Determination of Interfacial Charge-Transfer Rate Constants in Perovskite Solar Cells.
A simple protocol to study the dynamics of charge transfer to selective contacts in perovskite solar cells, based on time-resolved laser spectroscopy studies, in which the effect of bimolecular electron-hole recombination has been eliminated, is proposed. Through the proposed procedure, the interfacial charge-transfer rate constants from methylammonium lead iodide perovskite to different contact materials can be determined. Hole transfer is faster for CuSCN (rate constant 0.20 ns(-1) ) than that for 2,2',7,7'-tetrakis-(N,N-di-4-methoxyphenylamino)-9,9'-spirobifluorene (spiro-OMeTAD; 0.06 ns(-1) ), and electron transfer is faster for mesoporous (0.11 ns(-1) ) than that for compact (0.02 ns(-1) ) TiO2 layers. Despite more rapid charge separation, the photovoltaic performance of CuSCN cells is worse than that of spiro-OMeTAD cells; this is explained by faster charge recombination in CuSCN cells, as revealed by impedance spectroscopy. The proposed direction of studies should be one of the key strategies to explore efficient hole-selective contacts as an alternative to spiro-OMeTAD.


Selective disruption of genes transiently induced in differentiating mouse embryonic stem cells by using gene trap mutagenesis and site-specific recombination.
A strategy employing gene trap mutagenesis and site-specific recombination (Cre/loxP) has been used to identify genes that are transiently expressed during early mouse development. Embryonic stem cells expressing a reporter plasmid that codes for neomycin phosphotransferase and Escherichia coli LacZ were infected with a retroviral gene trap vector (U3Cre) carrying coding sequences for Cre recombinase (Cre) in the U3 region. Activation of Cre expression from integrations into active genes resulted in a permanent switching between the two selectable marker genes and consequently the expression of beta-galactosidase (beta-Gal). As a result, clones in which U3Cre had disrupted genes that were only transiently expressed could be selected. Moreover, U3Cre-activating cells acquired a cell autonomous marker that could be traced to cells and tissues of the developing embryo. Thus, when two of the clones with inducible U3Cre integrations were passaged in the germ line, they generated spatial patterns of beta-Gal expression.


FTO genotype and weight gain in obese and normal weight adults from a Norwegian population based cohort (the HUNT study).
The fat mass and obesity associated gene ( FTO) is associated with bodyweight and obesity. The aim of this study was to investigate if FTO genotype affects weight gain in adulthood. We investigated the weight development over a period of 11 years in a case-control study, consisting of 1,632 cases (BMI≥35 kg/m (2)) and 3,379 normal weight controls (BMI 20-24.9 kg/m (2)) from a Norwegian population based cohort, the HUNT study. Subjects were aged 20-80 at baseline, 25% men and 75% women. FTO genotype was assessed by genotyping of the SNP rs1421085. A strong association between FTO and obesity was found, consistent with an additive gene effect. Cases had an average weight gain of 11.1 kg, whereas controls had an average weight gain of 1.4 kg. Genotype was neither associated with weight gain in obese, nor controls. Cases had an average weight gain of 10.7 kg for individuals with zero risk alleles, 11.3 for one risk allele and 11.1 kg for two risk alleles. Controls had an average weight gain of 1.4 kg, 1.4 and 1.3 for the respective genotypes. In conclusion, FTO was associated with obesity, but not with weight gain in adults during 11 years of follow-up.


Measurement of the energy dependence of X-ray-induced decomposition of potassium chlorate.
We report the first measurements of the X-ray induced decomposition of KClO3 as a function of energy in two experiments. KClO3 was pressurized to 3.5 GPa and irradiated with monochromatic synchrotron X-rays ranging in energy from 15 to 35 keV in 5 keV increments. A systematic increase in the decomposition rate as the energy was decreased was observed, which agrees with the 1/E(3) trend for the photoelectric process, except at the lowest energy studied. A second experiment was performed to access lower energies (10 and 12 keV) using a beryllium gasket; suggesting an apparent resonance near 15 keV or 0.83 Ǻ maximizing the chemical decomposition rate. A third experiment was performed using KIO3 to ascertain the anionic dependence of the decomposition rate, which was observed to be far slower than in KClO3, suggesting that the O-O distance is the critical factor in chemical reactions. These results will be important for more efficiently initiating chemical decomposition in materials using selected X-ray wavelengths that maximize decomposition to aid useful hard X-ray-induced chemistry and contribute understanding of the mechanism of X-ray-induced decomposition of the chlorates.


Dynamic proteome changes of Shigella flexneri 2a during transition from exponential growth to stationary phase.
Shigella flexneri is an infectious pathogen that causes dysentery to human, which remains a serious threat to public health, particularly in developing countries. In this study, the global protein expression patterns of S. flexneri during transition from exponential growth to stationary phase in vitro were analyzed by using 2-D PAGE combined with MALDI-TOF MS. In a time-course experiment with five time points, the relative abundance of 49 protein spots varied significantly. Interestingly, a putative outer membrane protein YciD (OmpW) was almost not detected in the exponential growth phase but became one of the most abundant proteins in the whole stationary-phase proteome. Some proteins regulated by the global regulator FNR were also significantly induced (such as AnsB, AspA, FrdAB, and KatG) or repressed (such as AceEF, OmpX, SodA, and SucAB) during the growth phase transition. These proteins may be the key effectors of the bacterial cell cycle or play important roles in the cellular maintenance and stress responses. Our expression profile data provide valuable information for the study of bacterial physiology and form the basis for future proteomic analyses of this pathogen.


A high proportion of novel mycobacteria species identified by 16S rDNA analysis among slowly growing AccuProbe-negative strains in a clinical setting.
Sequencing of the 16S ribosomal DNA (rDNA) for identification of nontuberculous mycobacteria (NTM) has contributed to the establishment of more than 35 new species during the last decade. Increasingly, NTM are accepted as potential or proven pathogens. We identified, by 16S rDNA sequence analysis, slowly growing NTM isolates negative by AccuProbe (GenProbe, San Diego, CA) that previously were identified by using conventional biochemical techniques, to determine the accuracy of reporting AccuProbe-negative NTM prior to sequence-based identification. Of 82 strains, 30 were deemed novel. An attempt was made to determine the clinical importance of previously misidentified novel species. Clinical cases are described for a number of strains previously identified as Mycobacterium terrae complex, Mycobacterium scrofulaceum, and Mycobacterium avium complex. As sequence-based identification methods become more commonplace in clinical microbiology laboratories, there is a need to understand the significance of previously undescribed species, which often mimic and subsequently are identified as well-established species.


Treatment Trends, Complications, and Effects of Comorbidities on Distal Radius Fractures.
Background: Distal radius fractures (DRFs) are the most common upper extremity fractures in adults. This study seeks to elucidate the impact age, fracture type, and patient comorbidities have on the current treatment of DRFs and risk of complications. We hypothesized that comorbidities rather than age would relate to the risk of complications in the treatment of DRFs. Methods: A retrospective review of data was performed for patients treated between 2007 and 2014 using Truven Health MarketScan Research Databases. Patients who sustained a DRF were separated into "closed" versus "open" treatment groups, and the association between patient demographics, treatment type, and comorbidities with complication rates was analyzed, along with the trend of treatment modalities throughout the study time interval. Results: In total, 155 353 DRFs were identified; closed treatment predominated in all age groups with the highest percentage of open treatment occurring in the 50- to 59-year age group. Between 2007 and 2014, there was an increase in the rate of open reduction and internal fixation (ORIF) in all age groups <90 with the largest increase (11%) occurring in the 70- to 79-year age group. Higher complication rates were observed in the open treatment group in all ages <90 years with a trend toward decreasing complication rates as age increased. Comorbidities were more strongly associated with the risk of developing complications than age. Conclusions: Closed treatment of DRFs remains the predominant treatment method among all age groups, but DRFs are increasingly being treated with ORIF. Emphasis on the patients' comorbidities rather than chronological age should be considered in the treatment decision-making process of elderly patients with DRFs.


[Functional evaluation of the supraspinatus tendon repair comparing mini-open and open techniques].
To compare two surgical techniques to address the painful shoulder syndrome with partial or total supraspinous tendon tear. Patients with a diagnosis of complete supraspinous tendon tear who required surgical repair and subacromial decompression. One group was treated with acromioplasty and tendon plasty using an open approach (G1), and the second one underwent arthroscopy with tendon plasty using a minimally-invasive approach (G2). The surgical approach was not decided at random, but was based on the surgeons preference. The major outcome was functional assessment at postoperative month 12 using the UCLA scale. The variables compared were the operative time, anesthesia time, intraoperative bleeding, and immediate complications. Means and standard deviations were analyzed for the quantitative variables, and percentages for the qualitative variables. The U Mann-Whitney test was used to compare the ranges of non-related groups. Thirty-two patients were included in G1, and 13 in G2. No differences were found in age, gender, comorbid conditions, and the time elapsed before surgical treatment. G2 patients were found to have better function according to the UCLA scale (p = 0.032). No differences were reported in the operative time (60 versus 80 minutes, p = 0.12), anesthesia time (120 versus 97 minutes, p = 0.12), total bleeding (50 ml in both groups, p = 0.09), or length of stay (2 versus 1, p = 0.81). No immediate complications were reported. Arthroscopic repair plus a minimally-invasive approach to treat subacromial impingement and supraspinous tendon tear seems to provide better clinical outcomes based on function recovery and patient satisfaction.


[Cholaemic placentosis--a contribution to metabolic disorders of the placenta].
The deposition of bile substances produces intracellular metabolic disorders in the organs so affected. Since severe cholaemia is rare in pregnancy, similar disorders of the placental cells have been not discussed up to now. We report on morphological observations in a placenta of a stillbirth in the middle of pregnancy. Bile substances are deposited in the syncytiotrophoblast and Hofbauer cells, pointing to the probable function of the Hofbauer cells as macrophages.


