Tummy Time and Infant Health Outcomes: A Systematic Review.
The World Health Organization recommends tummy time for infants because of the benefits of improved motor development and reduced likelihood of plagiocephaly. Because of poor uptake of these recommendations, the association of tummy time with other health outcomes requires further investigation. To review existing evidence regarding the association of tummy time with a broad and specific range of infant health outcomes. Electronic databases were searched between June 2018 and April 2019. Peer-reviewed English-language articles were included if they investigated a population of healthy infants (0 to 12 months), using an observational or experimental study design containing an objective or subjective measure of tummy time which examined the association with a health outcome (adiposity, motor development, psychosocial health, cognitive development, fitness, cardiometabolic health, or risks/harms). Two reviewers independently extracted data and assessed their quality. Sixteen articles representing 4237 participants from 8 countries were included. Tummy time was positively associated with gross motor and total development, a reduction in the BMI-z score, prevention of brachycephaly, and the ability to move while prone, supine, crawling, and rolling. An indeterminate association was found for social and cognitive domains, plagiocephaly, walking, standing, and sitting. No association was found for fine motor development and communication. Most studies were observational in design and lacked the robustness of a randomized controlled trial. High selection and performance bias were also present. These findings guide the prioritization of interventions aimed at assisting parents meet the global and national physical activity guidelines.


Complications of Transradial Cardiac Catheterization and Management.
The transradial approach for coronary angiography has become an increasingly used alternative to the conventional transfemoral approach. Decreased access site complications and bleeding, reduced hospital stays and health care costs, and increased patient satisfaction contribute to the attractiveness of this approach. However, operators must be familiar with the distinct complications associated with the transradial approach. In this article, we discuss the common and less common complications of transradial catheterization, prevention strategies, and management options.


Clinicopathological Characteristics of Gastric-type Endocervical Adenocarcinoma Misdiagnosed as an Endometrial, Ovarian or Extragenital Malignancy, or Mistyped as Usual-type Endocervical Adenocarcinoma.
The diagnosis of gastric-type endocervical adenocarcinoma (GEA) is challenging because its differential diagnosis includes not only gynecological tumors, but also extragenital tumors. We reviewed the electronic medical records and all available slides to investigate the clinicopathological characteristics of eight misdiagnosed GEA cases. Three tumors were initially misdiagnosed as endometrial carcinoma. They displayed extensive endomyometrial involvement and complex glandular architecture, but no severe nuclear pleomorphism. Another three tumors were misclassified as usual-type endocervical adenocarcinoma because of mucin-poor, pseudoendometrioid glands, apical mitotic figures, and karyorrhectic debris. The two remaining tumors presenting as adnexal masses mimicked primary ovarian mucinous tumor and metastatic cholangiocarcinoma. The varying pathological characteristics of GEA reflect the variability in clinical manifestations and its diagnostic difficulties. It is challenging to make an accurate diagnosis based solely on histological features. When suspecting GEA, clinicians should consider more comprehensively the clinicopathological context, along with immunostaining results.


Keratin/alginate hybrid hydrogels filled with halloysite clay nanotubes for protective treatment of human hair.
Keratin/alginate hydrogels filled with halloysite nanotubes (HNTs) have been tested for the protective coating of human hair. Preliminary studies have been conducted on the aqueous colloidal systems and the corresponding hydrogels obtained by using Ca2+ ions as crosslinkers. Firstly, we have investigated the colloidal properties of keratin/alginate/HNTs dispersions to explore the specific interactions occurring between the biomacromolecules and the nanotubes. Then, the rheological properties of the hydrogels have been studied highlighting that the keratin/alginate interactions and the subsequent addition of HNTs facilitate the biopolymer crosslinking. Finally, human hair samples have been treated with the hydrogel systems by the dipping procedure. The protection efficiency of the hydrogels has been evaluated by studying the tensile properties of hair fibers exposed to UV irradiation. In conclusion, keratin/alginate hydrogel filled with halloysite represents a promising formulation for hair protective treatments due to the peculiar structural and rheological characteristics.


Synthetic polycistronic sequences in eukaryotes.
The need for co-ordinate, high-level, and stable expression of multiple genes is essential for the engineering of biosynthetic circuits and metabolic pathways. This work outlines the functionality and design of IRES- and 2 A-peptide-based constructs by comparing different strategies for co-expression in polycistronic vectors. In particular, 2 A sequences are small peptides, mostly derived from viral polyproteins, that mediate a ribosome-skipping event such that several, different, separate proteins can be generated from a single open reading frame. When applied to metabolic engineering and synthetic gene circuits, 2 A peptides permit to achieve co-regulated and reliable expression of various genes in eukaryotic cells.


Intravenous bisphosphonates do not improve knee pain or bone marrow lesions in people with knee osteoarthritis: a meta-analysis.
To summarize effects of intravenous bisphosphonates (IVBP) in patients with symptomatic knee OA and bone marrow lesions (BMLs), using a meta-analysis of randomized controlled trials (RCTs). Literature databases were searched for placebo-controlled RCTs of IVBPs for knee OA from inception, and included validated pain and function scales, BML size and incidence of adverse events. Efficacy was compared using standardized mean differences (SMD) and risk ratios (RR) with fixed-effect or random-effects models. Methodological quality was assessed using the Cochrane risk of bias tool, heterogeneity was assessed by I2 statistics. We included 428 patients in four RCTs of 2-24 months duration; most patients (84%) received zoledronic acid (ZA). Risk of bias was low-moderate. IVBP had large effect sizes on pain within 3 months [SMD = -2.33 (95% CI: -3.02, -1.65)] mainly driven by neridronate (resulting in substantial heterogeneity, I2 = 92%) with no effect for ZA alone. Differences in knee function were statistically significant at 3 months [SMD = -0.22 (-0.43, -0.01), I2 = 0.2%]. Effect sizes for pain did not reach statistical significance at any other time point. IVBPs improved a semi-quantitative measure of BML size within 6 months [SMD = -0.52 (-0.89, -0.14), I2 = 0%] but not at 12 months or two years. Adverse events [RR = 1.19 (1.00, 1.41) I2 = 52%], occurred more frequently with IVBP. ZA has no effect on knee pain, possibly a short-term effect on BML size and higher rates of adverse events. Neridronate may improve pain in the short term, but this is based on a single trial.


Measuring antenatal care use in Europe: is the content and timing of care in pregnancy tool applicable?
Measuring of antenatal care utilisation is important from a public health perspective. The Content and Timing of care in Pregnancy tool (CTP) focuses on the care process and includes aspects on quality of care. The aim of the study is to gain insight in the applicability of the CTP tool across Europe. National guidelines for routine antenatal care were examined, analysing the degree to which the four items in the CTP tool were included in these guidelines. From the 30 countries, 22 had a national guideline for routine antenatal care. The CTP tool is applicable in over 60% of the European countries with a national guideline. The CTP tool can be used to measure antenatal care delivery in Europe. The tool is useful to evaluate the care process, focusing on rates of interventions as the closest approximation to the delivery of health care, with a focus on content of visits rather than simply the number of visits. Together with indicators measuring structure and outcome of health care, conclusions about the quality of care can be made.


Weaker protection against tuberculosis in BCG-vaccinated male 129 S2 mice compared to females.
BCG - the only available vaccine against tuberculosis (TB) - was first given to babies 100 years ago in 1921. While it is effective against TB meningitis and disseminated TB, its efficacy against pulmonary TB is variable, notably in adults and adolescents. TB remains one of the world's leading health problems, with a higher prevalence among men. Male sex is associated with increased susceptibility to Mycobacterium tuberculosis in mice, but sex-specific responses to BCG vaccination have not been examined. In this study we vaccinated TB-susceptible 129 S2 mice with BCG and challenged with low-dose M. tuberculosis H37Rv by aerosol infection. BCG was protective against TB in both sexes, as unvaccinated mice lost weight more rapidly than vaccinated ones and suffered from worse lung pathology. However, female mice were better protected than males, showing lower lung bacterial burdens and less weight loss. Overall, vaccinated female mice had increased numbers of T cells and less myeloid cells in the lungs compared to vaccinated males. Principal component analysis of measured features revealed that mice grouped according to timepoint, sex and vaccination status. The features that had the biggest impact on grouping overall included numbers of CD8 T cells, CD8 central memory T cells and CD4 T effector cells, with neutrophil and CD11b+GR-1- cell numbers having a big impact at day 29. Hierarchical clustering confirmed that the main difference in global immune response was due to mouse sex, with only a few misgrouped mice. In conclusion, we found sex-specific differences in response to M. tuberculosis H37Rv -challenge in BCG-vaccinated 129 S2 mice. This highlights the need to include both male and female mice in preclinical testing of vaccine candidates.


Court-ordered removal in severe child maltreatment: an association to parental major affective disorder.
The authors report on a study of psychiatric diagnoses in parents whose children had been removed from their custody by court order because of child abuse and neglect. Compared to a similar group of parents who had not had children removed, the subject parents had a significantly greater lifetime incidence of affective disorders by Research Diagnostic Criteria (RDC) prior to their court involvement. Very few of these disorders had been rigorously diagnosed before or treated psychiatrically.


Reliability testing of the dermatology index of disease severity (DIDS). An index for staging the severity of cutaneous inflammatory disease.
To describe a new severity of illness index for inflammatory skin disease called the Dermatology Index of Disease Severity (DIDS), and to show its preliminary use and reliability in staging disease in patients with psoriasis and dermatitis. Interobserver rating study using the DIDS with as many as 10 observers independently rating the same patient at a single point in time. Ambulatory care clinics at an academic medical center with patients from various socioeconomic backgrounds. Thirty-four patients with psoriasis and 15 patients with dermatitis were included in the study. The severity of illness for each patient was rated as 1 of 5 stages: 0, no evidence of clinical disease; I, limited disease; II, mild disease; III, moderate disease; and IV, severe disease. The degree of interobserver concordance was measured by the Cohen kappa statistic. All 5 stages were represented in the study of patients with psoriasis. The overall kappa statistic was 0.76, which is defined as substantial interobserver concordance. The use of the instrument in dermatitis showed good consensus in staging, where the kappa statistic was 0.41. We introduce an easy and efficient instrument for staging the severity of illness in inflammatory cutaneous diseases. The reliability of the DIDS is demonstrated in patients with psoriasis and in patients with dermatitis.


