreased renal delivery of F and the decreased glomerular filtration rate were taken into account. Renal F clearance correlated best with endogenous creatinine clearance (ECC) and with F effects. Only ECC and plasma creatinine turned out to be useful patient characteristics to predict all F effects. Many drugs have an increased effect in elderly persons if a standard dose is used, based on the attainment of higher free plasma levels. In the case of F, however, the effects are decreased because they depend on decreased glomerular filtration of electrolytes and water and on decreased renal F secretion. These decreases are in part age dependent and in part disease dependent.


Patient experience and quality of urologic cancer surgery in US hospitals.
Care interactions as perceived by patients and families are increasingly viewed as both an indicator and lever for high-value care. To promote patient-centeredness and motivate quality improvement, payers have begun tying reimbursement with related measures of patient experience. Accordingly, the authors sought to determine whether such data correlate with outcomes among patients undergoing surgery for genitourinary cancer. The authors used the Nationwide Inpatient Sample and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) data from 2009 through 2011. They identified hospital admissions for cancer-directed prostatectomy, nephrectomy, and cystectomy, and measured mortality, hospitalization length, discharge disposition, and complications. Mixed effects models were used to compare the likelihood of selected outcomes between the top and bottom tercile hospitals adjusting for patient and hospital characteristics. Among a sample of 46,988 encounters, the authors found small differences in patient age, race, income, comorbidity, cancer type, receipt of minimally invasive surgery, and procedure acuity according to HCAHPS tercile (P<.001). Hospital characteristics also varied with respect to ownership, teaching status, size, and location (P<.001). Compared with patients treated in low-performing hospitals, patients treated in high-performing hospitals less often faced prolonged hospitalization (odds ratio, 0.77; 95% confidence interval, 0.64-0.92) or nursing-sensitive complications (odds ratio, 0.85; 95% confidence interval, 0.72-0.99). No difference was found with regard to inpatient mortality, other complications, and discharge disposition (P>.05). Using Nationwide Inpatient Sample and HCAHPS data, the authors found a limited association between patient experience and surgical outcomes. For urologic cancer surgery, patient experience may be optimally viewed as an independent quality domain rather than a mechanism with which to improve surgical outcomes. Cancer 2016;122:2571-8. © 2016 American Cancer Society.


Variation in postoperative narcotic prescribing after pediatric appendectomy.
Overuse of prescription opioids by both pediatric and adult patients has garnered significant attention in recent years. Educational interventions have been shown to decrease prescription opioids post-operatively in the adult population; similar data have not previously been reported in pediatrics. Educational interventions included staff education, institution of opioid standardization protocol, and distribution of educational materials to families. Chart review was performed pre- and post-intervention to compare prescribing practices following appendectomy in patients less than 19 years of age. Follow-up phone calls were used to assess patient satisfaction and pain control. Three hundred thirteen cases were identified pre-intervention [PRE] and compared to 119 cases postintervention [POST]. 84.3% of patients were given a prescription for opioids at time of discharge in the PRE cohort compared to 6.7% (p < 0.001) POST. There was a significant increase in non-opioid analgesia (p < 0.001) POST. There was no significant variability in opioid usage by type of surgery performed, attending provider, or patients' gender or age. Of the patients in the POST cohort, 60.5% were available for telephone follow-up. More than 80% of patients were given acetaminophen and/or ibuprofen POST and 94.4% reported adequate pain control; 88.9% reported that they would agree to avoid opioids again in the future. On follow-up survey, there was no increase in emergency department visits or phone calls for poorly controlled pain following the intervention. Low-fidelity educational interventions and creation of a standardized pathway is an effective tool to reduce opioid prescribing and promote alternative means of analgesia without an increase in readmissions or presentation for pain. III.


The medical care of children with autism.
The prevalence of autism spectrum disorder (ASD) has increased considerably in the past decades. The primary care paediatrician plays an important role not only in the early recognition of ASD but also in its chronic management. Paediatricians need to be comfortable with the global care of children with ASD. The diagnostic assessment of children with ASD comprises the medical investigations to identify associated or underlying medical conditions. The most important associated conditions are seizures, feeding and gastrointestinal problems, sleep disturbances and dental abnormalities. The care of ASD patients is very demanding since along with the purely medical issues there are challenging behavioural and psychiatric conditions that need consideration and professional skills.