Role of PTB-like protein, a neuronal RNA-binding protein, during the differentiation of PC12 cells.
PTB-like protein (PTBLP) is a new homologue of pyrimidine tract binding protein (PTB), and has been cloned as a possible autoantigen in cancer-associated retinopathy. PTBLP has two functional domains, the nuclear localization signal and the RNA recognition motifs (RRMs). Full-length PTBLP (PTBLP-L) has four RRMs, and its alternative splicing product (PTBLP-S) lacks the third and fourth RRMs. Although PTBLPs are expressed in neuronal tissues, the function of PTBLPs has not been determined. We have studed whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of nerve growth factor-induced neuronal differentiation of PC12 cells, PTBLP-L was down-regulated whereas PTBLP-S was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L.


Quantifying the Benefits of Genome-Driven Oncology.
<b/> The excitement surrounding genomically selected cancer therapy has led many to question whether this treatment paradigm is living up to its initial promise. The MOSCATO study suggests that a genome-driven strategy for cancer therapy improves outcomes in a significant minority of patients who undergo molecular screening. Cancer Discov; 7(6); 552-4. ©2017 AACR.See related article by Massard et al., p. 586.


The application of STEM and in situ controlled dehydration to bacterial systems using ESEM.
Transmission imaging with an environmental scanning electron microscope (ESEM) (Wet STEM) is a recent development in the field of electron microscopy, combining the simple preparation inherent to ESEM work with an alternate form of contrast available through a STEM detector. Because the technique is relatively new, there is little information available on how best to apply this technique and which samples it is best suited for. This work is a description of the sample preparation and microscopy employed by the authors for imaging bacteria with Wet STEM (scanning transmission electron microscopy). Three different bacterial samples will be presented in this study: first, used as a model system, is Escherichia coli for which the contrast mechanisms of STEM are demonstrated along with the visual effects of a dehydration-induced collapse. This collapse, although clearly in some sense artifactual, is thought to lead to structurally meaningful morphological information. Second, Wet STEM is applied to two distinct bacterial systems to demonstrate the novel types of information accessible by this approach: the plastic-producing Cupriavidus necator along with wild-type and ΔmreC knockout mutants of Salmonella enterica serovar Typhimurium. Cupriavidus necator is shown to exhibit clear internal differences between bacteria with and without plastic granules, while the ΔmreC mutant of S. Typhimurium has an internal morphology distinct from that of the wild type.


Preparation and visible light photocatalytic activity of N-doped titania.
N-doped titania powders were prepared with titanium tetraisopropoxide (TTIP) as the titanium source and urea as the nitrogen source by the sol-gel method. The samples were characterized using X-ray diffraction (XRD), diffuse reflectance spectrum (DRS), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). The XRD and TEM results indicated that urea played an important role in controlling the size and aggregation process of titania nanoparticles. As an appropriate amount of urea was added into the titania sol, the size of the particles decreased. However, the excess urea reduced the dispersion of the particles and resulted in the aggregation. At the same time, the size of particle increased, and the size distribution broadened. The XPS and DRS results showed that the nitrogen was incorporated into titania lattice successfully, which brought about the redshift of the absorption edge and induced the photocatalytic activity in the visible light region. The photocatalytic experiments showed that the N-doped titania nanoparticles could effectively photodegrade methyl orange (MO) aqueous solution under visible light irradiation. The photocatalytic activity increased with the increase of the nitrogen doping level in the titania lattice, but decreased with the increase of the particle size and the organic surface residues caused by excess urea.


Antioxidant activity of leaf extracts from different Hibiscus sabdariffa accessions and simultaneous determination five major antioxidant compounds by LC-Q-TOF-MS.
Hibiscus sabdariffa has gained attention for its antioxidant activity. There are many accessions of H. sabdariffa in the world. However, information on the quantification of antioxidant compounds in different accessions is rather limited. In this paper, a liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) method for simultaneous determination of five antioxidant compounds (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, and isoquercitrin) in H. sabdariffa leaves was developed. The method was validated for linearity, sensitivity, precision, repeatability and accuracy. The validated method has been successfully applied for determination of the five analytes in eight accessions of H. sabdariffa. The eight accessions of H. sabdariffa were evaluated for their antioxidant activities by DPPH free radical scavenging assay. The investigated accessions of H. sabdariffa were rich in rutin and exhibited strong antioxidant activity. The two accessions showing the highest antioxidant activities were from Cuba (No. 2) and Taiwan (No. 5). The results indicated that H. sabdariffa leaves could be considered as a potential antioxidant source for the food industry. The developed LC-Q-TOF-MS method is helpful for quality control of H. sabdariffa.


The forgetting health system.
Forgetting shapes learning in two different ways. It impedes learning when important lessons are forgotten. Equally, it can be difficult to enact new lessons if we do not let go of old beliefs and practices that are no longer useful. A learning health system (LHS) that wishes to improve health service delivery will need to find ways to remember processes that shape quality and safety - using data that often resides beyond electronic health records. An LHS will also need to "forget", or programmatically decommission, obsolete practices, whose persistence otherwise leads to unnecessary system complexity and inertia to change. New forms of data needed to improve health services include process metrics extracted from digital systems; human-level metrics that capture workflow patterns and clinician behaviors; and multivariate process patterns that can identify service "syndromes." To avoid inertia to change, system complexity must be reduced by retiring (or forgetting) inefficient or unhelpful work practices. Biological models of programmed cell death provide a rich set of mechanisms to decommission elements of health services. These models suggest health service elements should be able to detect the end of their useful life and should contain internal mechanisms to orchestrate decommissioning-in contrast to current service decommissioning, which is an externally initiated, top-down down-driven process. An LHS should take advantage of digital infrastructure to bring together people, sensors, analytics, and quasi-autonomous mechanisms for service adaptation. By drawing inspiration from biology, we can design LHSs that do not just remember but also actively forget.


Antibacterial activity of restorative dental biomaterials in vitro.
This study investigated the antibacterial effects against Streptococcus mutans of a fine-hybrid resin composite (FH-RC; Tetric ceram), an ion-releasing resin composite (Ariston pHc), a self-curing glass ionomer cement (SC-GIC; Ketac-Molar), a resin-modified GIC (RM-GIC; Photac-Fil), and a zinc oxide eugenol cement (ZOE; IRM). In a novel assay, bacterial suspensions were placed into narrow 20-microl conical cavities within the materials. After 0, 4, 8, 24, 48 h and 1 week of incubation, the suspensions were removed from the restoratives and the numbers of viable bacteria were determined. After incubation periods of 8 h or more, all restorative materials except the FH-RC showed significant growth inhibition when compared with controls. The strongest antibacterial activity was observed with ZOE. The inhibitory effect of Ariston pHc was similar to that of the SC-GIC and the RM-GIC. In the second assay, growth inhibition was evaluated in liquid cultures by incubating eluates of the materials with suspensions of S. mutans. Bacterial growth was determined up to 6 h by measuring absorption at 600 nm. The most marked inhibitory effect was again observed with ZOE. The SC-GIC caused a significant inhibition at all time intervals but the FH-RC, the RM-GIC and Ariston pHc exhibited no significant antibacterial effects. It is recommended to employ more than one method for assessing the antibacterial potential of restorative materials. Long-term clinical trials are necessary to determine whether the antimicrobial effects of dental materials are able to reduce the risk of secondary caries formation.


A Radical Reassessment of the Body in Social Cognition.
The main issue addressed in this paper is to provide a reassessment of the role and relevance of the body in social cognition from a radical embodied cognitive science perspective. Initially, I provide a historical introduction of the traditional account of the body in cognitive science, which I here call the cognitivist view. I then present several lines of criticism raised against the cognitivist view advanced by more embodied, enacted and situated approaches in cognitive science, and related disciplines. Next, I analyze several approaches under the umbrella of embodied social cognition. My line of argument is that some of these approaches, although pointing toward the right direction of conceiving that the social mind is not merely contained inside the head, still fail to fully acknowledge the radically embodied social mind. I argue that the failure of these accounts of embodied social cognition could be associated with so-called 'simple embodiment.' The third part of this paper focuses on elaborating an alternative characterization of the radically embodied social mind that also tries to reduce the remaining problems with 'simple embodiment.' I draw upon two turns in radically embodied cognitive science, the enactive turn, and the intersubjective turn. On the one hand, there is the risk of focusing too much on the individual level in social cognition that may result in new kinds of methodological individualism that partly neglect the social dimension. On the other hand, socially distributed and socially extended approaches that pay more attention to the dynamics within social interaction may encounter the risk of ignoring the individual during social interaction dynamics and simultaneously not emphasizing the role of embodiment. The approach taken is to consider several ways of describing and incorporating the (individual) social mind at the social level that includes language. I outline some ideas and motivations for how to study and expand the field of radical embodied social cognition in the future, as well as pose the ubiquitous hazard of falling back into a cognitivism view in several ways.


Rhapidosomes: 2'-O-methylated ribonucleoproteins.
Methylation of the RNA component from seven flexibacterial rhapidosomes varied in extent, distribution along the RNA chain, and distribution between nucleotides. Flexibacterial soluble and ribosomal RNA had normal (low) methylation.


Immunophenotypic differences between intestinal-type and low-grade papillary sinonasal adenocarcinomas: an immunohistochemical study of 22 cases utilizing CDX2 and MUC2.
Nonsalivary sinonasal adenocarcinomas can be divided into low-grade and high-grade tumors. The former are often papillary and the latter are usually of intestinal type, morphologically similar to metastatic colonic carcinoma. Antibodies to CDX2, a transcription factor gene highly specific for intestinal adenocarcinomas, MUC2, a mucin gene expressed in adenocarcinomas from various sites, and cytokeratins (CK) 7 and 20 were used to examine the two groups of tumors. Formalin-fixed, paraffin-embedded tissue from 22 sinonasal adenocarcinomas was reclassified into 9 high-grade intestinal-type, 3 high-grade nonintestinal, and 10 low-grade, predominantly papillary adenocarcinomas. Immunohistochemical staining was graded on a 0 to 4+ scale with 5% or greater tumor cell staining considered positive. Of the high-grade intestinal group, 78% demonstrated 4+ CDX2 positivity, with 44% MUC2 positive. Although 89% of this group was CK7 positive, the percent of staining was variable. A majority (67%) of the intestinal cases was 4+ CK20 positive. Almost every nonintestinal adenocarcinoma (90%) (low- and high-grade) was CK7 positive (7 of 9, 4+), without expression of any of the three colonic adenocarcinoma markers. The three high-grade nonintestinal tumors had the expression profile of the low-grade papillary group with the exception of focal MUC2 positivity in 1 case. Intestinal-type adenocarcinomas have an expression profile distinct from nonintestinal sinonasal adenocarcinomas. The former are similar, but not identical, to colonic adenocarcinomas. Immunohistochemical staining for CDX2, MUC2, and differential cytokeratins does not differentiate metastatic colorectal from primary sinonasal intestinal-type adenocarcinoma.