The experience of nurses participating in peer group supervision: A qualitative systematic review.
This systematic review will identify, appraise, and synthesise the best available qualitative studies exploring nurses' experiences of peer group supervision. The review purpose draws from the synthesised evidence recommendations to enhance policy and implementation of peer group supervision in practice. Clinical Supervision is increasing in acceptance as a means of professional and best practice support in nursing. Peer group supervision is a non-hierarchical, leaderless model of clinical supervision delivery and is an option for implementation by nursing management when prioritising staff support with limited resources. This systematic review will provide a synthesis of the qualitative literature regarding the nursing peer group supervision experience. Understanding the experience of peer group supervision from those participating may provide constructive insights regarding implementation of this practice to benefit both nurse and patient driven outcomes. Included are peer reviewed journals focused on nurses' experiences of participating in peer group supervision. Participants are registered nurses of any designation. Qualitative articles, written in English and relating to any area of nursing practice and/or speciality are included. The standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement were used to guide the review. Two investigators independently screened titles, abstracts and selected full text studies describing the experience of peer group supervision. Pre-designed data extraction tools were utilised, and the review followed the Joanna Briggs Institute qualitative meta-aggregation approach with a hermeneutic interpretive analysis. Results identified seven studies that met the inclusion criteria. A total of 52 findings that described the experiences of nursing peer group supervision are synthesised into eight categories. Four overarching synthesised findings resulted: 1. facilitating professional growth 2. trusting the group 3. professional learning experience and 4. shared experiences. Benefits such as sharing of experiences whilst receiving feedback and support were identified. Challenges identified related to group processes. The paucity of international research into nursing peer group supervision poses challenges for nurse decision makers. Significantly, this review provides insight into the value of peer group supervision for nurses regardless of clinical context and setting. The ability to share and reflect with nursing peers enhances both personal and professional aspects of practice. The worth of the peer group supervision model varied across studies however the outcomes provided important insights into facilitating professional growth, enabling a space to share experiences and reflect, and to build teams where trust and respect develops in groups.


Gene therapy for type 1 diabetes.
The most intensively studied autoimmune disorder, type 1 diabetes mellitus (DM1), has attracted perhaps the greatest interest for gene-based therapeutic and prophylactic interventions. The final clinical manifestation of this immunologically and genetically complex disease, the absence of insulin, is the major starting point for almost all the gene therapy modalities attempted to date. Insulin replacement by transplantation of islets of Langerhans or surrogate beta cells is the obvious choice, but the allogeneic nature of the transplants activates potent antidonor immunoreactivity necessitating gene and cell-based immunosuppressive strategies as an alternative to the toxic pharmacologic immunosuppressives indicated for classic solid organ transplants. Accumulating knowledge of the cellular mechanisms involved in onset, however, have yielded promising tolerance induction prophylactic approaches using genes and cells. Despite the early successes in a number of animal models, the true test of efficacy in humans remains to be demonstrated.


A construction and comprehensive analysis of ceRNA networks and infiltrating immune cells in papillary renal cell carcinoma.
As the second most common malignancy in adults, papillary renal cell carcinoma (PRCC) has shown an increasing trend in both incidence and mortality. Effective treatment for advanced metastatic PRCC is still lacking. In this study, we aimed to establish competitive endogenous RNA (ceRNA) networks related to PRCC tumorigenesis, and analyze the specific role of differentially expressed ceRNA components and infiltrating immune cells in tumorigenesis. CeRNA networks were established to identify the key ceRNAs related to PRCC tumorigenesis based on the 318 samples from The Cancer Genome Atlas database (TCGA), including 285 PRCC and 33 normal control samples. The R package, "CIBERSORT," was used to evaluate the infiltration of 22 types of immune cells. Then we identified the significant ceRNAs and immune cells, based on which two nomograms were obtained for predicting the prognosis in PRCC patients. Finally, we investigated the co-expression of PRCC-specific immune cells and core ceRNAs via Pearson correlation test. COL1A1, H19, ITPKB, LDLR, TCF4, and WNK3 were identified as hub genes in ceRNA networks. Four prognostic-related tumor-infiltrating immune cells, including T cells CD4 memory resting, Macrophages M1, and Macrophages M2 were revealed. Pearson correlation test indicated that Macrophage M1 was negatively related with COL1A1 (p < 0.01) and LDLR (p < 0.01), while Macrophage M2 was positively related with COL1A1 (p < 0.01), TCF4 (p < 0.01), and H19 (p = 0.032). Two nomograms were conducted with favorable accuracies (area under curve of 1-year survival: 0.935 and 0.877; 3-year survival: 0.849 and 0.841; and 5-year survival: 0.818 and 0.775, respectively). The study constructed two nomograms suited for PRCC prognosis predicting. Moreover, we concluded that H19-miR-29c-3p-COL1A1 axis might promote the polarization of M2 macrophages and inhibit M1 macrophage activation through Wnt signaling pathway, collaborating to promote PRCC tumorigenesis and lead to poor overall survival of PRCC patients.


Altered collagen of human pathological fibroblasts impairs the synthesis of fibronectin.
Human fibroblasts with mutated type I collagen have marked defective adhesive capacities on exogenous type I collagen and exogenous fibronectin in comparison to normal fibroblasts. This defective cell adhesion could be partly explained by the decreased level of cell surface receptors of the beta 1-integrin family, i.e., the alpha 2 integrin subunit for type I collagen and the alpha 5 integrin subunit for fibronectin, observed in pathological fibroblasts. However, it appeared that the presence of altered collagen interfered both with fibronectin biosynthesis and with its surface expression. Using a binding assay on immobilized fibronectin, we demonstrated that the mutated collagen had a weaker binding to fibronectin. In addition, the pathological fibroblasts plated on a mixture of normal exogenous type I collagen and fibronectin exhibited the same maximal level of adhesion as control fibroblasts. These results indicate that fibroblasts with the mutated collagen exhibit a decreased binding to normal fibronectin, a modification of synthesis and surface expression of fibronectin, and, finally, altered adhesive capacities.


The effects of systemic administration of dexametasone on periodontal structures of marmosets.
After the period of 28 days of experiment, marmosets, submitted to systemic action of Dexametasone (0,4 mg of Dexametasone every two days), showed: osteoporosis of the interdental septum, and cell reduction of the periodontal ligament, proportional to the time of administration of the drug.


Mink lung cells as a tool for detection of Mycoplasma hyorhinis contamination in cell cultures and virus stocks.
In an extensive host range study of M. hyorhinis mink lung cells (MvlLu, ATCC CCL 64) were found to be the cells of choice for the propagation of this mycoplasm, which otherwise is often difficult to grow in a cell-free medium. Furthermore, rapid plaque assay and plaque purification procedures were developed for M. hyorhinis. The titer of M. hyorhinis grew to 1 X 10(7) to 1 X 10(8) pfu/ml within three d postinoculation on mink lung cells. DNA restriction enzyme analysis of the genome of M. hyorhinis was performed. Endonucleases Bst EII and Xho I are the most suitable enzymes for cleaving M. hyorhinis DNA into distinct fragment patterns. Thus, the use of the combination mink lung cells for mycoplasma growth with subsequent restriction enzyme analysis leads to an unambiguous detection and identification of M. hyorhinis strains even in minute amounts.


Rapid identification of imported influenza viruses at Xiamen International Airport via an active surveillance program.
The cross-border transmission of infectious diseases is a worldwide public health issue. Current border screening measures are insufficiently sensitive. The study objectives were to describe the epidemiologic pattern of influenza infection among incoming travellers at Xiamen International Airport during nonpandemic periods and to assess the performance of a rapid influenza diagnostic test in border screening. Between May 2015 and May 2016, travellers with influenza-like illnesses entering China at Xiamen International Airport were screened with a rapid test, Flu Dot-ELISA, and the collected specimens were further subjected to virus isolation and phylogenetic analysis. Of the 1 540 076 incoming travellers, 1224 cases of influenza-like illness were identified; 261 tested positive in the rapid test, and 176 were confirmed to be influenza through virus culture. The sensitivity and specificity of the rapid test were demonstrated to be 96.6% (170/176) and 91.3% (957/1048), respectively, and the positive predictive and negative predictive values were 65.1% (170/261) and 99.4% (957/963), respectively. The epidemiologic study indicated that H3N2 and (H1N1)pdm09 were dominant in 2015 and 2016, respectively. In 2016, an increased number of influenza B isolates and cocirculation of both Victoria and Yamagata lineage influenza B viruses were observed, and mismatches between circulating influenza A(H1N1)pdm09 and influenza B Victoria lineage strains and vaccine strains also occurred. We demonstrated the suitability and value of a high-sensitivity rapid influenza test in border screening and highlighted the importance of incoming travellers as a source of imported infectious diseases.


Hippocampal parvalbumin and perineuronal nets: Possible involvement in anxiety-like behavior in rats.
The excitatory-inhibitory imbalance has been considered an important mechanism underlying stress-related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS-exposed rats exhibited increased anxiety-like behavior. Immunofluorescence showed that IFS rats had a decreased density of GAD67-immunoreactive interneurons in the dorsal hippocampal CA1 region, while no significant change in the density of CaMKIIα-immunoreactive glutamatergic neurons was seen. We investigated the expression of different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), and calretinin (CR), and noted a marked decline in the density of PV-immunoreactive interneurons in the dorsal CA1 region of IFS rats. The perineuronal net (PNN) is a specialized extracellular matrix structure primarily around PV interneurons. We used Wisteria floribunda agglutinin lectin to label the PNNs and observed that IFS rats had an increased proportion of PNN-coated PV-positive interneurons in CA1. The number of PSD95-positive excitatory synaptic puncta on the soma of PNN-free PV-positive interneurons was significantly higher than that of PNN-coated PV-positive interneurons. Our findings suggest that the effect of IFS on the hippocampal GABAergic interneurons could be cell-type-specific. Loss of PV phenotype in the dorsal hippocampal CA1 region may contribute to anxiety in rats. The dysregulated PV-PNN relationship in CA1 after traumatic stress exposure might represent one of the neurobiological correlates of the observed anxiety-like behavior.