Comparing the Water-Tight Closure of Barbed and Conventional Suture Under Static and Dynamic Conditions in an Ex-Vivo Human Knee Arthrotomy Model.
Barbed suture has become popular for closure of the arthrotomy and overlying tissues in total knee arthroplasty. STRATAFIX Symmetric PDS Knotless Tissue Control Device, a unique and novel barbed suture, with barbs formed integral to the suture core provides greater suture strength than the more common cut barbed suture designs. It is the only barbed suture commercially available with an indication in high tension areas, such as fascia. The purpose of this study was to evaluate the use of this novel barbed suture in the formation of a water-tight arthrotomy closure, using a continuous suture pattern, compared to conventional Coated VICRYL (polyglactin 910) Suture, using an interrupted suture pattern, in a cadaveric knee arthrotomy. Twenty fresh-frozen cadaver knees underwent randomization to provide donor-paired matching of the knee arthrotomy closures using barbed suture in a continuous pattern or conventional suture in an interrupted pattern. Each specimen underwent 5 phases of testing that included 1) predynamic static leak testing; 2) dynamic motion leak testing; 3) postdynamic static leak testing; 4) suture release static leak testing; and 5) postsuture release dynamic motion leak testing, to assess the fluid leak rate. Under the initial static conditions, watertightness was similar for the 2 types of sutures. However, in all subsequent phases of testing, continuous barbed suture created a better watertight closure than interrupted conventional suture. In this study, it was observed that closure of a knee arthrotomy using the novel barbed suture provided improved watertightness compared to conventional interrupted closure under dynamic conditions and suture release.


Latent addition in human motor and sensory axons: different site-dependent changes across the carpal tunnel related to persistent Na+ currents.
To compare site-dependent changes across the carpal tunnel in axonal persistent Na+ conductances in motor and sensory axons. Positive sensory symptoms are prominent features in carpal tunnel syndrome, and a persistent Na+ current is a major determinant of axonal excitability. The technique of latent addition was used to estimate persistent Na+ currents in median motor and sensory axons at the wrist and palm of 10 normal subjects. Brief hyperpolarizing conditioning current pulses were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of persistent Na+ currents. Threshold changes at 0.2 ms were greater in sensory than in motor axons at both the wrist and palm. In motor axons, the threshold changes were significantly smaller at the palm (mean, 4.9%) than at the wrist (10.0%). By contrast, the threshold changes were similar at the two sites of sensory axons (12.6 and 13.1%). The passive membrane time constant was similar for motor and sensory axons at the palm and wrist. Nodal persistent Na+ conductances have substantial site-dependent changes decreasing distally across the carpal tunnel in median motor axons, but not in sensory axons. Whereas sensory axons generally have higher excitability than motor axons, the sensory-motor differences become more prominent across, and possibly at the carpal tunnel than the nerve trunk, and it is suggested that this contributes to the predominance of positive sensory symptoms in carpal tunnel syndrome.


Framing issues in health care: do American ideals demand basic health care and other social necessities for all?
This paper argues for the necessity of universal health care (as well as universal free education) using a different argument than most that have been made heretofore. It is not meant to conflict with but to strengthen the arguments previously made by others. Using the second paragraph of the Declaration of Independence and the Preamble to the Constitution we argue that universal health care in this day and age has become a necessary condition if the ideals of life, liberty and the pursuit of happiness are to be more than an empty promise and if the discussion of "promoting of general welfare" in the preamble is to have any meaning.


Modulation of mammalian cell proliferation by a modified tRNA base of bacterial origin.
Addition of the q-base to q-deficient non-transformed mammalian cells stimulated their proliferation. The q-base also improved proliferation of some cancer-derived cell lines, but inhibited proliferation of others. The proliferation of HeLa-S3 carcinoma cells was stimulated by q under aerobic conditions, but was inhibited when the cells had shifted their energy metabolism towards glycolysis as the result of oxygen limitation. Q-deficient cells could not adapt their proliferation to the respective oxygen tension. The q-base stimulated the proliferation of non-transformed fibroblasts but inhibited proliferation of the same cell line, when aerobic glycolysis was increased after transformation with the ras gene. The results suggest that the q-base permits mammalian cells to adapt their proliferation to their specific metabolic state.