[Molecular design of fluorescent probes and development of novel fluorescent mother compounds].
Fluorescence imaging is one of the most powerful techniques for visualization of the temporal and spatial biological events in living cells, and is employed in many fields of research. Fluorescent probes, which allow visualization of cations such as Ca(2+), Zn(2+) etc., small biomolecules such as nitric oxide (NO) or enzyme activities in living cells by means of fluorescence microscopy, have become indispensable tools for clarifying functions in biological systems. This review deals with the general principles for the design of bioimaging fluorescent probes by modulating the fluorescence properties of fluorophores, employing mechanisms such as acceptor-excited photoinduced electron transfer (a-PeT), donor-excited photoinduced electron transfer (d-PeT), Förster resonance energy transfer (FRET), intramolecular charge transfer (ICT) and spirocyclization. Especially, the a-PeT and d-PeT mechanisms, which have been established by our group, are widely applicable for the design of bioimaging probes based on many fluorophores and the spirocyclization process is also expected to be useful as a fluorescence off/on switching mechanism. Fluorescence modulation mechanisms are essential for the rational design of novel fluorescence probes for target molecules. Based on these mechanisms, we have developed more than fifty bioimaging probes, of which fourteen are commercially available. The review also describes some applications of the probes developed by our group to in vitro and in vivo systems.


Visceral leishmaniasis in paediatrics.
Visceral leishmaniasis is a vector-borne systemic infection, which affects half a million people each year in many areas of the world. Typical disease manifests with fever, hepatosplenomegaly, pancytopenia, and progressive deterioration of the host. Although molecular methods appear promising as a non-invasive diagnostic tool, definite diagnosis still relies on the demonstration of the parasite in tissue. Pentavalent antimonial compounds remain the mainstay of treatment worldwide, except in India. During the past decade, short courses of lipid formulations of amphotericin B were assessed and proved effective; however, their cost precludes their wide use in developing countries. Miltefosine, an oral active agent, was recently identified, and might fulfil our expectations for an effective, safe, easily administered and affordable antileishmanial treatment.


Achieving the World Health Organization's vision for clinical pharmacology.
Clinical pharmacology is a medical specialty whose practitioners teach, undertake research, frame policy, give information and advice about the actions and proper uses of medicines in humans and implement that knowledge in clinical practice. It involves a combination of several activities: drug discovery and development, training safe prescribers, providing objective and evidence-based therapeutic information to ethics, regulatory and pricing bodies, supporting patient care in an increasingly subspecialized arena where co-morbidities, polypharmacy, altered pharmacokinetics and drug interactions are common and developing and contributing to medicines policies for Governments. Clinical pharmacologists must advocate drug quality and they must also advocate for sustainability of the Discipline. However for this they need appropriate clinical service and training support. This Commentary discusses strategies to ensure the Discipline is supported by teaching, training and policy organizations, to communicate the full benefits of clinical pharmacology services, put a monetary value on clinical pharmacology services and to grow the clinical pharmacology workforce to support a growing clinical, academic and regulatory need.


The Patients' Experiences of Burden of Neurofibromatosis: A Qualitative Study.
Neurofibromatosis Type 1 (NF1) is a common autosomal disorder; the criteria for the diagnosis of NF1 includes café au lait spots, freckling, and Neurofibromas (NF). Skin symptoms have a major impact on patients' Quality of Life (QOL) but little is known about the burden of the disease on patients. The aim of this study was to explore the experiences of patients with NF. Using purposive sampling, 20 participants were enrolled in this qualitative content analysis study. The study was carried out between 2019 and 2020. Unstructured interviews and field notes were used to gather data. Data collection was stopped when data saturation was achieved. Data analysis revealed 14 subcategories and 4 categories including "failing and falling behind in life", "deprivation and restriction", "social isolation", and "ineffective adaptation to the disease", which indicate the perception of patients with NF. In addition to the physical burden due to physical complications and problems, NF imposes a high degree of psychological and social burden on patients causing mental conflicts, which in turn results in them failing and falling behind in life. These findings illustrate the need to develop strategies and use multidisciplinary approaches to support patients, and thus to reduce the burden of NF.


Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride-induced liver cirrhosis.
Skeletal muscle myopathy is universal in cirrhotic patients, however, little is known about the main mechanisms involved. The study aims to investigate skeletal muscle morphological, histological, and functional modifications in experimental models of cirrhosis and the principal molecular pathways responsible for skeletal muscle myopathy. Cirrhosis was induced by bile duct ligation (BDL) and carbon tetrachloride (CCl4) administration in mice. Control animals (CTR) underwent bile duct exposure or vehicle administration only. At sacrifice, peripheral muscles were dissected and weighed. Contractile properties of extensor digitorum longus (EDL) were studied in vitro. Muscle samples were used for histological and molecular analysis. Quadriceps muscle histology revealed a significant reduction in cross-sectional area of muscle and muscle fibers in cirrhotic mice with respect to CTR. Kinetic properties of EDL in both BDL and CCl4 were reduced with respect to CTR; BDL mice also showed a reduction in muscle force and a decrease in the resistance to fatigue. Increase in myostatin expression associated with a decrease in AKT-mTOR expressions was observed in BDL mice, together with an increase in LC3 protein levels. Upregulation of the proinflammatory citochines TNF-a and IL6 and an increased expression of NF-kB and MuRF-1 were observed in CCl4 mice. In conclusion, skeletal muscle myopenia was present in experimental models of BDL and CCl4-induced cirrhosis. Moreover, reduction in protein synthesis and activation of protein degradation were the main mechanisms responsible for myopenia in BDL mice, while activation of ubiquitin-pathway through inflammatory cytokines seems to be the main potential mechanism involved in CCl4 mice.


Predictors of repeat pregnancies among low-income adolescents.
The authors compared a group of 58 adolescent girls who had been pregnant once during a two-year period with an age-matched group of 58 girls who had become pregnant at least twice during the same period. They found that the girls' attitudes toward contraception did not predict contraceptive use. Regular use of contraception was associated with a positive relationship between the girls and their mothers and with the presence of the girls' fathers in the home. The authors suggest that parental support of contraception plays a more important role in preventing repeat pregnancies than does the adolescents' reported attitudes toward contraception.


Longitudinal reference ranges for fetal ultrasound biometry in twin pregnancies.
The purpose of this study was to establish longitudinal reference ranges for fetal ultrasound biometry measurements and growth parameters in twin pregnancies. A total of 200 uncomplicated twin pregnancies before 21 weeks of gestation were recruited for this prospective, longitudinal study. Women who abandoned follow-up, pregnancies with unknown outcomes or pregnancies with complications were excluded. Ultrasound scans were performed every three weeks, and biparietal and occipitofrontal diameters, head and abdominal circumferences, and femur diaphysis length measurements were obtained for each fetus at each visit. Estimated fetal weight, biparietal/occipitofrontal diameter, head circumference/abdominal circumference, and femur diaphysis length/abdominal circumference ratios were also calculated. Multilevel regression analysis was performed on normalized data. A total of 807 ultrasound examinations were performed in 125 twin pregnancies between 14 and 38 weeks of gestation (6.5 ± 1.4 scans/pregnancy). Regression analysis demonstrated significant correlations for all variables with gestational age, namely log of the biparietal diameter (r = 0.98), log of the occipitofrontal diameter (r = 0.98), log of the head circumference (r = 0.99), log of the abdominal circumference (r = 0.98), square root of the femur length (r = 0.99), log of the estimated fetal weight (r = 0.99), biparietal/occipitofrontal ratio (r = -0.11), head/abdomen circumference ratio (r = -0.56), and log of the femur length/abdominal circumference ratio (r = 0.61). Values corresponding to the 10(th), 50(th), and 90(th) percentiles for estimated fetal weight at 28, 32, and 36 weeks, respectively, were as follows: 937, 1,096, 1,284 g; 1,462, 1,720, 2,025 g; and 2,020, 2,399, 2,849 g. In twin pregnancies, fetal ultrasound biometry measurements and growth parameters show a significant correlation with gestational age.


Distribution of major histocompatibility antigens in normal skin.
The distribution of major histocompatibility antigens HLA-A,B,C (HLA), beta 2-microglobulin (beta 2m), and Ia-like antigens (HLA-DR; Ia) in normal skin was studied in frozen tissue sections by a four-step immunoperoxidase method and an avidin-biotin method employing monoclonal antibodies. HLA and beta 2m were present on the basal and spinous keratinocytes of the epidermis, on the outer root sheath epithelium in the infundibulum of the hair follicle, and on the excretory sebaceous duct epithelium. Ia-positive dendritic cells were found in the epidermis and hair follicles, but they were more frequent in the infundibulum and isthmus of the hair follicle than in its inferior portion or in the epidermis. In the straight eccrine duct, HLA and beta 2m-positivity was most striking in its lower portion. In the superficial duct, there was a less intense staining using the four-step procedure, but when an avidin-biotin method was used, the difference was less apparent. In contrast, the acrosyringial epithelium was markedly Ia-positive with decreasing intensity of staining as the duct penetrated the dermis. No HLA or Ia antigens were identified in eccrine glands and apocrine glands. Eccrine glands were slightly beta 2m-positive. HLA and beta 2m were uniformly present in non-dilated and dilated intradermal apocrine ducts.