TiO2-based Photocatalytic Cementitious Composites: Materials, Properties, Influential Parameters, and Assessment Techniques.
Applications of heterogeneous photocatalytic processes based on semiconductor particles in cement-based materials have received great attention in recent years in enhancing the aesthetic durability of buildings and reducing global environmental pollution. Amongst all, titanium dioxide (TiO2) is the most widely used semiconductor particle in structural materials with photocatalytic activity because of its low cost, chemically stable nature, and absence of toxicity. Utilization of TiO2 in combination with cement-based materials would plunge the concentration of urban pollutants such as NOx. In fact, cementitious composites containing TiO2 have already found applications in self-cleaning buildings, antimicrobial surfaces, and air-purifying structures. This paper aims to present a comprehensive review on TiO2-based photocatalysis cement technology, its practical applications, and research gaps for further progression of cementitious materials with photocatalytic activity.


Heat generation and transfer behaviors of ti-coated carbon steel rod adaptable for ablation therapy of oral cancer.
For the purpose of developing a novel ablation therapy for oral cancer, the heat generation and transfer properties of a Ti-coated carbon steel rod with 20-mm length and 1.8-mm outer diameter were investigated by means of a high-frequency induction technique at 300 kHz. The heat generation measurement performed using water (15 mL) revealed that the difference of the inclination angles (θ = 0°, 45° and 90°) relative to the magnetic flux direction only slightly affects the heating behavior, exhibiting the overlapped temperature curves during an induction time of 1200 s. These results suggest that the effect of the shape magnetic anisotropy is almost eliminated, being convenient for the precise control of the ablation temperature in clinical use. In the experiments utilizing a tissue-mimicking phantom, the heat transfer concentrically occurred in the lateral direction for both the planar surface and a 10-mm deep cross-section. However, the former exhibited a considerably lower increase in temperature (ΔT), probably due to the effect of heat dissipation to the ambient air. No significant heat transfer was found to occur to the lower side of the inserted Ti-coated carbon steel rod, which is situated in the longitudinal direction.


The relative importance of environmental factors in predicting phytoplankton shifting and cyanobacteria abundance in regulated shallow lakes.
The phytoplankton community can be affected by multiple environmental factors such as climate, meteorology, hydrology, nutrients, and grazing. The complex interactive effects of these environmental factors as well as the resilience of phytoplankton communities further make the prediction of phytoplankton communities' dynamics challenging. In this study, we analyzed multiple environmental factors and their relative importance in predicting both phytoplankton shifting and cyanobacteria abundance in two regulated shallow lakes in central China. Our results indicated that the phytoplankton community in the study areas could be mainly classified into 1. Cryptophyta dominated group, 2. Biologically diverse group, and 3. Cyanobacteria dominated group. The Multinomial Logistic Regression model indicated the Cryptophyta dominated group was sensitive to temperature, while other groups were sensitive to both temperature and nutrients. The interactive effects of temperature and nutrients were synergistic in the cyanobacteria dominated group, while they were antagonistic or minor in other groups. The Negative Binomial Regression model suggested high total phosphorus and low total nitrogen but not temperature were responsible for high cyanobacteria abundance. The conditional plot indicated nutrients affected cyanobacteria abundance more significantly under low wind speeds and lake volume fluctuations, and cyanobacteria abundance in the cyanobacteria dominated group maintained high levels with increasing hydrological dynamics. Our results demonstrated that environmental factors played inconsistently significant roles in different phytoplankton groups, and reducing nutrients could decrease adverse effects of warming and water project constructions. Our models can also be applied to forecast phytoplankton shifting and cyanobacteria abundance in the management of regulated shallow lakes.


Characterization of the Complete Chloroplast Genome Sequences of Four Zanthoxylum L. Species (Sapindales: Rutaceae) from the Caribbean, Madagascar, the Mascarene Islands, and the South Pacific.
Zanthoxylum is a genus of woody plants in the Rutaceae family distributed pantropically, with some species extending to temperate regions in East Asia and North America. Here, we present the complete chloroplast genome sequences of four species, two of them critically endangered, endemic to tropical islands.


Biased confabulation in risky choice.
When people make risky decisions based on past experience, they must rely on memory. The nature of the memory representations that support these decisions is not yet well understood. A key question concerns the extent to which people recall specific past episodes or whether they have learned a more abstract rule from their past experience. To address this question, we examined the precision of the memories used in risky decisions-from-experience. In three pre-registered experiments, we presented people with risky options, where the outcomes were drawn from continuous ranges (e.g., 100-190 or 500-590), and then assessed their memories for the outcomes experienced. In two preferential tasks, people were more risk seeking for high-value than low-value options, choosing as though they overweighted the outcomes from more extreme ranges. Moreover, in two preferential tasks and a parallel evaluation task, people were very poor at recalling the exact outcomes encountered, but rather confabulated outcomes that were consistent with the outcomes they had seen and were biased towards the more extreme ranges encountered. This common pattern suggests that the observed decision bias in the preferential task reflects a basic cognitive process to overweight extreme outcomes in memory. These results highlight the importance of the edges of the distribution in providing the encoding context for memory recall. They also suggest that episodic memory influences decision-making through gist memory and not through direct recall of specific instances.


Multiple hemoglobins in Triturus cristatus: their degradation by sulfhydryl compounds.
1. Hemolysates of newt (Triturus cristatus) red cells contain four distinct hemoglobin species which have been observed consistently both in individual animals and pooled samples. 2. Hemoglobin heterogeneity in the species arises from existence of multiple hemoglobulins, with no indication of genetic polymorphism. 3. While the relative proportions of the different hemoglobins may vary in different samples, HbII is usually the most abundant, with HbIII and HbIV constituting most of the remainder of the total hemoglobin complement. HbI never exceeds 3-5% of the total hemoglobin. 4. Neither the electrophoretic migration nor the anion exchange properties of the four hemoglobin species are altered by conversion of oxyhemoglobin to the cyanmet derivative, excluding artifacts due to different oxidation states of iron. 5. The average molecular weight of newt total hemoglobulin is 67,182 with no indication of hemoglobin polymers. 6. The use of sulfhydryl-reducing agents (mercaptoethanol, dithiothreitol) as a precaution against aggregation results in extensive degradation of newt hemoglobin through a process similar to "coupled oxidation" by ascorbate. 7. The degradative effects of sulfhydryl-reducing agents on newt hemoglobin suggest that these reagents be used cautiously in any hemoglobin analysis.


The role of action inhibition for behavioral control in joint action.
When two individuals share a task with a common goal, coordinating one's own and the other's actions is pivotal. Inhibition of one's own actions when it is the other's turn to act is assumed to play a crucial role in this process. For instance, in the joint Simon task, two individuals share a two-choice task such that one of them responds to one stimulus type and ignores the stimulus type to which the other responds. Because stimuli can either appear on one's own or on the other's side, stimulus location can conflict with stimulus identity, thus slowing response time. It has previously been shown that such conflict leads to a reduction of the detrimental effects of conflict on immediately upcoming trials both following own responses and even more so following the other's responses. This amplified trial-to-trial adjustment following the other's responses has been assumed to reflect the inhibition of own responses on the other's trials. The present study tested this hypothesis by comparing sequential trial-to-trial adjustments following correct responses and commission errors on which the inhibition of own responses has failed. As expected, adjustments were stronger following the other's correct responses than following own correct responses. Crucially, such amplification of sequential adjustment was not observed following own commission errors on the other's trials. This shows that amplification of sequential adjustments following the other's trials depend on successful inhibition of own responses on these trials and points to a crucial role of response inhibition for behavioral control in joint action.


[Safety and efficiency of interventional electrophysiology utilizing the German "Belegarztsystem"].
Electrophysiology study (EPS) and catheter ablation (abl.), in particular for atrial fibrillation, are increasingly performed in Germany. Therefore, measures and steps to ensure quality assurance are indicated. Most of the procedures are performed by physicians employed by hospitals; however, some are also carried out by attending cardiologists on contract in private practice, applying the so-called Belegarztsystem. The aim of this study was to determine the safety and efficiency of an interventional electrophysiology performed in a German Belegarztsystem. Based on a prospective registry, we analyzed procedure-related data from 1400 consecutive EPS/abl. performed at our center between 2014 and 2018. One-year follow-up data (arrhythmia recurrences, complications, deaths) were collected for all procedures carried out during the first 2 years. In the total study cohort, no periprocedural death occurred, and there was a low cumulative incidence of groin complications (0.9%). The most common procedure (n = 772) was complex ablation for atrial fibrillation/flutter (55%). In this group, the success rate was 98% (acute) and 65% (1 year), and the cumulative rate of complications was 5.0% (transient ischemic attack/stroke 0.1%, pericardial tamponade 0.4%, relevant pericarditis/pericardial effusion 1.1%, groin complication 1.5%, other 1.9%). For the other procedures, rates for success and complications were comparable, and procedure times and x‑ray doses tended to be lower in our analysis as compared to prior reports. Interventional electrophysiology, carried out by experienced operators and qualified staff, can be performed safely and effectively by attending physicians in a Belegarztsystem.


A pilot study of two-day cognitive-behavioral therapy for panic disorder.
The present study investigated the short-term efficacy of brief, intensive cognitive-behavioral therapy (CBT) for panic disorder (PD). The treatment involved 9h of therapist contact over two consecutive days and was developed for the purpose of delivering CBT for PD to a largely rural patient population that must travel long distances to find a treatment provider. Ten patients who elected to participate in brief, intensive CBT instead of weekly CBT were recruited from routine clinical practice in a hospital-based anxiety disorders clinic. Patients were not excluded based on the presence of agoraphobia, diagnostic comorbidity, concurrent use of PRN benzodiazepine medications, or previous nonresponse to psychotherapy for PD. Assessments conducted at pre-treatment and 1-month follow-up revealed large, clinically significant reductions in PD symptoms, anxiety sensitivity, body vigilance, and anxiety and depressive symptoms. Most patients (60%) were panic-free after treatment and evidenced normative levels of symptomatology at follow-up. The present study suggests that brief, intensive treatment may be an effective means of delivering CBT for PD.