An efficient method for the overexpression and purification of active tyrosinase from Streptomyces castaneoglobisporus.
The melanin-synthesizing gene operon cloned from Streptomyces castaneoglobisporus HUT6202 consists of two genes, designated tyrC and orf378, which encode apotyrosinase (TYRC) and its activator protein (ORF378), respectively. We have suggested that ORF378 may facilitate the incorporation of Cu(II) into apotyrosinase to express tyrosinase activity. To overproduce ORF378 and TYRC in Escherichia coli BL21(DE3)-pLysS, tyrC, and orf378 were independently but not polycistronically placed under the control of a T7 promoter in a vector, pET-21a(+). His(6)-tagged TYRC and His(6)-tagged ORF378 were simultaneously overproduced in an E. coli strain harboring a plasmid, designated pET-mel2, and the two proteins were co-purified with a Ni(II)-bound affinity column. Gel filtration analysis revealed that the two proteins form a heterodimer complex. The complexed protein was retrieved at a high efficiency (11 mg/L). To obtain an active TYRC, which is a Cu(II)-bound form of tyrosinase, we constructed pET-mel3 that carries orf378 without His(6)-tag and His(6)-tagged tyrC. After the cell-free extract from E. coli harboring pET-mel3 was subjected to Cu(II)-bound affinity column chromatography, His(6)-tagged TYRC, eluted from the column, exhibited the tyrosinase activity. The k(cat) and K(m) values for l-3,4-dihydroxyphenylalanine (l-DOPA) of His(6)-tagged TYRC, which catalyzes the oxidation of l-DOPA to dopaquinone, were 880+/-80s(-1) and 8.1+/-0.9 mM, respectively.


Non-invasive assessment of liver fibrosis by serum metabolites in non-human primates and human patients.
Liver fibrosis, a rising cause of chronic liver diseases, could eventually develop into cirrhosis and liver failure. Current diagnosis of liver fibrosis relies on pathological examination of hepatic tissues acquired from percutaneous biopsy, which may produce invasive injuries. Here, for non-invasive assessment of liver fibrosis, we applied comparative multi-omics in non-human primates (rhesus macaques) and subsequent serum biopsy in human patients. Global transcriptomics showed significant gene enrichment of metabolism process, in parallel with oxidative stress and immune responses in fibrotic primates. Targeted metabolomics were concordant with transcriptomic patterns, identifying elevated lipids and porphyrin metabolites during hepatic fibrosis. Importantly, liquid biopsy results validated that specific metabolites in the serum (e.g., biliverdin) were highly diagnostic to distinguish human patients from healthy controls. Findings describe the interconnected transcriptional and metabolic network in primate liver fibrosis and provide potential indices for non-invasive detection of liver fibrosis in humans.


Voxel-based cortical thickness measurements in MRI.
The thickness of the cerebral cortex can provide valuable information about normal and abnormal neuroanatomy. High resolution MRI together with powerful image processing techniques has made it possible to perform these measurements automatically over the whole brain. Here we present a method for automatically generating voxel-based cortical thickness (VBCT) maps. This technique results in maps where each voxel in the grey matter is assigned a thickness value. Sub-voxel measurements of thickness are possible using sub-sampling and interpolation of the image information. The method is applied to repeated MRI scans of a single subject from two MRI scanners to demonstrate its robustness and reproducibility. A simulated data set is used to show that small focal differences in thickness between two groups of subjects can be detected. We propose that the analysis of VBCT maps can provide results that are complementary to other anatomical analyses such as voxel-based morphometry.