[Art Therapists in Health Care].
The members of the Bundesarbeitsgemeinschaft Künstlerische Therapien (BAG KT - "Working Committee of Art Therapies of the Federal Republic of Germany") decided to carry out an analysis of the occupational group of art therapists, in the form of an online inquiry. For this purpose, a questionnaire covering all fields of art therapies was developed, recording socio-demographic and qualification data, data of different fields of activity, patient characteristics, institutional conditions and setting as well as data on reimbursement. 2303 evaluable data sets are available. Here, the main focus is on art therapists in the health care sector according to SGB (N=2134). 83% of them are female, 56% work in the field of emergency medicine and curative treatment, followed by rehabilitation and youth welfare. In all sectors, specialization in music and art therapy predominates. 57% of the therapists have a special graduate degree in art therapy methods, 83% have a graduate degree. 42% have a license to work as an alternative non-medical practitioner. Nearly all of them use methods of quality management. The results highlight the implementation of art therapies in health care.


Column-Specific Distal Radius Fracture Fixation.
Despite the popularity and success of volar fixed angle plating, variations in distal radius fracture presentation underscore the importance of understanding different surgical treatment options to maximize patient outcomes. The 3-column theory of wrist mechanics provided the foundation for using a column-specific fixation approach. Implant placement within the ulnar column can be challenging because of anatomical constraints. Some have described "safe zones" for implant position to decrease the potential for tendon impingement. A thorough understanding of the surrounding anatomy can allow fixation decisions based on fracture fragment location. Literature reports have shown excellent results when using fragment specific fixation constructs and similar outcomes when comparing these constructs with volar locked plating. Achieving optimal outcomes in surgically treated distal radius fractures requires the surgeon to be competent along a spectrum of surgical approaches and fixation constructs.


Progress in Niobium Oxide-Containing Coatings for Biomedical Applications: A Critical Review.
Typically, pure niobium oxide coatings are deposited on metallic substrates, such as commercially pure Ti, Ti6Al4 V alloys, stainless steels, niobium, TiNb alloy, and Mg alloys using techniques such as sputter deposition, sol-gel deposition, anodizing, and wet plasma electrolytic oxidation. The relative advantages and limitations of these coating techniques are considered, with particular emphasis on biomedical applications. The properties of a wide range of pure and modified niobium oxide coatings are illustrated, including their thickness, morphology, microstructure, elemental composition, phase composition, surface roughness and hardness. The corrosion resistance, tribological characteristics and cell viability/proliferation of the coatings are illustrated using data from electrochemical, wear resistance and biological cell culture measurements. Critical R&D needs for the development of improved future niobium oxide coatings, in the laboratory and in practice, are highlighted.


A prognostic risk model based on DNA methylation levels of genes and lncRNAs in lung squamous cell carcinoma.
Recurrence is a risk factor for the prognosis of lung squamous carcinoma (LUSC). DNA methylation levels of RNAs are also associated with LUSC prognosis. This study aimed to construct a prognostic model with high performance in predicting LUSC prognosis using the methylation levels of lncRNAs and genes. The differentially expressed RNAs (DERs) and differentially methylated RNAs (DMRs) between the recurrent and non-recurrent LUSC tissues in The Cancer Genome Atlas (TCGA; training dataset) were identified. Weighted correlation network analysis was performed to identify co-methylation networks. Differentially methylated genes and lncRNAs with opposite expression-methylation levels were used for the screening of prognosis-associated RNAs. The prognostic model was constructed and its performance was validated in the GSE39279 dataset. A total of 664 DERs and 981 DMRs (including 972 genes) in recurrent LUSC tissues were identified. Three co-methylation modules, including 226 differentially methylated genes, were significantly associated with LUSC. Among prognosis-associated RNAs, 18 DERs/DMRs with opposite methylation-expression levels were included in the methylation prognostic risk model. LUSC patients with high risk scores had a poor prognosis compared with patients who had low risk scores (TCGA: HR = 3.856, 95% CI [2.297-6.471]; GSE39279: HR = 3.040, 95% CI [1.435-6.437]). This model had a high accuracy in predicting the prognosis (AUC = 0.903 and 0.800, respectively), equivalent to the nomogram model inclusive of clinical variables. Referring to the methylation levels of the 16-RNAs might help to predict the survival outcomes in LUSC.


[Evaluation of the quality of three-dimensional data acquired by using two kinds of structure light intra-oral scanner to scan the crown preparation model].
To quantitatively evaluate the quality and accuracy of three-dimensional (3D) data acquired by using two kinds of structure intra-oral scanner to scan the typical teeth crown preparations. Eight typical teeth crown preparations model were scanned 3 times with two kinds of structured light intra-oral scanner(A, B), as test group. A high precision model scanner were used to scan the model as true value group. The data above the cervical margin was extracted. The indexes of quality including non-manifold edges, the self-intersections, highly-creased edges, spikes, small components, small tunnels, small holes and the anount of triangles were measured with the tool of mesh doctor in Geomagic studio 2012. The scanned data of test group were aligned to the data of true value group. 3D deviations of the test group compared with true value group were measured for each scanned point, each preparation and each group. Independent-samples Mann-Whitney U test was applied to analyze 3D deviations for each scanned point of A and B group. Correlation analysis was applied to index values and 3D deviation values. The total number of spikes in A group was 96, and that in B group and true value group were 5 and 0 respectively. Trueness: A group 8.0 (8.3) μm, B group 9.5 (11.5) μm(P>0.05). Correlation analysis of the number of spikes with data precision of A group was r=0.46. In the study, the qulity of the scanner B is better than scanner A, the difference of accuracy is not statistically significant. There is correlation between quality and data precision of the data scanned with scanner A.


Comparison of fluorescent-antibody-to-membrane-antigen test, indirect immunofluorescence assay, and a commercial enzyme-linked immunosorbent assay for determination of antibody to varicella-zoster virus.
The demand for sensitive and specific assays to determine immune status to varicella can be expected to increase with the anticipated availability of a varicella-zoster virus vaccine for use in nonimmune adults, especially health care personnel, and in immunosuppressed children. Although the fluorescent-antibody-to-membrane-antigen (FAMA) test remains the reference standard to which other tests are compared, simpler alternative assays are needed. In this study, the FAMA was compared with a simple indirect immunofluorescence assay (IFA) and a commercially available enzyme-linked immunosorbent assay (ELISA) for the detection of antibody to varicella-zoster virus. One hundred and twelve serum samples were screened by the FAMA test and IFA at a 1:5 dilution, and 100% agreement was found. Of these samples, 101 were available for testing by ELISA, and identical results were obtained with 97 samples (96% agreement). When the samples were screened at a 1:2 dilution, 99 of 101 results agreed. In addition, 31 spinal fluid samples were tested by all three methods. When screening was at a 1:2 dilution, there was 96.8% agreement between the FAMA test and IFA. When the cutoff value established for sera was used for the spinal fluid samples, there was 90.3% agreement between the ELISA and the FAMA test. Thus, both IFA and ELISA can be considered sensitive and specific alternatives to the FAMA test, and in addition, both use commercially available reagents.


Diabetic retinopathy.
The course of diabetic retinopathy is related to the duration of the diabetes. If it is nonproliferative (small hemorrhages, microaneurysms and exudates), the risk of blindness after five years is 20 percent in patients over age 60, if it is proliferative (neovascularization and fibrosis), the risk of blindness after five years is 40 to 65 percent in all patients. While photocoagulation appears to be of benefit, vitrectomy seems a promising approach at this time.


Novel Vaccine Candidates against Brucella melitensis Identified through Reverse Vaccinology Approach.
Global health therapeutics is a rapidly emerging facet of postgenomics medicine. In this connection, Brucella melitensis is an intracellular bacterium that causes the zoonotic infectious disease, brucellosis. Presently, no licensed vaccines are available for human brucellosis. Here, we report the identification of potential vaccine candidates against B. melitensis using a reverse vaccinology approach. Based on a systematic screening of exoproteome and secretome of B. melitensis 16 M, we identified eight proteins as potential vaccine candidates, including LPS-assembly protein LptD, a polysaccharide export protein, a cell surface protein, heme transporter BhuA, flagellin FliC, 7-alpha-hydroxysteroid dehydrogenase, immunoglobulin-binding protein EIBE, and hemagglutinin. Among these, the roles of BhuA and hemagglutinin in the virulence of Brucella are essential to establish infection. Roles of other proteins in the virulence are yet to be studied. Prediction of protein-protein interactions revealed that these proteins can interact with other proteins involved in virulence, secretion system, metabolism, and transport. From these eight potential vaccine candidates, we predicted three surface exposed novel antigenic epitopes that can induce both B-cell and T-cell immune responses. These peptides can be used for the development of either exclusive peptide vaccines or multi-component vaccines against human brucellosis. Reverse vaccinology is an important strategy for discovery of novel global health therapeutics.