Rehabilitation Exercises Supported by Monitor-Augmented Reality for Patients with High-Grade Glioma Undergoing Radiotherapy: Results of a Randomized Clinical Trial.
Exercise has been shown to improve quality of life (QoL) and even treatment outcomes in cancer patients. However, the evidence to support the benefits of exercise in patients with high-grade glioma (HGG) is limited. Therefore, we performed a randomized clinical trial (RCT) to examine the effect of augmented-reality-based rehabilitation exercises on physical and functional fitness, cognitive function, fatigue, mood, QoL, selected blood parameters, brain derived neurotrophic factor (BDNF), and S100 protein in patients with HGG. Adult patients with HGG scheduled to undergo radiotherapy after tumor resection were randomized to participate in an exercise program (experimental group, n = 25) or to receive usual care (controls, n = 22). Physical and mental fitness was measured at baseline, after the completion of radiotherapy, and at 3 months. The following tests were administered: Handgrip Strength Test; 6-Minute Walk Test; Time Up and Go test; Functional Independent Measure scale; Addenbrooke's Cognitive Examination III (ACE III); Hospital Anxiety and Depression Scale; Functional Cancer Therapy Assessment-Brain; and Functional Assessment of Chronic Illness Therapy-Fatigue. We also measured blood parameters, BDNF, and S100 protein levels. No significant changes were observed in the exercise group. However, the controls experienced a significant decrease in HGS and in the ACE III attention domain. No significant changes were observed in QoL, fatigue, BDNF, or S100 levels in either group. Augmented-reality-based exercise during radiation therapy may prevent loss of muscle strength and attention in patients with HGG.


Genetic variants of the EGFR ligand-binding domain and their association with structural alterations in Arab cancer patients.
This study aimed to identify novel genetic variants in the CR2 extracellular domain of the epidermal growth factor receptor (EGFR) in healthy individuals and patients with six different types of adenocarcinoma, in Arabian peninsula populations. It also aimed to investigate the effects of these variants on the EGFR structure and their eventual relevance to tumorigenesis. We detected seven new EGFR genetic variants in 168 cancer patients and 114 controls. A SNP rs374670788 was more frequent in bladder cancer but not significantly associated to. However, a missense mutation (V550M) was significantly associated to colon, ovary, lung, bladder and thyroid cancer samples (p < 0.05). Three mutations (H590R, E602K and T605T) were found in the heterozygous form only in colon cancer patients. Genomic analysis of the synonymous mutation (G632G) showed that the T/A genotype could be associated to thyroid cancer in Arab patients (p < 0.05). An additional novel SNP rs571064657 was observed in control individuals. Computational analysis of the genetic variants revealed a reduction in the stabilization of the EGFR tethered form for both V550M and the common R521K variant with low energetic state (- ∆∆G). Molecular interactions analysis suggested that these mutations might affect the receptor's function and promote tumorigenesis.


Technical note: Controlling the attenuation of 3D-printed physical phantoms for computed tomography with a single material.
The purpose of this work was to characterize and improve the ability of fused filament fabrication to create anthropomorphic physical phantoms for CT research. Specifically, we sought to develop the ability to create multiple levels of X-ray attenuation with a single material. CT images of 3D printed cylinders with different infill angles and printing patterns were assessed by comparing their 2D noise power spectra to determine the conditions that produced minimal and uniform noise. A backfilling approach in which additional polymer was extruded into an existing 3D printed background layer was developed to create multiple levels of image contrast. A print with nine infill angles and a rectilinear infill pattern was found to have the best uniformity, but the printed objects were not as uniform as a commercial phantom. An HU dynamic range of 600 was achieved by changing the infill percentage from 40% to 100%. The backfilling technique enabled control of up to eight levels of contrast within one object across a range of 200 HU, similar to the range of soft tissue. A contrast detail phantom with six levels of contrast and an anthropomorphic liver phantom with four levels of contrast were printed with a single material. This work improves the uniformity and levels of contrast that can be achieved with fused filament fabrication, thereby enabling researchers to easily create more detailed physical phantoms, including realistic, anthropomorphic textures.


High frequency of micro- and meso-plastics ingestion in a sample of neonate sea turtles from a major rookery.
We studied marine litter ingestion in 380 neonate sea turtles that washed ashore dead onto Florida's central Atlantic coast (USA) following onshore winds. Our sample of "washbacks" included 284 loggerheads (Caretta caretta), 95 green turtles (Chelonia mydas), and one hawksbill (Eretmochelys imbricata). Of these, 78.7% had ingested plastics and 45.3% had ingested tar. There was a significant relationship between turtles' carapace length and total mass of ingested plastic. Ingested plastics included microplastics (<5 mm) and larger sizes up to 25% of carapace length. Washbacks' body condition indices were significantly poorer than condition indices of wild turtles captured at sea. Washbacks showed a negative association between plastic load and body condition index, evidence that high plastic loads resulted in diminished nutrition, with possible effects on somatic growth, stage duration, and survivorship. Evidence points to plastics ingestion being an important source of population-level effects in neonate sea turtles.


Characterization of mutations in the penicillinase operon Staphylococcus aureus.
Mutant penicillinase plasmids, in which penicillinase synthesis is not inducible by penicillin or a penicillin analogue, were examined by biochemical and genetic analyses. In five of the six mutants tested, penicillinase synthesis could be induced by growth in the presence of 5-methyltryptophan. It is known that the tryptophan analogue 5-methyltryptophan is readily incorporated into protein by S. aureus and that staphylococcal penicillinase lacks tryptophan. 5-methyltryptophan seems to induce penicillinase synthesis in wild-type plasmids by becoming incorporated into the repressor and thereby inactivating the operator binding function of the penicillinase repressor. Therefore, induction of penicillinase synthesis in the mutant plasmids by 5-methyltryptophan strongly suggests that the noninducible phenotype of these five plasmids is due to a mutation that inactivates the effector binding site of the penicillinase repressor (i.e., the five mutant plasmids carry an iS genotype for the penicillinase repressor). This conclusion was supported by heterodiploid analysis. The mutant plasmid that did not respond to 5-methyltryptophan either produces an exceedingly low basal level of penicillinase or does not produce active enzyme. This plasmid seems to carry a mutation in the penicillinase structural gene or in the promoter for the structural gene. Thus, a genetic characterization of many mutations in the penicillinase operon can be accomplished easily and rapidly by biochemical analysis.


Insights into neural mechanisms and evolution of behaviour from electric fish.
Both behaviour and its neural control can be studied at two levels. At the proximate level, we aim to identify the neural circuits that control behaviour and to understand how information is represented and processed in these circuits. Ultimately, however, we are faced with questions of why particular neural solutions have arisen, and what factors govern the ways in which neural circuits are modified during the evolution of new behaviours. Only by integrating these levels of analysis can we fully understand the neural control of behaviour. Recent studies of electrosensory systems show how this synthesis can benefit from the use of tractable systems and comparative studies.


Application of stable isotopes and dissolved ions for monitoring landfill leachate contamination.
We evaluated groundwater contamination by landfill leachate at a municipal landfill and characterized isotopic and hydrogeochemical evidence of the degradation and natural attenuation of buried organic matter at the study site. Dissolved ion content was generally much higher in the leachate than in the surrounding groundwater. The leachate was characterized by highly elevated bicarbonate and ammonium levels and a lack of nitrate and sulfate, indicating generation under anoxic conditions. Leachate δD and δ13CDIC values were much higher than those of the surrounding groundwater; some groundwater samples near the landfill showed a significant contamination by the leachate plume. Hydrochemical characteristics of the groundwater suggest that aquifer geology in the study area plays a key role in controlling the natural attenuation of leachate plumes in this oxygen-limited environment.


Kilovoltage imaging doses in the radiotherapy of pediatric cancer patients.
To investigate doses induced by kilovoltage cone-beam computed tomography (kVCBCT) to pediatric cancer patients undergoing radiotherapy, as well as strategies for dose reduction. An EGS4 Monte Carlo code was used to calculate three-dimensional dose deposition due to kVCBCT on 4 pediatric cancer patients. Absorbed doses to various organs were analyzed for both half-fan and full-fan modes. Clinical conditions, such as distance from organ at risk (OAR) to CBCT field border, kV peak energy, and testicular shielding, were studied. The mean doses induced by one CBCT scan operated at 125 kV in half-fan mode to testes, liver, kidneys, femoral heads, spinal cord, brain, eyes, lens, and optical nerves were 2.9, 4.7, 7.7, 10.5, 8.8, 7.6, 7.7, 7.8, and 7.2 cGy, respectively. Increasing the distances from OARs to CBCT field border greatly reduced the doses to OARs, ranging from 33% reduction for spinal cord to 2300% reduction for testes. As photon beam energy increased from 60 to 125 kV, the dose increase due to kVCBCT ranged from 170% for lens to 460% for brain and spinal cord. A testicular shielding made of 1-cm cerrobend could reduce CBCT doses down to 31%, 51%, 68%, and 82%, respectively, for 60, 80, 100, and 125 kV when the testes lay within the CBCT field. Generally speaking, kVCBCT deposits much larger doses to critical structures in children than in adults, usually by a factor of 2 to 3. Increasing the distances from OARs to CBCT field border greatly reduces doses to OARs. Depending on OARs, kVCBCT-induced doses increase linearly or exponentially with photon beam energy. Testicular shielding works more efficiently at lower kV energies. On the basis of our study, it is essential to choose an appropriate scanning protocol when kVCBCT is applied to pediatric cancer patients routinely.


Selenoproteins in brain development and function.
Expression of selenoproteins is widespread in neurons of the central nervous system. There is continuous evidence presented over decades that low levels of selenium or selenoproteins are linked to seizures and epilepsy indicating a failure of the inhibitory system. Many developmental processes in the brain depend on the thyroid hormone T3. T3 levels can be locally increased by the action of iodothyronine deiodinases on the prohormone T4. Since deiodinases are selenoproteins, it is expected that selenoprotein deficiency may affect development of the central nervous system. Studies in genetically modified mice or clinical observations of patients with rare diseases point to a role of selenoproteins in brain development and degeneration. In particular selenoprotein P is central to brain function by virtue of its selenium transport function into and within the brain. We summarize which selenoproteins are essential for the brain, which processes depend on selenoproteins, and what is known about genetic deficiencies of selenoproteins in humans. This review is not intended to cover the potential influence of selenium or selenoproteins on major neurodegenerative disorders in human.