Protective effects of oral immunization with formalin-inactivated whole-cell Citrobacter rodentium on Citrobacter rodentium infection in mice.
Evaluation of the efficacy of vaccine candidates that prevent enteropathogenic and enterohemorrhagic Escherichia coli (EPEC/EHEC) infection in mouse models is difficult due to their limited pathogenicity in mice. Citrobacter rodentium, a murine pathogenic bacterium that shares its infection strategy and virulence genes with EPEC/EHEC, has been used as a model pathogen to develop novel vaccine strategies or platforms for these bacteria. However, there are few reports on the comparative effectiveness of novel vaccine platforms as no C. rodentium vaccines have yet been prepared by standard methods such as bacteria attenuation or inactivation. In this study, we investigated the protective effect of the oral administration of formalin-inactivated C. rodentium (Fo-CR) on C. rodentium infection in two mouse strains, C57BL/6 and C3H/HeN, as these strains have different degrees of susceptibility to infection. In C57BL/6 mice, administration of Fo-CR induced significant C. rodentium-specific mucosal and systemic antibody responses, promoted bacterial clearance from the gut and inhibited colonic hyperplasia. Furthermore, in C3H/HeN mice, the administration followed by lethal C. rodentium infection induced significantly high avidity serum IgG specific to C. rodentium and inhibited death, body weight loss, and bacterial invasion to visceral organs. In conclusion, the oral administration of Fo-CR resulted in the protection of mice from C. rodentium infection, indicating that it serves as a reference method for evaluating the efficacy of novel oral vaccine candidates or platforms.


The impact of COVID-19 on the ride-sharing industry and its recovery: Causal evidence from China.
The COVID-19 pandemic has brought unprecedented disruptions to many industries, and the transportation industry is among the most disrupted ones. We seek to address, in the context of a ride-sharing platform, the response of drivers to the pandemic and the post-pandemic recovery. We collected comprehensive trip data from one of the leading ride-sharing companies in China from September 2019 to August 2020, which cover pre-, during-, and post-pandemic phases in three major Chinese cities, and investigate the causal effect of the COVID-19 pandemic on driver behavior. We find that drivers only slightly reduce their number of shifts in response to increased COVID-19 cases, likely because they have to make a living from providing ride-sharing services. Nevertheless, conditional on working, drivers exhibit strong risk aversion: As the number of new cases increases, drivers strategically adjust the scope of their search for passengers, complete fewer trips, and as a result, make lower daily earnings. Finally, our heterogeneity analyses indicate that the effects appear to vary both across drivers and over time, with generally stronger effects on drivers who are older, more experienced, more active before the pandemic, and higher-status within the firm. Our findings have strong policy implications: These drivers tend to contribute more to the focal company, and also rely more on providing ride-sharing services to make a living. Therefore, they should be prioritized in stimulus plans offered by the government or the ride-sharing company.


[Cancer of the breast. II. Prognostic factors (our experience)].
Data concerning different prognostic factors based upon results observed in a group of 212 women operated fro breast carcinoma and submitted to follow-up for 5 consecutive years from diagnosis are reported. Comparing this experience with other Italian and international series, it is concluded that the most reliable prognostic factors are the tumour's size and lymph-node status, while less incisive, though relevant, are the site of the tumour, invasiveness, the grade, the labeling index, hormonal receptor status, the levels of Ca 15.3 and of CEA and the age of the woman at diagnosis.


Fusarium species isolated from post-hatchling loggerhead sea turtles (Caretta caretta) in South Africa.
Species in the Fusarium solani species complex are fast growing, environmental saprophytic fungi. Members of this genus are filamentous fungi with a wide geographical distribution. Fusarium keratoplasticum and F. falciforme have previously been isolated from sea turtle nests and have been associated with high egg mortality rates. Skin lesions were observed in a number of stranded, post-hatchling loggerhead sea turtles (Caretta caretta) in a rehabilitation facility in South Africa. Fungal hyphae were observed in epidermal scrapes of affected turtles and were isolated. The aim of this study was to characterise the Fusarium species that were isolated from these post-hatchling loggerhead sea turtles (Caretta caretta) that washed up on beaches along the South African coastline. Three gene regions were amplified and sequenced, namely the internal transcribed spacer region (ITS), a part of the nuclear large subunit (LSU), and part of the translation elongation factor 1 α (tef1) gene region. Molecular characteristics of strains isolated during this study showed high similarity with Fusarium isolates, which have previously been associated with high egg mortality rates in loggerhead sea turtles. This is the first record of F. keratoplasticum, F. falciforme and F. crassum isolated from stranded post-hatchling loggerhead sea turtles in South Africa.