Accuracy of the clinical diagnosis of Down syndrome.
To determine the accuracy of clinical diagnosis of Down syndrome, identify problems in reaching a diagnosis, to provide recommendations for improvement and estimate a minimum prevalence for all types of Down syndrome. A retrospective observational study was carried out over a five-year period. Genesis, a database located in the Department of Medical genetics, was used to identify the number of Down syndrome karyotypes including trisomy, translocation, and mosaic sample variants. Age of diagnosis was determined using date of receipt. Karyotyping requests for a clinical diagnosis of Down syndrome were also identified. Patient notes and cytogenetic laboratory reports were used to identify clinical indication for karyotyping. Regional Genetics Centre, covering all cytogenetic analyses for referrals within the entire Northern Ireland population. 208 postnatal cases of Down syndrome were identified, 197 (94.7%) trisomy, 3 (1.45%) translocation, and 8 (3.85%) mosaic variants. 112 (54.8%) were male and 96 (46.2%) female. 268 samples were taken to confirm or exclude a clinical diagnosis of Down syndrome. 185 of these had Down syndrome, 77 were normal, and 6 had another abnormality. 90% and 100% of trisomy and translocation Down syndrome respectively were diagnosed on the basis of clinical features. This fell to 37.5% of mosaic Down syndrome patients being diagnosed clinically (p < 0.001). Simian crease, sandal gap, epicanthic folds, hypotonia, upslanting palpebral fissures, and protruding tongue are the most frequent characteristic features seen. Similarly epicanthic folds, protruding tongue, simian crease and sandal gap, hypotonia, and upslanting palpebral fissures are also described in a significant proportion of karyotypically normal individuals, thus arousing a suspicion of Down syndrome. 89.4% of patients were diagnosed between day 1 and 7 of life. Of 10.6% patients diagnosed after day 7 of life, 7.6% were adults and 3% children. The minimum prevalence was estimated at 167.9 per 100,000, or 1 in 595 births. In a defined population, with a prevalence of around 1 in 600 births, accurate clinical diagnosis occurred in 90%, 100%, and 37.5% of trisomy, translocation, and mosaic patients. 49.5% of patients had one or more of the following phenotypic findings: Simian crease, sandal gap, epicanthic folds, hypotonia, upslanting palpebral fissures, and protruding tongue. However, the same six features aroused a suspicion of Down syndrome in individuals with normal karyotyping, thus causing undue stress and worry to parents. Mosaic cases may be more common than previously recognised, and often do not have dysmorphic features. It is therefore a diagnosis that should always be considered in those who are educationally subnormal without a definitive diagnosis.


Combination of palbociclib and radiotherapy for glioblastoma.
The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro. Balb/c nude mice were intracranially injected with the PDCL, GBM-L1 and treated orally with palbociclib (with and without RT). Overall survival was measured. Palbociclib treatment resulted in a significant increase in the percentage of cells in the G1 cell cycle phase. Apoptotic cell death, measured by Annexin V was induced. Palbociclib combined with RT acted synergistically with the significant impediment of colony formation. The oral treatment of mice with palbociclib did not show any significant survival advantage when compared to control mice, however when combined with RT, a survival advantage of 8 days was observed. Our results support the use of palbociclib as an adjuvant treatment to RT and warrant translation to the clinic.


Evaluating the Acute Effect of Stereoscopic Recovery by Dichoptic Stimulation Using Electroencephalogram.
Amblyopia is a common developmental disorder in adolescents and children. Stereoscopic loss is a symptom of amblyopia that can seriously affect the quality of patient's life. Recent studies have shown that the push-pull perceptual learning protocol had a positive effect on stereoscopic recovery. In this study, we developed a stereoscopic training method using a polarized visualization system according to the push-pull protocol. Dichoptic stimulation for 36 anisometropic and amblyopic subjects and 33 children with normal visual acuity (VA) has been conducted. Electroencephalogram (EEG) was used to evaluate the neurophysiological changes before, during, and after stimulation. For the anisometropic and amblyopic subjects, the statistical analysis demonstrated significant differences (p < 0.01) in the beta rhythm at the middle temporal and occipital lobes, while the EEG from the normal VA subjects indicated no significant changes when comparing the results before and after training. We concluded that the dichoptic training in our study can activate the middle temporal visual area and visual cortex. The EEG changes can be used to evaluate the training effects. This study also found that the beta band EEG acquired during visual stimulation at the dorsal visual stream can be potentially used for predicting acute training effect. The results facilitated the optimization of the individual training plan.


Breast tissue decomposition with spectral distortion correction: a postmortem study.
To investigate the feasibility of an accurate measurement of water, lipid, and protein composition of breast tissue using a photon-counting spectral computed tomography (CT) with spectral distortion corrections. Thirty-eight postmortem breasts were imaged with a cadmium-zinc-telluride-based photon-counting spectral CT system at 100 kV. The energy-resolving capability of the photon-counting detector was used to separate photons into low and high energy bins with a splitting energy of 42 keV. The estimated mean glandular dose for each breast ranged from 1.8 to 2.2 mGy. Two spectral distortion correction techniques were implemented, respectively, on the raw images to correct the nonlinear detector response due to pulse pileup and charge-sharing artifacts. Dual energy decomposition was then used to characterize each breast in terms of water, lipid, and protein content. In the meantime, the breasts were chemically decomposed into their respective water, lipid, and protein components to provide a gold standard for comparison with dual energy decomposition results. The accuracy of the tissue compositional measurement with spectral CT was determined by comparing to the reference standard from chemical analysis. The averaged root-mean-square error in percentage composition was reduced from 15.5% to 2.8% after spectral distortion corrections. The results indicate that spectral CT can be used to quantify the water, lipid, and protein content in breast tissue. The accuracy of the compositional analysis depends on the applied spectral distortion correction technique.


Dynamics of Capillary-Driven Flow in 3D Printed Open Microchannels.
Microchannels have applications in microfluidic devices, patterns for micromolding, and even flexible electronic devices. Three-dimensional (3D) printing presents a promising alternative manufacturing route for these microchannels due to the technology's relative speed and the design freedom it affords its users. However, the roughness of 3D printed surfaces can significantly influence flow dynamics inside of a microchannel. In this work, open microchannels are fabricated using four different 3D printing techniques: fused deposition modeling (FDM), stereolithography (SLA), selective laser sintering, and multi jet modeling. Microchannels printed with each technology are evaluated with respect to their surface roughness, morphology, and how conducive they are to spontaneous capillary filling. Based on this initial assessment, microchannels printed with FDM and SLA are chosen as models to study spontaneous, capillary-driven flow dynamics in 3D printed microchannels. Flow dynamics are investigated over short (∼10-3 s), intermediate (∼1 s), and long (∼102 s) time scales. Surface roughness causes a start-stop motion down the channel due to contact line pinning, while the cross-sectional shape imparted onto the channels during the printing process is shown to reduce the expected filling velocity. A significant delay in the onset of Lucas-Washburn dynamics (a long-time equilibrium state where meniscus position advances proportionally to the square root of time) is also observed. Flow dynamics are assessed as a function of printing technology, print orientation, channel dimensions, and liquid properties. This study provides the first in-depth investigation of the effect of 3D printing on microchannel flow dynamics as well as a set of rules on how to account for these effects in practice. The extension of these effects to closed microchannels and microchannels fabricated with other 3D printing technologies is also discussed.


Circulatory responses to stimulation of the carotid body chemoreceptors in the cat.
Cardiovascular responses to carotid body chemoreceptor stimulation were followed in the 'curairzed', vagotomized, artificially ventilated cat. Stimulation of the chemoreceptors by perfusion of the carotid sinus regions with venous blood induced a reflex vasconstriction in skeletal muscle, kidney, intestine and skin, and, in most cases, an increased heart rate. A comparison of the chemoreceptor reflex responses with those obtained by direct electrical stimulation of the regional vasomotor fibres indicated that in chemorecptor reflexes the vasomotor fibre activity increased to the same extent in skeletal muscle and intestinal resistance vessels and, probably, in the nutritional skin vessels but to a smaller extent in the renal vessels and the skeletal muscle capacitance vessels. The renal vessels and the muscle capacitance vessels seemed, however, to respond more during chemoreceptor stimulation than when the barorecptors were unloaded, indicating that anexcitation of the bulbar vasomotor centre is more effective than the withdroawal of an inhibitory restraint in activating the vasomotor fibres to these vascular sections.


How can zygotes segregate entire parental genomes into distinct blastomeres? The zygote metaphase revisited.
Zygote cytokinesis produces two symmetric blastomeres, which contain one copy of each parental genome. Contrary to this dogma, we recently discovered that mammalian zygotes can spontaneously segregate entire parental genomes into different blastomeres and coined this novel form of genome segregation heterogoneic division. The molecular mechanisms underlying the emergence of blastomeres with different parental genomes during the first mitotic cycle remain to be elucidated. Here, we speculate on which parental genome asymmetries could provide a mechanistic foundation for these remarkable zygote divisions. In reviewing the field and considering our findings, we revisit the architecture of the first zygotic metaphase by invoking asymmetric interactions between the mitotic spindle and the parental kinetochores. We also speculate on how asynchronous parental cell cycles can be a source of heterogoneic zygote divisions through the formation of parental genome private spindles.


Effectiveness of perioperative pulmonary rehabilitation in thoracic surgery.
Functional condition is crucial for operability of patients with lung cancer and/or chronic respiratory diseases. The aim of the study was to measure changes of functional and quality of life parameters in terms of the effectiveness of perioperative pulmonary rehabilitation (PR). A total of 208 COPD patients (age: 63±9 years, man/woman: 114/94, FEV1: 62±14%pred) participated in a perioperative PR program. The indication was primary lung cancer in 72% of the patients. The 68 patients participated in preoperative (PRE) rehabilitation, 72 in a pre- and postoperative rehabilitation (PPO) and 68 patients only in postoperative rehabilitation (POS). PR program included respiratory training techniques, individualized training and smoking cessation. Lung function tests, 6 minutes walking distance (6MWD) were measured before and after the rehabilitation. Quality of life tests [COPD Assessment Test (CAT) and Modified Medical Research Council Dyspnoea Scale (mMRC)] were evaluated as well. There was a significant improvement in FEV1 (PRE: 64±16 vs. 67±16%pred; PPO: 60±13 vs. 66±13%pred before the operation, 48±13 vs. 52±13%pred after the operation; POS: 56±16 vs. 61±14%pred, P<0.05) and 6MWD (PRE: 403±87 vs. 452±86 m; PPO: 388±86 vs. 439±83 m before, 337±111 vs. 397±105 m after the operation; POS: 362±89 vs. 434±94 m, P<0 0001). Significant improvement was detected in FVC, grip strength, mMRC and CAT questionnaires as an effectiveness of PR, also. Average intensive care duration was 3.8±5.2 days with vs. 3.1±3.6 without preoperative PR. Improvements in exercise capacity and quality of life were seen following PR both before and after thoracic surgery.