Risks and Benefits of Adenotonsillectomy in Children With Cerebral Palsy With Obstructive Sleep Apnea: A Systematic Review.
Assess the risks and benefits of adenotonsillectomy (AT) for obstructive sleep apnea (OSA) in children with cerebral palsy (CP). Systematic review. We conducted a systematic review of Medline, Embase, and Cochrane Central Registry from 1946 to 2021. Broad search concepts included cerebral palsy, pediatric, tonsillectomy/adenoidectomy, and sleep. Additional articles were identified by searching reference lists. Studies on the safety and efficacy of AT for OSA management in children with CP were included. Fifteen articles met inclusion criteria. Articles were classified into one or more of four themes: intraoperative risk (n = 1), postoperative risk (n = 3), postoperative care requirements (n = 6), and surgical outcomes (n = 7). No intraoperative anesthetic complications were reported. Postoperatively, respiratory complications including pneumonia were common and necessitated additional airway management. Following AT, children with CP required close postoperative observation, experienced increased lengths of stay, and had increased odds of unplanned intensive care unit (ICU) admission. Benefits following AT were improvement in OSA as measured by a reduction in obstructive apnea-hypopnea index (OAHI) as well as improved quality of life in some; however, many patients went on to require tracheostomy due to persistent OSA. Children with CP who undergo AT have a significant risk of developing a postoperative respiratory complication. Realistic counseling of families around increased perioperative risks in this population is imperative and close postoperative monitoring is critical. Many children will obtain a reduction in OAHI, but additional surgical management is often required, including tracheostomy. Further research is needed to determine the best management strategy for OSA in children with CP. Laryngoscope, 132:687-694, 2022.


Investigating errors in medical imaging: medical malpractice cases in Finland.
The objectives of the study were to survey patient injury claims concerning medical imaging in Finland in 1991-2017, and to investigate the nature of the incidents, the number of claims, the reasons for the claims, and the decisions made concerning the claims. The research material consisted of patient claims concerning imaging, sent to the Finnish Patient Insurance Centre (PVK). The data contained information on injury dates, the examination code, the decision code, the description of the injury, and the medical grounds for decisions. The number of claims included in the study was 1054, and the average number per year was 87. The most common cause was delayed diagnosis (404 claims, 38.3%). Most of the claims concerned mammography (314, 29.8%), radiography (170, 16.1%), and MRI (162, 15.4%). According to the decisions made by the PVK, there were no delays in 54.6% of the examinations for which claims were made. About 30% of all patient claims received compensation, the most typical reason being medical malpractice (27.7%), followed by excessive injuries and injuries caused by infections, accidents and equipment (2.7%). Patient injury in imaging examinations and interventions cannot be completely prevented. However, injury data are an important source of information for health care. By analysing claims, we can prevent harm, increase the quality of care, and improve patient safety in medical imaging.


Evolving in islands of mud: old and structured hidden diversity in an endemic freshwater crayfish from the Chilean hotspot.
Parastacus is a genus of South American freshwater crayfishes disjunctively distributed in southern Chile, Northern Argentina, Uruguay and Southeastern Brazil. Parastacus pugnax is a Chilean endemic distributed along 700 km of latitude in central-southern Chile from the Pacific coast to the Andean piedmont, which is intensively captured for consumption for local communities. Considering the habitat (wet meadows) and natural history (primary burrower, non-migrant) of the species, we tested a hypothesis of highly structured genetic diversity using mtDNA of 465 specimens gathered at 56 localities across the species range. The crown age of P. pugnax was estimated at 38 Ma, predating the main Andean uplift. The genetic variation of P. pugnax is large and geographically structured. In some cases, genetic groups do not match basin limits, suggesting a previous to current dynamic of basin evolution. The uncovered intraspecific main lineages have different demographic histories. A latitudinal cline in past effective population size reduction suggests environmental singularities with a glacial effect in the southern populations. We suggest adding morphologic and more genetic data in order to assess species limits. Our results contribute to improve future conservation actions for this taxon, providing basic information to delimit conservation units.


Epidemiological Study Based on China Osteonecrosis of the Femoral Head Database.
The aim of the present study was to reveal the case characteristics of osteonecrosis of the femoral head (ONFH) in Mainland China. This cross-sectional epidemiological study derived data for ONFH patients from July 2016 to December 2018 from the China Osteonecrosis of the Femoral Head Database (CONFHD). The derived data included gender, age, body mass index (BMI), height, occupation, region, and etiology of femoral head necrosis. A descriptive analysis was performed to summarize the epidemiological characteristics of the case data in the CONFHD. A total of 1844 ONFH patients (2945 hips) were included in this study, comprising 1302 men and 542 women. The age of patients ranged from 18 to 95 years, with a median of 50 years, and the male to female ratio was 2.4. Male patients are younger than female patients (48.26 ± 12.56 years old and 55.56 ± 14.94 years old, respectively). Among the 1844 patients (2945 hips), there were 528 (17.92%) hips at ARCO stage I, 941 (31.99%) hips at ARCO stage II, 873 (29.63%) hips at ARCO stage III, and 603 (20.46%) hips at ARCO stage IV. In the subclassification of ARCO stages I and II, the majority of cases were type C; type A comprised the majority in the subclassification of ARCO stage III. According to the Kellgren-Lawrence classification system, among the 603 ARCO stage IV hips, there were 178 (29.52%) grade 1 hips, 201 (33.34%) grade 2 hips, 176 (29.18%) grade 3 hips, and 48 (7.96%) grade 4 hips. Most were from three provinces: Henan (27.3%), Shanxi (13.9%), and Shandong (11.9%). Regarding BMI, 982 patients (53.25%) were overweight or obese. Among all patients, the largest proportion of patients engaged in level IV manual work. Of all the patients, there were 495 (26.84%) with steroid-induced ONFH, 685 (37.15%) were alcoholics, and 290 (15.73%) had traumatic ONFH. The 495 patients with steroid-induced ONFH included 278 men (56.16%) and 217 women (43.84 %), had a complete history of hormone use. Among the primary diseases, there were 195 cases (39.39%) of immune system diseases, followed by dermatological diseases, respiratory diseases, nephropathy, and other diseases. There were a total of 685 patients with alcoholic ONFH, 589 of these patients (85.99%) were men. A total of 188 (27.45%) patients had drunk alcohol for 6-10 years (comprising the highest proportion), and 280 patients (40.88%) consumed 3001-3500 mL of alcohol each week (the highest proportion). Osteonecrosis of the femoral head most commonly occurs after the age of 40. Male patients have an earlier onset than female patients, and the number of male patients is approximately twice that of female patients. The BMI of patients was mainly in the overweight and obese range, and half of these patients engaged in level IV manual work. From the imaging findings, the numbers of hips at ARCO stages II and III were greatest, and the number at stage I was relatively small. Among all the causes of disease, alcohol, steroid use and trauma were the three most common reasons for ONFH.


Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC.
Single-agent osimertinib is the standard of care for the first-line treatment of advancedEGFR+ NSCLC and remained the only marketed third-generation EGFR tyrosine kinase inhibitor (TKI) until March 2020 when almonertinib (HS-10296) was approved in the People's Republic of China for the treatment of advanced EGFR T790M+ NSCLC based on a phase 2 expansion study of a phase 1/2 trial. In this review, we profiled many of the third-generation EGFR TKIs in late-stage clinical development (e.g., almonertinib, lazertinib, alflutinib1, rezivertinib, ASK120069, SH-1028, D-0316, and abivertinib) based on their interim results from phase 1 and phase 2 trials, and included the designs of the phase 3 trials and their chemical structures when publicly available. We also listed other third-generation EGFR TKIs in pipeline development based on the search of clinical trial registration websites. In addition, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, mavelertinib), including phase 3 results of rociletinib and naquotinib. We further profiled combination clinical trial design of the third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704), and ACROSS2 (NCT04500717) that if positive can potentially usher in the next standard of care for advanced EGFR+ NSCLC.


The challenge of posttraumatic thrombus embolization from abdominal aortic aneurysm causing acute limb ischemia.
We report the first documented case of distal thromboembolism originating from an abdominal aortic aneurysm (AAA) after a blunt trauma. A 72-year-old man with a known 6.2 cm AAA was brought to our emergency department with signs of bilateral acute limb ischemia developing immediately after an accidental fall. The occlusion was confirmed at computed tomographic angiography, and the aneurysm showed a fragmentated/ulcerated mural thrombus, morphologically different as compared to the previous computed tomography (CT). A thromboembolectomy was performed and, after treatment of the ischemic complications, the aneurysm was repaired by open surgery. Embolization from aneurysms in the setting of a trauma is a challenge for the vascular surgeon, also because of its rare occurrence. We describe the management and discuss the operative strategy we opted for in this patient.


Fighting restenosis after coronary angioplasty: contemporary and future treatment options.
Despite the widespread use of coronary stents, prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains a major challenge. The restenotic process is even higher after balloon angioplasty without stenting and has been shown to be in the range of 30-50%. Experimental data suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ("statins") might have a beneficial effect on restenosis after coronary angioplasty. Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis and inflammation. Although statins have documented efficacy in reducing clinical events and angiographic disease progression in patients with coronary atherosclerosis, the results of subsequent large prospective clinical trials using different types of statins clearly demonstrate that statins do not have a short-to-medium term effect on prevention of restenosis after successful conventional PTCA. The underlying pathological reasons for this shortcoming as well as promising innovative approaches including gene therapy and local drug delivery of vasoactive substances will be discussed in this review.


Granular cell tumor on the sole of a child: a case report.
Granular cell tumor, also known as Abrikossoff tumor, is a rare infrequent neoplasm of unclear etiology which has been rarely described in children. Involvement of the feet is extremely rare. We report a 7-year-old boy presenting a granular cell tumor on the sole.


cDNA cloning and characterization of porcine histamine H4 receptor.
The cDNA encoding histamine H4 receptor was cloned from the porcine spleen cDNA library. Porcine H4 receptor, which shares 72% homology with its human counterpart, bound to histamine in receptor-expressing mammalian cells. Isolation of the porcine H4 receptor, which is important for understanding of the pharmacology, will aid in better interpretation of physiological role of this subtype of histamine receptor.