Evaluation of the processing functions of a digital subtraction angiography image processor.
A large number of imaging systems for digital subtraction angiography (DSA) are now commercially available. Numerous evaluations of the performance of these systems have been reported in the literature. However systematic evaluations of the processing functions of DSA image processors have not been widely reported. Such an evaluation for one commercial system is presented in this paper. Functions evaluated include linear transformation, logarithmic transformation, integration, subtraction and temporal filtration. The observations indicate that image processing results are frequently achieved by indirect routes which compromise the fidelity of the image data.


RNAP II processivity is a limiting step for HIV-1 transcription independent of orientation to and activity of endogenous neighboring promoters.
Since HIV-1 has a propensity to integrate into actively expressed genes, transcriptional interference from neighboring host promoters has been proposed to contribute to the establishment and maintenance HIV-1 latency. To gain insights into how endogenous promoters influence HIV-1 transcription we utilized a set of inducible T cell lines and characterized whether there were correlations between expression of endogenous genes, provirus and long terminal repeat architecture. We show that neighboring promoters are active but have minimal impact on HIV-1 transcription, in particular, expression of the endogenous gene did not prevent expression of HIV-1 following induction of latent provirus. We also demonstrate that releasing paused RNAP II by diminishing negative elongation factor (NELF) is sufficient to reactivate transcriptionally repressed HIV-1 provirus regardless of the integration site and orientation of the provirus suggesting that NELF-mediated RNAP II pausing is a common mechanism of maintaining HIV-1 latency.


Combining a hip arthroplasty stem with trochanteric reattachment bolt and a polyaxial locking plate in the treatment of a periprosthetic fracture below a well-integrated implant.
Distally anchored uncemented modular tapered porous stems are often the preferred treatment in total hip arthroplasty revisions and failed subtrochanteric fractures. These conditions mainly affect elderly osteoporotic patients, with an increased risk of later fractures below the well-fixated implant. Treatment in secondary fractures with long looking plates is the recommended treatment, where stability is a key to fracture healing. We report a complicated case in which this was achieved by an innovative technique combing the trochanteric attachment bolt of the stem system and a locking plate with polyaxial screws.


[Malignant pleural mesothelioma: comparison of radical pleurectomy und extrapleural pneumonectomy].
The role of surgical resection per se and the type of surgery in the management of multimodality treated malignant pleural mesothelioma remains controversial. Patient selection for either extrapleural pneumonectomy or radical pleurectomy depends not only on the cardiopulmonary status of the patient, tumor stage and intraoperative findings but is also strongly influenced by surgeons' preference, experience and philosophy. The aim of this review is to compare extrapleural pneumonectomy and radical pleurectomy with regard to surgical technique, morbidity, mortality and survival.


Novel intrathecal delivery system for treatment of spinal cord injury.
A novel, localized method for potential delivery of therapeutic agents to the injured spinal cord was investigated. The strategy consists of a polymeric drug solution that gels after injection into the subarachnoid space (SAS). By dispersing therapeutic agents in the polymeric solution, a method is provided for localized delivery to the spinal cord. To determine whether intrathecal injection of this drug delivery system (DDS) would affect cerebrospinal fluid (CSF) flow, a spinal canal model was built using dimensional analysis. Blocking up to 52% of the modeled subarachnoid space of the spinal canal caused minimal pressure differences (9.22 +/- 1.45 Pa), suggesting that implantation of a DDS would not subject the spinal cord to increased pressure. The safety of the DDS was also assessed in vivo by injecting collagen into the SAS of Sprague Dawley rats. Controls received injections of artificial CSF (aCSF). Collagen or aCSF was injected at the T2-T3 spinal level of both uninjured rats and rats injured with a 20g compression clip. The injected collagen persisted in the SAS for at least 8 weeks post-implantation and did not elicit an inflammatory reaction in either uninjured or injured animals. Long-term functional behavior was evaluated with the Basso, Beattie, and Bresnahan (BBB) scale weekly for 8 weeks. Functional behavior was similar in the collagen and aCSF groups, also indicating that the DDS was safe. This minimally invasive DDS may provide an alternative, safe method to deliver therapeutic agents intrathecally.