Droplets: unconventional protocell model with life-like dynamics and room to grow.
Over the past few decades, several protocell models have been developed that mimic certain essential characteristics of living cells. These protocells tend to be highly reductionist simplifications of living cells with prominent bilayer membrane boundaries, encapsulated metabolisms and/or encapsulated biologically-derived polymers as potential sources of information coding. In parallel with this conventional work, a novel protocell model based on droplets is also being developed. Such water-in-oil and oil-in-water droplet systems can possess chemical and biochemical transformations and biomolecule production, self-movement, self-division, individuality, group dynamics, and perhaps the fundamentals of intelligent systems and evolution. Given the diverse functionality possible with droplets as mimics of living cells, this system has the potential to be the first true embodiment of artificial life that is an orthologous departure from the one familiar type of biological life. This paper will synthesize the recent activity to develop droplets as protocell models.


Irbesartan prevents sodium channel remodeling in a canine model of atrial fibrillation.
Activation of the renin-angiotensin system (RAS) plays an important role in atrial electrical remodeling (AER). The purpose of the present study was to evaluate the effects of irbesartan on cardiac sodium current (INa) in a canine model of atrial fibrillation. Eighteen dogs were randomized into sham, pacing or pacing+irbesartan groups ( n = 6 in each group). The dogs in the pacing and irbesartan group were paced at 500 bpm for two weeks. Irbesartan (60 mg·kg-1·d-1) was administered orally in the pacing+irbesartan groups. INa was recorded using the whole-cell patch clamp technique from canine atrial myocytes. The expressions of cardiac Na+ channels (Nav1.5) mRNA were semi-quantified by reverse transcription-polymerase chain reaction. Our results showed that INa density and Nav1.5 mRNA expression in the pacing group decreased significantly ( p < 0.05 vs. sham). However, rapid atrial pacing had no effects on the half-activation voltage (V1/2act) and half-inactivation voltage (V1/2inact) of INa ( p > 0.05 vs. sham). Irbesartan significantly increased INa densities and gene expression and hyperpolarized V1/2act without concomitant changes in V1/2inact. Irbesartan significantly increased INa densities, which contributed to improving intra-atrial conduction and prevented the induction and promotion of AF in atrial pacing dogs.


Development and application of a new general method for the asymmetric synthesis of syn- and anti-1,3-amino alcohols.
A general method is described for asymmetric synthesis of both syn- and anti-1,3-amino alcohols. The first application of metalloenamines derived from N-sulfinyl imines is reported for the highly diastereoselective addition to aldehydes. The reduction of the product beta-hydroxy N-sulfinyl imines 2 with catecholborane and LiBHEt(3) provides syn- and anti-1,3-amino alcohols with very high diastereomeric ratios. This method was found to be effective for a variety of substrates incorporating either aromatic or various aliphatic substituents. The convergent and efficient asymmetric syntheses of the two natural products, (-)-8-epihalosaline and (-)-halosaline, were also accomplished.


Current Understanding of the Role of Nesfatin-1.
Nesfatin-1 was discovered in 2006 and implicated in the regulation of food intake. Subsequently, its widespread central and peripheral distribution gave rise to additional effects. Indeed, a multitude of actions were described, including modulation of gastrointestinal functions, glucose and lipid metabolism, thermogenesis, mediation of anxiety and depression, as well as cardiovascular and reproductive functions. Recent years have witnessed a great increase in our knowledge of these effects and their underlying mechanisms, which will be discussed in the present review. Lastly, gaps in knowledge will be highlighted to foster further studies.


[Does a "senile heart" actually exist?].
The study of the aging heart raised for a long time difficulties in distinguishing the age-related physiological processes from the associated pathological changes. In recent years, however, several obscure or controversial items have been clarified through a wide use of imaging techniques such as echocardiography, positron emission tomography, and of molecular biology. The general notion of remodeling has been extended to include the arterial capacitance vessels, and the emerging concept of "ventricular-arterial coupling" has yielded a rational explanation for some structural and functional changes of the aging heart. Particular attention has been paid to the left ventricular diastolic dysfunction, while the new data have generally confirmed the old ones regarding the preserved systolic performance at rest. The aging of the heart should anyhow be considered in the context of the "cardiopulmonary unit" and by the light of the new acquisitions on the loss of skeletal muscle mass and strength (sarcopenia).


Hypothesis: structures, evolution, and ancestor of glucose kinases in the hexokinase family.
Glucose kinase, which we tentatively use in this review, represents the enzymes catalyzing the phosphorylation of glucose and other hexoses by means of phosphoryl donors (ATP, ADP, and inorganic polyphosphate [poly(P)]). Except for glucose kinases utilizing ADP, all other glucose kinases belong to the hexokinase (HK) family and are classified into three groups based on primary structural information, i.e., groups HK, A, and B. The structural and evolutionary relationships of glucose kinases belonging to the above three groups have been controversial due to the lack of tertiary structural information on those in groups A and B. However, recent studies on the tertiary structures of poly(P)/ATP-glucomannokinase (GMK: a glucose kinase in group B) from Arthrobacter sp. strain KM and glucokinase (GK) (ecoGK: a glucose kinase in group A) from Escherichia coli have shed light on this problem. A comparison of the tertiary structures of GMK and ecoGK with those of glucose kinases in group HK demonstrated that both GMK and ecoGK are structurally homologous with glucose kinases in group HK, and that glucose kinases belonging to groups HK, A, and B in the HK family evolved divergently from a common ancestor. Based on the simple structure of GMK compared to those of ecoGK and glucose kinases in group HK, and the putative poly(P)-binding site in GMK, we propose that the ancestor of glucose kinases in the HK family was similar to GMK and used poly(P). We also discuss the ancestor and evolutionary process of ROK proteins, whose primary structures are homologous with those of glucose kinases in group B, in connection with the ancestor and evolutionary process of glucose kinases in the HK family.


Dufour's gland: source of sex pheromone in a hymenopterous parasitoid.
Females of Apanteles melanoscelus and Apanteles liparidis produce a sex pheromone in Dufour's gland of their reproductive system. Males of both species exhibit premating behavior when in contact with filter paper smears of the gland of their respective females.


Sporadic cases of acute autochthonous hepatitis E in Spain.
In industrialized countries hepatitis E virus (HEV) infection is rare and its diagnosis is difficult because the utility of available tests is not well established. We studied the presence of acute HEV infection markers in a cluster of 11 cases of acute hepatitis with IgG anti-HEV antibodies. Three cases were confirmed as acute hepatitis E and 8 as presumptive hepatitis E, two as a past HEV infection and one could not be determined. Three different HEV strains were identified in serum from 3 patients. Two strains belonged to genotype 3, the predominant genotype found in local urban sewage and the other strain belonged to genotype 1 and was considered an imported strain. Our findings demonstrate the presence of some autochthonous, sporadic acute hepatitis E cases as well as an imported case in our area and the transitory nature of virological and serological markers for HEV.


Empowerment of the rural parents/caregivers of children with heart diseases in Namibia to facilitate coping with the demands of caring at home.
The purpose of this study was to describe how the parents/caregivers of children with heart diseases cope with the demands of caring for these children at home, with the purpose to develop a home-based health care programme to facilitate the parents/caregivers' coping with the demands of care. A qualitative, exploratory, descriptive, and contextual study was conducted. Phenomenological data on the lived experiences of coping with the demands to care by the parents/caregivers and of living with the burden of the disease by the children were gathered and interpreted from a purposefully selected sample of 5 multiple cases of parents/caregivers and children with heart disease from the rural areas. The findings have revealed poor coping with the demands of caring among the parents/caregivers, as characterized by the experiences of emotional challenges, disruptive social functioning and social relations, lack of support from the family and societal organizations, financial difficulties and of course the experiences of decreased vitality by the children. As a result, the need to empower the parents/caregivers for them to cope with providing a continuum care to their children who have heart disease was identified. The dynamics to mitigate the negative experiences were conceptualized. Therefore, the interventions of a home-based health care programme as an interface to facilitate the parents/caregivers to cope with the challenges caused by the demands to care were developed. The need for empowerment of these parents/caregivers can be met through the implementation of multi-component interventions, which draw together all the possible determinants factors and the coping methods to facilitate coping.


Management strategy for congenital choledochal cyst with co-existing intrahepatic dilation and aberrant bile duct as well as other complicated biliary anomalies.
The purpose of this study was to investigate and discuss imaging methods and management strategies for congenital choledochal cyst with co-existing intrahepatic dilation and aberrant bile duct as well as other complicated biliary anomalies. In this study we reviewed and analyzed 72 patients with congenital choledochal cyst, ranging in age from 15 days to 12 years old and who were seen at our hospital during the past 12 years, from January 1993 to October 2005. The image manifestation and clinical significance of patients with co- existing intrahepatic biliary dilation and aberrant bile duct were carefully examined during operation via MRCP, cholangiography and choledochoscope. Twenty-two cases (30.1%) presented with intrahepatic bile duct dilation and 12 of these were of the cystic type. That is, the orifice of the dilated intrahepatic tract that converged into the common hepatic duct showed membrane or septum-like stenosis. In 10 cases the dilation tapered off from the porta hepatis to the initiating terminals of the intra-hepatic bile ducts and was not accompanied by stenosis. An aberrant bile duct was observed in 2 of the cases. In 3 cases, the right and left hepatic ducts converged at the choledochal cyst. In conclusion, the imaging methods for intrahepatic bile duct dilation possess important clinical significance. Further, for hepatojejunostomy with radical excision of a choledochal cyst, additional operative procedures for intrahepatic stenosis, possible bile duct malformation and pancreaticobiliary common duct calculi can potentially reduce postoperative complications.