Chloroplast tRNA(Asp): nucleotide sequence and variation of in vivo levels during plastid maturation.
Two chloroplast tRNA(Asp) species from barely were purified by chromatography on benzoylated DEAE-cellulose and sequenced. They differ in the modification at position 34, where queuosine (Q) is present in one of the species. The same chromatographic procedure yielded only one tRNA(Glu) species, corroborating the assumption that the same tRNA(Glu) species participates in both protein and chlorophyll biosynthesis. The level of tRNA(Glu) remains unchanged after light treatment of etiolated seedlings, whereas the amount of tRNA(Asp) decreases to about 50% relative to the level of dark-grown plants.


Discordance between thallium-201 scintigraphy and coronary angiography in patients with Kawasaki disease: myocardial ischemia with normal coronary angiogram.
To assess the usefulness of radionuclide tests in detecting coronary occlusive lesions in children with Kawasaki disease, we compared the results of stress thallium-201 myocardial single photon emission computed tomography with dipyridamole infusion and coronary angiography in 34 patients (19 males and 15 females). Perfusion defects on the stress image only were categorized as transient and were attributed to coronary vascular disease in the presence of redistribution on the delayed image. Others were classified as persistent, due to myocardial damage. Five of the seven children (71%) with severe stenosis on coronary angiography showed persistent and/or transient perfusion defects. However, six of the 11 children (55%) with aneurysms but no obvious stenosis, and four of the 16 children (25%) with normal angiography, showed persistent and/or transient defects. After analyzing 20 individual segments of perfusion defects in the 15 children, six segments (30%) were attributed to the stenosis of supplying coronary arteries, six segments (30%) were related to the coronary aneurysms, and eight segments (40%) were unrelated to any abnormalities on angiography. Thus, significant discordance between the radionuclide and angiographic studies was demonstrated. These results suggest that coronary lesions, as conventionally defined by angiography and supplemented by echocardiography, may not completely identify all Kawasaki patients who may develop myocardial ischemia in the future or who had ischemia in the past.


Gene and protein expression for prolactin, growth hormone and somatolactin in Sparus aurata: seasonal variations.
The seasonal variation of PRL, GH and SL gene and protein expression has been analyzed in gilthead sea bream (Sparus aurata) pituitaries using Real-Time Q-PCR and Western Blots, respectively. Animals were cultured in earthen ponds under natural photoperiod, temperature and salinity conditions. Samples were taken during winter 2005 (January), spring 2005 (April), summer 2005 (July) and autumn 2005 (October). Beta-actin, used as the housekeeping gene both for Q-RT-PCR and Western analysis, did not present significant differences among seasons. Higher expression was observed during spring and autumn for PRL, summer and winter for GH, and spring for SL. Expression of PRI, GH and SL, presented seasonal variation, suggesting that these hormones could play a role in the molecular signal transduction of environmental factors (especially of photoperiod and temperature) in eurythermal fish.


Features of intrinsic ganglionated plexi in both atria after extensive pulmonary isolation and their clinical significance after catheter ablation in patients with atrial fibrillation.
The features of intrinsic ganglionated plexi (GP) in both atria after extensive pulmonary vein isolation (PVI) and their clinical implications have not been clarified in patients with atrial fibrillation (AF). The purpose of this study was to assess the features of GP response after extensive PVI and to evaluate the relationship between GP responses and subsequent AF episodes. The study population consisted of 216 consecutive AF patients (104 persistent AF) who underwent an initial ablation. We searched for the GP sites in both atria after an extensive PVI. GP responses were determined in 186 of 216 patients (85.6%). In the left atrium, GP responses were observed around the right inferior GP in 116 of 216 patients (53.7%) and around the left inferior GP in 57 of 216 (26.4%). In the right atrium, GP responses were observed around the posteroseptal area: inside the CS in 64 of 216 patients (29.6%), at the CS ostium in 150 of 216 (69.4%), and in the lower right atrium in 45 of 216 (20.8%). The presence of a positive GP response was an independent risk factor for AF recurrence (hazard ratio 4.04, confidence interval 1.48-11.0) in patients with paroxysmal, but not persistent, AF. The incidence of recurrent atrial tachyarrhythmias in patients with paroxysmal AF with a positive GP response was 51% vs 8% in those without a GP response (P = .002). The presence of GP responses after extensive PVI was significantly associated with increased AF recurrence after ablation in patients with paroxysmal AF.


A PacI/SwaI map of the Pseudomonas aeruginosa PAO chromosome.
The PacI/SwaI macrorestriction map of the 5.9 Mb Pseudomonas aeruginosa PAO (DSM 1707) genome was constructed by fragment size comparisons of complete single and double digests and hybridization with probes of known genomic localization. P. aeruginosa PAO contains five recognition sites for PacI and six sites for SwaI. An integrated DpnI/PacI/SpeI/SwaI map was obtained by fragment pattern and Southern blot hybridization analyses of all combinations of double digestions and by two-dimensional pulsed-field gel electrophoresis mapping protocols.


Screening for deficits on intrinsic capacity domains and associated healthcare costs.
Intrinsic capacity (IC) defined by the World Health Organization is divided into six domains (locomotion, psychological, vitality/nutrition, cognition, vision and hearing). The main objective of this study therefore is to explore the association between healthcare costs and IC domains deficits among older patients. This longitudinal secondary analysis was performed on data from the Multidomain Alzheimer Preventive Trial (MAPT), a 3-year randomized controlled trial with non-demented community-dwelling participants aged 70 years or over. We used an adapted version of the ICOPE (Integrated Care for Older People) Step 1 to screen for the six operational IC domains deficits at three time-points: baseline, one year and two years. We performed bivariate and multivariate analyzes using generalized linear models and generalized estimating equation models to identify associations between healthcare cost and deficits on IC domains. We analyzed 693 patients (aged 75.2 ± 4.22 years; 64% women (N = 442)). At baseline, among the included patients, 89% had at least one impairment in IC domains (N = 619). A deficit on visual capacity was associated with increased immediate healthcare costs (CR: 1.48; 95CI: [1.16-1.89]). Regarding persistent impairment of IC, locomotor (CR: 1.27; 95CI: [1.01-1.60], additional annual healthcare cost: €1092 per patient) and psychological (CR: 1.28; 95CI: [1.03-1.59], additional annual healthcare cost: €817 per patient) capacities were associated with increased healthcare costs. In conclusion, this study showed that some deficits on IC domains, as measured by simple screening tests and questions, can be associated with higher healthcare costs. gov identifier: NCT00672685.


Do CNS anlagen have plasticity in differentiation? Analysis in quail-chick chimera.
Heterotopic transplantations of brain vesicles of a quail embryo into a chick embryo were carried out in order to elucidate if CNS anlagen have plasticity in differentiation at the 7-10 somite stage. Quail cells are distinguished from chick cells due to the difference in nuclear morphology. The prosencephalon did not differentiate into the cerebellum when transplanted into the metencephalon, although previous study showed that the prosencephalon has the capacity to differentiate into the optic tectum. The mesencephalon differentiated as an optic tectum when transplanted into the prosencephalon or into the rhombencephalon. The metencephalon differentiated as a cerebellum in the telencephalon. It is concluded that only the prosencephalon has limited plasticity, but the mesencephalon and rhombencephalon are determined by the 7-10 somite stage.


Financial Incentives to Enhance Participation of Resident Physicians in Hospital-Based Quality Improvement Projects.
Methods to promote successful trainee participation in quality improvement projects are poorly studied. This project studied the effects of a trainee pay-for-performance program and quality improvement education at a safety-net hospital. In this program, trainees worked with quality improvement faculty, participated in projects aligned with the hospital's priorities, and designed their program-specific project. Each trainee who worked at least 88 days in the institution was eligible to earn $400 for every target achieved for at least six months (maximum of $1,200). Among hospitalwide goals, needlestick injuries per quarter decreased from [mean (standard deviation; SD)] 18 (4.6) to 12 (2.6), 95% confidence interval (CI) = -10.1-1.9, p = 0.02; percentage of excellent provider communication improved from 76.8% to [mean (SD)] 80.5% (2.9), 95% CI = 0.8-8.3, p = 0.08; and mean length of stay for discharged emergency department patients requiring specialist consultation decreased from [mean (SD)] 523 (120) to 461 (40) minutes, 95% CI = -162-37.2, p = 0.11. Among resident-initiated projects, the percentage of Family Medicine patients undergoing colorectal screening increased from 65.1% to [mean (SD)] 67.7% (0.4), 95% CI = 1.7-3.5, p = 0.01; percentage of at-risk patients receiving naloxone at hospital discharge increased from 9% to [mean (SD)] 63% (7.2), 95% CI = 36.1-71.9, p = 0.01; percentage of adolescents screened for chlamydia increased from 34% to [mean (SD)] 55.8% (6.4), 95% CI = 5.9-37.6, p = 0.03; and percentage of high-dose opioid prescriptions following cesarean section decreased from 28% to [mean (SD)] 1.7% (2.9), 95% CI = -33.5 to -19.2, p = 0.001. Eleven of 14 programs achieved three goals. All resident-led goals were met. A pay-for-performance improvement program that aligns educational and hospital priorities can provide meaningful experiential learning for trainees and improve patient care.


[Primary cutaneous CD4+ small to medium-sized T-cell lymphoma in an adolescent patient].
A rare finding of primary cutaneous CD4+ small to medium-sized T‑cell lymphoma (SMPTCL) in a fifteen-year-old patient is reported. This is a rare tumor entity for which there is currently no standardized treatment recommendation. At the interdisciplinary tumor board, the decision was made to resect the tumor and reconstruct the defect with a nasolabial advancement flap in a two-stage process. Follow-up examinations, currently over 3 years, have shown the patient to be free of recurrences.


Advances in Tea Chemistry.
The origins of tea, a traditional beverage in China, can be traced back to the Shennong period, about 2737 years before the birth of Christ [...].