Rehabilitation for Parkinson's disease: Current outlook and future challenges.
Rehabilitation is considered as an adjuvant to pharmacological and surgical treatments for Parkinson's disease (PD) to maximize functional ability and minimize secondary complications. Originally, approaches were based on empirical experience, but growing evidence suggests that exercise-dependent plasticity constitutes the main mechanism underlying the effects of physiotherapy. Exercise increases synaptic strength and influences neurotransmission, thus potentiating functional circuitry in PD. In addition, exercise is a pivotal element of motor learning. PD patients retain a sufficient capacity of motor learning, though learning rates and performance are reduced in comparison to normal controls. Recent meta-analyses demonstrated that rehabilitation could induce short-lasting, but clinically important benefits, particularly for gait and balance. However, the interventions are largely heterogeneous (stretching, muscle strengthening, balance, postural exercises, occupational therapy, cueing, treadmill training), and there is still no consensus about the optimal approach. Innovative techniques have been recently proposed: virtual reality and exergaming, motor imagery and action observation, robot-assisted physiotherapy and non-conventional therapies (e.g.: dance, martial arts). The rehabilitative program for PD should be "goal-based" (targeted to practicing and learning specific activities in the core areas), but a number of practice variables (intensity, specificity, complexity) need to be identified and the program should tailored to the individual patients' characteristics.


Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury.
Evidence indicates that both necrotic and apoptotic cell death contribute to tissue injury and neurological dysfunction following spinal cord injury. Caspases have been implicated as important mediators of apoptosis following acute central nervous system insults. We investigated whether caspase-1 and caspase-3 are involved in spinal cord injury-mediated cell death, and whether caspase inhibition may reduce tissue damage and improve outcome following spinal cord injury. We demonstrate a 17-fold increase in caspase-1 activity in traumatized spinal cord samples when compared with samples from sham-operated mice. Caspase-1 and caspase-3 activation were also detected by western blot following spinal cord injury, which was significantly inhibited by the broad caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. By immunofluorescence or in situ fluorogenic substrate assay, caspase-1 and caspase-3 expression were detected in neuronal and non-neuronal cells following spinal cord injury. N-Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone treated mice, and transgenic mice expressing a caspase-1 dominant negative mutant, demonstrated a significant improvement of motor function and a reduction of lesion size compared with vehicle-treated mice. Our results demonstrate for the first time that both caspase-1 and caspase-3 are activated in neurons following spinal cord injury, and that caspase inhibition reduces post-traumatic lesion size and improves motor performance. Caspase inhibitors may be one of the agents to be used for the treatment of spinal cord injury.


Targeted delivery of a PD-1-blocking scFv by CD133-specific CAR-T cells using nonviral Sleeping Beauty transposition shows enhanced antitumour efficacy for advanced hepatocellular carcinoma.
CD133 is considered a marker for cancer stem cells (CSCs) in several types of tumours, including hepatocellular carcinoma (HCC). Chimeric antigen receptor-specific T (CAR-T) cells targeting CD133-positive CSCs have emerged as a tool for the clinical treatment of HCC, but immunogenicity, the high cost of clinical-grade recombinant viral vectors and potential insertional mutagenesis limit their clinical application. CD133-specific CAR-T cells secreting PD-1 blocking scFv (CD133 CAR-T and PD-1 s cells) were constructed using a sleeping beauty transposon system from minicircle technology, and the antitumour efficacy of CD133 CAR-T and PD-1 s cells was analysed in vitro and in vivo. A univariate analysis showed that CD133 expression in male patients at the late stage (II and III) was significantly associated with worse progression-free survival (PFS) (P = 0.0057) and overall survival (OS) (P = 0.015), and a multivariate analysis showed a trend toward worse OS (P = 0.041). Male patients with advanced HCC exhibited an approximately 20-fold higher PD-L1 combined positive score (CPS) compared with those with HCC at an early stage. We successfully generated CD133 CAR-T and PD-1 s cells that could secrete PD-1 blocking scFv based on a sleeping beauty system involving minicircle vectors. CD133 CAR-T and PD-1 s cells exhibited significant antitumour activity against HCC in vitro and in xenograft mouse models. Thus, CD133 CAR-T and PD-1 s cells may be a therapeutically tractable strategy for targeting CD133-positive CSCs in male patients with advanced HCC. Our study provides a nonviral strategy for constructing CAR-T cells that could also secrete checkpoint blockade inhibitors based on a Sleeping Beauty system from minicircle vectors and revealed a potential benefit of this strategy for male patients with advanced HCC and high CD133 expression (median immunohistochemistry score > 2.284).