Di-Huang-Yi-Zhi herbal formula attenuates amyloid-β-induced neurotoxicity in PC12 cells.
Traditional Chinese medicine can be used for Alzheimer's disease management, such as the modern herbal formula Di-Huang-Yi-Zhi (DHYZ). In the present study, neuronal differentiated PC12 cells were used as a model to evaluate the effects of DHYZ against amyloid-β peptide 25-35 (Aβ25-35) induced neurotoxicity, particularly regarding cell proliferation, apoptosis and related events. Following treatment with DHYZ, cell viability, cell membrane damage, apoptosis, mitochondrial membrane potential, cytochrome c release, caspase-3 activity and levels of reactive oxygen species in PC12 cells were detected. The results demonstrated that pretreatment with DHYZ significantly protected PC12 cells from Aβ25-35-induced proliferation inhibition, lactate dehydrogenase release and apoptosis, as well as upregulating mitochondrial membrane potential and downregulating cytochrome c release and caspase-3 activation. DHYZ also inhibited the Aβ25-35-induced reactive oxygen species generation in PC12 cells. These observations suggest that DHYZ protected PC12 cells from the Aβ-induced neurotoxicity.


Bicuspid aortic root spared during ascending aorta surgery: an update of long-term results.
Bicuspid aortic valve (BAV) aortopathy is well known in literature even if only few data exist regarding isolated supra-coronary aneurysm with normally functioning valve and root. Aim of this study is to clarify the long-term fate of bicuspid aortic root spared at the time of ascending aorta surgery. We identified forty-seven patients (mean age, 57±11 y; range, 35-81 y, 31 males) who were treated by means of supracoronary aortic replacement in presence of normally functioning BAV and not significantly enlarged sinues of Valsalva. Clinical follow-up (mean 93±50 months; range, 21-207) was 98.9% complete. Freedom from cardiac death at 5- and 10-year was 95%±5% and 83%±16%. Three surviving patients required reoperation for the development of aortic insufficiency [2 cases treated by aortic valve replacement (AVR)] or for progression of aortic stenosis (AS) [1 case treated by transcatheter aortic valve implantation (TAVI)]. Freedom from new procedure on aortic valve was 100% and 94.4%±5.6% at 5- and 10-year. Composite event-free survival at 5- and 9-year was 82%±18% and 69%±30%. Although in the setting of a BAV, aortic root integrity seems to remain stable during long term follow up with low rate of reoperation and occurrence of new adverse event.


[Neutralisation of interferon gamma--a new trend in therapy of rheumatoid arthritis].
To evaluate objectively therapeutic potentialities of a novel method of biological therapy--blocking interferon gamma (IF-gamma)--by means of a comparative analysis of using antibodies to IF-g (anti-IF-gamma) and tumor necrosis factor alpha (anti-TNF-alpha) in resistant rheumatoid arthritis (RA). A double blind trial included 55 patients with resistant RA. They received 5 intramuscular injections of anti-IF-gamma (n = 20), anti-TNF-alpha (n = 20) and placebo (15 patients). The results were assessed on the treatment day 7 and 28. 16 patients withdrew because of the treatment uneffectiveness (2 from the group on anti-IF-g, 3--on anti-TNF-alpha, 11--on placebo). To the treatment day 28 the patients given anticytokines achieved significant improvement of all clinical indices while placebo group had no improvement. The highest response was observed in the group on anti-IF-gamma (ACR 70). As shown by ultrasound investigation, a significant reduction of the synovial membrane thickness took place also in administration of anti-IF-gamma. Most frequent side effect of the anticytokine therapy was mild dermatitis at injection site on treatment day 8-11. Therapeutic efficacy of anti-IF-gamma was comparable with efficacy of anti- TNF-alpha and even was superior in some aspects. The block of IF-gamma holds much promise in the treatment of RA.


Exploring the binding pathways of the 14-3-3ζ protein: Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints.
The 14-3-3 protein family performs regulatory functions in eukaryotic organisms by binding to a large number of phosphorylated protein partners. Whilst the binding mode of the phosphopeptides within the primary 14-3-3 binding site is well established based on the crystal structures of their complexes, little is known about the binding process itself. We present a computational study of the process by which phosphopeptides bind to the 14-3-3ζ protein. Applying a novel scheme combining Hamiltonian replica exchange molecular dynamics and distancefield restraints allowed us to map and compare the most likely phosphopeptide-binding pathways to the 14-3-3ζ protein. The most important structural changes to the protein and peptides involved in the binding process were identified. In order to bind phosphopeptides to the primary interaction site, the 14-3-3ζ adopted a newly found wide-opened conformation. Based on our findings we additionally propose a secondary interaction site on the inner surface of the 14-3-3ζ dimer, and a direct interference on the binding process by the flexible C-terminal tail. A minimalistic model was designed to allow for the efficient calculation of absolute binding affinities. Binding affinities calculated from the potential of mean force along the binding pathway are in line with the available experimental estimates for two of the studied systems.


Spontaneous rupture of inferior vena cava.
Spontaneous ruptures of the inferior vena cava (IVC) are rare. The mortality rate is high associated with all IVC injuries despite prompt resuscitation or operation. We present a case of 68-year-old women with spontaneous IVC dissection, presented as acute chest pain. Chest CT demonstrated a large amount of hemopericardium, and dilated inferior vena cava (IVC), suggesting cardiac tampon. Subsequently, hypovolemic shock and cardiac arrest occurred. After resuscitation, abdomen CT angiography was taken to find bleeding focus. Second CT demonstrated massive contrast extravasation to pericardial space due to rupture of IVC. Patient expired due to multi-organ failure.


Differences in home cage behavior and endocrine parametres in rats of four strains.
The majority of studies that involve behavioral testing in different rat strains is based on measuring behavioral responses to stressful situations in a novel environment. Very little is known on the spontaneous behavior in rat strains. The aim of the present study was to compare home cage behavior and basal hormone levels in two outbred rat strains, Sprague-Dawley (SD) and Wistar as well as two inbred strains, Lewis and Spontaneously Hypertensive Rats (SHR). Twenty-eight male rats from four strains of rats (n=7/strain) were used in this study. Behavior of each rat in his home cage was recorded by a video camera for 45 minutes during the dark phase of the day. The parameters considered included rearing, jumps, ambulation, grooming, feeding/drinking and no movements. Blood plasma was analyzed for aldosterone, plasma renin activity (PRA), adrenocorticotropin hormone (ACTH) and corticosterone by specific radioimmunoassays. One-way ANOVA revealed significant inter-strain differences in counts of jumps and rearing. In comparison with Sprague-Dawley and Wistar rats, Lewis rats displayed significantly more jumps and rearing. Statistical analysis showed significant inter-strain differences in the levels of aldosterone and of plasma renin activity. The highest levels of aldosterone were found in Lewis rats. Plasma renin activity was significantly lower in SHR than in Sprague-Dawley rats. Correlation analysis failed to reveal any relationships between behavioral and endocrine parameters. Significant strain differences were observed also in relative weights of the spleen, adrenals and thymus. Plasma renin activity and basal mineralocorticoid secretion did not show parallel pattern if compared among different rat strains. Locomotor activity in the home cage, which could represent general activity to be considered in evaluating emotional responses, was highest in the Lewis rats.


A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage.
Stroke is a major reason for persistent disability due to insufficient treatment strategies beyond reperfusion, leading to oligodendrocyte death and axon demyelination, persistent inflammation and astrogliosis in peri-infarct areas. After injury, oligodendroglial precursor cells (OPCs) have been shown to compensate for myelin loss and prevent axonal loss through the replacement of lost oligodendrocytes, an inefficient process leaving axons chronically demyelinated. Phenotypic screening approaches in demyelinating paradigms revealed substances that promote myelin repair. We established an ex vivo adult organotypic coronal slice culture (OCSC) system to study repair after stroke in a resource-efficient way. Post-photothrombotic OCSCs can be manipulated for 8 d by exposure to pharmacologically active substances testing remyelination activity. OCSCs were isolated from a NG2-CreERT2-td-Tomato knock-in transgenic mouse line to analyze oligodendroglial fate/differentiation and kinetics. Parbendazole boosted differentiation of NG2+ cells and stabilized oligodendroglial fate reflected by altered expression of associated markers PDGFR-α, CC1, BCAS1 and Sox10 and GFAP. In vitro scratch assay and chemical ischemia confirmed the observed effects upon parbendazole treatment. Adult OCSCs represent a fast, reproducible, and quantifiable model to study OPC differentiation competence after stroke. Pharmacological stimulation by means of parbendazole promoted OPC differentiation.


Electronic Properties of Sulfur Covered Ru(0001) Surfaces.
The structural properties of sulfur superstructures adsorbed on Ru(0001) have been widely studied in the past. However, much less effort has been devoted to determine their electronic properties. To understand the connection between structural and electronic properties, we have carried out density functional theory periodic boundary calculations mimicking the four long-range ordered sulfur superstructures identified experimentally by means of scanning tunneling microscopy (STM) techniques. Our simulations allow us to characterize the nature of the sulfur-Ru bond, the charge transfer between the Ru substrate and the sulfur adlayers, the interface states, and a parabolic state recently identified in STM experiments. A simple analysis, based on a one-dimensional model, reveals that this parabolic state is related to a potential well state, formed in the surface when the concentration of sulfur atoms is large enough to generate a new minimum in the surface potential.


Transfer of patients--from the spoke to the hub.
We describe the nature, frequency, and characteristics of transfers to a regional centre. This was a three month prospective descriptive study of all transfers into the hospital through the ED and a further sample survey of 100 patients received into the resuscitation room over a 2 year period. 105 patient transfers were surveyed over the three month period. A significant number (43 patients) arrived at the ED without prior notification being received by ED staff, a proportion (7 patients) warranting resuscitation room assessment. The rate of Doctor Transfer was 22%. Of the 23 patients that warranted assessment in the resuscitation room 10 were unaccompanied by a Doctor and 5 were unaccompanied by either a Doctor or a Nurse. 11% of transfers had no transfer letter or radiographs. Only 51% of transferred patients had an IV line in situ. 4 out of the 8 transfers into the resuscitation room performed by interns were associated with adverse events. There continues to be problems with the quality of care that these patients receive. Clinicians must be actively involved in the development of regional transfer protocols and interfacility agreements to ensure the safe transfer of patients to definitive care.