Lymphokine-activated killer (LAK) and adherent LAK (A-LAK) activity in multiple sclerosis.
The cytotoxic activity of lymphokine-activated killer (LAK) cells against enriched cultures of oligodendrocytes (OL) was investigated in multiple sclerosis (MS) and controls. Human LAK cells, derived from macrophage-depleted peripheral blood mononuclear cells (PBMC) and incubated with recombinant human interleukin-2 (IL-2) (20-80 U/ml), mediated high levels of cytotoxicity against Raji cells but low levels of cytotoxicity against primary cultures of bovine OL. Cytotoxicity was not enhanced by incubation with a high level of IL-2 (500 U/ml). No statistically significant differences in LAK cell activity against bovine OL were observed among the study groups. Enriched adherent LAK (A-LAK) cells mediated greater levels of cytotoxicity against both bovine OL and tumor cell lines than unfractionated LAK cells. Flow cytometric analysis indicated that A-LAK effector cells were CD4-, CD8+, and CD16+. Furthermore, A-LAK cells mediated lysis of OL derived from several different animal species. Our results suggest that LAK and A-LAK cells can mediate cytolysis of OL in culture similar to that observed with a number of different tumor cell lines. However, no significant difference in cytolysis was identified between MS and control groups in this study.


[The individualization and organogenesis of the embryonic gonad in the gonochoric prosobranch molluscViviparus viviparus L.]
The origin and evolution of the embryonic gonad ofViviparus viviparus were studied ultrastructurally. The gonad is formed by migration and multiplication of pericardial cells.There are several successive stages during gonad organogenesis: during the sexually undifferentiated stage with one cellular type, the gonad is made up of primordial cells which seem to be identical. The sexually undifferentiated stage with two cell types is characterized by the differentiation of germinal and non-germinal cells. The non-germinal cells are linked to one another by septate junctions and their long extensions completely surround the germinal cells which remain isolated and do not form junctions with their neighbours. The gonad sexualisation does not appear until after organogenesis, towards the end of embryonic development, or even after birth.


Bacterial community in saline farmland soil on the Tibetan plateau: responding to salinization while resisting extreme environments.
Salinization damages the health of soil systems and reduces crop yields. Responses of microbial communities to salinized soils and their functional maintenance under high salt stress are valuable scientific problems. Meanwhile, the microbial community of the salinized soil in the plateau environment is less understood. Here, we applied metagenomics technology to reveal the structure and function of microorganisms in salinized soil of the Tibetan Plateau. The diversity of composition and function of microbial community in saline soil have changed significantly. The abundances of chemoautotrophic and acidophilic bacteria comprising Rhodanobacter, Acidobacterium, Candidatus Nitrosotalea, and Candidatus Koribacter were significantly higher in saline soil. The potential degradation of organic carbon in the saline soil, as well as the production of NO and N2O via denitrification, and the production of sulfate by sulfur oxidation were significantly higher than the non-saline soil. Both types of soils were rich in genes encoding resistance to environmental stresses (i.e., cold, ultraviolet light, and hypoxia in Tibetan Plateau). The resistance of the soil microbial communities to the saline environment is based on the absorption of K+ as the main mechanism, with cross-protection proteins and absorption buffer molecules as auxiliary mechanisms in our study area. Network analysis showed that functional group comprising chemoautotrophic and acidophilic bacteria had significant positive correlations with electrical conductivity and total sulfur, and significant negative correlations with the total organic carbon, pH, and available nitrogen. The soil moisture, pH, and electrical conductivity are likely to affect the bacterial carbon, nitrogen, and sulfur cycles. These results indicate that the specific environment of the Tibetan Plateau and salinization jointly shape the structure and function of the soil bacterial community, and that the bacterial communities respond to complex and harsh living conditions. In addition, environmental feedback probably exacerbates greenhouse gas emissions and accelerates the reduction in the soil pH. This study will provide insights into the microbial responses to soil salinization and the potential ecological risks in the special plateau environment.


Endoscopic correction of primary VUR by using polyacrylate polyalcohol copolymer (Vantris) in young girls: 2-year follow-up.
Our aim was to evaluate the efficacy and safety of single endoscopic injection of Vantris in young girls affected by primary vesicoureteral reflux (VUR) at more than 2 years of prospective follow-up. Over the last 4 years, 73 girls with primary VUR of grades (G) I-IV underwent a single endoscopic injection of Vantris. The mean age was 8.48 (SD=4.8) years. VUR was unilateral in 73 and bilateral in 13 patients, comprising 86 renal refluxing units (RRUs). Pre-operative evaluation consisted of: blood biochemistry, urine analysis and culture, ultrasound scan, voiding cystourethrogram (VCUG), and dimercaptosuccinic acid (DMSA) renal isotope scan. Patients were followed using ultrasound scans at 1 month and every 3 months for the first year and then 2 years after injection. Direct radionuclide cystography with technetium pertechnetate was performed at 3 and 12 months after injection. VCUG was performed only in confirmed cases of failure and downgraded VUR at 3, 12, and 24 months after endoscopic correction. Sixty-nine (95%), 61 (83.4%), and 52 (71%) patients completed 3, 12, and 24 months' follow-up respectively. VUR was corrected and downgraded to G I in 81% and 3.3% of RRUs at 3 months' follow-up. The corrected and downgraded RRUs at 12 and 24 months' follow-up were 77%, 10%, and 77%, 11% respectively. De novo contralateral G I VUR was demonstrated in 8.6% of normal ureters. Contralateral GI VUR with normal DMSA isotope renal scans was resolved in 71% of RRUs. Febrile urinary tract infection decreased to 4.1% in the patients. According to our study, a single Vantris injection provides a high level of efficacy and safety in the treatment of primary G I-IV VUR in young girls, at 2 years' prospective follow-up.


Melatonin modulates proliferation of pancreatic stellate cells through caspase-3 activation and changes in cyclin A and D expression.
In this study, the effects of melatonin (1 μM-1 mM) on pancreatic stellate cells (PSC) have been examined. Cell viability and proliferation, caspase-3 activation, and the expression of cyclin A and cyclin D were analyzed. Our results show that melatonin decreased PSC viability in a time- and concentration-dependent manner. This effect was not inhibited by treatment of cells with MT1, MT2, calmodulin, or ROR-alpha inhibitors prior to melatonin addition. Activation of caspase-3 in response to melatonin was detected. The expression of cyclin A and cyclin D was decreased in cells treated with melatonin. Finally, changes in BrdU incorporation into the newly synthesized DNA of proliferating cells were also observed in the presence of melatonin. We conclude that melatonin, at pharmacological concentrations, modulates proliferation of PSC through activation of apoptosis and involving crucial regulators of the cell cycle. These actions might not require specific melatonin receptors. Our observations suggest that melatonin, at high doses, could potentially exert anti-fibrotic effects and, thus, could be taken into consideration as supportive treatment in the therapy of pancreatic diseases.


Age at natural menopause and mortality: A survival analysis of elderly residents of São Paulo, Brazil.
To conduct a survival analysis according to age at natural menopause (NM) in a representative sample of elderly women from the municipality of São Paulo, Brazil. We analyzed data from the Health, Well-Being and Aging study (SABE), a cohort that started in 2000. Mortality data up to September 2016 were obtained by linkage from the Program for Mortality Information of São Paulo (PRO-AIM). We used Cox regression to analyze all-cause and cause-specific mortality rates for cardiovascular diseases, respiratory diseases and cancer, according to age at menopause, categorized as <40, 41-44, 45-49, 50-54 (reference) and ≥55. After 16 years of follow-up, there were 444 deaths, of which 199 were from cardiovascular diseases, 73 from respiratory diseases and 65 from cancer. After adjustment for socioeconomic, reproductive and lifestyle factors, having an early menopause (at age 41-44) was associated with an increased risk of all-cause mortality (HR = 1.48, 95% IC: 1.03, 2.14) relative to NM at 50-54 years. Women aged 41-44 and 45-49 at NM had twice the risk of cancer mortality of the reference group. We did not find significant associations between age at NM and cause-specific mortality for respiratory and cardiovascular diseases. Our findings suggest that early menopause is associated with all-cause mortality in the largest city of Latin America. In addition, earlier age at NM was associated with cancer mortality. These results suggest that age at NM may be a biomarker for mortality, irrespective of country of residence.


Feedback by simulated patients in undergraduate medical education: a systematic review of the literature.
Although the importance of feedback by simulated patients (SPs) is generally recognised, knowledge is scarce about the most effective ways in which SPs can provide feedback. In addition, little is known about how SPs are trained to provide feedback. This study aimed to provide a systematic overview of the ways in which SPs provide feedback to undergraduate medical students, the domains in which SPs provide feedback and the ways in which SPs are trained to provide feedback. We performed a systematic search of the literature using PubMed, PsychINFO and ERIC and searched for additional papers cited in reference lists. Papers were selected on the basis of pre-established inclusion and exclusion criteria and were classified, using a pre-established form, according to three aspects of SP feedback: training in giving feedback; the process of delivering feedback, and the domain(s) in which feedback is given. A total of 49 studies were included and described in detail on the basis of the three aspects of SP feedback described above. The ways in which SPs were trained to give feedback were largely heterogeneous, as were the processes by which feedback was provided by SPs. Only a few studies described feedback processes that were in accordance with general recommendations for the delivery of effective feedback. Although feedback from the patient's perspective is generally recommended, most SPs provided feedback on clinical skills and communication skills. There appear to be no clear standards with regard to effective feedback training for SPs. Furthermore, the processes by which feedback is provided by SPs and the selection of domain(s) in which SPs give feedback often seem to lack a solid scientific basis. Suggestions for further research are provided.


An example of cocaine tolerance in a gunshot wound fatality.
A 29-year-old male received a fatal gunshot wound to the head during an altercation. Routine toxicological followup on the victim revealed a concentration of 30 mg/L of cocaine in the blood. The case history presented suggests that the concentration achieved by this individual was the result of a physiological tolerance developed from years of consistent recreational use and not by an intentional or accidental overdose.