Response of brain tissue to chronically implanted neural electrodes.
Chronically implanted recording electrode arrays linked to prosthetics have the potential to make positive impacts on patients suffering from full or partial paralysis. Such arrays are implanted into the patient's cortical tissue and record extracellular potentials from nearby neurons, allowing the information encoded by the neuronal discharges to control external devices. While such systems perform well during acute recordings, they often fail to function reliably in clinically relevant chronic settings. Available evidence suggests that a major failure mode of electrode arrays is the brain tissue reaction against these implants, making the biocompatibility of implanted electrodes a primary concern in device design. This review presents the biological components and time course of the acute and chronic tissue reaction in brain tissue, analyses the brain tissue response of current electrode systems, and comments on the various material science and bioactive strategies undertaken by electrode designers to enhance electrode performance.


Problems and approaches to the control and surveillance of sexually transmitted agents associated with pelvic inflammatory disease in the United States.
The national gonorrhea control program has expanded since its inception in 1972 and now reflects new information and program evaluations. Initial program objectives to reduce the incidence of disease and the resistance of gonococci to antibiotics have been expanded to reduce the occurrence of pelvic inflammatory disease and to limit the sequelae of PID. The changes since 1972 in the national venereal disease control program have increased the number of people helping control programs and have enhanced our ability to control other sexually transmitted diseases.


Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis.
Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell(+)] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes.


Tight finite-key analysis for quantum cryptography.
Despite enormous theoretical and experimental progress in quantum cryptography, the security of most current implementations of quantum key distribution is still not rigorously established. One significant problem is that the security of the final key strongly depends on the number, M, of signals exchanged between the legitimate parties. Yet, existing security proofs are often only valid asymptotically, for unrealistically large values of M. Another challenge is that most security proofs are very sensitive to small differences between the physical devices used by the protocol and the theoretical model used to describe them. Here we show that these gaps between theory and experiment can be simultaneously overcome by using a recently developed proof technique based on the uncertainty relation for smooth entropies.


Synthesis and SAR of ⁹⁹mTc/Re-labeled small molecule prostate specific membrane antigen inhibitors with novel polar chelates.
Prostate specific membrane antigen (PSMA) is recognized as an attractive molecular target for the development of radiopharmaceuticals to image and potentially treat metastatic prostate cancer. A series of novel (99m)Tc/Re-tricarbonyl radiolabeled PSMA inhibitors were therefore synthesized by the attachment of glutamate-urea-lysine (Glu-urea-Lys) and glutamate-urea-glutamate (Glu-urea-Glu) pharmacophore to single amino acid chelate (SAAC) where the SAAC ligand was either bis(pyridin-2-ylmethyl)amino (DPA), bis((1-methyl-1H-imidazol-2-yl)methyl)amino (NMI), bis((1-(carboxymethyl)-1H-imidazol-2-yl)methyl)amino (CIM) or bis((1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino (TIM). The in vitro binding affinity of the rhenium complexes was evaluated using PSMA-expressing human prostate cancer LNCaP cells. IC(50) values ranged from 3.8 ± 2 to >2000 nM. A linker between the SAAC chelate and pharmacophore was required for high affinity binding. However, extending the length of the linker did not substantially improve binding. PSMA binding was also influenced by the nature of the SAAC chelate. One of the most potent compounds, 23b (IC(50)=4.8 ± 2.7 nM), was radiolabeled with technetium tricarbonyl ({(99m)Tc(CO)(3)}(+)) to afford the {(99m)Tc(CO)(3)}(+) complex in excellent yield and high purity. This effort has led to the identification of a diverse series of promising high affinity {(99m)Tc(CO)(3)}(+) radiolabeled PSMA inhibitors.