The Battle for Iron between Humans and Microbes.
Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment. To describe complex 'tug of war' for iron that has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. A review of current literature was performed, to assess current approaches and controversies in iron therapy and chelation in humans. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection. The administration of iron chelating agents and siderophore- conjugate drugs to infected hosts seems a biologically plausible approach as adjunctive therapy in the treatment of infections caused by pathogens dependent on host iron supply (e.g. tuberculosis, malaria, and many bacterial and fungal pathogens); however, thus far, studies in humans have proved unsuccessful.


Repeat Mild Traumatic Brain Injury in Adolescent Rats Increases Subsequent β-Amyloid Pathogenesis.
Single moderate-to-severe traumatic brain injuries (TBIs) may increase subsequent risk for neurodegenerative disease by facilitating β-amyloid (Aβ) deposition. However, the chronic effects on Aβ pathogenesis of repetitive mild TBIs (rTBI), which are common in adolescents and young adults, remain uncertain. We examined the effects of rTBI sustained during adolescence on subsequent deposition of Aβ pathology in a transgenic APP/PS1 rat model. Transgenic rats received sham or four individual mild TBIs (rTBIs) separated by either 24- or 72-h intervals at post-natal day 35 (before Aβ plaque deposition). Animals were euthanized at 12 months of age and underwent immunohistochemical analyses of Aβ plaque deposition. Significantly greater hippocampal Aβ plaque deposition was observed after rTBI separated by 24 h relative to rTBI separated by 72 h or sham injuries. These increases in hippocampal Aβ plaque load were driven by increases in both plaque number and size. Similar, though less-pronounced, effects were observed in extrahippocampal regions. Increases in Aβ plaque deposition were observed both ipsilaterally and contralaterally to the injury site and in both males and females. rTBIs sustained in adolescence can increase subsequent deposition of Aβ pathology, and these effects are critically dependent on interinjury interval.


Redox Self-Adaptation of a Nitrene Transfer Catalyst to the Substrate Needs.
The development of iron catalysts for carbon-heteroatom bond formation, which has attracted strong interest in the context of green chemistry and nitrene transfer, has emerged as the most promising way to versatile amine synthetic processes. A diiron system was previously developed that proved efficient in catalytic sulfimidations and aziridinations thanks to an FeIII FeIV active species. To deal with more demanding benzylic and aliphatic substrates, the catalyst was found to activate itself to a FeIII FeIV L. active species able to catalyze aliphatic amination. Extensive DFT calculations show that this activation event drastically enhances the electron affinity of the active species to match the substrates requirements. Overall this process consists in a redox self-adaptation of the catalyst to the substrate needs.


[Hemoglobin anomalies at the university hospital center in Lome, Togo].
Togo is a sub-Saharan African nation with a number of public health problems including endemic tropical disease. The country is also located in the Lehmann sickle cell belt characterized by a high incidence of genetic red blood cell disorders. The purpose of this study was to identify the main hemoglobin variants, evaluate their incidence and discuss diagnostic pitfalls. Data on 5604 subjects was compiled from the 3 studies, i.e., a 405-case prospective study conducted in a rheumatology department, a 5028-case retrospective study using electrophoresis and a 171-case transversal study in newborns. Diagnosis of hemoglobinopathy was based on alkaline electrophoresis. Rare hemoglobins were identified in the Biochemistry Laboratory of the Henri Mondor Hospital in Paris, France. Diagnosis of alpha-thalassemia was checked by PCR. The main abnormal hemoglobins were the S and C variants with respective incidence ranges of 15.8 to 16.7% for the AS trait and 12.1 to 15.8% for AC trait. SS sickle cell disease was observed in 1.2 to 2% of subjects and SC sickle disease in 2.3 to 4.2%. Rare hemoglobulinopathies involved the fast hemoglobulin variant, hemoglobin D, and hereditary persistence of hemoglobin F. Alpha-thalassemia was detected in 47% of the 171 newborns studied with a predominance of the heterozygous form (36.8%), followed by the homozygous form (8%). The incidence of alpha gene triplication in the newborns was about 2.4%. Hemoglobin Barts was not a consistent finding in association with diagnosis of alpha-thalassemia since it was present in 15 newborns with normal alpha genotype (8.8%) and absent in 10 newborns with heterozygous alpha genotype (5.9%). This study demonstrates that molecular biology is the best method for the detection of the alpha-globin gene abnormalities.


Deformation Properties of Concentrated Metal-in-Polymer Suspensions under Superimposed Compression and Shear.
Concentrated metal-in-polymer suspensions (55 and 60 vol.%) of aluminum powder dispersed in low molecular weight polyethylene glycol) demonstrate elastoplastic properties under compression and shear. The rheological behavior of concentrated suspensions was studied in a rotational rheometer with uniaxial compression (squeezing), as well as shearing superimposed on compression. At a high metal concentration, the elasticity of the material strongly increases under strain, compared with the plasticity. The elastic compression modulus increases with the growth of normal stress. Changes in the shear modulus depend on both normal and shear stresses. At a low compression force, the shear modulus is only slightly dependent on the shear stress. However, high compression stress leads to a decrease in the shear modulus by several orders with the growth of the shear stress. The decrease in the modulus seems to be rather unusual for compacted matter. This phenomenon could be explained by the rearrangement of the specific organization of the suspension under compression, leading to the creation of inhomogeneous structures and their displacement at flow, accompanied by wall slip. The obtained set of rheological characteristics of highly loaded metal-in-polymer suspensions is the basis for understanding the behavior of such systems in the powder injection molding process.


New dimensions of asymmetric division in vertebrates.
Traditionally, we imagine that cell division gives rise to two identical daughter cells. Nevertheless, all cell divisions, to some degree, display asymmetry. Asymmetric cell division is defined as the generation of two daughter cells with different physical content and/or developmental potential. Several organelles and cellular components including the centrosome, non-coding RNA, chromatin, and recycling endosomes are involved in the process of asymmetric cell division. Disruption of this important process is known to induce profound defects in development, the immune response, regeneration of tissues, aging, and cancer. Here, we discuss recent advances that expand our understanding of the mechanisms and consequences of asymmetric cell division in vertebrate organisms.


On the role of melatonin in skin physiology and pathology.
Melatonin has been experimentally implicated in skin functions such as hair growth cycling, fur pigmentation, and melanoma control, and melatonin receptors are expressed in several skin cells including normal and malignant keratinocytes, melanocytes, and fibroblasts. Melatonin is also able to suppress ultraviolet (UV)-induced damage to skin cells and shows strong antioxidant activity in UV exposed cells. Moreover, we recently uncovered expression in the skin of the biochemical machinery involved in the sequential transformation of l-tryptophan to serotonin and melatonin. Existence of the biosynthetic pathway was confirmed by detection of the corresponding genes and proteins with actual demonstration of enzymatic activities for tryptophan hydroxylase, serotonin N-acetyl-transferase, and hydroxyindole-O-methyltransferase in extracts from skin and skin cells. Initial evidence for in vivo synthesis of melatonin and its metabolism was obtained in hamster skin organ culture and in one melanoma line. Therefore, we propose that melatonin (synthesized locally or delivered topically) could counteract or buffer external (environmental) or internal stresses to preserve the biological integrity of the organ and to maintain its home-ostasis. Furthermore, melatonin could have a role in protection against solar radiation or even in the management of skin diseases.


Epidemiological analysis of the early 38 fatalities in Hubei, China, of the coronavirus disease 2019.
Since the emergence of coronavirus disease 2019 (COVID-19) in Hubei province of China by the end of 2019, it has burned its way across the globe, resulting in a still fast-growing death toll that far exceeded those from severe acute respiratory syndrome (SARS) in less than two months. As there is a paucity of evidence on which population is more likely to progress into severe conditions among cases, we looked into the first cluster of death cases, aiming to add to current evidence and reduce panic among the population. We prospectively collected the demographic and clinical data of the first 38 fatalities whose information was made public by the Health Commission of Hubei province and the official Weibo account of China Central Television news center, starting from 9 January through 24 January 2020. The death cases were described from four aspects (gender and age characteristics, underlying diseases, the time course of death, symptoms at the incipience of illness and hospital admission). Among the 38 fatalities, 71.05% were male, and 28.95% were female, with the median age of 70 years (interquartile range (IQR) = 65-81). Persons aged 66-75 made up the largest share. Twenty-five cases had a history of chronic diseases. The median time between the first symptoms and death was 12.50 days (IQR = 10.00-16.25), while the median time between the admission and death was 8.50 (IQR = 5.00-12.00) days. In persons aged over 56 years, the time between the first symptoms and death decreased with age, and so did the time between the admission and death, though the latter increased again in persons aged over 85 years. The major first symptoms included fever (52.63%), cough (31.58%), dyspnea (23.68%), myalgia and fatigue (15.79%). Among the death cases, persons with underlying diseases and aged over 65 made up the majority. The time between the first symptoms and death decreased with the advanced age. In all the age groups, males dominated the fatalities.


Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation.
Local translation of proteins in distal dendrites is thought to support synaptic structural plasticity. We have previously shown that metabotropic glutamate receptor (mGluR1) stimulation initiates a phosphorylation cascade, triggering rapid association of some mRNAs with translation machinery near synapses, and leading to protein synthesis. To determine the identity of these mRNAs, a cDNA library produced from distal nerve processes was used to screen synaptic polyribosome-associated mRNA. We identified mRNA for the fragile X mental retardation protein (FMRP) in these processes by use of synaptic subcellular fractions, termed synaptoneurosomes. We found that this mRNA associates with translational complexes in synaptoneurosomes within 1-2 min after mGluR1 stimulation of this preparation, and we observed increased expression of FMRP after mGluR1 stimulation. In addition, we found that FMRP is associated with polyribosomal complexes in these fractions. In vivo, we observed FMRP immunoreactivity in spines, dendrites, and somata of the developing rat brain, but not in nuclei or axons. We suggest that rapid production of FMRP near synapses in response to activation may be important for normal maturation of synaptic connections.