Three-year changes of cortical 18F-FDG in amnestic vs. non-amnestic sporadic early-onset Alzheimer's disease.
To examine and compare longitudinal changes of cortical glucose metabolism in amnestic and non-amnestic sporadic forms of early-onset Alzheimer's disease and assess potential associations with neuropsychological performance over a 3-year period time. Eighty-two participants meeting criteria for early-onset (< 65 years) sporadic form of probable Alzheimer's disease and presenting with a variety of clinical phenotypes (47 amnestic and 35 non-amnestic forms) were included at baseline and followed up for 1.44 ± 1.23 years. All of the participants underwent a work-up at baseline and every year during the follow-up period, which includes clinical examination, neuropsychological testing, genotyping, cerebrospinal fluid biomarker assays, and structural MRI and 18F-FDG PET. Vertex-wise partial volume-corrected glucose metabolic maps across the entire cortical surface were generated and longitudinally assessed together with the neuropsychological scores using linear mixed-effects modeling as a function of amnestic and non-amnestic sporadic forms of early-onset Alzheimer's disease. Similar evolution patterns of glucose metabolic decline between amnestic and non-amnestic forms were observed in widespread neocortical cortices. However, only non-amnestic forms appeared to have a greater reduction of glucose metabolism in lateral orbitofrontal and bilateral medial temporal cortices associated with more severe declines of neuropsychological performance compared with amnestic forms. Furthermore, results suggest that glucose metabolic decline in amnestic forms would progress along an anterior-to-posterior axis, whereas glucose metabolic decline in non-amnestic forms would progress along a posterior-to-anterior axis. We found differences in spatial distribution and temporal trajectory of glucose metabolic decline between amnestic and non-amnestic early-onset Alzheimer's disease groups, suggesting that one might want to consider treating the two forms of the disease as two separate entities.


[Renal Dysfunction in Patients With Ischemic Heart Disease].
We studied effects of various forms of coronary heart disease on the progression of renal dysfunction. Three groups of patients were examined: 1 - patients with exertional angina (n=29), 2 - patients with old myocardial infarction (postinfarction cardiosclerosis) and exertional angina (n=22), 3 - patients with atrial fibrillation and exertional angina (n=21). Most pronounced anatomic and functional abnormalities of cardiac action and respective statistically more significant renal dysfunction were revealed in group 3.


Impact of Human Immunodeficiency Virus Infection on Takotsubo Cardiomyopathy Outcomes in a Large Nationwide Sample.
Takotsubo cardiomyopathy (TCM) or stress-induced cardiomyopathy is characterized by transient wall-motion abnormalities often preceded by physical or emotional stress. Various baseline medical comorbidities were associated with worse outcomes, theoretically due to their effect on chronic stress exposure. The effect of concurrent human immunodeficiency virus (HIV) infection on outcomes of TCM has not been well-established. We conducted a US-wide analysis of TCM hospitalizations from 2006 to 2014 by querying the National Inpatient Sample database for the International Classification of Diseases, Ninth Revision TCM code, baseline characteristics, and inpatient outcomes. TCM patients with HIV were compared to TCM patients without HIV. Multivariate regression models were constructed to account for potential confounders. We identified 123,050 patients hospitalized with TCM; of those patients, 304 had positive HIV status. In an unadjusted analysis, in-hospital outcomes were worse in TCM patients with HIV infection in terms of development of acute kidney injury (16.8% vs 33.3%, P-value 0.002), use of invasive mechanical ventilation (18.3% vs 34.5%, P-value 0.003), and mortality (5.3% vs 17.1%, P-value <0.0001). After adjusting for age, gender, and comorbidities, there was no significant difference in the captured outcomes. TCM patients with concurrent HIV had numerically worse outcomes. After adjusting for potential confounders, the statistical significance no longer existed, suggesting that statistical difference was primarily driven by difference in baseline sociodemographic parameters and coexisting comorbidities.


Daqu microbiota exhibits species-specific and periodic succession features in Chinese baijiu fermentation process.
Daqu, a brick-shaped product spontaneously fermented under an open environment, has been regarded as the starter of fermentation, raw enzyme preparation and raw materials for baijiu production. However, its contribution in baijiu fermentation has not been fully elaborated yet. Here, the effects of daqu microbiota on baijiu fermentation were investigated under both field-scale and lab-scale conditions. In field-scale baijiu fermentation, the dominant daqu microbes (average relative abundance>10.0%), including unclassified_Leuconostocaceae, Thermoascus, and Thermomyces, tended to dominate the early stage (0-7 d). However, the rare daqu microbes (average relative abundance <0.1%, e.g., Kazachstania) tended to dominate the middle and late stages (11-40 d). In addition, some genera showed differences in species diversity between daqu and fermented grains. The average relative abundance of Lactobacillus was over 75% during baijiu fermentation, and most of them were affiliated with Lactobacillus acetotolerans, while Lactobacillus crustorum dominated the Lactobacillus OTUs in daqu. The similar patterns were also observed during lab-scale baijiu fermentation. The results of function prediction showed the enriched metabolic pathways were associated with glycolysis and long-chain fatty acid esters in baijiu fermentation. These results improved the understanding of daqu microbiota function during baijiu fermentation and provided a basic theory to support the regulation of baijiu production.


Biochanin A inhibits lipopolysaccharide-induced inflammatory cytokines and mediators production in BV2 microglia.
Biochanin A, one of the major isoflavonoids in red clover or cabbage, has been reported to have anti-inflammatory effects. However, the molecular mechanism underlying the anti-inflammatory effects of biochanin A has not been completely elucidated. The aim of this study was to investigate the anti-inflammatory effect and mechanism on lipopolysaccharide (LPS)-stimulated BV2 microglia. The results showed that biochanin A suppressed LPS-induced inflammatory mediators nitric oxide, prostaglandin E2 and inflammatory cytokines TNF-α and IL-1β production. LPS-induced NF-κB activation was also inhibited by biochanin A. In addition, biochanin A up-regulated the expression of PPAR-γ and the anti-inflammatory effects of biochanin A can be abolished by PPAR-γ antagonist GW9662. These results suggest that biochanin A exerts an anti-inflammatory property by activating PPAR-γ, thereby attenuating NF-κB activation and the release of pro-inflammatory mediators.


Predicting allergic diseases in children using genome-wide association study (GWAS) data and family history.
The recent rise in the prevalence of chronic allergic diseases among children has increased disease burden and reduced quality of life, especially for children with comorbid allergic diseases. Predicting the occurrence of allergic diseases can help prevent its onset for those in high risk groups. Herein, we aimed to construct prediction models for asthma, atopic dermatitis (AD), and asthma-AD comorbidity (also known as atopic march) using a genome-wide association study (GWAS) and family history data from patients of Korean heritage. Among 973 patients and 481 healthy controls, we evaluated single nucleotide polymorphism (SNP) heritability for each disease using genome-based restricted maximum likelihood (GREML) analysis. We then compared the performance of prediction models constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and penalized ridge regression methods. Our results indicate that the addition of family history risk scores to the prediction model greatly increase the predictability of asthma and asthma-AD comorbidity. However, prediction of AD was mostly attributable to GWAS SNPs.


Emphysematous pyelonephritis: a 5-year experience with 13 patients.
Emphysematous pyelonephritis is a life-threatening necrotizing renal infection characterized by the production of gas. Of 8,105 admissions to our diabetes service during the last 5 years we identified 13 cases. The patients were managed aggressively with fluids and antibiotics, followed by immediate nephrectomy. The mortality rate is 40 to 50 per cent, primarily owing to sudden septic complications.


Histone H3 phospho-regulation by KimH3 in both interphase and mitosis.
Histone H3 is phosphorylated at Ser10 by multiple kinases, and many of them are anti-cancer targets. Here, we report the first kinase that can phosphorylate H3Ser10 in both interphase and mitosis, which we named KimH3 (kinase of interphase and mitotic Histone H3). Meta-analysis indicates that KimH3 is upregulated in a broad spectrum of human cancers and its high expression is correlated with reduced the median survival time of cancer patients. In mitosis, CDK1 phosphorylates KimH3, which then phosphorylates H3Ser10 to regulate cell cycle procession. In interphase, EGF induces KimH3 activation and H3Ser10 phosphorylation, which is involved in MAPK-ERK1/2 signaling pathway to activate immediate-early genes transcription. Consequently, a small molecule inhibitor of KimH3 significantly inhibited tumor growth in mice. This is not only consistent with the dual roles of KimH3 in both interphase and mitotic Histone H3 phosphorylation, but also reveals it as an important potential anti-cancer target.


Effects of the dopaminergic agonist cianergoline on blood pressure, the renin-angiotensin-aldosterone axis and the sympathetic nervous system in patients with essential hypertension.
Cianergoline is a new dopaminergic agonist with a predominant cardiovascular action. Its effects on blood pressure, the renin-angiotensin-aldosterone axis, the sympathetic nervous system and lipid metabolism were assessed in 20 patients with benign essential hypertension. Cianergoline given in increasing doses for 4 weeks (maximum daily dose 12 +/- 2 mg (SD)) and placebo both caused a slight decrease in arterial pressure, (from 159/104 to 152/98 mm Hg and from 154/104 to 149/103 mm, respectively; difference not significant). Supine and upright plasma renin activity, plasma aldosterone, norepinephrine, epinephrine and dopamine levels, urinary catecholamine excretion rates as well as serum prolactin, low and high density cholesterol and triglyceride concentrations were not changed after cianergoline or placebo. Total serum cholesterol and triglyceride levels decreased significantly after placebo, but were unchanged after cianergoline. 3 out of 10 patients in the cianergoline group complained of nausea. The findings indicate that the new dopaminergic agonist cianergoline exerts only a mild blood pressure lowering effect in patients with essential hypertension and does not modify the release of prolactin, lipid metabolism or the basal activity or postural responsiveness of the renin-angiotensin-aldosterone axis and of the sympathetic nervous system.


Attentional engagement, appearance comparisons, and rumination as predictors of body dissatisfaction: Evaluation of a serial mediation model in men.
Elevated body dissatisfaction is underpinned by an attentional bias towards images portraying appearance ideals. However, very little is known about the specific attentional mechanisms and mediating factors involved in this relationship in the context of male body dissatisfaction. The present study sought to replicate and extend on previous research among women showing that the relationship between attentional engagement bias and body dissatisfaction is sequentially mediated by appearance comparisons and rumination. Seventy undergraduate males completed an attentional task capable of independently assessing biased attentional engagement with images of muscular and non-muscular bodies followed by self-report measures of appearance comparisons, eating disorder-specific rumination, and body dissatisfaction. Results revealed that a heightened tendency to engage in appearance comparisons was associated with increased attentional engagement with muscular bodies, relative to non-muscular bodies. Moreover, a serial mediation analysis revealed that increased attentional engagement with muscular bodies was associated with appearance comparisons, which in turn were associated with eating disorder-specific rumination and, consequently, body dissatisfaction. The current findings replicate among men the serial mediation model of body dissatisfaction previously described among women and implicate heightened attentional engagement with idealized images as a potential pathway to body dissatisfaction in men.