Principles and applications of polymerase chain reaction: basic science for the practicing physician.
To review the technology of polymerase chain reaction (PCR) and its use in diagnostic medicine and biomedical research. A literature review was performed using the PubMed database for English-language articles published between January 1, 1985, and November 31, 2007, using the following keywords: polymerase chain reaction, real-time polymerase chain reaction, and applications of real-time polymerase chain reaction. Select review articles and primary articles relevant to medical applications of PCR were chosen. As a revolutionary technique, PCR provides a rapid and accurate means of amplifying DNA. It has enabled the cloning and manipulation of genes for biomedical research and has facilitated the diagnosis of genetic, infectious, and oncologic diseases. The use of reverse transcriptases to evaluate RNA levels and the extension of PCR technology to quantify DNA amplification in real time has brought major advances to the application of PCR. By allowing the determination and quantification of changes in gene expression, these techniques have provided a greater understanding of disease processes and now serve as a foundation for diagnostics and basic science research. Both PCR and real-time PCR have dramatically changed the field of basic science and diagnostic medicine. These technologies are now a well-established, indispensable part of research and clinical laboratories.


Understanding the antioxidant behavior of some vitamin molecules: a first-principles density functional approach.
The structures, energetics, vertical and adiabatic ionization potentials, electron affinities, and global reactivity descriptors of antioxidant vitamins (both water- and fat-soluble) in neutral, positively charged, and negatively charged states were investigated theoretically. We worked within the framework of first-principles density functional theory (DFT), using the B3LYP functional and both localized (6-311G+(d,p) and plane-wave basis sets. Solvent effects were modeled via the polarizable continuum model (PCM), using the integral equation formalism variant (IEFPCM). From the computed structural parameters, ionization potentials, electron affinities, and spin densities, we deduced that these vitamins prefer to lose electrons to neutral reactive oxygen species (·OH and ·OOH), making them good antioxidants. Conceptual DFT was used to determine global chemical reactivity parameters. The computed chemical hardnesses showed that these antioxidant vitamins are more reactive than neutral reactive oxygen species (ROS), thus supporting their antioxidant character towards these species. However, in the neutral state, these vitamins do not act as antioxidants for [Formula: see text]. The reactivity of vitamins towards ROS depends on the nature of the solvent. Amongst the ROS, ·OH has the greatest propensity to attract electrons from a generic donor. The reactivities of fat-soluble vitamins towards neutral reactive oxygen species were found to be larger than those of water-soluble vitamins towards these species, showing that the former are better antioxidants.


Patterns of care as a risk factor for the development of vision-threatening diabetic retinopathy: a population-based matched case-control study using insurance claims (Medicare) data.
To evaluate systematically the effectiveness of the primary healthcare system in Australia in preventing the development of advanced diabetes complications. Diabetes patients (n = 4632) who had received their first laser photocoagulation treatment in 2000 were compared with a random sample of diabetes patients who had never received this treatment (n = 4632). Patterns of health care utilization were compared over a 7-year period (1993-1999) using the Australian Medicare database. There were significant differences in levels of healthcare utilization: cases were less likely to attend a general practitioner, from odds ratio (OR) = 0.21 (P < 0.0001) in 1993 to 0.53 (P < 0.0001) in 1999; less likely to be tested for HbA(1c), from OR = 0.24 in 1997 (P < 0.0001) to 0.38 in 1999 (P < 0.0001); for HDL-cholesterol, from OR = 0.017 (P < 0.0001) in 1999 to 0.04 (P < 0.0001) in 1993; and to attend specialists and consultant physicians, from OR = 0.25 (P < 0.0001) in 1994 to 0.44 (P < 0.0001) in 1999. The multivariate analysis emphasized the importance of timely diagnosis, HDL-cholesterol testing and optometry attendances in the prevention of advanced diabetes complications. The study supports the contention that healthcare utilization may be as important a determinant of health outcomes as clinical risk factors such as blood glucose control. This highlights the importance of early diagnosis and the need to address systemic barriers so as to increase primary care utilization for people at risk of advanced diabetes complications.